BLOOD RADOSTITS Veterinary Medicine 10th Edition

VETERINARY

MEDICINE

A textbook of the diseases of cattle, sheep
goats, pigs and horses

10th Edition

Otto M Radostits,
Clive C Gay,

Kenneth W Hinchcliff,
Peter D Constable

v\i,sm KS

VETERINARY

MEDICINE

A textbook of the diseases of cattle,
horses, sheep, pigs and goats

I

For Elsevier:

Commissioning Editor: Joyce Rodenhuis
Development Editor: Rita Demetriou-Swanwick
Project Manager: Elouise Ball
Designer: Andy Chapman
Illustration Manager: Gillian Richards
Illustrator: Oxford Illustrations

A textbook of the diseases of cattle,
horses, sheep, pigs and goats

TENTH EDITION

O. M. Radostits

C. C. Gay

K. W. Hinchcliff

P. D. Constable

With contributions by

S. H. Done

D. E. Jacobs
B. O. Ikede

R. A. McKenzie
D. Colwell
G. Osweiler
R. J. Bildfell

ELSEVIER

Edinburgh London New York Oxford

Philadelphia St Louis Sydney Toronto

DR. OTTO M. RADOSTITS, August 31, 1934 - December 15, 2006.
Senior author 5th to 7th editions. Lead author 8th to 10th editions.

Otto Martin Radostits died after a difficult but courageous battle
with renal carcinoma and it is sad that he died a few days before
the release of the first printing of this 10th edition. His passing
marked the end of his remarkable career as an educator in large
animal veterinary medicine. Through his writings, not the least
this text, Otto had a profound influence on students and practic-
ing veterinarians throughout the world.

Otto was raised on a small mixed farm in Alberta, Canada; the
eldest son of Austrian immigrants. His early farm experiences and
those obtained from working with a local veterinarian while
attending high school sparked an interest in pursuing a career in
veterinary science and were the beginning of his lifelong passion
with large animal veterinary medicine. He was admitted to the
Ontario Veterinary College in 1954, at that time the only English-
speaking veterinary school in Canada. During his undergraduate
years his clinical interests and potential were recognized such.-
that following graduation he was invited to join the faculty as a •
member of the ambulatory clinic practice of the College - at that
time a vigorous practice in a rural area. Otto spent the next five
years teaching in this position, with the exception of a year spent
at the veterinary school at Purdue University in West Lafayette,
Indiana.

The Western College ofVeterinary Medicine in Saskatchewan,
Canada, was established in the mid 1960s and Otto was one of
thefoundingfaculty. He established the ambulatory practice and
helped design the college clinical buildings and finalize the cur-
riculum. He remained a faculty member at the Western College of
Veterinary Medicine until he retired in June 2002 and was
awarded the title Emeritus Professor. Here he matured as a clini-
cal teacher to influence students and veterinarians locally and
internationally through his writings and presentations at veteri-
nary meetings.

Otto's international recognition in large animal veterinary
medicine rests mainly in the strength of his writing and author-
ship of veterinary texts. These span the spectrum of large animal
veterinary medicine from the clinical examination of the individ-
ual animal, the epidemiology, diagnosis, treatment and control of
livestock diseases, to herd health and preventive medicine.

The most notable are his contributions to this textbook, which
has been used by veterinary students and practicing veterinarians
around the world for the past 45 years. Otto joined the original
authors, Doug Blood and Jim Henderson, for the 5th edition of this
text in 1979 and, in 1994, became the senior author for the 8th and
subsequent editions. During his sojourn as senior author the text
continued its original design as a student textbook with many

student friendly features. It also continued its significance as a refer-
ence book including the available information on all the diseases of
large animals, a truly formidable task. Otto did a large part of the
work and would surely have been very proud of this new edition.

In the writing of these and his other texts Otto read the veteri-
nary literature and was a firm believer in evidenced-based medi-
cine. He insisted that all statements in these texts were supported
by references in the literature and he maintained the format of a
very large bibliography at the end of each disease description. He
believed that other veterinary educators should also be current
with the veterinary literature and had little brief for those who
were not. He could be a forceful presence in discussions but Otto
was also one of the quickest to recognize new information that
negated previous theories concerning a disease and was one who
was always responsive to reasoned argument.

Otto taught that making a correct diagnosis was the crux to
the solution of a disease problem and he had a passion for the art
and science of clinical examination. And many of his students
affectionately remember his admonition "We make more mis-
takes by not looking than by not knowing". Otto's insistence on
the need for accurate diagnosis did not preclude this realization
that what the practicing veterinarian needed as the final message
from his books was what was the best current information on
what to do to cure or prevent it.

Otto has authored other texts. In the late 1990's he became
concerned that traditional skills of physical clinical examination
were being supplanted by laboratory and instrumental analysis.
As a consequence he consulted with veterinary clinicians around
the world and in 2000 was a senior author of the text"Veterinary
clinical examination and diagnosis". With his work on farms Otto
recognized that disease in farm animals commonly was a popu-
lation concern and recognized the limitations of "fire brigade"
medicine. He authored the first major text in herd health and pre-
ventive medicine with its first edition in 1985. Otto has many
other publications of significance to global veterinary medical
education and presented more than 250 invited lectures and
seminars in veterinary medicine in countries around the world.

Dr Radostits' contributions have been recognized in many
awards. For him, probably the most important was the award of
Master Teacher from his university and, nationally, the Order of
Canada. The early requirement for a second printing of this 10th
edition attests Dr Radostits excellence as the senior author of this
text and also allows us to insert this dedication to him. We thank
Elsevier and the Publishing Editor ofVeterinary Medicine for the
opportunity to include this dedication in this second printing.

Table of Contents

List of tables vii

List of illustrations ix

List of contributors x

Preface to Tenth Edition xiii

Introduction xv

How to use this book xxi

PART ONE: GENERAL MEDICINE
1. Clinical examination and making

a diagnosis 3

Clinical examination of the individual

animal 3

Making a diagnosis 22

Prognosis and therapeutic

decision-making 29

Examination of the herd 31

2. General systemic states 39

Hypothermia, hyperthermia, fever . . .39

Septicemia/viremia 51

Toxemia and endotoxemia 53

Hypovolemic, hemorrhagic,

maldistributive and obstructive

shock 63

Allergy and anaphylaxis 69

Edema 72

Disturbances of free water,
electrolytes and acid-base balance . .73

Pain 102

Stress 107

Localized infections 110

Disturbances of appetite, food

intake and nutritional status 112

Weight loss or failure to gain

weight (ill-thrift) 115

Physical exercise and associated

disorders 117

Diagnosis and care of recumbent

adult horses 120

Sudden or unexpected death 124

3. Diseases of the newborn 127

Perinatal and postnatal diseases . . . .127

Congenital defects 132

Physical and environmental causes

of perinatal disease 138

Diseases of cloned offspring 145

Neonatal infection 146

Clinical assessment and care of
critically ill newborns 160

4. Practical antimicrobial

therapeutics 173

Principles of antimicrobial therapy . .173
Practical usage of antimicrobial
drugs 177

5. Diseases of the alimentary

tract - I 189

Principles of alimentary tract

dysfunction 189

Manifestations of alimentary tract

dysfunction 191

Special examination 195

Principles of treatment in alimentary

tract disease 203

Diseases of the buccal cavity and

associated organs 205

Diseases of the pharynx and

esophagus 209

Diseases of the nonruminant
stomach and intestines 215

Congenital defects of the alimentary

tract 280

Neoplasms of the alimentary tract . .281
Diseases of the peritoneum 282

6. Diseases of the alimentary

tract -II 293

Diseases of the forestomach of

ruminants 293

Special examination of the
alimentary tract and abdomen of

cattle 301

Diseases of the rumen, reticulum

and omasum 311

Diseases of the abomasum 353

Diseases of the intestines of
ruminants 375

7. Diseases of the liver and

pancreas 383

Diseases of the liver - introduction .383
Principles of hepatic dysfunction . . .383
Manifestations of liver and biliary

disease 384

Special examination of the liver . . . .387
Principles of treatment in diseases

of the liver 391

Diffuse diseases of the liver 391

Focal diseases of the liver 395

Diseases of the pancreas 396

8. Diseases of the cardiovascular

system 399

Principles of circulatory failure 399

Manifestations of circulatory

failure 401

Special examination of the

cardiovascular system 405

Arrhythmias 413

Diseases of the heart 421

Diseases of the blood vessels 434

9. Diseases of the hemolymphatic and

immune systems 439

Abnormalities of plasma protein

concentration 439

Hemorrhagic disease 441

Disorders of red cell number or

function 450

Disorders of white cells 460

Lymphadenopathy (lymphadenitis) . .464
Diseases of the spleen and

thymus 464

Immune deficiency disorders (lowered

resistance to infection) 466

Amyloidoses 467

Porphyrias 469

10. Diseases of the respiratory

system 471

Principles of respiratory

insufficiency 471

Principal manifestations of respiratory

insufficiency 473

Special examination of the respiratory

system 480

Principles of treatment and control of

respiratory tract disease 493

Diseases of the lungs 498

Diseases of the pleura and

diaphragm 519

Diseases of the upper respiratory
tract 530

1 1. Diseases of the urinary system . . .543

Introduction 543

Principles of renal insufficiency . . . .543
Clinical features of urinary tract

disease 545

Special examination of the urinary

system 548

Principles of treatment of urinary

tract disease 553

Diseases of the kidney 555

Diseases of the bladder, ureters and

urethra 561

Congenital defects of the urinary
tract 571

12. Diseases of the nervous

system 575

Principles of nervous dysfunction . . .576
Clinical manifestations of disease

of the nervous system 577

Special examination of the nervous

system 583

Principles of treatment of diseases

of the nervous system 594

Pathophysiological mechanisms

of nervous system disease 596

Diffuse diseases of the brain 596

Focal diseases of the brain 606

Diseases of the meninges 609

Toxic and metabolic

encephalomyelopathies 611

Psychoses or neuroses 61 2

Epilepsy 613

Diseases of the spinal cord 613

Diseases of the peripheral nervous

system 618

Congenital defects of the central
nervous system': 619

13. Diseases of the musculoskeletal

system 621

Principal manifestations of

musculoskeletal disease 621

Diseases of muscles 626

Diseases of bones 632

Diseases of joints 637

Congenital defects of muscles,
bones and joints 648

14. Diseases of the skin, conjunctiva

and external ear 651

Principles of treatment of diseases

of the skin 653

Diseases of the epidermis and

dermis 654

Diseases of the hair, wool, follicles,
skin glands, horns and

hooves 661

Diseases of the subcutis 664

Granulomatous lesions of the

skin 667

Cutaneous neoplasms 667

Congenital defects of the skin 669

Congenital skin neoplasms 669

Diseases of the conjunctiva 670

Congenital defects of the eyelids

and cornea 670

Diseases of the external ear 670

15. Diseases of the mammary

gland 673

Introduction 673

Bovine mastitis 673

Mast itis pathogens of cattle 697

Table of contents

VIII

Mastitis of cattle associated with
common contagious pathogens . . .697
Mastitis associated with teat skin

opportunistic pathogens 708

Mastitis of cattle associated with
common environmental

pathogens 709

Mastitis of cattle associated with

less common pathogens 724

Miscellaneous causes of bovine

mastitis 726

Control of bovine mastitis 728

Miscellaneous abnormalities of the

teats and udder 749

Mastitis-metritis-aga lactia

syndrome in sows 754

Mastitis of sheep 759

Mastitis of goats 761

Mastitis of mares 762

PART TWO: SPECIAL MEDICINE

16. Diseases associated with

bacteria - I 765

Introduction to infectious

disease 765

Diseases associated with

Streptococcus species 768

Diseases associated with

Staphylococcus species 783

Diseases associated with
Corynebacterium, Rhodococcus,
Actinobaculum and Arcanobacterium

species 787

Diseases associated with Listeria

species 805

Diseases associated with Erysipelothrix

rhusiopathiae (insidiosa) 81 0

Diseases associated with
Bacillus species 81 5

17. Diseases associated with

bacteria - II 821

Diseases associated with Clostridium
species 821

18. Diseases associated with

bacteria - III 847

Diseases associated with

Escherichia coli 847

Escherichia coli infections in

weaned pigs 888

Diseases associated with Salmonella

species 896

Diseases associated with Pasteurella

species 921

Diseases associated with Brucella

species 963

Diseases associated with Moraxella,
Histophilus and Haemophilus
species 994

19. Diseases associated with

bacteria - IV 1007

Diseases associated with

Mycobacterium spp 1 007

Diseases associated with Actinomyces,
Actinobacillus, Nocardia and
Dermatophilus spp 1044

20. Diseases associated with

bacteria -V 1061

Diseases associated with Fusobacterium
and Bacteroides spp 1061

Diseases associated with Pseudomonas

and Burkholderia spp 1081

Diseases associated with

Campylobacter spp 1085

Diseases associated with

Leptospira Borrelia spp 1094

Diseases associated with
Mycoplasma spp 1123

21. Disease associated with viruses

and Chlamydia - I 1157

Viral diseases with manifestations
attributable to involvement of the

body as a whole 1157

Viral diseases characterized by
alimentary tract signs 1223

22. Diseases associated with viruses

and chlamydia - II 1307

Viral diseases characterized by

respiratory signs 1307

Viral diseases characterized by

nervous signs 1368

Viral diseases characterized by skin

lesions 1418

Diseases associated with
Chlamidiae 1433

23. Diseases associated with

prions 1439

24. Diseases associated with

Rickettsiales 1455

25. Diseases associated with algae

and fungi 1471

Algal diseases 1471

Fungal diseases . .1471

Dermatomycoses 1476

26. Diseases associated with

protozoa 1483

Diseases associated with
trypanosomes 1531

27. Diseases associated with

helminth parasites 1541

Nematode diseases of the

alimentary tract 1541

Nemotode diseases of other

organs 1564

Diseases associated with trematodes
and cestodes 1576

28. Diseases associated with

arthropod parasites 1585

Ked and louse infestations 1596

Tick infestations 1599

Miscellaneous flies, midges and

mosquitoes 1603

Mite infestations 1606

29. Metabolic diseases 1613

Production diseases . .1618

30. Diseases associated with nutritional

deficiencies 1691

Deficiencies of energy and protein .1697
Diseases associated with deficiencies

of mineral nutrients 1698

Disease associated with deficiencies

of fat-soluble vitamins 1771

Diseases associated with deficiency
of water-soluble vitamins 1778

31. Diseases associated with physical

agents 1785

32. Diseases associated with inorganic

and farm chemicals 1798

Diseases associated with inorganic

poisons 1799

Diseases associated with farm

chemicals 1830

Miscellaneous farm chemicals . . . .1846

33. Diseases associated with toxins in

plants, fungi, cyanobacteria,
clavibacteria, insects and

animals 1851

Diseases associated with major

phytotoxins 1851

Poisoning by mycotoxins 1897

Poisoning by cyanophyte

(cyanobacterial) toxins 1913

Poisoning by tunicaminyluracils

(corynetoxins) 1914

Diseases associated with zootoxins
(animal bites and stings) 191 5

34. Diseases associated with

allergy 1921

35. Diseases associated with the

inheritance of undesirable

characteristics 1937

Diseases characterized by

chromosomal anomalies 1939

Inherited defects of the body as a

whole 1940

Inherited defects of the alimentary

tract 1943

Inherited defects of the circulatory

system 1 944

Inherited defects of the urinary

tract 1948

Inherited defects of the nervous

system 1948

Inherited defects of the

musculoskeletal system 1957

Inherited defects of the skin 1973

Miscellaneous inherited defects . . .1976

36. Specific diseases of uncertain

etiology 1981

Diseases characterized by systemic

involvement 1981

Diseases characterized by alimentary

tract involvement 1988

Diseases characterized by respiratory

tract involvement 1996

Diseases characterized by nervous

system involvement 2004

Diseases characterized by involvement
of the musculoskeletal system . . .2021
Diseases characterized by involvement
of the skin 2035

APPENDICES

Conversion factors 2045

Reference laboratory values 2047

Drug doses - horses and ruminants . . .2051

Drug doses - pigs 2064

Index 2067

List of Tables

1 . 1 Normal average temperatures with

critical points 13

1.2 Resting pulse rates 14

1.3 Method for determining sensitivity,
specificity, likelihood ratio for positive
and negative tests, positive predictive
value and negative predictive value

of a test 27

1 .4 Effect of changes in prevalence
(pretest probability of disease) on the
positive predictive value (PPV) and
negative predictive value (NPV) of
tests with 95% sensitivity and
specificity (Test A) and 60%
sensitivity and specificity

(Test B) 27

2.1 Representative laboratory values in

body water and electrolyte
disturbances 89

2.2 Summary of disturbances of body
water, electrolytes and acid-base
balance in some common diseases
of cattle and horses, and suggested

fluid therapy 92

2.3 Summary of effective strong ion

difference and osmolarity of
parenterally administered
crystalloid solutions 93

2.4 Estimated daily energy requirements

of fasting cattle 95

2.5 Composition and indications for
use of electrolyte solutions used

in fluid therapy 97

2.6 Examples of approximate
amounts of fluid required for
hydration and maintenance

therapy 98

2.7 Causes and diagnostic features
of recumbency of more than

8 hours duration in adult

horses 121

3.1 Concentrations and relative
percentage of immunoglobulins in
serum and mammary secretions

of cattle and pigs 150

3.2 Immunoglobulin concentrations

in the first milking of colostrum of
Holstein cattle by weight of
colostrum produced 151

3.3 Worksheet for calculating a sepsis
score for foals less than 12 days

of age 1 61

3.4 Criteria to assess stage of maturity

of the newborn foal 161

3.5 Hematological values of normal foals

and calves 165

3.6 Serum biochemical values of

normal foals and calves 166

3.7 Antimicrobials used in neonatal

foals 169

3.8 Variables associated with survival in

sick foals 171

4.1 Mode of action of antimicrobial

drugs 182

5.1 Guidelines for the classification and

interpretation of bovine peritoneal
fluid 199

5.2 Characteristics of equine peritoneal
fluid in selected diseases of

horses 200

5.3 Etiological classification of

equine colic 216

5.4 Disorders of the equine

gastrointestinal tract causing colic.

by anatomical site 217

5.5 Rectal findings and associated

causes of equine colic 221

5.6 Differential diagnosis of common

equine colics .226

5.7 Analgesics and spasmolytics for

use in equine colic 227

5.8 Promotility agents, lubricants
and fecal softeners for use in

horses with colic 228

5.9 Diseases causing colic in foals . . . .231

5.10 Differential diagnosis of common

foal colics 232

5.11 Drugs used in the treatment of
gastroduodenal ulcer disease of

foals and adult horses 236

5.12 Epidemiological and clinical
features of diseases of cattle in
which diarrhea is a significant

clinical finding 260

5.13 The epidemiological and clinical
features of horses with diarrhea . .261

5.14 Epidemiological and clinical
features of diseases of the pig in
which diarrhea is a significant

clinical finding 262

5.15 Epidemiological and clinical
features of the diseases of sheep
and goats in which diarrhea

is a significant clinical finding . . . .263

5.16 Epidemiological and clinical

features of suckling foals with
diarrhea 274

6.1 Effects of some common clinical
excitatory and inhibitory
influences on primary cycle
movements of the

reticulorumen 295

6.2 Differential diagnosis of

causes of gastrointestinal
dysfunction of cattle 298

6.3 Differential diagnosis of abdominal

distension in cattle 302

6.4 Differential diagnosis of diseases
of the digestive tract and
abdomen of young calves
presented with distension

of the abdomen 309

6.5 Pathogenesis and interpretation of

clinical findings associated with
diseases of the digestive tract and
abdomen of cattle 310

6.6 Diseases of the digestive tract and

abdomen of cattle in which a
laparotomy is indicated if the
diagnosis can be made 311

6.7 Clinical and laboratory indications
for an exploratory laparotomy

in cattle when the diagnosis is

not obvious . : 311

6.8 Guidelines for the use of clinical
findings in assessing the severity
of grain overload in cattle for the
selection of the treatment of

choice 320

6.9 Condensed tannin content of

legumes, grasses and herbs fed to
ruminants in temperate grazing

systems 328

8.1 Base-apex electrocardiographic

parameters in cattle and horses . .408

8.2 Mean cardiopulmonary values
for adult horses, cattle and

calves and pigs ,.412

8.3 Common arrhythmias and
conduction disturbances in the

horse and cow 413

9.1 Characteristic or expected

changes in hematological and serum
biochemical variables in anemic
animals 454

10.1 Identification and clinical significance

of breath sounds 477

10.2 Guidelines for radiographic pulmonary

pattern recognition in foals 483

1 0.3 Representative results of cytology of
bronchoalveolar lavage fluid of
cattle, sheep, pigs, and horses . . .488

10.4 Changes in blood gas tensions in
various disease states compared to
values in normal animals breathing

air at sea level 491

10.5 Causes of epistaxis in horses 505

10.6 Antimicrobial agents and
recommended closes for treatment

of pleuropneumonia in horses . . .528

12.1 Correlation between clinical

findings and location of lesions
in the nervous system of farm
animals: abnormalities of mental
state (behavior) 584

12.2 Correlation between clinical findings

and location of lesion in the nervous
system of farm animals: involuntary
movements 585

12.3 Correlation between clinical findings

and location of lesion in the nervous
system of farm animals: abnormalities
of posture 586

1 2.4 Correlation between clinical findings

and location of lesion in the nervous
system of farm animals: abnormalities
of gait 587

12.5 Correlation between clinical findings

and location of lesion in the nervous
system of farm animals: abnormalities
of the visual system 588

12.6 Correlation between clinical findings
and location of lesion in the nervous
system of farm animals: disturbances

of prehension, chewing or
swallowing 588

1 3. 1 Differential diagnosis of diseases

of the musculoskeletal system . . .622

13.2 Laboratory evaluation of synovial

fluid in diseases of the joints 641

14.1 Terms used to identify skin

lesions 652

15.1 Estimated prevalence of infection

and losses in milk production
associated with bulk tank milk
somatic cell count 683

1 5.2 California Mastitis Test reactions
and equivalent somatic cell

counts and linear scores for bovine

milk and somatic cell counts for

bovine colostrum 686

1 5.3 Linear score calculation from

the somatic cell count 686

1 5.4 Conversion of linear scores to

somatic cells counts and predicted
loss of milk 687

List of tables

15.5 Summary of three-compartment

model for anatomical location of
infection due to mastitis
pathogens in cattle 690

15.6 Scale used in rating udder

edema 752

1 5.7 Diagnosis of free electricity

problems 753

16.1 Differential diagnosis of diseases

of the upper respiratory tract of
horses 772

16.2 Aims and associated measures

used to control transmission of
Streptococcus equi in affected
premises and herds 773

16.3 Differential diagnosis of diseases of

pigs with skin lesions 785

16.4 Differential diagnosis of respiratory
diseases of older (not newborn)

foals 803

18.1 Risk factors and their role in acute

undifferentiated diarrhea of
newborn calves 847

1 8.2 Age occurrence of the common

enteropathogens in calves 849

18.3 Possible causes of bacteremia/

septicemia and acute neonatal
diarrhea in farm animals 852

18.4 Degree of dehydration in calves

with experimentally induced
diarrhea 859

18.5 Differential diagnosis of bovine

respiratory disease 924

1 8.6 Antimicrobials for treatment and

prevention of bovine pneumonic
pasteurellosis 941

1 8.7 Diagnostic summary of causes of

abortion in cattle 975

19.1 The relationship between the
stages in the pathogenesis of
Johne's disease, the presence
of clinical disease and the results
of diagnostic tests 1024

19.2 Standard-Track Certification from the

US Voluntary Johne's Disease Herd
Status Program for Cattle 1039

19.3 Fast-Track Certification from the
US Voluntary Johne's Disease
Herd Status Program for

Cattle 1039

20.1 Differential diagnosis of lameness

accompanied by foot lesions in
sheep 1075

20.2 Diagnostic summary of common

causes of abortion, mummification
and stillbirth in swine 1095

20.3 Forms of leptospirosis in the

animal species 1100

20.4 Differential diagnosis of diseases of
cattle characterized by acute
hemolytic anemia with or

without hemoglobinuria 1106

20.5 Major pathogenic Mycoplasmas of
ruminants, swine and horses . . .1124

20.6 Summary of systemic mycoplasmoses

of sheep and goats 1125

20.7 Comparative properties of the two

most important cattle
mycoplasmas 1125

20.8 Members of the Mycoplasma

mycordes cluster 1131

21.1 Algorithm for testing horses for

infection by equine infectious
anemia virus when the prevalence
rate is less than 1 in 1000 1176

21.2 Nursery depopulation and clean-up
protocol for elimination

of PRRS 1202

21 .3 Differentiation of acute vesicular

disease 1226

21.4 Differential diagnosis of diseases of
cattle in which there are either oral
lesions or diarrhea alone or together

in the same animal 1265

22.1 Diseases of horses characterized by

signs of intra-cranial or disseminated
lesions of the central nervous
system 1375

22.2 Differential diagnosis of diseases
characterized by lesions of the

teat skin only 1381

22.3 Differential diagnosis of diseases of

horses characterized by discrete
lesions of the skin only 1433

22.4 Differential diagnosis of diseases of
horses characterized by lesions

of the skin of the lower limbs

only 1434

23.1 Transmissible spongiform

encaphalopathies in animals and
humans 1439

23.2 PrP genotype and susceptibility to

scrapie in National Scrapie Program
(NSP) in Great Britain 1442

23.3 Scrapie susceptibility and genotype

as defined by the USA scrapie
eradication plan 1443

26.1 Major Babesia species infective to
domestic animals, their tick vectors
and geographical distribution . . .1484

26.2 Differential diagnosis of diseases of

cattle in which red urine is a
principal manifestation 1491

26.3 Differential diagnosis of anemia, with
or without edema, in horses . . . .1492

26.4 Chemotherapeutics recommended
for treatment and control of
coccidiosis in calves and lambs . .1505

26.5 Definitive and intermediate hosts for

Sarcocystis spp. Associated infections
in agricultural animals 1507

26.6 Summary of the theilerioses of

domestic ruminants 1527

26.7 Summary of the trypanosomoses of
domestic animals and humans . .1532

27.1 Anatomical distribution of

trichostrongylid worms in
ruminants 1542

28.1 Single and multiple host ticks ...1599

28.2 Ticks reported to cause paralysis .1 599

28.3 Ticks reported to transmit

protozoan disease 1600

28.4 Diseases associated with bacteria,
viruses and rickettsia and reported

to be transmitted by ticks 1601

29.1 Salient features of metabolic

diseases of farm animals 1614

29.2 Metabolic profile parameters in

cattle. Optimum values 1623

29.3 Annual (April-March) percentages
outside optimum ranges of
metabolic results in blood plasma

in adult dairy cows 1624

29.4 Relationship between the 10-point
BCS scale used in New Zealand and
the 5-point BCS scale used in Ireland
and the USA, and the 8-point

scale in Australia 1626

29.5 Differential diagnosis of common

causes of recumbency in parturient
adult cattle 1633

29.6 Molecular weights, equivalent weights
and conversions from percent to
milliequivalents (%-mEq) of anions
and cations used in calculating
dietary cation-anion difference . .1639

29.7 To convert from the SI unit to the
conventional unit divide by the
conversion factor. To convert from
the conventional unit to the 9 unit
multiply by the conversion

factor 1664

29.8 Serum or plasma concentration of
thyroid hormones and thyroid
stimulating hormone (TSH) in

foals and horses 1689

30.1 Principal pathological and metabolic

defects in essential trace element
deficiencies 1699

30.2 Secondary copper deficiency

status 1708

30.3 Copper levels of soils and plants in

primary and secondary copper
deficiency 1711

30.4 Copper levels in body tissues and

fluids in primary and secondary
copper deficiency 1715

30.5 Diseases considered to be associated
with a deficiency of either selenium
or vitamin E or both (including
'selenium-responsive' disease) . . .1735

30.6 Glutathione peroxidase (GSH-PX)

activity and selenium levels in blood
and body tissues of animals
deficient in selenium 1747

30.7 Selenium reference range to

determine selenium status of sheep
and cattle in New Zealand 1748

30.8 Dose rates and duration for selected

selenium supplements for adult
cattle 1754

30.9 Some examples of estimated daily

requirements of calcium,
phosphorus and vitamin D 1758

30.10 Approximate levels of phosphorus in

soil and pasture (quoted as phosphate
radical) at which phosphorus
deficiency occurs in cattle 1759

30.11 Daily dietary allowances of

vitamin A 1777

32.1 Maximum tolerance levels of dietary
minerals for domestic animals . . .1798

32.2 Lead levels in blood and feces of
normal and poisoned animals . . .1803

32.3 Differential diagnosis of diseases
of cattle with clinical findings
referable to brain dysfunction . . .1806

32.4 Toxic oral doses and maximum
concentrations of insecticides . . .1833

33.1 Plants causing glucosinolate

poisoning 1867

33.2 Common mycotoxicoses in farm

animals : . .1899

33.3 Important venomous snakes of the

world (adapted from Dorland's
Illustrated Medical Dictionary,

28 edition, 1994,

W. B. Saunders) 1916

34.1 Method for performing the
jaundiced foal agglutination test .1924

34.2 Drugs used i n the treatment of

heaves in horses 1933

35.1 Defects acquired immunity
causing disease in foals and

horses 1943

36.1 Diseases of the lungs of cattle in

which the essential lesion is
interstitial pneumonia 1998

36.2 Differential diagnosis of comatose

('sleeper') neonatal foals 2013

36.3 Differential diagnosis of disease
causing spinal ataxia in horses . .2018

List of illustrations

1.1 Making a diagnosis 23

1.2 A decision tree for choosing

between two interventions 29

1.3 Example of the construction

and use of a decision tree 30

1 .4 Examination of the herd with the
objective of making a diagnosis . . .33

2.1 Etiology and pathogenesis of

dehydration 74

2.2 Etiology and pathogenesis of

hyponatremia 77

2.3 Types of dehydration 78

2.4 Etiology and pathogenesis of

hypochloremia 78

2.5 Etiology and pathogenesis of

hypokalemia 79

2.6 Etiology and pathogenesis of

acidemia 85

2.7 Etiology and pathogenesis of

alkalemia 86

2.8 The interrelationships between the

changes in body water, electrolytes
and acid-base balance that can
occur in diarrhea 88

3.1 Examples of forms used to

document and record historical
aspects and findings on physical
examination of foals less than

1 month of age 162

5.1 Left lateral view of abdomen of a
normal horse and left dorsal
displacement of the left colon . . .249

5.2 Right dorsal displacement of
the colon, right lateral

view 250

5.3 A 360° clockwise volvulus of the
colon viewed from the right

side 250

5.4 Steps in correction of left dorsal
displacement of the colon
(renosplenic entrapment) 251

6. 1 Silhouettes of the contour of the

abdomen of cattle, viewed from the
rear, with different diseases of the
abdominal viscera 302

6.2 Schematic illustration of the rectal

findings in cattle affected with
different diseases of the abdominal
viscera 306

6.3 Some common causes of physical

and functional obstruction of the
alimentary tract of cattle 307

6.4 Sequelae of traumatic perforation

of the reticular wall 337

6.5 Ultrasonogram and schematic of a
reticular abscess in a cow with
chronic traumatic

reticuloperitonitis 342

6.6 Ultrasonogram and schematic of the

reticulum in a cow with chronic
traumatic reticuloperitonitis 343

6.7 Causes of grunting in cattle 345

6.8 Ultrasonogram and schematic of
the abdomen in a cow with ileus
due to obstruction of the jejunum

with coagulated blood (hemorrhagic
bowel syndrome) 382

7.1 Classification of jaundice 384

7.2 Ultrasonogram and schematic of

the liver in a cow with obstructive
cholestasis due to fasciolosis 388

10.1 The causes of dyspnea 474

10.2 Ultrasonogram and schematic of the

thorax in a cow with pleuropneumonia
due to infection with Mannheimia
haemolytica 523

15.1 The causes of porcine agalactia . . .758

21.1 Possible pathways after exposure to

BVL virus (percentage figures indicate
proportion of seroconverted animals
that develop the particular form
referred to) 1214

21.2 Clinical diagnosis: frequency of
predominant signs of bovine
leukaemia - 1 100 field cases.

(By courtesy of Canadian

Veterinary Journal ) 1215

21 .3 The objectives of herd testing

for BVDV 1267

21.4 Flow chart for testing a beef
herd pre-breeding to detect and
eliminate BVDV carrier cattle . . .1268

21 .5 Flow chart for testing a dairy
herd to detect and eliminate

BVDV PI carrier cattle 1269

23.1 Annual reports of incidence of

BSE in the UK (1987-1998) 1447

26.1 The development life cycle of

Babesia bigemina in cattle and the
ixodid tick vector Boophilus microplus
(adapted from Mehlhom, Shein 1984;

Mackenstedt et al. 1995;

gough et al. 1998) 1486

29.1 Body condition scoring chart
adapted from Edmonson et al.

(1989) 1625

30.1 The four phases of copper

deficiency 1716

List of Contributors

Otto M. Radostits cm, dvm, ms, mrcvs,

DipACVIM

Emeritus Professor, Department of Large Animal Clinical
Sciences, Western College of Veterinary Medicine,
University of Saskatchewan, Saskatoon, Saskatchewan,
Canada

Clive C. Gay dvm, mvsc, facvsc

Emeritus Professor and Emeritus Director, Field Disease
Investigation Unit, Department of Veterinary Clinical
Science, College of Veterinary Medicine, Washington
State University, Pullman, Washington, USA

Kenneth W. Hinchdiff bvsc, PhD, DipACVIM

Professor, Equine Medicine, Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, Ohio
State University, Columbus, Ohio, USA

Peter D. Constable bvsc, ms, PhD, DipAcviM

Professor and Head, Department of Veterinary Clinical
Sciences, School of Veterinary Medicine, Purdue
University, West Lafayette, Indiana, USA

Contributors:

Stanley H. Done, BA, BVetMed, DVetMed, Dipl
ECVP, Dipl ECPHM FRCVS, FRCPath

Visiting Professor of Veterinary Pathology, The Veterinary
School, University of Glasgow, Glasgow, UK, Senior
Veterinary Investigation Officer, Veterinary
Laboratories Agency (VLA), Thirsk, North Yorkshire

Dennis Jacobs bvms, PhD, DipEVPc frcvs,
FRCPath

Professor, Veterinary Parasitology, Department of
Pathology and Infectious Diseases, Royal Veterinary
College, University of London, London, UK

Basil Ikede DVM, PhD, Diagn Path, FCVSN

Professor Department of Pathology and Microbiology,
Atlantic Veterinary College, Charlottetown, Prince
Edward Island, Canada

R. A. (Ross) McKenzie bvsc, mvsc, dvsc

Senior Lecturer, University of Queensland, and Principal
Veterinary Pathologist, Queensland Department of
Primary Industries, Animal Research Institute,
Yeerongpilly, Queensland, Australia

D. D. (Doug) Colwell bsc, msc, PhD

Sustainable Production Systems Program, Agriculture and
Agri-Food Canada, Lethbridge Research Centre,
Lethbridge, Alberta, Canada

Gary Osweiler DVM, PhD, dabvt

Veterinary Diagnostic and Production Animal Medicine,
College of Veterinary Medicine, Iowa State University,
Ames, Iowa, USA

Rob Bildfell DVM, MSc, DiplACVP

Associate Professor, Department of Biomedical Sciences,
College of Veterinary Medicine, Oregon State
University, Corvallis, Oregon, USA

Dedicated to Professor Douglas Charles Blood OBE, BVSc (Sydney), MVSc,
FACVSc, Hon LLD (Sask), Hon LLD (Guelph), Hon Assoc RCVS

The Tenth Edition of this text. Veterinary Medicine, marks the
passing of an era. For the first time Professor D. C. Blood, the
originator of this text, is not a contributor and author. Doug
Blood has had a passion for veterinary science and over the past
60 years he has made a remarkable contribution to the science of
clinical veterinary medicine and to the profession of veterinary
medicine. Not the least of these contributions is this text, in print
for the past 45 years. He has taught clinical veterinary medicine
to 40 years of veterinary students. The undergraduate education
of all four of the senior authors of this edition has been
profoundly impacted by Doug Blood's teaching and philosophy
and the period of time of this influence ranges from the late
1950s to the early 1980s. Our postgraduate education and
experience has also had significant influence from Doug Blood
and we reflect on his influence on the profession and dedicate
this edition to him.

As a background, Doug received his veterinary degree from
the University of Sydney in 1942 and served in the Australian
ArmyVeterinary Corps until the end of the Second World War. He
then returned to teach and practice clinical veterinary medicine
in the Clinical Department of the Faculty of Veterinary Science in
the University of Sydney for 12 years, during which he spent a
year on a Fulbright stipend at the veterinary school at Cornell
University. In 1957 he joined the Department of Clinical
Medicine at the Ontario Veterinary College in Guelph, then part
of the University of Toronto, Canada.

In these early years Doug Blood revolutionized the teaching of
clinical veterinary medicine. For those of us privileged to have
been taught by him at this time he was a superlative teacher.
Doug was one of the first teachers in veterinary clinical medicine
to recognize that pathophysiology was the basis for teaching the
disease processes in large animals. He also concentrated on its
principles for the explanation of disease syndromes and in
teaching clinical examination and diagnosis. This was an
approach that he developed from the teaching of his mentor, the
Oxford veterinary scientist, H. B. Rarry, to whom this text was
dedicated in the first edition. This approach to clinical teaching
was in marked contrast to the rote learning that was common in
many of the disciplines taught at that time and in stark contrast
to the teaching in clinical examination and diagnosis, which then
primarily relied on pattern recognition.

Doug Blood also taught that the method of clinical exam-
ination should be system-based, that it should be conducted in a
systematic manner and that it should be conducted using all
available senses and techniques. He further taught that the
intellectual diagnostic rule-out process should also incorporate a
consideration of the presenting epidemiology of the disease
problem, the probability of disease occurrence and an examin-
ation of the environment. Although these approaches might
seem obvious to recent graduates, in the 1950s and early 1960s
they were revolutionary. In fact, they set the foundation for
current teaching principles in large-animal clinical veterinary
medicine. Students of that older vintage recall with great
appreciation the understanding of clinical veterinary medicine
imparted by Doug Blood and his particular contribution to their
education. Throughout subsequent years in his teaching career
Doug has shown the ability to inspire students and is held in
respect, admiration and even veneration by the generations of
students that he has taught.

The first edition of this text was published in 1960 and
authored by D. C. Blood and J. A. Henderson. It was entitled
Veterinary Medicine-. A Textbook of the Diseases of Cattle, Horses,
Sheep, Pigs and Goats and was based on Doug Blood's and Jim

Henderson's lectures and Doug's teaching and philosophical
approach. At that time there were few textbooks in the disciplines
of veterinary science and none that were either current, or
published in English, that were primarily concerned with clinical
veterinary medicine and diseases in agricultural animal species.
The text was divided into two major sections: one, entitled
General Medicine, covered system dysfunction and the other.
Special Medicine, covered the specific diseases of the large
animal species. This format has been followed in subsequent
editions. The second edition was published in 1963 and had an
additional two chapters covering parasitic diseases. Sub-
sequently, new editions have been published approximately
every 5 years with major or minor changes in format in most
editions, such as the addition of new chapters dealing with new
subjects or the addition of material in specific subheadings to
highlight, for example, the epidemiology or zoonotic implications
of disease. However, always, with each edition there was an
extensive revision of disease descriptions based on current
literature. Professor Henderson's involvement with the text
ceased with the Fifth Edition and that edition recruited Professor
O. M. Radostits as a senior author and others as contributing
authors. The list of senior and contributing authors has expanded
since the Fifth Edition but, until this present edition, Doug Blood
has always been a major author.

In the preface to the First Edition it was stated that the book
was directed primarily at students of veterinary medicine,
although it was expected that the book would be of value to
practicing veterinarians and field workers. The latter expectation
has certainly proved true and the book has come to be

XIV

Dedication to Professor Douglas Blood

extensively used as a reference by veterinarians in large- and \
mixed-animal practice around the English-speaking world.
Editions of the text have also been translated into French, Italian, j
Spanish, Portuguese, Japanese and Chinese.

In addition to his passion for the method and accuracy of
diagnosis of disease in individual animals and herds, Doug Blood
also has had a passion for preventive medicine and has been a firm
proponent of the thesis that subclinical disease is economically
more important than clinical disease in agricultural animal
populations. With other colleagues at the University of Melbourne
he developed, and trialed practically in private herds and flocks,
health programs for dairy cattle, beef cattle and sheep. These ■
programs were based on a whole-farm approach and centered on j
the concept that performance targets could be monitored by
computer-based productivity monitoring to detect deviation from ■
target performance. Doug Blood was a very early proponent of the j
use of computers to manage and analyze data in clinical diagnosis
and herd health management. These herd health programs have j
been successfully commercially adopted in several countries. j

Doug has stated on many formal occasions that he is |
immensely proud to be a member of the veterinary profession :
and in addition to his teaching and writing in clinical veterinary ;
medicine he has attested this by his other outstanding
contributions to the profession. In 1962 he returned to Australia
to establish a Faculty ofVeterinary Science within the University
of Melbourne. He was appointed Professor ofVeterinary Clinical :
Medicine and was also the Founding Dean of the current |
veterinary school in the university. The successful formation and
funding of a new Faculty (College) within the University was a ;
remarkable political achievement requiring cooperation with
agricultural commodities, veterinarians, politicians and the public.

Doug has always been active in promoting the profession of
veterinary medicine and active in organized veterinary medicine.
He has actively encouraged his colleagues to have equivalent
involvement and commonly would invite, pick up and transport

new graduates or new faculty to the local veterinary association
meetings in Melbourne.

In the 1970s Doug was instrumental in establishing the
Australian College of Veterinary Science, which continues to
provide continuing education and specialty certification for
practicing veterinarians in Australia and New Zealand. He has
served on a large number of state and national veterinary associ-
ation committees including service as President of the Victorian
Veterinary Association. In recognition of his service to the
veterinary profession he was awarded the Gilruth prize by the
Australian Veterinary Association. This is the highest honor that
the Australian Veterinary Association can bestow. Other honors
include prestigious international honors such as the award of the
Order of the British Empire (OBE) for outstanding service in
veterinary science, the award of an Honorary Associate in the
Royal College ofVeterinary Surgeons in the UK and the bestowment
of Honorary Doctor of Laws awarded by both the University of
Guelph and the University of Saskatchewan.

With all of his activities, Doug acknowledged the strong
support of his wife Marion, recently deceased, and his family of
five daughters. His house was always open to students and
graduate students to discuss anything from subjects in veterinary
medicine to a discussion of the current book of the month, for the
enjoyment of a tasting of Australian wines or to meet with an
overseas veterinarian, who so often had come to meet with Doug
on the visit to Australia and had ended up staying as a guest in
the Blood household during the period of this visit.

Doug is currently retired in Werribee, Victoria with a
continuing interest in his many past students and a major
interest in ornithology and photography.

Otto M. Radostits
Clive C. Gay
Kenneth W Hinchcliff
Peter D Constable

Preface to the Tenth Edition

We are pleased to present the Tenth Edition of Veterinary
Medicine, 45 years since the first'Blood and Henderson' Veterinary
Medicine was published in 1960. Because the demand for this
book continues undiminished, we assume that we have a
philosophy, a format and a price that is attractive and meets the
demands of undergraduate veterinary students and graduate
veterinarians working in the field of large-animal medicine. For
this edition, significant changes were needed to keep up to date
with the increasingly rapid expansion of knowledge about the
diseases of large animals. The entire book was reviewed and
revised as necessary, and new diseases added, based on literature
published worldwide since 2000. We have attempted to ensure
the book continues to have an international scope by including
most of the diseases occurring in large animals worldwide.

Professor D. C. Blood continues to be an important
inspiration and guiding light but retired from this edition of the
book. We dedicate this edition to him.

Dr Clive Gay revised the chapters on diseases of the new-
born, practical antimicrobial therapy, diseases caused by physi-
cal agents, the infectious diseases of sheep and goats, a new
chapter on diseases associated with prions, and some of the
metabolic and protozoan diseases and diseases of unknown
etiology.

Dr Kenneth Hinchcliff, Ohio State University, completely
revised the sections on specific equine diseases and added many
newly described diseases of the horse. The section on equine
colic, which had been expanded in the Ninth Edition, was
completely revised for this edition. A section on care and man-
agement of the recumbent horse is a new addition. Dr Hinchcliff
also revised the chapter on diseases of the respiratory system
and diseases of the hemolymphatic and immune system.
Dr Hinchcliff's section on the formulary of drugs used in large
animal practice has been highly successful and useful to students,
clinicians, and practitioners. It serves as a quick reference for the
busy practitioner who needs to know the dosage schedule of a
certain drug.

Dr Peter Constable has joined us a co-author. He reviewed
major parts of Chapter 2, on systemic states, and revised the
chapters on diseases of the cardiovascular system, the urinary
system, the nervous system, and the mammary gland.

Dr Otto Radostits continued his role as senior author with
major responsibilities for chapters in general medicine including
systemic states, alimentary tract, ruminant stomachs, respiratory
system, and musculoskeletal system. He also revised the chapters
on metabolic diseases, nutritional diseases and most of the infec-
tious diseases of cattle and some of the diseases of uncertain
etiology.

Professor Dennis Jacobs, University of London, revised the
chapter on diseases caused by helminths and completely
reorganized the material into more distinct groups according to
effects of the various helminths on body systems.

Dr Ross A. McKenzie revised the chapter on diseases caused
by toxins in plants, fungi, cyanophytes, clavibacteria, and venoms
in ticks and vertebrate animals.

Professor Basil O. Ikede, revised the major exotic viral and
protozoan diseases and introduced some new tabular
information that may be useful to the reader.

Dr Doug Colwell joined our book by revising the chapter on
diseases caused by arthropod parasites.

Professor Stanley Done also joined our book as a major
contributor and revised all the diseases of pigs. It was a major
task given the very large literature base on infectious diseases of
pigs on a worldwide basis.

Dr Rob Bildfell, reviewed and revised the necropsy findings
for most of the specific diseases. His contribution in the Ninth
Edition, Samples for confirmation of diagnosis, has been a
successful section to serve as a guideline for the collection of
samples at necropsy. The details of the guidelines are described in
the section dealing with 'How to use this book'.

Computerized word processing greatly facilitates the
achievement of our long-term objective to produce an up-to-
date review of the field of large-animal veterinary medicine as it
is practiced, and the parallel stream of research work into the
etiology, epidemiology, pathogenesis, treatment and control
of diseases of large animals. We continue to emphasize a good
understanding of pathogenesis of each disease, which is import-
ant in understanding the rationale for the diagnosis, treatment
and control. This means that we strive to maintain an optimum
balance between published research and what field veterinarians
find useful in their daily work, which necessitates that our
authors and contributors maintain a strong contact with clinical
work, especially with the clinical techniques and treatment and
control measures.

The knowledge base in veterinary epidemiology, parti-
cularly risk factors for disease, continues to increase and become
more complex. A system of subheadings has been introduced
and the material has been rearranged under them in order to
simplify the reader's task in locating material in these presen-
tations. A major change for this edition is giving special emphasis
to the risk factors for disease, which are so important to the
veterinarian in the clinical management and control of disease,
particularly on a herd basis. We also continue to include the
zoonotic implications of many diseases and how the large-
animal veterinarian is becoming more involved in the control of
diseases transmissible to humans. We also indicate those
diseases of concern as agents of bioterrorism.

The use of individual diagnostic tests, described under
clinical pathology of each disease, continues to be a challenge for
all of us. A very large number of publications deal with the
development of laboratory diagnostic tests but most of them
have little information on their sensitivity and specificity for
diagnostic purposes and will likely never be employed in routine
diagnosis. There is also regional and national variation in tests
that are used and it is not possible nor desirable to detail these in
the book. We have chosen to concentrate on those tests that are
accepted through common use, to discuss their limitations if they
are known, and to provide a reference to newer tests that have
future promise in diagnosis.

Restraining the size of the book has been a constant pre-
occupation and a difficult task with the ever increasing volume of
published information and the constantly growing list of
diseases. Our intention has always been to provide information
on all recorded diseases. In spite of reductions in reference lists,
word paring editing made possible by word processing, and
overall editing to minimize repetition, thebook is still quite large.
The references have been culled and those included are
considered to be current. Synopses have been included for each
disease topic for which the material exceeded approximately
1000 words. To make it easier for the reader to find particular
pieces of information, long passages of prose have been divided
into smaller sections using more headings and subheadings.
Key words, terms and phrases have been emboldened for
emphasis and to make it easier for the reader to identify
important points.

Other reference books to which the readers are referred,
include the 3rd edition of Herd Health (2001), the companion

Preface to the tenth edition

reference to animal health management of farm animals, and the
3rd edition of Saunders Comprehensive Veterinary Dictionary (2006)
with its complete coverage of definitions and spellings of all
words used by undergraduate and graduate veterinarians.

We are satisfied that we have completed another authoritative,
responsible and comprehensive review of the literature of large
animal medicine, at a standard at least equal to that of the
previous nine editions, and we hope that it will provide the

information necessary for the needs of students and practitioners
for the next 5 years.

O. M. Radostits
C. C. Gay
K. W. Hinchcliff
R C. Constable

November 2006

Introduction

Objectives and principles of farm animal
practice

The primary objective of this book is to provide the veterinary
student and the practitioner with the knowledge and information
necessary to provide animal health management for farm
animals. This is a commentary on the objectives and principles of
veterinary practice related to the animal health and production of
cattle, sheep, goats, pigs and horses.

FOOD -P RODUCING ANIMALS

Food-producing-animal veterinary practice provides service
primarily to the owners of the meat-, milk- and fiber-producing
animals such as dairy and beef cattle, pigs, sheep and goats.
Veterinarians also provide service to owners of captive ungulates,
such as red deer, elk and bison, that are being raised under farm
conditions for the production of meat and byproducts such as
hides. While some commercially processed horsemeat is con-
sumed by humans, the market is small compared to beef and
pork, and horses are not usually included in discussions about
food-producing animal veterinary practice. Poultry, fish and
rabbits are also important sources of human food but are not the
subject of this book.

For the past several decades, the major activity in food-
producing-animal practice, and a major source of income for
veterinarians, was the provision of emergency veterinary
service to the owners of herds or flocks in which a single animal
was affected with one of the common diseases. Occasionally,
outbreaks of disease affecting several animals occurred. In
addition, routine elective veterinary services such as castration,
vaccination, dehorning, deworming, the testing for diseases such
as brucellosis and tuberculosis and the dispensing of veterinary
drugs, pharmaceuticals and biologicals accounted for a signifi-
cant source of revenue for the veterinarian. Since about the early
1970s, there has been a shift from emphasis and dependence on
emergency veterinary medicine and routine procedures to more
attention being paid by the veterinarian and the producer to
planned animal health and production management using
the whole-farm approach. Livestock producers are now much
more knowledgeable about animal agriculture and are concerned
about the cost-effectiveness and the scientific basis of the
recommendations made by veterinarians and agricultural
advisors. More and more producers are doing the routine elective
procedures themselves. From firsthand experience and extension
courses provided for them they have also learned how to
diagnose and treat many of the common diseases of farm
livestock. Many veterinary pharmaceuticals antimicrobials and
biologicals can now be purchased by producers from either
veterinary or nonveterinary sources.

INDUSTRIALIZED ANIMAL AGRICULTURE

The intensification of animal agriculture has created complex
animal health and production problems for which there are no
simple and reliable therapeutic and preventive procedures, and
this has made the task of the veterinarian much more challenging.
For example, acute undifferentiated respiratory disease is a
common disease of feedlot cattle that is difficult to treat and
control effectively because the etiology and epidemiology are
complex. Acute diarrhea of calves under 30 days of age may be
caused by several different enteropathogens but a knowledge of
the risk factors or epidemiological determinants such as colostral

immunity and population density is probably more important for
effective clinical management and control of the disease. The
rearing of pigs intensively and in complete confinement ' has
exaggerated a number of disease problems, many exacerbated by
inadequacies of the environment.

Suboptimal reproductive performance due to a variety of
management and environmental factors is common, and pneu-
monia in growing and finishing pigs may be almost impossible to
eradicate unless the herd is depopulated and repopulated with
minimal-disease breeding stock. Infectious diseases such as
porcine reproductive and respiratory syndrome are difficult to
control. The solutions to these complex problems are not always
readily apparent, in part because of insufficient research on
etiology and epidemiology and different control strategies in the
herds where the problems are occurring. The veterinarian must
be knowledgeable and skillful in the principles of epidemiology,
applied nutrition and animal housing, the education and training
of animal attendants and the analysis of production indices,
including profit and loss, which includes the use of computers, in
addition to being skilled in the traditional veterinary disciplines
of medicine, reproduction, pharmacology and pathology. Thus,
the food-producing-animal practitioner must become more
skilled in the simultaneous management of animal health and
production; the modem livestock producer is cost-conscious and
anything veterinarians do or recommend must be cost-effective.

COMPANION ANIMAL PRACTICE

In contrast, developments in companion animal medicine (small
animals) have followed in the footsteps of human medicine with
an ever-increasing emphasis and reliance on extensive use of
clinical pathology for the in-depth evaluation of the hematology,
clinical chemistry, enzymology, immune status and many other
body functions of the individual animal.

Diagnostic techniques such as ultrasonography, endoscopy,
nuclear imaging and computed tomography are being used both
in veterinary teaching hospitals and in referral veterinary
practices. These in-depth'diagnostic workups' presumably lead to
a greater understanding of the etiology and pathophysiology of
disease, with the ultimate aim of a more accurate and early
diagnosis that allows much more effective medical and surgical
therapy than is economically possible or necessary in food-
producing animals. There is not the same emphasis on the
efficiency of production, epidemiology and cost-effectiveness
that constantly faces the food-producing-animal practitioner.
More and more companion animal owners, because of the
sentimental value of their animals and the growing importance
of the human-companion-animal bond, are willing to pay for the
costs associated with extensive laboratory and sophisticated
diagnostic tests and intensive and prolonged veterinary hospital
care. Palliative care for dogs and cats affected with diseases that
may not be curable over the long term is now a recognized fact
in small-animal practice.

EQUINE PRACTICE

Equine practice has evolved along similar lines to small-animal
practice. Some aspects of it, such as reproduction, intensive
clinical care of the newborn foal and the treatment of medical
and surgical diseases of valuable athletic and competitive horses,
have advanced a great deal. The great strides that have been
made in our understanding of the diagnosis, prognosis and
medical and surgical therapy of colic in the horse are due to the
in-depth diagnostic laboratory work and the medical and surgical

Introduction

expertise that have been used. Our improved understanding of j
the prognosis of equine colic has in part been due to prospective I
studies of the clinical and laboratory findings in horses with colic. ■
However, the large advances in improvement in survival made in [
the early years of surgical and intensive medical treatment of ;
colic have not continued, and there is an urgent need for '
appropriately designed prospective clinical trials to determine ;
optimal treatment regimes in these horses. The same is true for j
intensive treatment of sick foals. In addition to the advanced j
diagnostic and therapeutic procedures being done on valuable ;
horses at veterinary teaching hospitals, there are now many
privately owned equine veterinary centers that provide the same
service. Undoubtedly the high financial value of some horses has :
provided the impetus for the development of these services.

While the increasingly sophisticated diagnostic and thera-
peutic techniques used in equine practice are readily noted,
advances in the understanding of infectious and contagious
diseases of horses has also increased markedly. This is parti-
cularly true for economically important diseases that have the
potential to affect large numbers of horses, consequently causing
disruption to important athletic events, sales and shipment of
horses. These diseases are typically the infectious respiratory
diseases and those diseases, such as African horse sickness, that
are exotic to most of the horse population worldwide. The
economic incentive to control these diseases has resulted in
considerable increases in knowledge of their etiology (and
consequently vaccinology), epidemiology, immunology, diag-
nosis and prevention. Few advances have been made in treat-
ment of what are for the most part self- limiting diseases with low
case fatality rates.

CONTRASTING OBJECTIVES

It is clear that there are major differences between the objectives
and principles of companion-animal practice and those of food-
producing-animal practice. In companion -animal practice, the
objective is the restoration of the clinically ill animal to a normal
state, if possible, or in some cases a less than normal state is
acceptable providing it is a quality life, using all the readily
available diagnostic and therapeutic techniques that can be
afforded by the client. In sharp contrast, in food-producing-
animal practice, the objective is to improve the efficiency of
animal production using the most economical methods of diag-
nosis, treatment and control, including the disposal by culling or
slaughter of animals that are difficult to treat and are economic
losses.

This growing dichotomy in the delivery of veterinary services
to the food-producing-animal owner and to the companion-
animal owner prompted us to present a short introductory
commentary on the objectives and principles of food-producing
animal practice.

The objectives of food-producing animal
practice

EFFICIENCY OF LIVESTOCK PRODUCTION

The most important objective in food-producing-animal practice
is the continuous improvement of the efficiency of livestock
production by the management of animal health. This involves
several different but related activities and responsibilities, which
include the following:

• Providing the most economical method of diagnosis and
treatment of sick and injured animals and returning them to
an economically productive status, or to a point where
slaughter for salvage is possible in the shortest possible time.

The financially conscious producer wants to know the
probability of success following treatment of a disease in an
animal and to minimize the costs of prolonged
convalescence and repetitive surgery

• Monitoring animal health and production of the herd on
a regular basis so that actual performance can be compared
with targets and the reasons for the shortfalls in production
or increases in the incidence of disease can be identified as
soon as possible, so that appropriate and cost-effective
action can be taken. The routine monitoring of production
records and the regular monitoring of bulk tank milk somatic
cell counts in dairy herds are examples

• Recommending specific disease control and prevention
programs such as herd biosecurity, vaccination of cattle
against several important infectious diseases that occur
under a variety of conditions, and the strategic use of
anthelmintics in cattle and sheep

• Organizing planned herd and flock health programs for
the individual farms with the objective of maintaining
optimum productivity through animal health management.
This subject is presented in the companion volume to this
book, Radostits OM Herd Health: Food Animal Production
Medicine, 3rd edn. WB Saunders, 2001

• Advising on nutrition, breeding and general
management practices. Food-producing-animal
practitioners must be interested in these matters when they
affect animal health. It is a large part of production -oriented
health management, and it is now common for veterinarians
to expand their health -oriented animal husbandry advisory
service to include an animal production advisory service. To
do so is a matter of individual preference, an option that
some veterinarians take up and others do not. Some
veterinarians will rely on consultation with agricultural
scientists. However, veterinarians still require a working
knowledge of the relevant subjects, at least enough to know
when to call in the collaborating advisor for advice. Members
of both groups should be aware of the extensive list of
subjects and species-oriented textbooks on these subjects,
which should be used to support this kind of service.

ANIMAL WELFARE

Encouraging livestock producers to maintain standards of animal
welfare that comply with the views of the community is
emerging as a major responsibility of the veterinarian. The
production of food- producing animals under intensified
conditions has now become an animal welfare concern that
practitioners must face and in which they must become
proactive.

ZOONOSES AND FOOD SAFETY

Promoting management practices that ensure that meat and milk
are free of biological and chemical agents capable of causing
disease in humans must also become a preoccupation for food-
producing-animal veterinarians. This is because the general
public is concerned about the safety of the meat and milk
products it consumes and the most effective way to minimize
hazards presented by certain infectious agents and chemical
residues in meat and milk is to control these agents at their point
of entry into the food-chains, namely, during the production
phase on the farm. Veterinarians will undoubtedly become
involved in the surveillance of the use of antimicrobial
compounds and other chemicals that are added to feed supplies
to promote growth or prevent infections, and will be expected to
minimize the risk of the occurrence of zoonotic disease agents in
farm animal populations.

Introduction

XIX

Principles of food-producing animal
practice

REGULAR FARM VISITS

A unique feature of a food-producing animal veterinary practice
is that most of the service is provided by the veterinarian who
makes emergency or planned visits to the farm. In some areas of
the world, where veterinarians had to travel long distances to
farms, large-animal clinics were established and producers
brought animals that needed veterinary attention to the clinic.
For the past 25 years these clinics have provided excellent
facilities in which, for example, surgical procedures such as
cesarean sections could be done and intensive fluid therapy for
dehydrated diarrheic calves could be administered much more
effectively and at a higher standard than on the farm. However,
much less veterinary service is being provided in these clinics
now because of the high operating costs of providing hospital
care and the limited economic returns that are possible for the
treatment of food-producing animals, which have a fixed
economic value. Producers have also become less enthusiastic
about transporting animals to and from a veterinary clinic
because of the time and expertise involved.

CLINICAL EXAMINATION AND D I AGNOSIS

The diagnosis, treatment and control of diseases of food-
producing animals are heavily dependent on the results of the
clinical examination of animals on the farm and the careful
examination of the environment and management techniques.
This means that the veterinarian must become highly skilled in
obtaining an accurate and useful history on the first visit to an
animal or group of animals and in conducting an adequate
clinical examination in order to make the best diagnosis possible,
and economically so that the treatment and control measures can
be instituted as soon as possible. On the farm, during the day or
in the middle of the night, the veterinarian will not have ready
access to a diagnostic laboratory for the rapid determination of a
cow's serum calcium level if milk fever is suspected. The
practitioner must become an astute diagnostician and a skillful
user of the physical diagnostic skills of visual observation,
auscultation, palpation, percussion, succussion, ballottement and
olfactory perception. On the farm, the clinical findings, including
the events of the recent disease history of an animal, are
often much more powerful, diagnostically, than laboratory
data. It therefore becomes increasingly important that the clini-
cal examination should be carefully and thoughtfully carried
out so that all clinically significant abnormalities have been
detected.

An outline of the clinical examinations of an animal and the
different methods for making a diagnosis are presented in
Chapter 1. Becoming efficient in clinical examination requires the
diligent application of a systematic approach to the task and,
most importantly, evaluation of the outcome. A most rewarding
method of becoming a skillful diagnostician is to retrospectively
correlate the clinical findings with the pathology of those cases
that die and are submitted for necropsy. The correlation of the
clinical findings with the clinical pathology date, if available, is
also an excellent method of evaluation but is not routinely ;
available in most private practices. The food-producing-animal ■
practitioner must also be a competent field pathologist and be :
able to do a useful necropsy in the field, usually under less than !
desirable conditions, and to make a tentative etiological diag- i
nosis so that additional cases in the herd can be properly handled |
or prevented. Doing necropsies on the farm or having them done I
by a local diagnostic laboratory can be a major activity in a j
specialty pig or beef feedlot practice, where clinical examination 1

of individual animals is done only occasionally, compared with
dairy practice.

EXAMINATION OF THE HERD

The clinical examination of the herd in which many animals may
be affected with one or a number of clinical or subclinical
diseases or in which the owned s complaint is that performance is
suboptimal but the animals appear normal, has become a major
and challenging task. This is particularly true in large dairy herds,
large pig herds, beef feedlots, lamb feedlots and sheep flocks
where the emphasis is on health management of the herd.
Intensified animal agriculture may result in an increased
frequency of herd epidemics or outbreaks of diseases such as
pneumonic pasteurellosis, bloat, acute diarrhea in beef calves and
peracute coliform mastitis in dairy cattle. Such well known
diseases are usually recognizable and a definitive etiological
diagnosis can usually be made and in some cases the disease can
be controlled by vaccination. However, in some cases of herd
epidemics of respiratory disease, salmonellosis, Johne's disease,
for example, the veterinarian may have to make repeated visits to
the herd in order to develop effective treatment and control
procedures. The steps involved in the examination of the herd
affected with a clinical disease or suboptimal performance are
presented in Chapter 1.

VETERINARY TECHNICIANS

Veterinary technicians are now employed by veterinary practices
to assist in a wide variety of tasks. They can collect and
computerize animal health and production records from
individual herds, collect laboratory samples and assist in the
preparation of reports. Under the veterinary supervision they can
do routine elective surgical procedures such as dehorning,
castration, foot-trimming and vaccinations. The veterinarian is
thus provided with more time to pursue the diagnosis and
correction of health and production problems in the herd. In
large commercial beef feedlots, veterinary technicians commonly
identify and treat cattle affected with acute undifferentiated
respiratory disease and the veterinarian will analyze the
therapeutic responses, do necropsies and interpret the data,
which have been stored in a computer.

VET ERINA R Y EPIDEMIOLOGY

As animal agriculture continues to intensify, an increasing
number of herd problems are evolving that have a multifactorial
etiology and we are entering the era of the epidemiological
diagnosis, in which the definitive etiology may not be
determined but removal or modification of the risk factors may
successfully and economically control the disease. For example,
recent epidemiological observations revealed that certain skeletal
abnormalities of beef calves were associated with the use of grass
or clover silage as the sole diet of pregnant beef cows during the
winter months in Canada. The precise etiology was
undetermined but in a controlled clinical trial, supplementation
of the silage with grain eliminated the abnormality. This is an
example of a modern-day epidemiological diagnosis comparable
to the observation by John Snow that cholera in humans was
associated with the use of the community water pump, long
before the causative bacterium was identified. Bovine spongiform
encephalopathy, first recognized in the UK in 1986, has resulted
in some excellent research in veterinary epidemiology, which has
demonstrated its power in the investigation of a disease that has
such important zoonotic implications.

It is clear that the next wave of development in food-
producing-animal practice will be associated with the increased
use of applied and analytical epidemiology. The tools of

PARTI PART TITLE ■ Chapter 1: Chapter Title

epidemiology are now readily available to allow the veterinarian
to identify and quantify the risk factors associated with the
disease, to provide a more accurate prognosis, to accurately
assess treatment responses and not depend on clinical
impressions, to scientifically evaluate control procedures and to
conduct response trials. There is a large and challenging
opportunity for veterinarians to become involved in clinical
research in the field where the problems are occurring. It will
require that they become knowledgeable about the use of
computerized databases. These now provide an unlimited
opportunity to capture and analyze data and generate useful
information, which heretofore was not considered possible. The
technique of decision analysis is also a powerful tool for the
veterinarian who is faced with making major decisions about
treatment and control procedures.

COLLECTION AND ANALYSIS OF ANIMAL HEALTH
DATA

With the shift in emphasis to the problems of the herd, the
collection, analysis and interpretation of animal health and
production data will be a major veterinary activity. Livestock
producers must keep and use good records if the veterinarian is
to make informed decisions about animal health and production.
The once tedious and unpopular work of recording and
analyzing animal health and production data is now done by the
computer. Veterinarians will have to move in the direction of
developing a computer-based animal health and production
profile of each herd for which they are providing a service.
Veterinary colleges will also have to provide leadership and
provide undergraduate and graduate student education in the
collection, analysis and interpretation of animal health data. This
activity will include methods of informing the producer of the
results and the action necessary to correct the herd problem and
to improve production.

PUBLIC HEALTH AND FOOD SAFETY

Veterinarians have a major responsibility to ensure that the meat
and milk produced by the animals under their care are free from
pathogens, chemicals, antimicrobials and other drugs that may
be harmful to humans. The prudent use of antimicrobials,
including adherence to withdrawal times for meat and milk, are
becoming major concerns of the veterinary associations such as
the American Association of Bovine Practitioners and Swine
Practitioners. Traditionally, veterinary public health was not an
attractive career for veterinarians because it was perceived as an
unimportant activity. However, because of the recent concern
about the contamination of meat supplies by pathogens and
xenobiotics (any substance foreign to an animal's biological
system), and the potentially serious economic effects of such
contamination on the export markets of a country, it is now clear
that veterinarians, using a variety of testing techniques, will
become involved in monitoring the use of veterinary drugs so
that treated animals are not placed in the food-chain until the
drugs have been excreted. The same principles apply to the
contamination of milk supplies with antimicrobials, a major
responsibility of the veterinarian.

ECONOMICS OF VETERINARY PRACTICE

The successful delivery of food-producing-animal practice will
depend on the ability of the veterinarian to provide those services
that the producer needs and wants at a price that is profitable to
both the producer and veterinarian. Several constraints interfere
with this successful delivery. Maximizing net profit is not a high
priority for many farmers. Being independent and making a
living on the farm are commonly ranked higher. Consequently,

when veterinarians make recommendations to control a disease
their subsequent enthusiasm for giving advice may be dampened
if farmers do not adopt the control procedures even though the
advice is based on good information about expected economic
returns.

The frustrations that many veterinarians experience in
attempting to get dairy producers to adopt the principles of an
effective and economical mastitis control program are well
known. In some cases, producers do not use modem methods of
production and disease control because they are unaware of their
importance. The variable financial returns that farmers receive for
their commodities, particularly the low prices received during
times of oversupply of meat and milk, may also influence
whether they purchase professional veterinary service or attempt
to do the work themselves.

VETERINARY EDUCATION

We have described our views on the state of food-producing-
animal medicine and what it requires of veterinarians who
practice it. Traditionally, veterinary colleges have provided
undergraduate students with the knowledge and clinical skills
necessary to enter veterinary practice and begin to engage in
food-producing-animal practice. Field service units and large-
animal in-clinics devoted to clinical teaching were an integral
part of most veterinary colleges. The clinical caseload is for the
students, clinicians and the paraclinical sciences such as
microbiology, toxicology, clinical pathology and pathology.
However, recently, it seems that veterinary colleges have not
maintained their farm-animal teaching clinics and, in fact, some
of these teaching clinics have ceased to exist. The demise of in-
house food animal practice in veterinary teaching hospitals, as
opposed to the care of agricultural animals from hobby farms, is
contributed to by the increasing use of stringent biosecurity
measures on medium- and large-scale operations. Animals
brought to veterinary teaching hospitals for diagnosis and
possible treatment cannot be returned to the farm because of the
fear of introducing infectious disease. Regardless, the demise of
in-house food-animal practice in universities should be of major
concern to the veterinary profession, which should have an
obligation to serve the veterinary needs of animal agriculture.
Some veterinary colleges have developed extensive programs in
which undergraduate students spend time in private veterinary
practice to gain clinical experience. However, the failure to
maintain and support viable farm-animal teaching clinics will
diminish the clinical experience of clinicians and the paraclinical
sciences, who have a primary responsibility for teaching. In
addition, the lack of clinical cases will adversely affect the clinical
research activities of clinicians. Clinicians must experience a
critical number of clinical cases in order to maintain credibility as
a veterinary scholar.

To study the phenomena of disease without books is to sail an

unchartered sea, while to study books without patients is not to

go to sea at all.

Sir William Osier,
Books and Men. Boston Surgical Journal. 1901

The practicing veterinarian must become knowledgeable about
various aspects of farm animal management, especially those
that cause or contribute to clinical or subclinical disease and
impaired animal production. Such veterinarians will become
species-industry specialists who can provide totally integrated
animal health and production management advice either to the
dairy herd, the beef cow-calf herd, the beef feedlot, the pig herd
or the sheep flock. To be able to do this veterinarians will need to
undertake a postgraduate clinical residency program or develop
the expertise on their own by diligent self-education in a

Introduction

XXI

veterinary practice that is committed to the concept of a total
animal health management and allows the veterinarian the time
and the resources to develop the specialty.

OPTIMAL UTILIZATION OF THE FOOD-PRODUCING-
ANIMAL PRACTITIONER

All that we have said in this introduction is related to enhancing
and improving the performance of the professional food-
producing-animal veterinarian. In developed countries this could
mean greater utilization of each veterinarian by farmers and
improved financial viability of their farming enterprises. In
developing countries it could mean a greater volume of pro-
duction at a time when malnutrition appears to be the fate of so
many groups of the world community. These could be the

outcomes if the world's agricultural situation was a stable one. As
it is, there is currently a great upheaval in agriculture; developed
countries are heavily overproduced and there is a sharp decline
in farming as an industry and way of life. In developing countries,
the decisions governing the health and welfare of animals and
the people that depend on them often seem to depend more, on
political expediency than on the basic needs of humans and their
animals. In these circumstances we do not feel sufficiently
courageous and farsighted to predict our individual futures but
with the hindsight of how far the human population and their
attendant agricultural and veterinary professions have come in
the past 50 years we are confident that you will have an oppor-
tunity to properly pursue the objectives and principles that we
have described.

How to use this book

We would like you to get the most out of this book. To do that you
should follow the directions below. And if you keep doing this
every time you use the book you will develop a proper diagnostic
routine of going from:

. . . and become what we wish for every one of you: a thinking
clinician.

FOR EXAMPLE

A yearling bull has a sudden onset of dyspnea, fever, anorexia,
abnormal lung sounds and nasal discharge.

Step 1 The bull's problem is dyspnea. Go to the index and find
the principal entry for dyspnea.

Step 2 The discussion on dyspnea will lead you to respiratory
tract dyspnea and cardiac dyspnea.

Step 3 Via the index consult these and decide that the system
involved is the respiratory system and that the lungs are the
location of the lesion in the system.

Step 4 Proceed to diseases of the lungs and decide on the basis
of the clinical and other findings that the nature of the lesion is
inflammatory and is pneumonia.

Step 5 Proceed to pneumonia, and consult the list of
pneumonias that occur in cattle. Consult each of them via the
index and decide that pneumonic pasteurellosis is the probable
specific cause.

Step 6 Proceed to the section on pneumonic pasteurellosis
determine the appropriate treatment for the bull and the chances
of saving it.

Step 7 Don't forget to turn to the end of the section on
pneumonic pasteurellosis and remind yourself of what to do to
protect the rest of the herd from sharing the illness.

Guidelines for selection and submission of
necropsy specimens for confirmation of
diagnosis

In this edition we continue with the subheading Samples for
confirmation of diagnosis to serve as a rough guideline for the
collection of samples at necropsy. Several points must be
emphasized with regard to this section. First and foremost,

collection of these samples is not advocated as a substitute
for a thorough necropsy examination. Furthermore, the
samples listed are selected in order to confirm the diagnosis but

a conscientious diagnostician should also collect samples that
can be used to rule out other disease processes. Even the best of
practitioners can make an incorrect tentative diagnosis but it is
| an even more humbling experience if there are no samples
! available to pursue alternate diagnoses. Also, recall that some
; diseases may be the result of several different etiological factors
! (e.g. neonatal diarrhea of calves) and the veterinarian who
j samples to confirm one of these factors, while not attempting to
j investigate others, has not provided a good service to the client.
A huge variety of veterinary diagnostic tests have been
developed but each veterinary diagnostic laboratory (VDL) offers
only a selected panel, chosen after consideration of a number of
| factors. Such factors may include: cost, demand, reliability,

: sensitivity and specificity, and the availability of appropriate
; technology at the lab. The array of diagnostic tests is constantly
1 improving and it is beyond the scope of this text to list all the
i tests available for a given disease, or to recommend one test
method to the exclusion of others. Under the samples for con-
firmation of diagnosis section we have merely listed some of the
more common tests offered. Advances in molecular biology are
providing exciting avenues for disease diagnosis, but many of
these tests have limited availability in VDLs at present. For
optimal efficiency in the confirmation of a diagnosis at necropsy,

1 the practitioner must contact their VDL to determine what tests
are offered and to obtain the preferred protocol for sample
collection and submission to that particular laboratory. Most
VDLs publish user guidelines, which include the tests available
and the samples required. The guidelines listed below are broad,
and individual VDLs may have very specific requirements for
sample handling.

Several general statements can be made with regard to the
submission of samples to VDLs:

• The samples should be accompanied by a clearly written and
concise clinical history, including the signalment of the
animal, as well as feeding and management information.
Failure to provide this information deprives the owner of the
full value of the expertise available from the laboratory staff

• If a potentially zoonotic disease is suspected, this should be
clearly indicated in a prominent location on the submission
form

• All specimens should be placed in an appropriate sealed,
leakproof container and clearly labeled with a waterproof
marker to indicate the tissue/fluid collected, the animal
sampled and the owner's name. At some VDLs, pooling of
tissues within a single bag or container is permitted for
specific tests (such as virus isolation), but in general all fresh
samples should be placed in separate containers. When
packaging samples for shipment recall that condensation
from ice packs and frozen tissues will damage any loose
paper within the package; the submission sheet should be
placed within a plastic bag for protection or taped to the
outside of the shipping container

• Samples for histopathology can be pooled within the same
container of 10% neutral-buffered formalin. An optimal
tissue sample of a gross lesion should include the interface
between normal and abnormal tissue. For proper fixation,
tissue fragments should not be more than 0.5 cm in width
and the ratio of tissue to formalin solution should be 1:10. If
necessary, large tissues such as brain can be fixed in a larger
container and then transferred to a smaller one containing
only a minimal quantity of formalin for shipping to the
laboratory. To speed fixation and avoid artifactual changes.

XXIV

How to use this book

formalin containers should not be in direct contact with
frozen materials during shipment.

In the Samples for confirmation of diagnosis section, the tests are
listed under various discipline categories (bacteriology, virology,
etc.). The appropriate sample(s) is noted, followed by the types of
test that might be applied to these samples. The following is a list
of these different tests, including any abbreviation used in this
section of the text. A brief discussion of how the samples
collected for each test should be handled is also provided. Again,
it must be emphasized that this is by no means a complete listing
of diagnostic tests available, and that different VDLs often have
differing sample handling procedures.

• Aerobic culture = (CULT). These samples should generally
be kept chilled during shipment. If a transit time of greater
than 24 hours is anticipated the samples should be frozen,
then packaged appropriately so that they are still frozen
upon arrival at the VDL. Various bacterial species cannot be
recovered using routine culture techniques and most of these
are highlighted in the text by the phrase 'special culture
requirements'

• Agar gel immunodiffusion = (AGID). A type of serological
test. Chilled or frozen serum may be submitted

• Anaerobic culture = (ANAEROBIC CULT). Confirmation of
the diagnosis requires that any swabs be transported in
special transport media and that the VDL attempts to grow
bacteria from the samples under anaerobic culture
conditions. Transport requirements are as for (CULT) (aerobic
culture) specimens

• Analytical assay = (ASSAY). This refers to a broad range of
tests in which a substance is quantitatively measured. The
substance to be assayed is listed in brackets, e.g. (ASSAY
(Ca)) denotes a test for calcium levels. The method used to
perform the assay is not listed but in general frozen samples
may be submitted for most of these analytical assays.

• Blood urea nitrogen = (BUN). A useful test to determine
degree of renal compromise. Sample can be shipped chilled
or frozen

• Bioassay = (BIO AS SAY). This typically refers to tests in
which the sample material is administered to an animal
under experimental conditions. Preserved material is
inappropriate and some bioassays cannot be performed
using samples which have been frozen. The VDL performing
the test should be contacted for instructions prior to sample
collection

• Complement fixation = (CF). A serological test. Ship chilled
or frozen serum

• Cytology = (CYTO). Air-dried impression smears are usually
adequate. Keep dry during transport

• Direct smear = (SMEAR). The type of test is usually given in
brackets (e.g. (Gram)). Air-dried smears are usually adequate
but must be kept dry during shipment

• Enzyme-linked immunosorbent assay = (ELISA). Chilled
or frozen samples are usually acceptable. There are many
variants of ELISA (e.g. antigen-capture, kinetic, indirect,
direct, etc.) and the specific type used is not specified in this
portion of the text

• Electron microscopic examination = (EM). Appropriate
sample collection and handling varies with the specimen
being examined. Most of the diagnostic specimens submitted
to VDLs for EM are fecal samples, and these do not require
any special preservative

• Fecal floatation = (FECAL). Sample can be fresh, chilled or
frozen

• Fluorescent Antibody Test = (FAT). This may refer to either
a direct or indirect method of antigen detection. Generally,
cryostat sections are utilized and therefore the tissue received
by the laboratory should still be frozen upon arrival to
provide the best results. Freeze/thaw cycles should be
avoided. If impression smears are being shipped, they should
be kept dry

• Fungal culture = (FCULT). Special media is required.
Transport as per (CULT) specimens

• Immunohistochemical testing = (IHC). Many of these tests
can be performed on formalin-fixed material but in some
instances frozen tissues must be delivered to the laboratory.
In such instances the test is listed under a heading distinct
from histology (e.g. virology, bacteriology, etc.)

• Indirect hemagglutination = (IHA). A serological test. Ship
chilled or frozen serum

• In-situ hybridization = (IN- SITU HYBRID). Samples
should be shipped chilled although some test methods can
use formalin -fixed material. These tests utilize nucleic acid
probes which bind with complementary nucleic acid
sequences in the specimen. Although not widely used in
routine diagnostics at present, these methods may gain more
prominence as their use is refined

• Virus isolation = (ISO). Samples should be kept chilled
during shipment or maintained in a frozen state if prolonged
transit times are anticipated

• Latex agglutination = (LATEX AGGLUTINATION). Fresh,
chilled or frozen samples are acceptable

• Light microscopic examination = (LM). Formalin-fixed
tissues are preferred. The shipment of fresh tissues to the
VDL permits more tissue autolysis prior to fixation, resulting
in less useful specimens. If Bouin's fixative is available, it is
the preferred preservative for eye globes.

• Microagglutination test = (MAT) . A type of serologic test.
Ship chilled or frozen serum.

• Mycoplasmal culture = (MCULT) . These types of organism
have specific growth requirements that are usually not met
by standard bacteriological culture techniques. Transport as
per (CULT) specimens. Culture swabs cannot be submitted
in media containing charcoal or glycerol

• Polymerase chain reaction = (PCR) . Tissues should be
frozen and maintained in that state until arrival at the VDL.
Swabs and fluids submitted for PCR testing should be chilled
but not frozen. These tests are capable of detected minute
quantities of nucleic acid, so if multiple animals are tested
the samples should be 'clean' in order to avoid false-positives
through cross-contamination (i.e. blood/tissue from one
animal contaminating the sample from another)

• Virus neutralization = (VN). A serological test. Ship chilled
or frozen serum.

GENERAL MEDICINE

PART 1 GENERAL MEDICINE

Clinical examination and making a
diagnosis

INTRODUCTION 3

CLINICAL EXAMINATION OF THE
INDIVIDUAL ANIMAL 3

History-taking 3

Examination of the environment 7
Examination of the patient 7

Introduction

The focal point of any investigation of
animal disease is the making of a diag-
nosis, and the critical part in making that
decision is the clinical examination of the
individual animal or group of animals.
Therefore, it is appropriate that the first
chapter of this book deals with this
important subject.

However, before we begin that exercise,
it is important that we be quite clear and
agree upon what we mean by 'disease'.
Let us assume that disease can be defined
as 'inability to perform physiological
functions at normal levels even though
nutrition and other environmental require-
ments are provided at adequate levels'.
When this definition is accepted, then not
only does a clinically ill animal come into
the area of examination but so also do
those animals or herds that are not
clinically ill but that do not perform as
expected. As veterinarians working with
food-producing animals and horses, we
are required to recognize individual
animals that are affected with a particular,
recognizable pathological lesion, or bio-
chemical or metabolic deficit, or nutritional
deficiency, that results in recognizable
clinical signs such as fever, dyspnea,
convulsions or lameness. This is traditional
veterinary medicine based on a trans-
position of attitudes and behavior from
human medicine. However, it is also
necessary for us to investigate disease
that the owner recognizes simply as
failure to perform or to reach pre-
determined objectives. This is not necess-
arily subclinical disease: it is recognizable
clinically but perhaps only as poor per-
formance, such as unthriftiness, without
any specific system-oriented clinical signs.
In other situations, the owner may not
recognize any abnormality unless pro-
ductivity is measured, e.g. milk production
or growth rate per day.

There has been considerable emphasis
on the clinical and laboratory examin-
ation of individual animals affected with

MAKING A DIAGNOSIS 22

Diagnostic methods 22
Interpretation of laboratory data 25
Computer-assisted diagnosis 28

PROGNOSIS AND THERAPEUTIC
DECISION-MAKING 29

Decision analysis 29

clinical disease or that have not per-
formed normally and the large body of
information now available in laboratory
medicine testifies to this preoccupation.
Its greatest importance is in animals, such
as companion and racing animals, that
are kept as singles and, unless the diag-
nosis is simple and readily obvious, if a
laboratory is available there may be a
tendency to make one or more laboratory
examinations. The more valuable the
animal, the greater the tendency towards
some laboratory work. Many biochemical,
hematological and biophysical examin-
ations of each body system can yield valu-
able clues about system or organ function,
which usually lead to more accurate and
detailed examination of that system or
organ. In animals kept in herds or flocks
these laboratory tests are also important
but are equalled in importance overall by
epidemiological investigations. There is
little to be gained by this form of examin-
ation in animals kept as singles.

With a herd of animals affected with
clinical disease, or which is failing to achieve
expected objectives, an epidemiological
investigation, in addition to the clinical
examination of individual animals, may
make a valuable contribution to the making
of a diagnosis. This is not to suggest that
clinical and laboratory examinations are de-
emphasized in the examination of herd
problems. In some instances, the clinical
and laboratory examinations assume major
importance to ensure that animals in a herd
that is not performing normally are in fact
not clinically ill. But when the presenting
complaint is poor performance, it is
necessary to collect all the pertinent
epidemiological data, including accu-
rate production measurements, and to
decide whether or not an abnormality is
present and, if so, its magnitude. It is at this
point that veterinarians become the
arbiters of what is 'health' and what is
'illness'. In herd health programs this is a
continuing and positive service provided
by veterinarians to farmer clients.

In this chapter on clinical examination
and making a diagnosis, we have described

1

EXAMINATION OF THE HERD 31

Approach to herd examination 31
Techniques in examination of the herd
or flock 35

the standard procedure for the clinical
examination of an individual animal
followed by some guidelines for the
examination of the herd. The level of the
examination set out is sufficient to enable
the clinician to determine the nature of
the abnormality and the system involved.
For more detailed examination it is
recommended that subsequent chapters,
which deal with individual systems, be
consulted. Each of them sets out a method
for a special examination of the particular
system.

Clinical examination of the
individual animal

A clinical examination has three parts:

• The animal
® The history
° The environment.

Inadequate examination of any of these
may lead to error. The examination of the
affected animal represents only a part
of the complete investigation. Careful
questioning of the owner or attendant can
yield information about the diet or the prior
diet, about recent vaccinations or surgery or
about the introduction of animals into the
group, that will provide the clues to a
successful diagnosis. However, in certain
instances, for example in lead poisoning of
cattle, the most detailed examination of the
animal and the most careful questioning of
the owner may fail to elicit the evidence
necessary for a correct diagnosis. Only a
careful physical search of the environment
for a source of lead can provide this infor-
mation. Thus neglect of one aspect of the
clinical examination can render valueless a
great deal of work on the other aspects
and lead to an error in diagnosis.

HISTORY-TAKING

In veterinary medicine, history- taking is
often the most important of the three
aspects of a clinical examination. The
significance of the results obtained by

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

examination of the patient and the
environment is liable to be modified by a
number of factors. Animals are unable to
describe their clinical symptoms; they
vary widely in their reaction to handling
and examination, and a wide range of
normality must be permitted in the criteria
used in a physical examination. These
variations are much greater in some
species than in others. Dairy cattle, horses,
sheep and goats are usually easy to
examine while beef cattle and pigs may be
difficult to examine adequately under
some conditions. A satisfactory examin-
ation of the environment may prove
difficult because of lack of knowledge of
the factors concerned or because of the
examiner's inability to assess their signifi-
cance. Problems such as the measurement
of the relative humidity of a bam and its
importance as a predisposing factor in an
outbreak of pneumonia or the deter-
mination of pH of the soil with reference
to the spread of leptospirosis can present
virtually insuperable difficulties to the
veterinarian in the field. On the other
hand, a search for a specific factor such as
a known poison may be relatively simple.

Nevertheless, history-taking is an
important key to accurate diagnosis in
veterinary medicine, and to be worth-
while it must be accurate and complete.
Admittedly, human fallibility must be
taken into consideration; there may be
insufficient time, the importance of parti-
cular factors may not be appreciated, and
there may be misunderstanding. Although
these are excusable up to a point, failure
to recognize the importance of the history
can lead only to error. To avoid being
misled, it is essential that the veterinarian
assesses the accuracy of the history by ]
careful examination of what the owner 1
relates about his or her animals. j

The history should suggest not only ■
the diagnostic possibilities but also the 1
probabilities. A 1-year-old heifer is unlikely
to have clinical Johne's disease, an adult .
cow is more likely to have parturient
paresis than a first-calf heifer, which in i
turn is more likely to have maternal ]
obstetric paralysis than is the adult cow. i
The history may often indicate that j
special attention should be paid to the
examination of a particular system in the :
animal, or a particular factorin the environ-
ment. For example, in hypovitaminosis-A
in beef calves from 6-10 months of age, j
the animals may be seen when they are
clinically normal and the only means of [
reaching a diagnosis may be a con- ;
sideration of the history of the clinical i
findings and the nutritional status. j

HISTORY-TAKING METHOD

Successful history-taking involves many ’
veterinarian-client relationships, which j

must be learned by experience. Some
suggestions are presented here as guide-
lines that may prove useful to the clinician.

The veterinarian should introduce
himself or herself to the owner, and the
usual greetings of the day will help to
establish a veterinarian-client relationship.
Asking the owner 'How can I help you
today?' is an effective opening question,
which provides the owner the opportunity
to relate his or her concerns about the
animals.

The owner or attendant must be
handled with diplomacy and tact. The use
of nontechnical terms is essential, since
livestock owners are likely to be confused
by technical expressions or reluctant to
express themselves when confronted with
terms they do not understand. Statements,
particularly those concerned with time,
should be tested for accuracy. Owners,
and more especially herdsmen and
agents, may attempt to disguise their
neglect by condensing time or varying the
chronology of events. If a detailed cross-
examination of the owner seems likely to
arouse some antagonism, it is advisable
for the veterinarian to forego further
questioning and be content with his or
her own estimate of the dependability of
the history. The clinician must try to
separate owners' observations from their
interpretations. A statement that the
horse had a bout of bladder trouble may,
on closer examination, mean that the
horse had an attack of abdominal pain in
which it assumed a posture usually
associated with urination. Often, how-
ever, it is impossible to avoid the use of
leading questions - 'Did the pigs scour?',
'Was there any vomiting?' - but it is
necessary to weigh the answers in accord-
ance with the general veracity of the
owner.

Absence of a sign can only be deter-
mined by inquiring whether or not it
occurred. Simply to ask for a complete
history of what has happened almost
invariably results in an incomplete
history. The clinician must, of course,
know the right questions to ask; this
knowledge comes with experience and
familiarity with disease. Owners seldom
describe clinical signs in their correct time
sequence; part of the clinician's task is to
establish the chronology of events.

For completeness and accuracy in
history-taking the clinician should con-
form to a set routine. The system outlined
below includes patient data, disease
history and management history. The
order in which these parts of the history
are taken will vary. In general it is best to
take the disease history first. The psycho-
logical effect is good: the owner appreciates
the desire to get down to the facts about
his or her animal's illness.

PATIENT DATA

If records are to be kept at all, even if only
for financial purposes, accurate identifi-
cation of the patient is essential. An
animal's previous history can be referred
to, the disease status of a herd can be
examined, specimens for laboratory
examination can be dispatched with the
knowledge that the results can be related
to the correct patient. Accurate records
are also necessary for the submission of
accounts for veterinary services rendered
and the details of the owner's address and
of the animals examined and treated must
be accurate. These points may have no
importance in establishing the diagnosis
but they are of primary importance in the
maintenance of a successful practice.

The relevant data include:

° Owner's name and initials
o Postal address and telephone number
0 Species, type, breed (or estimate of
parentage in a crossbred)

° Sex, age, name or number, body
weight

0 If necessary, a description, including
color markings, polledness and other
identifying marks, of the patient.

Such a list may appear formidable but
many of the points, such as age, sex, breed,
type (use made of animal, e.g. beef, dairy,
mutton, wool), are often of importance in
the diagnosis. A case history of a parti-
cular animal may suggest that further
treatment is likely to be uneconomic
because of age, or that a particular disease
is assuming sufficient importance in a
herd for different control measures to be
warranted.

Computers are now being used exten-
sively in veterinary practices for recording
the details of farm calls, the animals
examined and treated, the amounts
charged for travel and professional services,
j the costs of laboratory services, the drugs
1 used and dispensed, and the diseases that
i occur on a particular farm on an ongoing
! basis. It is now possible for veterinary
practices to provide regular and annual
i health reports to herd owners so that
| planned health management programs
can be assessed and evaluated. The ability
to retrieve and summarize this infor-
| mation on an individual farm basis is a
j major step forward in providing optimal
veterinary service to livestock herds
\ regardless of their size and complexity.

DISEASE HISTORY

History-taking will vary considerably
i depending on whether one animal or a
i group of animals is involved in the disease
problem under examination. As a general
; rule, in large animal work, all disease
states should be considered as herd
: problems until proved to be otherwise.

Clinical examination of the individual animal

5

It is often rewarding to examine the
remainder of a group and find animals
that are in the early stages of the disease.

Present disease

Attempts should be made to elicit the
details of the clinical abnormalities
observed by the owner in the sequence in
which they occurred. If more than one
animal is affected, a typical case should be
chosen and the variations in history in
other cases should then be noted. Vari-
ations from the normal in the physiological
functions such as intake of food or drink,
milk production, growth, respiration,
defecation, urination, sweating, activity,
gait, posture, voice and odor should be
noted in all cases. There are many specific
questions that need to be asked in each
case but they are too numerous to list
here and for the most part they are
variations on the questions already
suggested.

If a number of animals are affected,
information may be available from clinical
pathological examinations carried out on
living animals or necropsy examinations
on fatal cases. The behavior of animals
before death and the period of time
elapsing between the first observable
signs and death or recovery are important
items of information. Prior surgical or
medical procedures such as castration,
docking, shearing, or vaccination may be
important factors in the production of
disease.

Morbidity, case fatality and
population mortality rates

The morbidity rate is usually expressed as
the percentage of animals that are
clinically affected compared with the total
number of animals exposed to the same
risks. The case fatality rate is the percent-
age of affected animals that die. The popu-
lation mortality rate is the percentage
of all exposed animals that die. The
estimates may be important in diagnosis
because of the wide variations in
morbidity, case fatality and population
mortality rates that occur in different
diseases. An equally important figure is
the proportion of animals at risk that are
clinically normal but show abnormality
on the basis of laboratory or other tests.

Prior treatment

The owner may have treated animals
before calling for assistance. Exact details
of the preparations used and doses given
may be of value in eliminating some diag-
nostic possibilities. They will certainly be
of importance when assessing the prob-
able efficiency of the treatment and the
significance of clinical pathological tests,
and in prescribing additional treatment.
Drug withdrawal regulations now require
that treated animals or their products,

such as milk, be withheld from slaughter
or market for varying lengths of time to
allow drug residues to reach tolerable
limits. This necessitates that owners reveal
information about the drugs that they
have used.

Prophylactic and control measures

It should be ascertained whether preven-
tive or control procedures have already
been attempted. There may have been
clinical pathological tests, the introduction
of artificial insemination to control
venereal disease, vaccination, or changes
in nutrition, management or hygiene. For
example, in an outbreak of bovine
mastitis careful questioning should be
pursued regarding the method of dis-
infecting the cows' teats after each
milking, with particular reference to the
type and concentration of the disinfectant
used and whether or not back-flushing of
teat cups is practiced. Spread of the disease
may result from failure of the hygiene
barrier at any one of a number of such
points. When written reports are available
they are more reliable than the memory of
the owner.

Previous exposure

The history of the group relative to
additions is of particular importance. Is
the affected animal an established member
of the group, or has it been introduced,
and if so how long ago? If the affected
animal has been in the group for some
time, have there been recent additions? Is
the herd a 'closed herd' or are animals
introduced at frequent intervals? Not all
herd additions are potential carriers of
disease - they may have come from herds
where control measures are adequate,
they may have been tested before or after
sale or kept in quarantine for an adequate
period after arrival, or they may have
received suitable biological or antibiotic
prophylaxis. Herd additions may have
come from areas where a particular disease
does not occur, although a negative
history of this type is less reliable than a
positive history of derivation from an area
where a particular disease is enzootic.

A reverse situation may occur where
imported animals have no resistance to
endemic infection in the home herd, or
: have not become adapted to environ-
| mental stressors such as high altitudes,
i high environmental temperatures and 1
I particular feeding methods, or are not i
I accustomed to poisonous plants occurring ;
\ in the environment.

! Transit

\ The possibility of infection during transit
! is always a potential risk and pre-sale
i certificates of health may be of little value
if an animal has passed through a sale
barn, a show or communal trucking yards

while in transit. Highly infectious diseases
may be transmitted via trucks, railroad
cars or other accommodation contaminated
by previous inhabitants. Transient intro-
ductions, including animals brought in for
work purposes, for mating or on temporary
grazing, are often overlooked as possible
vectors of disease. Other sources of infec-
tion are wild fauna that graze over the
same area as domestic livestock and
inanimate objects such as human foot-
wear, car tires and feeding utensils.

Culling rate

There may be considerable significance in
the reasons for culling, and the number of
animals disposed of for health reasons.
Failure to grow well, poor productivity
and short productive life will suggest the
possible occurrence of a number of
chronic diseases, including some associ-
ated with infectious agents, by nutritional
deficiencies or by poisons.

Previous disease

Information elicited by questioning on
previous history of illness maybe helpful.
If there is a history of previous illness,
inquiries should be made on the usual
lines, including clinical observations,
necropsy findings, morbidity, case fatality
rates, the treatments and control measures
used and the results obtained. If necess-
ary, inquiries should be made about herds
from which introduced animals have
originated and also about herds to which
other animals from the same source have
been sent.

MANAGEMENT HISTORY

The management history includes nutri-
tion, breeding policy and practice,
housing, transport and general handling.
It is most important to learn whether or
not there has been any change in the
prevailing practice prior to the appear-
ance of disease. The fact that a disease has
occurred when the affected animals have
been receiving the same ration, deriving
from the same source over a long period,
suggests that the diet is not at fault,
although errors in preparation of con-
centrate mixtures, particularly with the
present-day practice of introducing
additives to feeds, can cause variations
that are not immediately apparent.

Nutrition

The major objective in the examination of
the nutritional history is to determine
how the quantity and quality of the diet
which the animals have been receiving
compares with the nutrient requirements
that have been recommended for a
similar class of animal. In some situations
it may be necessary to submit feed and
water samples for analyses to assess
quality.

6

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

Livestock at pasture

Pastured livestock present a rather differ-
ent problem from those being stall-fed in
that they receive a diet that is less con-
trolled and thus more difficult to assess.
The risk of parasitic infestation and, in
some cases, infectious disease is much
greater in grazing animals. Inquiries should
be made about the composition of the
pasture, its probable nutritive value with
particular reference to recent changes
brought about by rain or drought, whether
rotational grazing is practiced, the fertilizer
program and whether or not minerals and
trace elements are provided by top-
dressing or mineral mixtures. The origin
of mineral supplements, particularly phos-
phates, which may contain excess fluorine,
and homemade mixtures, which may
contain excessive quantities of other ingre-
dients, should receive attention. Actual
examination of the pasture area is usually
more rewarding than a description of it.

Hand-fed/stall-fed animals
Hand-fed or stall-fed animals are sub-
jected to a more or less controlled feed
supply but, because of human error, they
are frequently exposed to dietary mistakes.
Types and amounts of feeds fed should be
determined. Examples of disease caused
by inadequate hand-fed diets include:
osteodystrophia fibrosa in horses on diets
containing excess grain; azoturia in the
same species when heavy-carbohydrate
diets are fed during periods of rest, and
lactic acid indigestion in cattle introduced
to high-level grain diets too rapidly. The
sources of the dietary ingredients may
also be of importance. Grains from some
areas are often much heavier and contain
a much greater proportion of starch to
husk than grains from other areas so that
when feed is measured, rather than
weighed, overfeeding or underfeeding
may occur.

Because the digestive enzyme capacity
of newborn farm animals is most efficient
in the digestion of whole milk, the use of
non-milk sources of carbohydrates and
proteins in the formulation of milk replacers
may result in indigestion and nutritional
diarrhea.

Exotic diseases may be imported in
feed materials: anthrax, foot-and-mouth
disease and hog cholera are well-known
examples.

Variations in the preparation of ingre-
dients of rations may produce variable
diets. Overheating, as in pelleting or the
cooking of feeds, can reduce their vitamin
content; contamination with lubricating
oil can result in poisoning by chlorinated
naphthalene compounds; pressure
extraction of linseed can leave consider-
able residues of hydrocyanic acid in the
residual oil cake.

Feeding practices may in themselves
contribute to the production of disease.
Pigs fed in large numbers with in-
adequate trough space or calves fed from
communal troughs are likely to be affected
by overeating or inanition, depending on
their size and vigor. High-level feeding
and consequent rapid growth may create
deficiency states by increasing the
requirement for specific nutrients.

In both hand-fed and grazing animals
changes in diet should be carefully noted.
Movement of animals from one field to
another, from pasture to cereal grazing,
from unimproved to improved pasture
may all precipitate the appearance of
disease. Periods of sudden dietary de-
ficiency can occur as a result of bad weather
or transportation, or during change to
unfamiliar feeds. Rapid changes are more
important than gradual alterations, parti-
cularly in pregnant and lactating ruminants
when metabolic diseases, including those
caused by hypocalcemia, hypoglycemia
and hypomagnesemia, are likely to occur.

The availability of drinking water
must be determined: salt poisoning of
swine occurs only when the supply of
drinkingwater is inadequate.

Reproductive management and
performance

In the examination of a single animal the
breeding and parturition history may
suggest or eliminate some diagnostic
possibilities. For example, pregnancy
toxemia occurs in sheep in late pregnancy
while acetonemia in dairy cows occurs
primarily 2-6 weeks after parturition.
Acute septic metritis is a possibility within
a few days after parturition in any species
but unlikely several weeks later.

Breeding history

The breeding history may be of importance
with regard to inherited disease. The
existence of a relationship between sires
and dams should be noted. Hybrid vigor
in crossbred animals should be con-
sidered when there is apparent variation
in resistance to disease between groups
maintained under similar environmental
conditions. A general relationship between
selection for high productivity and
susceptibility to certain diseases is appar-
ent in many breeds of animal and even in
certain families. The possibility of geneto-
trophic disease, i.e. the inheritance of a
greater requirement than normal of a
specific nutrient, should be considered.

Reproductive history

The examination of the herd reproductive
history involves comparing past and
present reproductive performance with
certain optimum objectives. The mean
length of the interval between parturition
and conception, the mean number of

services per conception and the percent-
age of young animals weaned relative to
the number of females that were originally
exposed for breeding (calf or lamb crop,
pigs weaned) are general measures of
reproductive performance and efficiency.

Using cattle as an example, certain
other observations may assist in determin-
ing the cause of failure to reach repro-
ductive performance objectives. These
are:

° Percentage of abortions
0 Length of breeding season
° Percentage of females pregnant at
specified times after the onset of
breeding period
° Bull/cow ratio

9 Size and topography of breeding
pastures

* Fertility status of the females and
males at breeding time.

The percentage of females that need
assistance at parturition and the percent-
age of calves that die at birth are also
indices of reproductive performance that
are indicative of the level of reproductive
management provided.

Climate

Many diseases are influenced by climate.
Foot rot in cattle and sheep reaches its
peak incidence in warm, wet summers
and is relatively rare in dry seasons.
Diseases spread by insects are encouraged
when climatic conditions favor the
propagation of the vector. Internal para-
sites are similarly influenced by climate.
Cool, wet seasons favor the development
of hypomagnesemia in pastured cattle.
Anhidrosis in horses is specifically a
disease of hot, humid countries. The
direction of prevailing winds is of import-
ance in many disease outbreaks, parti-
cularly in relation to the contamination of
pasture and drinking water by fumes from
factories and mines and the spread of
diseases carried by insects.

General management

There are so many items in the proper
management of livestock that, if neglected,
can lead to the occurrence of disease that
they cannot be related here; animal
management in the prevention of disease
is a subject in its own right and is dealt
with in all parts of this book. Some of the
more important factors include:

9 Hygiene, particularly in milking
parlors and in parturition and rearing
stalls

9 Adequacy of housing in terms of
space, ventilation, draining, situation
and suitability of troughs
9 Opportunity for exercise
9 Proper management of milking
machines to avoid udder injury.

The class of livestock under consideration
is also of importance; for example,
enterotoxemia is most common in finish-
ing lambs and pigs, parturient paresis in
milking cows, obstructive urolithiasis in
lambs and steers in feedlots and preg-
nancy toxemia in ewes used for fat lamb
production.

EXAMINATION OF THE
ENVIRONMENT

An examination of the environment is a
necessary part of any clinical investigation
because of the possible relationship
between environmental factors and the
incidence of disease. A satisfactory exam-
ination of the environment necessitates
an adequate knowledge of animal
husbandry and, with the development of
species specialization, it will be desirable
for the veterinarian to understand the
environmental needs of a particular
species or class of farm animal.

Depending on the region of the world,
some animals are kept outside year round,
some are housed for part of the year
during the winter months, and some are
kept under total confinement. For animals
raised on pasture, the effects of topo-
graphy, plants, soil type, ground surface
and protection from extremes of weather
assume major importance. For animals
housed indoors, hygiene, ventilation and
avoiding overcrowding are of major
concern. Some of these items will be
briefly presented here as guidelines. Each
observation should be recorded in detail
for preparation of reports for submission
to the owners. Detailed records and even
photographs of environmental character-
istics assume major importance when
poisonings are suspected and where
litigation proceedings appear possible.

OUTDOOR ENVIRONMENT
Topography and soil type

The topography of grasslands, pastures
and wooded areas can contribute to
disease or inefficient production and
reproduction. Flat, treeless plains offering
no protection from wind predispose cattle
to lactation tetany in inclement weather.
Low, marshy areas facilitate the spread of
insect-borne diseases and soil-borne
infections requiring damp conditions,
such as leptospirosis; Johne's disease and
diseases associated with liver fluke infes-
tation and lungworm pneumonia are
more prevalent in such areas. Rough
grasslands with extensive wooded areas
can have an adverse effect on reproductive
performance in beef herds because of the
difficulty the bulls have in getting to the
females during peak periods of estrus
activity.

The soil type of a district may provide
important clues to the detection of

Clinical examination of the individual animal

T/l

nutritional deficiencies; copper and cobalt
deficiencies are most common on littoral
sands and the copper deficiency/
molybdenum excess complex usually
occurs on peat soils. The surface of the
ground and its drainage characteristics
are important in highly intensive beef
feedlots and in large dairy herds where
fattening cattle and dairy cows are kept
and fed under total confinement. Ground
surfaces that are relatively impermeable
and/or not adequately sloped for drainage
can become a sea of mud following a
heavy rainfall or snowstorm. Constant
wetting of the feet and udders commonly
results in outbreaks of foot rot and
mastitis. Dirty udders increase the time
required for udder washing prior to
milking and can seriously affect a mastitis
control program.

In some regions of the world, beef cows
are calved in outdoor paddocks in the
spring when it is wet and cold with an
excess of surface water; this increases the
spread of infectious disease and results in
a marked increase in neonatal mortality.
A lack of sufficient protection from the
prevailing winds, rain, snow or the heat of
the sun can seriously affect production
and can exacerbate an existing disease
condition or precipitate an outbreak.
Dusty feedlots during the hot summer
months may contribute to an increase in
the incidence of respiratory disease or
delay the response to treatment of disease
such as pneumonia.

Stocking rate (population density)

Overcrowding is a common predisposing
cause of disease. There may be an excess-
ive buildup of feces and urine, which
increases the level of infection. The
relative humidity is usually increased and
more difficult to control. Fighting and
cannibalism are also more common in
overcrowded pens than when there is
adequate space for animals to move
around comfortably. The detection and
identification of animals for whatever
reason (illness, estrus) can be difficult and
inaccurate under crowded conditions.

Feed and water supplies

Pasture and feed

On pastures the predominant plant types,
both natural and introduced, should be
observed as they are often associated with
certain soil types and may be the cause of
actual disease; the high estrogen content
of some clovers, the occurrence of func-
tional nervous diseases on pastures domi-
nated by Phalaris aquatica (syn. P. tuberosa)
and perennial rye grass and the presence
of selective absorbing 'converter' plants
on copper-rich and selenium-rich soils
are all examples of the importance of the
dominant vegetation. The presence of
specific poisonous plants, evidence of

overgrazing and the existence of a bone-
chewing or bark-chewing habit can be
determined by an examination of the
environment.

Vital clues in the investigation of poss-
ible poisoning in a herd may be .the
existence of a garbage dump or ergotized
grass or rye in the pasture, or the chewing
of lead- based painted walls in the bam, or
careless handling of poisons in the feed
area. The possibility that the forage may
have been contaminated by environmental
pollution from nearby factories or high-
ways should be examined. In some cases
the physical nature of the pasture plants
may be important; mature, bleached grass
pasture can be seriously deficient in
carotene, whereas lush young pasture can
have rachitogenic potency because of its
high carotene content or it may be
capable of causing hypomagnesemia if it
is dominated by grasses. Lush legume
pasture or heavy concentrate feeding with
insufficient roughage can cause a serious
bloat problem.

The feed supplies for animals raised in
confinement outdoors must be examined
for evidence of moldy feed, contami-
nation with feces and urine and excessive
moisture due to lack of protection from
rain and snow. Empty feed troughs may
confirm a suspicion that the feeding
system is faulty.

Water

The drinking water supply and its origin
may be important in the production of
disease. Water in ponds may be covered
with algae containing neurotoxins ■ or
hepatotoxic agents and flowing streams
may carry effluent from nearby industrial
plants. In a feedlot, water may suddenly
become unavailable because of frozen
water lines or faulty water tank valves.
This should not go unnoticed if one
recognizes the anxiety of a group of cattle
trying to obtain water from a dry tank.

Waste disposal

The disposal of feces and urine has become
a major problem for large intensified live-
stock operations. Slurry is now spread on
pastures and may be important in the
spread of infectious disease. Lagoons can
provide ideal conditions for the breeding
of flies, which can be troublesome to a
nearby livestock operation. The inadequate
disposal of dead animals may be an
important factor in the spread of certain
diseases.

INDOOR ENVIRONMENT

There are^few aspects of livestock pro-
duction that have aroused more interest,
development and controversy in the last
(few years than the housing and environ-
mental needs of farm animals. Several
textbooks on the subject have been

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

written and only some of the important
items will be mentioned here, with the aid
of some examples. The effects of housing
on animal health have not received the
consideration they deserve, partly because
of insufficient knowledge of animals'
environmental needs and partly because
there has been a failure to apply what is
already known.

As a general statement, it can be said
that inadequate housing and ventilation,
overcrowding and uncomfortable con-
ditions are considered to have detrimental
effects on housed animals that make
them not only more susceptible to infec-
tious disease but also less productive.
Moreover, this reduction in productive
efficiency may be a greater cause of
economic loss than losses caused by
infectious disease. For this reason, the
veterinarian must learn to examine and
assess all aspects of an indoor environ-
ment, which may be the primary cause of,
or a predisposing factor to, disease. By
way of illustration, the major causes of
preweaning mortality of piglets are
chilling and crushing of piglets in the first
few days of life, and not infectious
disease. These physical causes are com-
monly related to a combination of poorly
designed farrowing crates, slippery floors,
inadequate heating and perhaps over-
crowding of the farrowing facilities.

Hygiene

One of the first things to observe is the
level of sanitation and hygiene, which is
usually a reliable indicator of the level of
management; poor hygiene is often
associated with a high level of infectious
disease. For example, the incidence of
diarrhea in piglets may be high because
the farrowing crates are not suitably
cleaned and disinfected before the preg-
nant sows are placed in them. A similar
situation applies for lambing sheds, calving
pens and foaling boxes. An excessive
buildup of feces and urine with insufficient
clean bedding will result in a high level of
neonatal mortality. The methods used for
cleaning and disinfection should be
examined carefully. The removal of dried
feces from animal pens that have been
occupied for several months is a difficult
and laborious task and often not done
well. Undue reliance may be placed on the
use of chemical disinfectants.

The total length of time that animals
have occupied a pen without cleaning
and disinfection (occupation time) should
be noted. As the occupation time increases,
there is a marked increase in the infection
rate and the morbidity and mortality from
infectious disease often increase.

Ventilation

Inadequate ventilation is considered to be
a major risk factor contributing to the

severity of swine enzootic pneumonia in
finishing pigs. The primary infection has a
minimal effect on the well-housed pig,
but inadequate ventilation results in over-
heating of the bam in the summer months
and chilling and dampness during the
winter months, commonly resulting in
subclinical and clinical pneumonia, which
severely affects productive efficiency.
Similarly, in young calves, which are
raised indoors in most of the temperate
zones of the world, protection from the
cold during the winter is necessary. The
effects of enzootic pneumonia of housed
calves are much more severe when
ventilation is inadequate than when the
calves are comfortable and have clean,
fresh air.

The evaluation of the adequacy of
ventilation of a farm animal barn that is
filled to economic capacity with animals is
a difficult task and a major subject.
Ventilation is assessed by a determination
of the number of air changes per unit of
time, the relative humidity during the day
and night, the presence or absence of
condensation on the hair coats of the
animals or on the walls and ceilings, the
presence of drafts, the building and
insulation materials used, the positions
and capacities of the fans and the size and
location of the air inlets. The measurement
of the concentration of noxious gases in
animal barns, such as ammonia and
hydrogen sulfide, may be a valuable aid in
assessing the effectiveness of a ventilation
system.

Animals raised indoors are frequently
overcrowded, which may predispose to
disease, and measurements of population
density and observations of animal
behavior in such conditions assume major
importance. When pigs are raised indoors
in crowded conditions with inadequate
ventilation, their social habits may change
drastically and thev begin to defecate and
urinate on the ciean floor and on their
pen-mates rather than over the slatted
floor over the gutter. This can result in
outbreaks of diseases that are transmitted
by the fecal-oral route.

Flooring

The quality of the floor is often responsible
for diseases of the musculoskeletal system
and skin. Fborly finished concrete floors
with an exposed aggregate can cause
severe foot lesions and lameness in adult
swine. Recently calved dairy cows are very
susceptible to slipping on poor floors in
, dairy barns, a common cause of the
downer cow syndrome. Loose-housing
systems, particularly those with slatted
; floors, have resulted in a new spectrum of
diseases of the feet of cattle because of the
■ sharp edges of some of the slats. The
i quality and quantity of bedding used

should be noted. Bedding is now rarely
used in intensified swine operations. The
use of sawdust or shavings in loose-
housing systems for dairy cattle may be
associated with outbreaks of coliform
mastitis. Wet bedding, particularly during
the winter months, is commonly associated
with endemic pneumonia in calves.

Floor plan

The floor plan and general layout of an
animal house must be examined for
evidence that the routine movements
of animal attendants, the movements of
animals and feeding facilities may
actually be spreading disease. Communal
gutters running through adjacent pens
may promote the spread of disease
through fecal or urinary contamination.
The nature of the partitions between
pens, whether solid or open grid type,
may assist the control or spread of infec-
tious disease. The building materials used
will influence the ease with which pens,
such as farrowing crates and calf pens,
can be cleaned and disinfected for a new
batch of piglets or calves.

Lighting

The amount of light available in a bam
should be noted. With insufficient light it
may be difficult to maintain a sufficient
level of sanitation and hygiene, sick
animals may not be recognized early
enough, and in general errors in manage-
ment are likely to occur.

In the investigation of a herd problem
of mastitis in dairy cattle the veterinarian
should visit the farm at milking time and
observe how the cows are prepared for
milking, examine the teats and udders
before and after they are washed, observe
the use of the milking machine, and the
level of sanitation and hygiene practiced.
Several successive visits may be necessary
to reveal possible weakness in a mastitis
control program.

EXAMINATION OF THE PATIENT

A complete clinical examination of an
animal patient includes, in addition to
history-taking and an examination of the
environment, physical and laboratory
examinations. A complete clinical examin-
ation of every patient is unnecessary
because of the simplicity of some diseases.
However, a general clinical examination
of every patient is necessary and the
inexperienced clinician should spend as
much time and effort as is practicable and
economical in carrying it out. This will
help to avoid the sort of embarrassing
error in which a calf is operated on for
umbilical hernia when it also has a
congenital cardiac defect.

As learned experience develops, the
clinician will know the extent to which a

Clinical examination of the individual animal

9

clinical examination is necessary. All the
laboratory tests that are likely to be
informative and that are practical and
economical should be used. Because of
the cost of laboratory tests, the clinician
must be selective in the tests used. The
most economical method is to examine
the patient and then select those laboratory
tests that will support or refute the
tentative clinical diagnosis. In this section
a system for the examination of a patient
is outlined in a general way. There is a
great deal of difference between species
in the ease with which this examination is
done and the amount of information that
can be collected. Additional detailed
examination techniques are described
under the individual body systems.

The examination of a patient consists
of a general inspection done from a
distance (the distant examination, and
the particular distant examination of
body regions), followed by a close
physical examination of all body regions
and systems. Only the major body systems
that are routinely examined are presented
here as part of the general examination.

GENERAL INSPECTION (DISTANT
EXAMINATION)

The importance of a distant examination
of the animal cannot be overemphasized,
and yet it is often overlooked. Apart from
the general impression gained from
observation at a distance, there are some
signs that can best be assessed before the
animal is disturbed. The proximity of the
examiner is particularly disturbing to
animals that are unaccustomed to frequent
handling.

Behavior and general appearance

The general impression of the health of
an animal obtained by an examination
from a distance should be assessed
according to the following.

Behavior

Separation of an animal from its group is
often an indication of illness. The behavior
is also a reflection of the animal's health.

If it responds normally to external stimuli,
such as sound and movement, it is
classified as bright. If the reactions are
sluggish and the animal exhibits relative
indifference to normal stimuli, it is said to
be dull or apathetic. Cattle with carbo- j
hydrate engorgement are commonly
reluctant to move unless coaxed. A pro-
nounced state of indifference in which the
animal remains standing and is able to j
move but does not respond at all to j
external stimuli is the 'dummy' syndrome.
This occurs in subacute lead poisoning, j
listeriosis and some cases of acetonemia j
in cattle, and in encephalomyelitis and j
hepatic cirrhosis in horses. The terminal j
stage of apathy or depression is coma, in ;

which the animal is unconscious and
cannot be roused.

Excitation states

Excitation states vary in severity. A state of
anxiety or apprehension is the mildest
form: here the animal is alert and looks
about constantly but is normal in its
movements. Such behavior is usually
expressive of moderate constant pain or
other abnormal sensation, as in early
parturient paresis or in recent blindness.

A more severe manifestation is restless-
ness, in which the animal moves about a
good deal, lies down and gets up and may
go through other abnormal movements
such as looking at its flanks, kicking at its
belly and rolling and bellowing. Again,
this demeanor is usually indicative of pain.

More extreme degrees of excited
demeanor include mania and frenzy. In
mania, the animal performs abnormal
movements with vigor. Violent licking at
its own body, licking or chewing inanimate
objects and pressing forward with the
head are typical examples. In frenzy, the
actions are so wild and uncontrolled that
the animals are a danger to anyone
approaching them. In both mania and
frenzy there is usually excitation of the
brain, as in rabies, acute lead poisoning
and some cases of nervous acetonemia.

Voice

Abnormality of the voice should be noted.

It may be hoarse in rabies or weak in gut
edema; there may be continuous lowing
in nervous acetonemia or persistent
bellowing indicative of acute pain. Sound-
less bellowing and yawning are commonly
seen in rabid cattle and yawning is a com-
mon sign in animals affected with hepatic
insufficiency.

Eating

The appetite of the animal can be
assessed by observing its reaction to the
offering of feed or by the amount of feed
available that has not been eaten. It is
important to determine the total amount
of feed that the animal is eating per day.

In a patient that has retained its appetite,
there may be abnormality of prehension,
mastication or swallowing and, in
ruminants, of belching and regurgitation.

Prehension may be interfered with by
inability to approach feed, paralysis of the
tongue in cattle, in cerebellar ataxia,
osteomyelitis of cervical vertebrae and
other painful conditions of the neck. When
there is pain in the mouth, prehension
may be abnormal and affected animals
may be able to take only certain types of
feed. Mastication may be slow, one-sided
or incomplete when mouth structures,
particularly teeth, are affected. Periodic
cessation of chewing when feed is still in
the mouth occurs commonly in the j

'dummy' syndrome, when there are
space-occupying lesions of the cranium
or an encephalomyelitis exists.

Swallowing may be painful because of
inflammation of the pharynx or esophagus,
as is found in strangles in the horse,, in
calf diphtheria, and where improper use
of bailing and drenching guns or bottles
has caused laceration of the pharyngeal
mucosa. Attempts at swallowing followed
by coughing up of feed or regurgitation
through the nostrils can also be the result
of painful conditions but are most likely
to be due to physical obstructions such as
esophageal diverticula or stenosis, a
foreign body in the pharynx, or paralysis
of the pharynx. It is important to differ-
entiate between material that has reached
the stomach and ingesta regurgitated
from an esophageal site. Partial esophageal
obstruction resulting in difficult swallow-
ing is usually manifested by repeated
swallowing movements, often with
associated flexion of the neck and grunting.

In ruminants there may be abnor-
malities of rumination and eructation.
Absence of cudding occurs in many
diseases of cattle and sheep; violent efforts
at regurgitation with grunting suggests
esophageal or cardiac obstruction. There
may be inability to control the cud -'cud-
dropping'- due to pharyngeal paralysis or
painful conditions of the mouth. Failure
to eructate is usually manifested by the
appearance of bloat.

Defecation

In constipation and rectal paralysis or
stenosis, the act of defecation may be
difficult and be accompanied by straining
or tenesmus. When there is abdominal
pain or laceration of the mucocutaneous
junction at the anus, defecation may
cause obvious pain. Involuntary defecation
occurs in severe diarrhea and when there
is paralysis of the anal sphincter. Con-
sideration of frequency, volume and
character of feces is given later under the
section on special examination of the
digestive tract. Constipation must not be
mistaken for scant feces, particularly
in mature cattle with diseases of the fore -
stomachs and failure of movement of
ingesta in a caudad direction.

Urination

This may be difficult when there is partial
obstruction of the urinary tract, and
painful when there is inflammation of
the bladder or urethra. In cystitis and
urethritis, there is increased frequency
with the passage of small amounts of
fluid, and the animal remains in the
urination posture for some time after the
flow ceases. Incontinence, with constant
'(dribbling of urine, is usually due to partial
: obstruction of the urethra or paralysis of
; its sphincter. If the animal urinates during

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

the visual inspection, a sample of urine
should be obtained, examined grossly and
submitted for urinalysis.

Posture

Abnormal posture is not necessarily
indicative of disease, but when associated
with other signs it may indicate the site
and severity of a disease process. One of
the simplest examples is resting of a limb
in painful conditions of the extremities; if
a horse continually shifts its weight from
limb to limb it may indicate the presence
of laminitis or early osteodystrophia
fibrosa. Arching of the back with the
limbs tucked under the body usually
indicates mild abdominal pain; down-
ward arching of the back and 'saw horse'
straddling of the legs is characteristic of
severe abdominal pain, usually spasmodic
in occurrence; a 'dog-sitting' posture in
the horse associated with rolling and
kicking at the belly is usually associated
with abdominal pain and pressure on the
diaphragm, such as occurs in acute gastric
dilatation after engorgement on grain.
This posture is commonly adopted by
normal cattle but will occur in painful
conditions of the pelvic limbs such as
degenerative osteoarthritis in young
cattle. Abduction of the elbows is usually
synonymous with chest pain or difficulty
in breathing. Elevation and rigidity of the
tail, and rigidity of the ears and limbs, are
good indications of tetanus in animals.
The carriage of the tail in pigs is a useful
barometer of their state of health. Sheep
that are blind, as in early pregnancy
toxemia, are immobile but stand with the
head up and have an expression of
extreme alertness.

When the animal is recumbent, there
also may be abnormalities of posture. In
cattle affected by dislocation of the hip or
by sciatic nerve paralysis, the affected
limb is not held flexed next to the
abdomen but sticks straight out in an
awkward position; unilateral pain in the
chest may cause an animal to lie habitually
on the other side; a weak hindleg may be
kept under the animal. The head may be
carried around towards the flank in
parturient paresis in cows and in colic in
horses. Sheep affected with hypocalcemia,
and cattle with bilateral hip dislocation,
often lie in sternal recumbency with the
hindlegs extended behind in a frog-like
attitude. Inability or lack of desire to rise
are usually indicative of muscle weakness
or of pain in the extremities as in enzootic
muscular dystrophy or laminitis.

Gait

Movements of the limbs can be expressed
in terms of rate, range, force and direction
of movement. Abnormalities may occur in
one or more of these categories. For
example, in true cerebellar ataxia all

qualities of limb movement are affected.
In louping-ill in sheep it is the range and
force that are excessive, giving a high-
stepping gait and a bounding form of
progression; in arthritis, because of pain
in the joints, or in laminitis, because of
pain in the feet, the range is diminished
and the patient has a shuffling, stumbling
walk. The direction of progress may be
affected. Walking in circles is a common
abnormality and is usually associated
with rotation or deviation of the head; it
may be a permanent state as in listeriosis
or occur spasmodically as in acetonemia
and pregnancy toxemia. Compulsive
walking or walking directly ahead regard-
less of obstructions is part of the 'dummy 7
syndrome mentioned earlier and is
characteristic of encephalomyelitis and
hepatic insufficiency in the horse.

Body condition

The animal may be in normal bodily
condition, or obese, thin or emaciated.
The difference between thinness and
emaciation is one of degree: the latter is
more severe but there are additional signs
that are usually taken into consideration.
In an emaciated (cachectic) animal the
coat is poor, the skin is dry and leathery
and work performance is reduced. Thin
animals, on the other hand, are physio-
logically normal. The difference between
fatness and obesity is of the same order.
Most beef cattle prepared for the show-
ring are obese. In order to inject some
degree of numerical assessment it is now
customaiy in all farm animal species and
in horses to use body condition on a scale
of 1-5 or preferably 1-10.

Body conformation

The assessment of conformation or shape
is based on the symmetry and the shape
and size of the different body regions
relative to other regions. An abdomen
that is very large relative to the chest and
hindquarters can be classified as an
abnormality of conformation. To avoid
repetition, points of conformation are
included in the description of body
regions.

Skin

Skin abnormalities can usually be seen at
a distance. They include changes in the
hair or wool, abnormal sweating, the
presence of discrete or diffuse lesions,
evidence of soiling by discharges and of
itching. The normal luster of the coat may
be absent: it may be dry as in most chronic
debilitating diseases or excessively greasy
as in seborrheic dermatitis. In debilitated
animals the long winter coat may be
retained past the normal time. Alopecia
may be evident: in hyperkeratosis it is
diffuse; in ringworm it may be diffuse
but more commonly occurs in discrete

areas. Sweating may be diminished, as in
anhidrosis of horses; patchy as in
peripheral nerve lesions; or excessive as in
acute abdominal pain. Hypertrophy and
folding of the skin may be evident,
hyperkeratosis being the typical example.
Discrete skin lesions range in type from
urticarial plaques to the circumscribed
scabs of ringworm, pox and impetigo.
Diffuse lesions include the obvious enlarge-
ments due to subcutaneous edema,
hemorrhage and emphysema. Enlarge-
ments of lymph nodes and lymphatics are
also evident when examining an animal
from a distance.

INSPECTION OF BODY REGIONS
(PARTICULAR DISTANT
EXAMINATION)

As a general rule, as much of a clinical
examination as possible should be carried
out before the animal is handled. This is
partly to avoid unnecessary excitement of
the patient but also because some abnor-
malities are better seen at a distance and in
some cases cannot be discerned at close
range. The general appearance of the
animal should be noted and its behavior
assessed. Some time should also be devoted
to an inspection of the various body
regions - a particular distant examination.

Head

The facial expression may be abnormal.
The rigidity of tetanus, the cunning leer or
maniacal expression of rabies and acute
lead poisoning are cases in point. The
symmetry and configuration of the bony
structure should be examined. Doming of
the forehead occurs in some cases of con-
genital hydrocephalus and in chondro-
dysplastic dwarfs, and in the latter there
may be bilateral enlargement of the
maxillae. Swelling of the maxillae and
mandibles occurs in osteodystrophia
fibrosa; in horses swelling of the facial
bones is usually due to frontal sinusitis; in
cattle enlargement of the maxilla or
mandible is common in actinomycosis.
Asymmetry of the soft structures may be
evident and is most obvious in the
carriage of the ears, degree of closure of
the eyelids and situation of the muzzle
and lower lip. Slackness of one side and
drawing to the other are constant features
in facial paralysis. Tetanus is accompanied
by rigidity of the ears, prolapse of the
third eyelid and dilatation of the nostrils.

The carriage of the head is most
important: rotation is usually associated
with defects of the vestibular apparatus
on one side, deviation with unilateral
involvement of the medulla and cervical
cord; opisthotonos is an excitation
phenomenon associated with tetanus,
strychnin^ poisoning, acute lead poisoning,
hypomagnesemic tetany, polioencephalo-
malacia and encephalitis.

Clinical examination of the individual animal

T/l

The eyes merit attention. Visible dis-
charge should be noted; protrusion of the
eyeball, as occurs in orbital lympho-
matosis, and retraction of the bulb, as
occurs commonly in dehydration, are
important findings; spasm of the eyelids
and excessive blinking usually indicate
pain or peripheral nerve involvement;
prolapse of the nictitating membrane
usually characterizes central nervous
system derangement, generally tetanus.

Dilatation of the nostrils and nasal
discharge suggest the advisability of
closer examination of the nasal cavities at
a later stage. Excessive salivation or
frothing at the mouth denotes painful
conditions of the mouth or pharynx or is
associated with tremor of the jaw muscles
due to nervous involvement. Swellings
below the jaw may be inflammatory, as
in actinobacillosis and strangles, or
edematous, as in acute anemia, protein
starvation or congestive heart failure.
Unilateral or bilateral swelling of the
cheeks in calves usually indicates necrotic
stomatitis.

Neck

If there is enlargement of the throat this
region should be more closely examined
later to determine whether the cause is
inflammatory and whether lymph nodes,
salivary glands (or guttural pouches in the
horse) or other soft tissues are involved.
Goiter leads to local enlargement located
further down the neck. A jugular pulse,
jugular vein engorgement and edema
should be looked for and local enlarge-
ment due to esophageal distension should
be noted.

Thorax

The respiration should be examined from
a distance, preferably with the animal in a
standing position, as recumbency is likely
to modify it considerably. Allowance
should be made for the effects of exercise,
excitement, high environmental tempera-
tures and fatness of the subject: obese
cattle may have respiratory rates two to
three times that of normal animals. The
rate, rhythm, depth and type of respir-
ation should be noted.

Respiratory rate

In normal animals under average con-
ditions the rate should fall within the
following limits:

° Horses, 8-16/min
0 Cattle, 10-30/min
0 Sheep and pigs, 10-20/min
° Goats, 25-35/min.

An increased respiratory rate is designated
as polypnea, decreased rate as oligopnea
and complete cessation as apnea. The rate
may be counted by observation of rib or
nostril movements, by feeling the nasal

air movements or by auscultation of the
thorax or trachea. A significant rise in
environmental temperature or humidity
may double the normal respiratory rate.
Animals that are acclimatized to cold
outdoor temperatures are susceptible
to heat stress when exposed suddenly to
warmer temperatures. When brought
indoors the respiratory rate may increase
to six or eight times the normal, and
panting open- mouth breathing may be
evident within 2 hours.

Respiratory rhythm

The normal respiratory cycle consists of
three phases of equal length: inspiration,
expiration and pause; variation in the
length of one or all phases constitutes an
abnormality of rhythm. The breathing
pattern of the neonatal foal is markedly
different from that of the adult horse, and
similar to that of other neonates. It has a
higher respiratory rate, a higher airflow
rate, and a higher minute ventilation on a
body weight basis. In addition, in the
standing neonatal foal, both the inspir-
atory and expiratory airflow patterns are
essentially monophasic, whereas the adult
horse typically has a biphasic inspiratory
and expiratory airflow pattern. The tran-
sition from monophasic to biphasic flow
patterns occurs within the first year of life.

Prolongation of phases
Prolongation of inspiration is usually due
to obstruction of the upper respiratory
tract; prolongation of the expiration is
often due to failure of normal lung collapse,
as in emphysema. In most diseases of the
lungs there is no pause and the rhythm
consists of two beats instead of three. There
may be variation between cycles: Cheyne-
Stokes respiration, characteristic of
advanced renal and cardiac disease, is a
gradual increase and then a gradual
decrease in the depth of respiration; Biot's
breathing, which occurs in meningitis
affecting the medullary region, is charac-
terized by alternating periods of hyperpnea
and apnea, the periods often being of
unequal length. Periodic breathing also
occurs commonly in animals with
electrolyte and acid-base imbalances -
there are periods of apnea followed by
short bursts of hyperventilation.

Respiratory depth

The amplitude or depth of respiratory
movements may be reduced in painful
conditions of the chest or diaphragm and
increased in any form of anoxia. Moderate
increase in depth is referred to as
hyperpnea and labored breathing as
dyspnea. In dyspnea, the accessory respir-
atory movements become more prominent:
there is extension of the head and neck,
dilatation of the nostrils, abduction of the
elbows and breathing through the mouth

plus increased movement of the thoracic
and abdominal walls. Loud respiratory
sounds, especially grunting, may also be
heard.

Type of respiration

In normal respiration there is movement
of the thorax and abdomen. In painful
conditions of the thorax, e.g. acute pleurisy,
and in paralysis of the intercostal muscles,
there is relative fixation of the thoracic
wall and a marked increase in the move-
ments of the abdominal wall; there also
may be an associated pleuritic ridge
caused by thoracic immobility with the
thorax expanded. This syndrome is usually
referred to as an abdominal-type respir-
ation. The reverse situation is thoracic-
type respiration, in which the movements
are largely confined to the thoracic wall,
as in peritonitis, particularly when there is
diaphragmatic involvement.

Thorax symmetry

This can also be evaluated by inspection.
Collapse or consolidation of one lung
may lead to restriction of movements of
the thoracic wall on the affected side. The
'rachitic rosar/ of enlarged costochondral
junctions is typical of rickets.

Respiratory noises or stridors
These include:

• Coughing - due to irritation of the
pharynx, trachea and bronchi

® Sneezing - due to nasal irritation
0 Wheezing - due to stenosis of the
nasal passages

• Snoring - when there is pharyngeal
obstruction, as in tuberculous adenitis
of the pharyngeal lymph nodes

® Roaring - in paralysis of the vocal
cords

• Grunting - a forced expiration against
a closed glottis, which happens in
many types of painful and labored
breathing.

An important part of the clinical exam-
ination of a horse that produces an
externally audible noise, usually a grunt,
while working is to determine when the
noise occurs in the respiratory cycle. This
can be related to limb movements,
expiration occurring as the leading foot
hits the ground at the canter or gallop.
Flexion of the head by the rider will
exacerbate the noise.

Abdomen

Variations in abdominal size are usually
appreciated during the general inspection
of the animal. An increase in size may be
due to the presence of excessive feed,
fluid, feces, flatus or fat, the presence of a
fetus or a neoplasm. Further differentiation
4 is usually possible only on close exam-
ination. In advanced pregnancy, fetal
movements may be visible over the right

PARTI GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

flank of cattle. In severe distension of the
intestines with gas, the loops of intestine
may be visible in the flank, especially in
calves. Intestinal tympany usually results
in uniform distension of the abdomen
whereas fluid tends to result in increased
distension ventrally.

The term 'gaunt' is used to describe an
obvious decrease in the size of the
abdomen. It occurs most commonly in
starvation, in severe diarrhea and in many
chronic diseases where appetite is reduced.
An umbilical hernia, omphalophlebitis, or
dribbling of urine from a previous urachus
may be apparent on visual inspection of
the ventral abdominal wall. Ventral edema
is commonly associated with approaching
parturition, gangrenous mastitis, con-
gestive heart failure, infectious equine
anemia, and rupture of the urethra due to
obstructive urolithiasis. A grossly enlarged
asymmetrical swelling of the flank may
suggest herniation of the abdominal wall.
Ruminal movements can be seen in the
left paralumbar fossa and flank of cattle
but a complete examination of the rumen j
requires auscultation, palpation and
percussion, which are described later.

External genitalia

Gross enlargements of the preputial
sheath or scrotum are usually inflammatory
in origin but varicocele or tumors can also
be responsible. Degenerative changes in
the testicles may result in a small scrotum.
Discharges of pus and blood from
the vagina indicate infection of the
genitourinary tract.

Mammary glands

Disproportionate size of the udder sug-
gests acute inflammation, atrophy or
hypertrophy of the gland. These con-
ditions can be differentiated only by
further palpation and examination of the
milk or secretions.

Limbs

General abnormalities of posture and gait
have been described. Symmetry is
important and comparison of the various
aspects of pairs of limbs should be used
when there is doubt about the signifi-
cance of an apparent abnormality. Enlarge-
ment or distortion of bones, joints,
tendons, sheaths and bursae should be
noted and so should any enlargement of
peripheral lymph nodes and lymphatic
vessels.

CLOSE PHYSICAL EXAMINATION

Some of the techniques used in making a
close physical examination are set out
below.

Palpation

Direct palpation with the fingers or
indirect palpation with a probe is aimed
at determining the size, consistency.

temperature and sensitivity of a lesion or
organ. Terms used to describe palpation
findings include the following:

- Doughy - when the structure pits on
pressure, as in edema
Firm - when the structure has the
consistency of normal liver
Hard - when the consistency is bone-
like

Fluctuating - when the structure is
soft, elastic and undulates on pressure
but does not retain the imprint of the
fingers

Tense - when the structure feels like a
viscus distended with gas or fluid
under some considerable pressure
Emphysematous - when the structure
is puffy and swollen, and moves and
crackles under pressure because of the
presence of gas in the tissue.

Percussion

In percussion, the body surface is struck
so as to set deep parts in vibration and
cause them to emit audible sounds. The
sounds vary with the density of the parts
set in vibration and may be classified as
follows:

Resonant - the sound emitted by
organs containing air, e.g. normal
lung

Tympanitic - a drum-like note
emitted by an organ containing gas
under pressure such as a tympanitic
rumen or cecum

Dull - the sound emitted by solid
organs such as heart and liver.

Percussion can be performed with the
fingers using one hand as a plexor and
one as a pleximeter. In large animals a
pleximeter hammer on a pleximeter disk
is recommended for consistency.

The quality of the sound elicited is
governed by a number of factors. The
strength of the percussion blow must be
kept constant as the sound volume
increases with stronger percussion.
Allowances must be made for the thick-
ness and consistency of overlying tissues.
For example, the thinner the thoracic
wall, the more resonant the lung.
Percussion on a rib must not be compared
with percussion on an intercostal space.
The size and body condition score of the
animal are also important considerations.
The technique may be relatively ineffective
in a fat animal. Pigs and sheep are of a
suitable size but the fatness of the pig and
the wool coat of the sheep plus the
uncooperative nature of both species
make percussion impracticable. In mature
cattle and horses the abdominal organs
are too large and the overlying tissue too
j thick for satisfactory outlining of organs
j or abnormal areas, unless the observer is
i highly skilled. The lungs of cattle and

horses can be satisfactorily examined by
percussion but this requires practice and
experience to become skillful and accurate.

Percussion is a valuable aid in the
diagnosis of diseases of the lungs and
abdominal viscera of all large animals.
Increased dullness over the thorax indi-
cates consolidation of the lung, a pleural
j effusion, or space-occupying lesion such
! as tumor or abscess. Increased resonance
j over the thorax suggests emphysema or
j pneumothorax.

| Ballottement

Ballottement is a technique used to detect
floating viscera or masses in the abdominal
cavity. Using the extended fingers or the
| clenched fist the abdominal wall is
j palpated vigorously with a firm push to
j move the organ or mass away and then
- allow it to rebound on to the fingertips.

I Ballottement of a fetus is a typical
example; the fetal prominences can be
easily felt by pushing the gravid uterus
through the abdominal wall over the right
flank in pregnant cattle. Impaction of the
I abomasum, large tumors and abscesses of
' the abdominal cavity may also be
! detected by ballottement. Ballottement
i and auscultation of the flanks of cattle is
j also useful to detect fluid-splashing
| sounds. Their presence on the left side
suggests carbohydrate engorgement and
1 excessive quantities of fluid in the rumen,

; or left-side displacement of the abomasum.

Over the right flank, fluid -splashing
; sounds may indicate intestinal obstruc-
' tion, abomasal volvulus, cecal dilatation
; and torsion, and paralytic ileus.

Ballottement and auscultation of the
abdomen of the horse with colic may
j elicit fluid-splashing sounds indicative of
intestines filled with fluid, as in intestinal
; obstruction or paralytic ileus. A modifi-
i cation of the method is tactile percussion,
when a cavity containing fluid is percussed
sharply on one side and the fluid wave
thus set up is palpated on the other. The
sensation created by the fluid wave is
called a fluid thrill. It is felt most acutely
j by the palm of the hand at the base of the
i fingers. Diseases that cause ascites and
accumulation of fluid in the peritoneal
cavity are examples where this technique
. is useful.

Auscultation

Direct listening to the sounds produced
by organ movement is performed by
placing the ear to the body surface over
the organ. Indirect auscultation by a
, stethoscope is the preferred technique. A
j considerable amount of work has been
; done to determine the most effective
stethoscopic equipment, including investi-
; gation Qf such things as the shape and
proportions of bell chest pieces, the
| thickness of rubber tubes and the diameter

Clinical examination of the individual animal

33

and depth of phonendoscope chest pieces.
A comparatively expensive unit from a
reputable instrument firm is a wise invest-
ment. For large animal work, a stethoscope
with interchangeable 5 cm diameter
phonendoscope and rubber (to reduce
hair friction sounds) bell chest pieces is all
that is required. The details of the sounds
heard on auscultations of the various
organs are described in their respective
sections. Auscultation is used routinely to
assess heart sounds, lung sounds and
gastrointestinal sounds.

Percussion and simultaneous
auscultation of abdomen

Percussion and simultaneous auscultation
of the left and right sides of the abdomen
is a useful technique for examination of
the abdomen of large animals. The
stethoscope is placed over the area to be
examined and the areas around the
stethoscope and radiating out from it are
percussed. This is a valuable diagnostic
aid for the detection and localization of a
gas-filled viscus in the abdomen of cattle
with left-side displacement of the abo-
masum, right-side dilatation and volvulus
of the abomasum, cecal dilatation and
torsion, intestinal tympany associated with
acute obstruction or paralytic ileus, or
pneumoperitoneu m.

Simultaneous percussion and auscul-
tation of the abdomen of the horse with
colic is useful to detect pings indicative
of intestinal tympany associated with
intestinal obstruction or paralytic ileus. In
diaphragmatic hernia the presence of
gas-filled intestines in the thorax may be
determined by this method. To elicit the
diagnostic 'ping', it is necessary to percuss
and auscultate side by side and to percuss
with a quick, sharp, light and localized
force. The obvious method is a quick tap
with a percussion hammer or similar
object. Another favored method is a 'flick'
with the back of a forefinger suddenly
released from behind the thumb. A gas-
filled viscus gives a characteristic clear,
sharp, high-pitched 'ping' which is
distinctly different from the full, low-
pitched note of solid or fluid-filled viscera.
The difference between the two is so
dramatic that it is comparatively easy to
define the borders of the gas-filled viscus.

The factors that determine whether a
'ping' will be audible are the force of the
percussion, the size of the gas -filled viscus
and its proximity to the abdominal wall. The
musical quality of the ping is dependent on
the thickness of the wall of the viscus
(e.g. rumen, abomasum, small or large
intestines) and the amount and nature of
the fluid and gas in the intestines or viscus.

Succussion

This technique, which involves moving
the body from side to side to detect the

presence of fluid, is an adaptation of the
above method. By careful auscultation
while the body is moved, free fluid in the
intestines or stomach will result in fluid-
splashing or tinkling sounds.

Other techniques

Special physical techniques including
biopsy and paracentesis are described
under special examination of the various
systems to which they apply. With suitable
equipment and technique, one of the
most valuable adjuncts to a physical
examination is a radiographic examination.
The size, location and shape of soft tissue
organs are often demonstrable in animals
of up to moderate size. Radiology, other
than of limbs and neonates, is not com-
monly practiced in larger animals. Ultra-
sound appears to have much more general
application but will require its own
textbook.

SEQUENCE USED IN THE CLOSE
PHYSICAL EXAMINATION

The close physical examination should be
performed as quietly and gently as possible
to avoid disturbing the patient and thus
increasing the resting heart and respir-
atory rates. At a later stage it may be
necessary to examine certain body systems
after exercise, but resting measurements
should be carried out first. If possible the
animal should be standing, as recumbency
is likely to cause variation in heart and
pulse rates, respiration and other functions.

The sequence used in the close physical
examination will vary with the species
being examined, the results of the distant
examinations, the history obtained, and
the diagnostic hypotheses that the clinician
has generated. The various parts of the
close physical examination that are
described here can be modified according
to individual circumstances but it is
important to do a thorough clinical exam-
ination based on the circumstances.

Following the distant examination,
and the particular distant examination, it
is recommended that the vital signs be
determined before the animal is handled
for examination of body regions such as
the oral cavity.

In general, an appropriate sequence
for the close physical examination would
be as follows:

Vital signs: temperature, heart and
pulse rates, respirations, state of
hydration

Thorax: heart sounds (rate, rhythm,
intensity); lung sounds
Abdomen: nasogastric intubation
’ Head and neck: including eyes, oral
cavity, facial structures, and the
jugular veins
Rectal examination
Urinary tract

® Reproductive tract
a Mammary gland
a Musculoskeletal system
a Nervous system
° Skin: including ears, hooves and

horns.

The important principle is to determine
the vital signs before handling and
examining other body systems, which
may distort the vital signs. The sequence
that follows taking the vital signs can
vary, based on individual circumstances,
the urgency of the case, if any, and the
ease of doing the particular examinations.
For example, it may be very important to
pass a nasogastric tube as one of the first
diagnostic techniques in a horse with
severe colic associated with gastric dis-
tension. When presented with a lactating
dairy cow with peracute mastitis, the
sequence will be recording the tempera-
ture, heart rate and sounds, respirations
and status of the lungs, status of the
rumen, followed by careful examination
of the mammary gland. The close physical
examination of each body region or body
systems is outlined below.

Vital signs

Temperature

Normally the temperature is taken per
rectum. When this is impossible the
thermometer should be inserted into the
vagina. Ensure that the mercury column is
shaken down, moisten the bulb to facili-
tate entry and, if the anus is flaccid or the
rectum full of hard feces, insert a finger
also to ensure that the thermometer bulb
is held against the mucosa. When the
temperature is read immediately after
defecation, or if the thermometer is stuck
into a ball of feces or is left in the rectum
for insufficient time, a false, low reading
will result.

As a general rule the thermometer
should be left in place for 2 minutes. If
there is doubt as to the accuracy of the
reading, the temperature should be taken
again. The normal average temperature
range for the various species at average
environmental temperature is as shown
in Table 1.1.

The reference values in Table 1.1
indicate the average resting temperature

U/

1 lN|6)jlffi]g|ll

Species

Normal

temperature

Critical point

Horse

38.0°C (100 5°F)

39.0°C (102. 0°F)

Cattle

38.5°C (101. 5°F)

39,5°C (103. 0°F)

Pig

39.0°C (102. 0°F)

40.0°C (103. 5°F)

Sheep

39.0°C (102. 0°F)

40.0°C (104.0°F)

Goat

39.5°C (103. 0°F)

40.5°C (105.0°F)

Temperature conversions are approximate.

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

for the species and the critical tempera-
ture above which hyperthermia can be
said to be present. Normal physiological
variations occur in body temperature and
are not an indication of disease: a diurnal
variation of up to 1°C (2°F) may occur,
with the low point in the morning and the
peak in the late afternoon. There may be a
mild rise of about 0.6°C (1°F) in late
pregnancy, but a precipitate although
insignificant decline just before calving is
not uncommon in cows and ewes and
lower temperatures than normal occur just
before estrus and at ovulation - the
degree of change (about 0.3°C; 0.6°F) is
unlikely to attract clinical attention.

In sows the body temperature is
subnormal before farrowing and there is a
significant rise in body temperature
coinciding with parturition. This rise is
commonly high enough to exceed the
critical temperature of 40°C and may be
considered erroneously as evidence of
disease. The elevation of temperature that
occurs in sows at the time of parturition,
of the order of 1°C, is maintained through
lactation and disappears at weaning.

High environmental humidity and
temperature and exercise will cause
elevation of the temperature; the deviation
may be as much as 1.6°C (3°F) in the case
of high environmental temperatures and
as much as 2.5-3°C (4.5°F) after severe
exercise; in horses, after racing, 2 hours
may be required before the temperature
returns to normal.

If animals that have been acclimatized
to cold outside temperatures are brought
indoors to a warmer temperature their
body temperatures may exceed the critical
temperature within 2-4 hours. Marked
temperature variations are an indication
of a pathological process:

° Hyperthermia is simple elevation of
the temperature past the critical point,
as in heat stroke

e Fever or pyrexia is the state where
hyperthermia is combined with
toxemia, as in most infectious diseases
® Hypothermia, a subnormal body
temperature, occurs in shock,
circulatory collapse (as in parturient
paresis and acute rumen impaction of
cattle), hypothyroidism and just
before death in most diseases.

Pulse

The pulse should be taken at the middle
coccygeal or facial arteries in cattle, the
facial artery in the horse and the femoral
artery in sheep and goats. With careful
palpation a number of characters may
be determined, including rate, rhythm,
amplitude, tone, maximum and minimum
pulse pressures and the form of the
arterial pulse. Some of these characters
are more properly included in special

Species

Pulse rate per minute

Adult horses

30-40

Foals up to 1 year

70-80

Adult cattle

60-80

Young calves

100-120

Sheep and goats

70-90

examination of the circulatory system and
are dealt with under that heading.

Rate

The pulse rate is dependent on the heart
alone and is not directly affected by
changes in the peripheral vascular system.
The pulse rate may or may not represent
the heart rate; in cases with a pulse
deficit, where some heartbeats do not
produce a pulse wave, the rates will differ.
Normal resting rates (per minute) for the
various species are shown in Table 1.2.

Although there are significant differ-
ences in rate between breeds of dairy cow,
and between high- and low-producing
cows, the differences would not be notice-
able to a clinician performing a routine
examination. In newborn thoroughbred
foals the pulse rate is 30-90 in the first
5 minutes, then 60-200 during the
first hour, and then 70-130 during the
first 48 hours after birth. Draught horses
have heart rates slightly higher than those
quoted, which are based on a light horse
population. The pulse is not readily
palpable in the pig but the comparable
heart rate is 60-100 per minute. The same
techniques are used in intensive clinical
examinations for horses afflicted with the
poor performance syndrome.

Bradycardia, or marked slowing of
the heartbeat, is unusual unless there is
partial or complete heart block, but it
does occur in cases of space- occupying
lesions of the cranium, in cases of
diaphragmatic adhesions after traumatic
reticulitis in cattle, or when the rumen is
much emptier than normal.

Tachycardia, or increased pulse rate, is
common and occurs in most cases of
septicemia, toxemia, circulatory failure
and in animals affected by pain and
excitement. Counting should be carried
out over a period of at least 30 seconds.

Rhythm

The rhythm may be regular or irregular.
All irregularities must be considered as
abnormal except sinus arrhythmia, the
phasic irregularity coinciding with the
respiratory cycle. There are two components
of the rhythm, namely the time between
peaks of pulse waves and the amplitude
of the waves. These are usually both
irregular at the one time, variations in
diastolic filling of the heart causing vari-

ation in the subsequent stroke volume.
Regular irregularities occur with constant
periodicity and are usually associated
with partial heart block. Irregular irregu-
larities are due to ventricular extrasystoles
or atrial fibrillation. Most of these irregu-
larities, except that due to atrial fibrillation,
disappear with exercise. Their significance
lies chiefly in indicating the presence of
myocardial disease.

Amplitude

The amplitude of the pulse is determined
by the amount of digital pressure required
to obliterate the pulse wave. It is largely a
measure of cardiac stroke volume and
may be considerably increased, as in the
'water hammer' pulse of aortic semilunar
valve incompetence, or decreased, as in
most cases of myocardial weakness.

State of hydration

The state of hydration is assessed by
inspection of the eyes for evidence of
dehydration and evaluating the elasticity
of the skin. Dehydration is characterized
by sunken eyes of varying degrees, and
the skin will 'tent' when lifted with the
fingers and remain tented for varying
lengths of time.

EXAMINATION OF BODY REGIONS

After the examination of the temperature,
pulse and respirations the physical
examination proceeds with an examination
of the various body regions.

Thorax

Examination of the thorax includes
palpation, auscultation and percussion of
the cardiac area (precordium) and the lung
area. The wide variations between species
in the thickness of the thoracic wall, the
size of the animal and the respiratory rate
require careful and methodical examin-
ation. For example, in the adult horse the
thick thoracic wall and the normally slow
respiratory rate contribute to an almost
soundless respiration on auscultation of the
thorax. There is, too, the need to detect
minor pulmonary lesions, which may
reduce the work performance of the horse
only slightly but, because of the importance
of perfect fitness in a racing animal, may
have major significance. Another important
factor that emphasizes the care that must
be taken with the examination of the
respiratory system of the horse is the ability
of racing animals to compensate for even
major pulmonary lesions from their
immense functional reserve. Because of
this, one is likely to encounter horses with
massive pulmonary involvement and yet
with little obvious impairment of respir-
atory function.

Cardiac area

Auscultation of the heart is aimed at
determining the character of normal heart

Clinical examination of the individual animal

15

sounds and detecting the presence of
abnormal sounds. Optimum auscultation
sites are the fourth and fifth intercostal
spaces and, because of the heavy shoulder
muscles that cover the anterior border of
the heart, the use of a flat phonendoscope
chest piece pushed under the triceps
muscles is necessary. Extension of the
forelimb may facilitate auscultation if the
animal is quiet. Areas where the various
sounds are heard with maximum intensity
are not directly over the anatomical sites
of the cardiac orifices, because conduction
of the sound through the fluid in the
chamber gives optimum auscultation at
the point where the fluid is closest to the
chest wall.

The first (systolic) sound is heard best
over the cardiac apex, the tricuspid
closure being most audible over the right
apex and mitral closure over the left apex.
The second (diastolic) sound is heard best
over the base of the heart, the aortic
semilunar closure posteriorly and the
pulmonary semilunar anteriorly, both on
the left side.

In auscultation of the heart, the points
to be noted are the rate, rhythm, intensity
and quality of sounds and whether abnor-
mal sounds are present. Comparison of
the heart and pulse rates will determine
whether there is a pulse deficit due to
weak heart contractions failing to cause
palpable pulse waves; this is most likely to
occur in irregular hearts. Normally the
rhythm is in three time and can be
described as

LUBB - DUPP - pause,

the first sound being dull, deep, long and
loud and the second sound sharper and
shorter. As the heart rate increases the
cycle becomes shortened, mainly at the
expense of diastole and the rhythm
assumes a two-time quality. More than
two sounds per cycle is classified as a
'gallop' rhythm and may be due to
reduplication of either the first or second
sounds. Reduplication of the first sound is
common in normal cattle and its signifi-
cance in other species is discussed under
diseases of the circulatory system.

The rhythm between successive cycles
should be regular except in the normal
sinus arrhythmia associated with respir-
ation. With irregularity, there is usually
variation in the time intervals between
cycles and in the intensity of the sounds -
louder sounds coming directly after
prolonged pauses and being softer than
normal sounds after shortened intervals,
as in extrasystolic contractions. The
intensity of the heart sounds may vary in
two ways, absolutely or relatively: absol-
utely when the two sounds are louder
than normal, and relatively when one
sound is increased compared to the other

in the cycle. For example, there is
increased absolute intensity in anemia
and in cardiac hypertrophy.

The intensity of the first sound depends
on the force of ventricular contraction and
is thus increased in ventricular hyper-
trophy and decreased in myocardial
asthenia. The intensity of the second
sound depends upon the semilunar
closure, i.e. on the arterial blood pressure,
and is therefore increased when the blood
pressure is high and decreased when the
pressure is low.

Abnormal sounds may replace one or
both of the normal sounds or may
accompany them. The heart sounds are
muffled when the pericardial sac is
distended with fluid. Sounds that are
related to events in the cardiac cycle are
murmurs or bruits and are caused mainly
by endocardial lesions such as valvular
vegetations or adhesions, by insufficiency
of closure of valves and by abnormal
orifices such as a patent interventricular
septum or ductus arteriosus. Interference
with normal blood flow causes the
development of turbulence with resultant
eddying and the creation of murmurs. In
attempting to determine the site and type
of the lesion it is necessary to identify its
time of occurrence in the cardiac cycle: it
may be presystolic, systolic or diastolic
and it is usually necessary to palpate the
arterial pulse and auscultate the heart
simultaneously to determine accurately
the time of occurrence. The site of maxi-
mum audibility may indicate the probable
site of the lesion, but other observations,
including abnormalities of the arterial
pulse wave, should be taken into account.

In many cases of advanced debility,
anemia and toxemia, soft murmurs can be
heard that wax and wane with respiration
(hemic murmurs) and are probably due to
myocardial asthenia. In cases of local
pressure on the heart by other organs, for
example in diaphragmatic hernia in cattle,
loud systolic murmurs may be heard,
probably due to distortion of the valvular
orifices.

Abnormal sounds not related to the
cardiac cycle include pericardial friction
rubs, which occur with each heart cycle
but are not specifically related to either
systolic or diastolic sounds. They are more
superficial, more distinctly heard than
murmurs and have a to-and-fio character.
Local pleuritic friction rubs may be con-
fused with pericardial sounds, especially if
respiratory and cardiac rates are equal.

Palpation of the heart beat has real
value: the size of the cardiac impulses can
j be assessed and palpable thrills may on
| occasion be of more value than auscul-
| tation of murmurs. It is best carried out s
with the palm of the hand and should be
performed on both sides. An increased

cardiac impulse, the movements of the
heart against the chest wall during
systole, may be easily seen on close
inspection of the left precordium and can
be felt on both sides. It may be due to
cardiac hypertrophy or dilatation associ-
ated with cardiac insufficiency or anemia
or to distension of the pericardial sac with
edema or inflammatory fluid. Care should
be taken not to confuse a readily palpable
cardiac impulse due to cardiac enlarge-
ment with one due to contraction of lung
tissue and increased exposure of the heart
to the chest wall.

Normally, the heart movements can be
felt as distinct systolic and diastolic thumps.
These thumps are replaced by thrills
when valvular insufficiencies or stenoses
or congenital defects are present. When
the defects are large the murmur heard on
auscultation may not be very loud but the
thrill is readily palpable. Early pericarditis
may also produce a friction thrill. The
cardiac impulse should be much stronger
on the left than the right side and reversal
of this situation indicates displacement of
the heart to the right side. Caudal or
anterior displacement can also occur.

Percussion to determine the boundaries
of the heart is of little value in large animal
work because of the relatively large size of
the heart and lungs and the depth of
tissue involved. The area of cardiac dull-
ness is increased in cardiac hypertrophy
and dilatation and decreased when the
heart is covered by more than the usual
amount of lung, as in pulmonary
emphysema. More detailed examination
of the heart by electrocardiography, radio-
graphic examination, test puncture and
blood pressure are described under
diseases of the heart.

Lung area

Auscultation, percussion and palpation

are the major methods used for examin-
ation of the lungs.

The lung area available for satisfactory
auscultation is slightly larger than that
available for percussion. The normal
breath sounds are heard over most of the
lungs, particularly in the middle third
anteriorly over the base of the lung, and
consist of a soft, sipping VEE-EFF, the
latter, softer sound occurring at expiration.
The sounds are heard with variable ease
j depending on the thickness of the chest
I wall and the amplitude of the respiratory
j excursion. In well-fleshed horses and fat
beef cattle the sounds may not be
discernible at rest. The amplitude or
loudness of the breath sounds is increased
in dyspnea and in early pulmonary con-
gestion and inflammation. The amplitude
i of the breath sounds is decreased or
totally inaudible when there is pleural
effusion, and in space-occupying lesions

16

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

in the lung or pleural cavity. Abnormal
lung sounds include crackles, wheezes
and pleuritic friction rubs. They are the
result of interference with the free
movement of air in and out of the lungs,
and of the presence of lesions that
interfere with the normal movement of
the lung and thus create additional
respiratory sounds, which are an indi-
cation of disease. The descriptions and
interpretations of the normal and abnormal
lung sounds, and other respiratory noises
are described in Chapter 10.

The intensity of abnormal lung sounds
may be increased and their clarity
improved by measuring the rate and
depth of respirations with forced mild
exercise such as walking for a few minutes
followed by immediate auscultation. If
exercise is undesirable the occlusion of
both nostrils for 30-45 seconds will be
followed by some deep inspirations and
accentuation of abnormal lungs. An
alternative maneuver which is effective in
both horses and cattle is to pull a plastic
bag over the muzzle and lower face.
When respiratory movements become
exaggerated the bag is removed and the
lungs auscultated immediately.

Sounds of peristalsis are normally
heard over the lung area on the left side in
cattle and in horses. In cattle, these
sounds are due to reticular movement
and in horses to movements of the colon.
Their presence is not of much significance
in these species unless there are other
signs. In cattle, too, sounds of swallowing,
eructation and regurgitation may be
confused with peristaltic sounds; ruminal
movements and the esophagus should be
observed for the passage of gas or a bolus
to identify these sounds. Other techniques
for examination of the thorax are described
under diseases of the respiratory system
(Ch. 10).

Fhlpation of the thoracic wall may reveal
the presence of a pleuritic thrill, bulging of
the intercostal spaces when fluid is present
in the thoracic cavity, or narrowed inter-
costal spaces and decreased rib movement
over areas of collapsed lung.

Percussion may be by the usual direct
means, or indirectly by tracheal per-
cussion when the trachea is tapped gently
and the sound is listened for over the lung
area. By direct percussion within the
intercostal spaces the area of normal lung
resonance can be defined and abnormal
dullness or resonance detected. Increased
dullness may indicate the presence of a
space-occupying mass, consolidated lung,
edematous lung or an accumulation of
fluid. In a pleural effusion the upper limit
of the area of dullness can be determined
by percussion and the fluid line can be
delineated and identified and used to
assess the progress of therapy.

An overloud normal percussion note is
obtained over tissue containing more air
than usual, e.g. emphysematous lung. A
definite tympanitic note can be elicited
over pneumothorax or a gas-filled viscus
penetrating through a diaphragmatic
hernia. For percussion to be a satisfactory
diagnostic aid, affected areas need to be
large with maximum abnormality, and the
chest wall must be thin.

Abdomen

Clinical examination of the abdomen
includes:

0 Visual inspection of the abdominal
contour for evidence of distension or
gauntness

0 Auscultation of the gastrointestinal
sounds

° Palpation and percussion through
the abdominal wall
° Rectal palpation
• Passage of the nasogastric tube
0 Paracentesis of the abdomen.

Auscultation

Auscultation of the abdomen is an
essential part of the clinical examination
of cattle, horses and sheep. It is of limited
value in pigs. The intestinal or stomach
sounds will indicate the nature of the
intraluminal contents and the frequency
and amplitude of gastrointestinal move-
ments, which are valuable aids in clinical
diagnosis. The intensity, duration and
frequency of the sounds should be noted.
All these characteristics will be increased
in animals that have just eaten or
immediately following excitement.

Auscultation of the rumen of cattle and
sheep

This is a very useful part of the clinical
examination. In normal animals there are
1-2 primary contractions per minute,
involving the reticulum and the dorsal
and ventral sacs of the rumen; the fre-
quency depends on the amount of time
that has elapsed since feeding and the
type of food consumed. Secondary con-
tractions of the dorsal and ventral sacs of
the rumen occur at about 1 per minute
and are commonly associated with
eructation. The examination is made in
the left paralumbar fossa and a normal
sequence of sounds consists of a lift of the
flank with a fluid gurgling sound, followed
by a second more pronounced lift
accompanied by a booming, gassy sound.
Auscultation over the lower left ribs will
reveal the fainter fluid sounds of reticular
contractions just prior to the contractions
of the dorsal and ventral ruminal sacs
described above. The reticular and ruminal
sounds are the predominant abdominal
sounds in the normal ruminant.

A grunt, detectable by auscultation
over the trachea, may occur during the

reticular contraction phase of a primary
contraction in cattle with traumatic
reticuloperitonitis. The factors that result
in a decrease in the intensity and frequency
of ruminal sounds are discussed in detail
in Chapter 6.

The intestinal sounds that are audible
on auscultation of the right flank of cattle
and sheep consist of frequent faint
gurgling sounds, which are usually diffi-
cult to interpret. The contraction of the
abomasum and the intestines result in a
mixture of sounds that are difficult to
distinguish.

Intestinal sounds of the horse
These sounds are clearly audible and their
assessment is one of the most vital parts
of the clinical examination and surveil-
lance of the horse with suspected
abdominal disease. Over the right and
ventral abdomen there are the loud,
booming sounds (borborygmi) of the
colon and cecum, which are at peak
intensity about every 15-20 seconds. Over
the left abdomen there are the much
fainter rushing fluid sounds of the small
intestines. An increase in the intensity
and frequency of sounds with a distinct
fluid quality are heard in enteritis and
loud, almost crackling, sounds in
spasmodic colic. In impaction of the large
intestine there is a decrease in the intensity
and frequency of the borborygmi, and in
thromboembolic colic due to verminous
aneurysm and infarction of the colon
there may be complete absence of
sounds. In intestinal obstruction the
intestinal sounds due to peristalsis are
markedly decreased and usually absent
and fluid tinkling sounds occur in-
frequently. In intestinal stasis in the
horse, auscultation in the right flank often
detects the tinkling sound of fluid
dropping from the ileocecal valve through
gas into the dorsal sac of the cecum.

Palpation and percussion through the
abdominal wall

Because of the thickness and weight of
the abdominal wall in mature cattle and
horses, deep palpation of viscera and
organs through the abdominal wall has
limited value in these species compared
to its usefulness in small animals. No
viscera or organ, with the exception of the
fetus, can be palpated with certainty
through the abdominal wall in the horse.
In cattle, the rumen and its contents can
usually be palpated in the left paralumbar
fossa. Ruminal distension is usually
obvious while an inability to palpate the
rumen may be due to a small, relatively
empty rumen or to medial displacement,
as in lift-side displacement of the
abomasum.

Percussion and simultaneous
auscultation

In left-side displacement of the abomasum,
percussion and simultaneous auscultation
over the upper third of the costal arch
between the 9th and 12th ribs of the left
side will elicit the typical high-pitched
musical-quality sounds or ping. These
may be mistaken for similar sounds
present in ruminal atony. A markedly
enlarged liver in a cow may be palpable
by ballottement immediately behind the
right costal arch. Using a combination of
palpation, percussion and simultaneous
auscultation over the right paralumbar
fossa and caudal to the entire length of
the right costal arch it may be possible to
detect any of the following in cattle:

° Dilatation and torsion of the
abomasum

° Cecal dilatation and torsion
° Impaction of the abomasum and
omasum

o Intestinal obstructions, including
torsion of the coiled colon.

Percussion and auscultation over viscera
that are distended with fluid and gas may
be undertaken and the size and location
of the tympanitic area will provide some
indication of the viscera likely to be
involved.

Tactile percussion of the abdomen
This technique aids detection of an
excessive quantity of fluid in the peritoneal
cavity: ascites due to a ruptured bladder,
transudate in congestive heart failure and
exudate in diffuse peritonitis. A sharp
blow is struck on one side of the abdomen
and a fluid wave, a 'blip' or undulation of
the abdominal wall, can be seen and felt
on the opposite side of the abdomen. The
peritoneal cavity must be about one-third
full of fluid before a fluid wave can be
elicited.

Abdominal pain

The location of abdominal pain may be
located by deep external palpation of the
abdominal wall in cattle. Deep palpation
with a firm uniform lift of the closed hand
or with the aid of a horizontal bar held by
two people under the animal immediately
caudal to the xiphoid sternum is a useful
aid for the detection of a grunt associated
with traumatic reticuloperitonitis in cattle.
Superficial pain may be elicited by a firm
poke of the hand or extended finger in
cattle or horses. In cattle, pain may be
elicited over the right costal arch when
there are liver lesions or generally over
the abdomen in diffuse peritonitis.

The response to palpation of a focus of
abdominal pain in cattle is a' grunt' which
may be clearly audible without the aid of
a stethoscope. However, if there is doubt
about the audibility of the grunt, the

Clinical examination of the individual animal

1 ?

simultaneous auscultation of the trachea
will detect a perceptible grunt when the
affected area is reached. In calves with
abomasal ulceration, a focus of abdominal
pain may be present on deep palpation
over the area of the abomasum.

In cases of severe abdominal distension
(ruminal tympany in cattle, torsion of the
large intestine) it is usually impossible to
determine, by palpation and percussion,
the viscera that are distended. Pneumo-
peritoneum is rare and thus gross dis-
tension of the abdomen is usually due to
distension of viscera with gas, fluid or
ingesta. A combination of rectal examin-
ation, passage of a stomach tube, para-
centesis and exploratory laparotomy may
be necessary to determine the cause.

The abdomen of pigs is difficult to
examine by palpation because pigs are
seldom sufficiently quiet or relaxed and
the thickness of the abdominal wall limits
the extent of deep palpation. In late preg-
nancy in sows the gravid uterus may be
ballotted but it is usually not possible to
palpate fetal prominences.

In sheep, the rumen, impacted abo-
masum and the gravid uterus are usually
palpable through the abdominal wall.
Positioning the sheep on its hindquarters
will shift the viscera to a more easily
palpable position.

Nasogastric intubation
An important part of the examination of
the abdomen and gastrointestinal tract of
large animals, especially cattle and horses,
is the passage of the nasogastric tube into
the rumen of cattle and into the stomach
of horses. Gastric reflux occurs commonly
in the horse with colic and it is important
to determine if the stomach is distended
with fluid and to relieve it as necessary.
This topic is presented in detail in the
chapter dealing with equine colic. In
cattle, when disease of the rumen is
suspected, the nasogastric tube is passed
into the rumen to relieve any distension
and to obtain a sample of rumen juice for
determination of rumen pH and the
presence or absence of rumen protozoa.

Head and neck

Eyes

Any discharge from the eyes should be
noted: it may be watery in obstruction of
the lacrimal duct, serous in the early
stages of inflammation and purulent in
the later stages. Whether the discharge is
unilateral or bilateral is of considerable
importance; a unilateral discharge may be
due to local inflammation, a bilateral
discharge may denote a systemic disease.
Abnormalities of the eyelids include
abnormal movement, position and thick-
ness. Movement may be excessive in
painful eye conditions or in cases of
1 nervous irritability including hypo-

magnesemia, lead poisoning and encepha-
litis. The lids may be kept permanently
closed when there is pain in the eye or
when the eyelids are swollen, as for
instance in local edema due to photo-
sensitization or allergy. The membrana
nictitans may be carried across the eye
when there is pain in the orbit or in
tetanus or encephalitis. There may be
tumors on the eyelids.

Examination of the conjunctiva
This examination is important because it
is a good indicator of the state of the
peripheral vascular system. The pallor of
anemia and the yellow coloration of
jaundice may be visible, although they are
more readily observed on the oral or
vaginal mucosa. Engorgement of the scleral
vessels, petechial hemorrhages, edema of
the conjunctiva as in gut edema of pigs or
congestive heart failure, and dryness due
to acute pain or high fever are all readily
observable abnormalities.

Corneal abnormalities
These include opacity, varying from the
faint cloudiness of early keratitis to the
solid white of advanced keratitis, often
with associated vascularization, ulceration
and scarring. Increased convexity of the
cornea is usually due to increased pressure
within the eyeball and rnay be due to
glaucoma or hypopyon.

Size of the eyeball

Eyeball size does not usually vary but
protrusion is relatively common and
when unilateral is due in most cases to
pressure from behind the orbit. Periorbital
lymphoma in cattle, dislocation of the
mandible and periorbital hemorrhage are
common causes. Retraction of the eyeballs
is a common manifestation of reduction
in volume of periorbital tissues, e.g. in
starvation when there is disappearance of
fat and in dehydration when there is loss
of fluids.

Abnormal eyeball movements
Abnormal movements occur in nystagmus
due to anoxia or to lesions of the cerebellum
or vestibular tracts. In nystagmus there is
periodic, involuntary movement with a
slow component in one direction and a
quick return to the original position. The
movement may be horizontal, vertical or
rotatory. In paralysis of the motor nerves
to the orbital muscles there is restriction
of movement and abnormal position of
the eyeball at rest.

Examination of the deep structures
Assessment of the deep structures of the
| eye necessitates an ophthalmoscope but
j gross abnormalities may be observed by
direct vision. Pus in the anterior chamber,
hypopyon, is usually manifested by
I yellow to white opacity often with a

18

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

horizontal upper border obscuring the
iris. The pupil may be of abnormal shape
or abnormal in position due to adhesions
to the cornea or other structures. An
abnormal degree of dilatation is an
important sign, unilateral abnormality
usually suggesting a lesion of the orbit.

Bilateral excessive dilatation (mydriasis)
occurs in local lesions of the central
nervous system affecting the oculomotor
nucleus, or in diffuse lesions including
encephalopathies, or in functional dis-
orders such as botulism and anoxia.
Peripheral blindness due to bilateral
lesions of the orbits may have a similar
effect. Excessive constriction of the pupils
(miosis) is unusual unless there has been
overdose with organic phosphatic insecti-
cides or parasympathomimetic drugs.
Opacity of the lens is readily visible,
especially in advanced cases.

Vision tests

Several tests of vision and of ocular
reflexes are easily carried out, and when
warranted should be done at this stage of
the examination. Tests for blindness
include the menace reflex and an obstacle
test. In the former a blow at the eye is
simulated, care being taken not to cause
air currents. The objective is to elicit the
eye preservation reflex manifested by
reflex closure of the eyelids. This does not
occur in peripheral or central blindness
and in facial nerve paralysis there may be
withdrawal of the head but no eyelid
closure. An obstacle test in unfamiliar
surroundings should be arranged and the
animal's ability to avoid obstacles assessed.
The results are often difficult to interpret
if the animal is nervous. A similar test for
night-blindness (nyctalopia) should be
arranged in subdued light, either at dusk
or on a moonlit night. Nyctalopia is one
of the earliest indications of avitaminosis-
A. Total blindness is called amaurosis,
partial blindness is called amblyopia. The
pupillary light reflex - closure and dila-
tation of the iris in response to lightness
and darkness - is best tested with a strong
flashlight.

Nostrils

Particular attention should be paid to the
odor of the nasal breath. There may be a
sweet sickly smell of ketosis in cattle or a
fetid odor, which may originate from
any of a number of sources including
gangrenous pneumonia, necrosis in the
nasal cavities or the accumulation of nasal
exudate. Odors originating in the respir-
atory tract are usually constant with each
breath and may be unilateral. The sour
smell of alimentary tract disturbance is
detectable only periodically, coinciding
with eructation. Odors originating in the
mouth from bad teeth or from necrotic
ulcers associated with Fusobacterium

necrophorum in calves may be smelled on
the nasal breath but are stronger on the
oral breath.

In certain circumstances it may be
important to note the volume of the
breath expelled through the nostrils: it
may be the only way of determining
whether the animal is breathing and, in
some cases, of counting the respiratory
rate. Variation in volume between nostrils,
as felt on the hands, may indicate
obstruction or stenosis of one nasal cavity.
This can be examined further by closing
off the nostrils one at a time; if obstruc-
tion is present in one nostril, closure of
the other causes severe respiratory
embarrassment.

Any nasal discharge that is present
should receive special attention and its
examination should be carried out at the
same time as an inspection of the nasal
mucosa. Discharges may be restricted to
one nostril in a local infection or be
bilateral in systemic infection. The color
and consistency of the exudate will
indicate its source. In the early stages of
inflammation the discharge will be a
clear, colorless fluid, which later turns to a
white to yellow exudate as leukocytes
accumulate in it. In Channel Island cattle
the color may be a deep orange, especially
in allergic rhinitis. A rust or prune juice
color indicates blood originating from the
lower respiratory tract, as in pneumonia
and in equine infectious anemia in the
horse. Blood clots derived from the upper
respiratory tract or pharynx may be
present in large quantities, or appear as
small flecks. In general, blood from the
upper respiratory tract is unevenly mixed
with any discharge, whereas that from the
lower tract comes through as an even
color.

The consistency of the nasal discharge
will vary from watery in the early stages of
i inflammation, through thick, to cheesy in
j longstanding cases. Bubbles or foam may
! be present. When the bubbles are coarse
I it signifies that the discharge originates in
! the pharynx or nasal cavities; fine bubbles
originate in the lower respiratory tract. In
all species, vomiting or regurgitation
i caused by pharyngitis or esophageal
obstruction may be accompanied by the
discharge of food material from the nose
i or the presence of food particles in the
j nostrils. In some cases the volume of
! nasal discharge varies from time to time,
often increasing when the animal is
j feeding from the ground, leading to
j infection of cranial sinuses.

Inflammation of the nasal mucosa
I varies from simple hyperemia, as in
j allergic rhinitis, to diffuse necrosis, as in
> bovine malignant catarrh and mucosal
■ disease, to deep ulceration as in glanders,
i In hemorrhagic diseases variations in

mucosal color can be observed and
petechial hemorrhages may be present.

Mouth

Excessive salivation, with ropes of saliva
hanging from the mouth and usually
accompanied by chewing movements,
occurs when a foreign body is present in
the mouth and also in many forms of
inflammation of the oral mucosa or of the
tongue. Actinobacillosis of the tongue,
foot-and-mouth disease and mucosal
disease are typical examples. Excessive
salivation may also occur in diseases of
the central nervous system, as in acute
lead poisoning in young cattle. Hyper-
salivation is a characteristic sign in
epidermic hyperthermia associated with
the mycotoxins of Acremonium comophialum
and Claviceps puipurea and by the fungus
Rhizoctonia leguminicola sometimes found
on red clover. Dryness of the mouth
occurs in dehydration and poisoning with
belladonna alkaloids, or when high levels
of urea are fed.

Abnormalities of the buccal mucosa
include local lesions, hemorrhages in
purpuric diseases, the discolorations of
jaundice and cyanosis and the pallor of
anemia. Care must be taken to define the
exact nature of lesions in the mouth,
especially in cattle; differentiation between
vesicles, erosive and ulcerative lesions is
of diagnostic significance in the mucosal
diseases of this species.

Teeth

Examination of the teeth for individual
defects is a surgical subject but a general
examination of the dentition can yield
useful medical information. Delayed
eruption and uneven wear may signify
mineral deficiency, especially calcium
deficiency in sheep; excessive wear with
mottling and pitting of the enamel is
suggestive of chronic fluorosis.

Tongue

The tongue may be swollen by local
: edema or by inflammation as in actino-
bacillosis of cattle, or shrunken and
| atrophied in post-inflammatory or nervous
| atrophy. Lesions of the lingual mucosa
; are part of the general buccal mucosal
| response to injury.

i Pharynx

j Examination of the pharyngeal region in
j large animals requires some dexterity and
I the use of a speculum of appropriate size.

! The oral cavity and pharynx of calves,

I lambs and goat kids is examined by hold-
. ing the mouth open, depressing the base
i of the tongue with the fingers or a tongue
depressor and viewing the pharynx, the
; glottis and the proximal part of the larynx
and arytenoid cartilages. In adult cattle, a
metal orfPlexiglass cylindrical speculum,
45 cm in length and 4 cm in diameter.

Clinical examination of the individual animal

33

placed in the oral cavity and over the base
of the tongue will allow viewing of the
pharynx and the larynx. Foreign bodies,
diffuse cellulitis and pharyngeal lymph
node enlargement can also be detected by
this means. The use of a speculum
wedged between the upper and lower
molar teeth in cattle allows manual
exploration and evaluation of lesions of
the pharynx and proximal part of the
larynx. In the horse, the pharynx cannot
be viewed from the oral cavity and
manual exploration of the pharynx requires
general anesthesia. Endoscopy is a useful
method of examination in this species,
and the modem fiberoptiscope has made
it possible to visualize lesions in the
posterior nares and pharynx-esophagus,
larynx-trachea in the standing, conscious
horse or ox.

Submaxillary region

Abnormalities of the submaxillaiy region
that should be noted include enlargement
of lymph nodes due to local foci of infec-
tion, subcutaneous edema as part of a
general edema, local cellulitis with swell-
ing and pain, enlargement of salivary
glands or guttural pouch distension in the
horse. Thyroid gland enlargement is often
missed or mistaken for other lesions, but
its site, pulsation and surrounding edema
are characteristic.

Neck

The most important part of the exam-
ination of the neck of cattle and horses is
to determine the state of the jugular veins.
Bilateral engorgement of the jugular veins
may be due to obstruction of the veins by
compression or constriction, or to right-
side congestive heart failure. A jugular
pulse of small magnitude moving up the
jugular vein about one-third of the way
up the neck is normal in most animals but
it must be differentiated from a transmitted
carotid pulse, which is not obliterated by
compression of the jugular vein at a lower
level. Variations in size of the vein may
occur synchronously with deep respiratory
movements but bear no relation to the
cardiac cycles. When the jugular pulse is
associated with each cardiac movement it
should be determined whether it is
physiological or pathological. The physio-
logical pulse is presystolic and due to
atrial systole, and is normal. The patho-
logical pulse is systolic and occurs simul-
taneously with the arterial pulse and the
first heart sound; it is characteristic of an
insufficient tricuspid valve.

Local or general enlargement of the
esophagus associated with vomiting or
dysphagia occurs in esophageal diverticu-
lum, stenosis and paralysis, and in cardial
obstructions. Passage of a stomach tube
or probang can assist in the examination
of esophageal abnormalities.

Tracheal auscultation is a useful diag-
nostic aid. Normally, the sounds that are
audible are louder and more distinct than
breath sounds audible over the lung. In
upper respiratory tract disease such as
laryngitis and tracheitis, the sounds are
louder and harsher and may be whistling
in the presence of stenosis. Very loud
stenotic tracheal sounds are characteristic
of calves with tracheal collapse. Abnormal
tracheal sounds, regardless of their cause,
are usually transferred down the major
bronchi and are audible on auscultation
over the thorax, primarily during inspir-
ation. They are commonly confused with
abnormal lung sounds due to pneumonia,
but in pneumonia the abnormal sounds
are usually present both on inspiration
and on expiration.

Rectal examination

Rectal exploration of the abdomen is a
vital part of the complete examination of
the abdomen of large animals, especially
cattle and horses. Abnormalities that are
completely unexpected may be present
and maybe the cause of illness in animals
in which no other significant clinical
abnormalities were detected on clinical
examination. Special care is necessary to
avoid injuring the patient and causing it
to strain. Suitable lubrication and avoid-
ance of force are the two most important
factors. Rectal examination enables obser-
vations to be made on the alimentary,
urinary and genital tracts and on the
vessels, peritoneum and pelvic structures.
The amount and nature of the feces in the
rectum should be determined.

Fhlpable abnormalities of the digestive
tract include paralysis and ballooning of
the rectum, distension of the loops of the
intestine with fluid or gas, the presence of
hard masses of ingesta as in cecal and
colonic impactions in the horse, and
intestinal obstruction due to volvulus,
intussusception or strangulation. The
detection of tight bands of mesentery
leading to displacement segments may be
a valuable guide. In cattle, the caudal sacs
of the rumen are readily palpable. When
the rumen is distended as in bloat or
vagus indigestion they may push well into
the pelvis or be only just within reach
when the rumen is empty. A distended
abomasum may be felt in the right half of
the abdomen in cases of abomasal torsion
and occasionally in vagus indigestion. In
healthy animals there is little to feel
because of the space occupied by normal
intestines. Fhlpable objects should be
carefully examined.

The left kidney in the cow can be felt in
the midline and distinct lobulations are
evident. In the horse, the caudal pole of
the left kidney is easily palpable, but the
right kidney is not. There mav Hp abnor-

malities of size in pyelonephritis, hydro-
nephrosis and amyloidosis, and pain on
pressure in pyelonephritis. The ureters are
not normally palpable nor is the empty
bladder. A distended bladder or chronic
cystitis with thickening of the wall can
be felt in the midline at the anterior
end of the pelvic cavity. Abnormalities
of the bladder and ureters in cattle
are also palpable through the ventral
aspects of the vagina. Large calculi have a
stone-like hardness and are occasionally
observed in horses in the same position.
Pain with spasmodic jerking of the penis
on palpation of the urethra occurs in
urinary obstruction due to small calculi,
cystitis and urethritis. Enlarged, thickened
ureters such as occur in pyelonephritis
can be felt between the kidney and the
bladder.

On the peritoneum and mesentery
one may feel the small, grape-like lesions
of tuberculosis, the large, irregular, hard
masses of fat necrosis and the enlarged
lymph nodes of lymphomatosis. The
abdominal aorta is palpable, and in
horses the anterior mesenteric artery and
some of its branches can be felt. This
may be an important examination if a
verminous aneurysm is suspected, in
which case the vessels are thickened but
still pulsate, have an uneven rough
surface and may be painful. In horses the
caudal edge of the spleen is usually
palpable in the left abdomen. During
a rectal examination in a horse it is
advantageous in some cases to palpate the
inguinal ring from inside the abdomen
and, by pushing the other hand between
the horse's thighs, to palpate the external
ring simultaneously. It is then easier to
decide whether any abnormal structures
are passing through the ring.

Feces and defecation
Examination of the feces may provide
valuable information on the digestive and
motor functions of the tract. They should
be examined for volume, consistency,
form, color, covering, odor and composi-
tion. Note should be made of the
frequency and the time taken for material
to pass through the tract. Laboratory
examinations may be advisable to detect
the presence of helminth eggs, occult
blood, bile pigments, pathogenic bacteria
or protozoa.

The volume of feces is usually described
scant, normal or copious but, in certain
circumstances, it may be advisable to
weigh or measure the daily output. The
normal output for each species is as
follows:

§ Horses: 15-20 kg/day
0 Cattle: 25-45 kg/day
° Pigs: 1-2 .5 kg/day

q onrl rmofe • H C 1

20

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

There is an increased bulk when much
fiber is fed or during attacks of diarrhea.
The consistency and form of the feces
varies with each species and varies widely
within a normal range, depending parti-
cularly on the nature of the food.
Variations in consistency not explainable
by changes in the character of the feed
may indicate abnormalities of any of the
functions of the tract. The consistency is
more fluid in diarrhea and less fluid than
normal in constipation. The consistency
and form of the feces may provide some
indication of the location of the dys-
function of the gastrointestinal tract. In
general, large quantities of liquid feces
suggest a dysfunction of the small
intestine where normally most of the fluid
is absorbed. If the feces contain large quan-
tities of undigested feed this suggests over-
feeding, incomplete mastication, a
digestive enzyme deficiency or an acute
disorder of the small intestine or stomachs.
Large quantities of soft feces that contain
well-digested ingesta suggest a dys-
function of the large intestine. However,
these are only guidelines and are subject
to error.

Color of the feces This also varies
widely with the color of the food, but
feces of a lighter color than normal may
be caused by an insufficient secretion of
bile or by simple dilution of the pigments,
as occurs in diarrhea. The effect of blood
on the appearance of feces has already
been described. Discoloration by drugs
should be considered when the animal is
undergoing treatment.

Fecal odor This depends largely on the
nature of the food eaten but in severe
enteritis the odor is characteristically one
of putrefaction.

Composition The composition of the
feces should be noted. In herbivorous
animals, there is always a proportion of
undigested fiber but excessive amounts
suggest incomplete digestion due to, for
example, bad teeth and faulty mastication.
Excessively pasty feces are usually associ-
ated with a prolonged sojourn in the tract
such as occurs in vagal indigestion or
abomasal displacement in cattle. Foreign
material of diagnostic significance
includes sand or gravel, wool, and shreds
of mucosa. Mucus is a normal constituent
but, in excessive amounts, indicates either
chronic inflammation, when it is associ-
ated with fluid, copious feces, or consti-
pation when the feces are small in volume
and hard. Mucosal shreds or casts always
indicate inflammation.

Frequency of defecation Frequency and
the length of sojourn in the gastro-
intestinal tract are usually closely allied,
increased frequency and decreased sojourn

occurring in diarrhea and the reverse in
constipation. Most animals defecate eight
to 12 times a day but the sojourn varies
widely with the species. Omnivores and
carnivores with simple stomachs have an
alimentary sojourn of 12-35 hours. In
ruminants it is 2-4 days and in horses
1-4 days, depending on the type of feed.

Other observations

Observation of other acts associated with
the functions of the alimentary tract may
provide information of diagnostic value.
Prehension, mastication, swallowing,
vomiting and defecation should be
observed and an attempt made to analyze
the behavior of the animal when there is
evidence of abdominal pain.

Paracentesis of the abdomen
Paracentesis of the abdomen includes
obtaining a sample of peritoneal fluid
when peritonitis or inflammation of the
serosae of the intestines or other viscera
of the abdomen is suspected. Aspiration
of fluid from a distended abdominal
viscus is also possible and may aid in the
diagnosis.

Urinary system

Examination of the urinary tract consists
of observations of the act of urination,
evidence of difficult and painful uri-
nation, abnormal urine, collection of
urine and urinalysis, and, depending on
the species, palpation of the kidneys,
bladder and urethra. Details of the
examination of the urinary tract are
presented in Chapter 11.

Reproductive tract

Examination of the reproductive tract is
usually carried out at this stage but is not
discussed here because it is dealt with
adequately in texts on diseases of the
genital system. In the immediate post-
partum period, the vagina, cervix and
uterus should be examined thoroughly for
evidence of gross abnormalities such as
metritis, retained placenta and ruptured
uterus, which may be the cause of illness
not obvious on examination of other body
systems.

Mammary gland

The mammary gland(s) of all species is
examined by inspection and palpation of
the udder and teats, and gross examin-
ation of the milk or abnormal secretions
of the glands. Details of this examination
are presented in Chapter 15.

Musculoskeletal system and feet

Examination of the musculoskeletal
system and feet is necessary when there is
lameness, weakness, or recumbency.
Inspection of the gait during the walk and
trot is used to determine the origin of the
lameness. The muscles, joints, ligaments, j
tendons, and bones are inspected and

palpated to determine abnormalities
associated with lameness, weakness or
recumbency. The feet are examined by
inspection, palpation and the trimming of
hooves in farm animals to identify lesions
associated with lameness. Medical imaging
is commonly used to define lesions not
readily recognizable by routine clinical
examination. Details of examination of
the musculoskeletal system and feet are
presented in Chapter 13.

Nervous system

In routine veterinary practice, veterinarians
will commonly include several components
of a neurological examination in a
complete clinical examination. Most often
a diagnosis and differential diagnosis can
be made from consideration of the history
and the clinical findings. However, if the
diagnosis is uncertain it may be necessary
to conduct a complete neurological exam-
ination, which may uncover additional
clinical findings necessary to make a
diagnosis and give a prognosis.

A complete neurological examination
includes examination of the mental status,
head and posture, cranial nerve function,
gait and posture, function of the neck and
forelimbs, function of the trunk and
hindlimbs, palpation of the bony encase-
ment of the central nervous system,
examination of cerebrospinal fluid, medical
imaging of the bony skeleton of the head
and vertebral column. The details of the
neurological examination are presented
in Chapter 12.

Skin including ears, hooves and
horns

A systematic method for the examination
of the skin is necessary to avoid mis-
interpretation of the lesions. Inspection of
the behavior of the animal and of the skin
and hair, and palpation and smelling of
the skin are the most common physical
methods used for clinical examination of
the skin. The important prerequisites for
an adequate examination of the skin are
good lighting such as natural light or day-
type lamps, clipping the animal's hair
when necessary to adequately visualize
lesions, magnification of the lesions with
a hand lens to improve visualization of
the changes, and adequate restraint and
positioning of the animal. Palpation can
be used to assess the consistency of lesions,
the thickness and elasticity of skin, and to
determine the presence of pain associated
with diseases of the skin.

Close inspection and palpation of
the skin and hair coat are necessary to
identify and characterize lesions. Magnify-
ing spectacles or an illuminated magnifying
glass may prove useful. The dorsal aspect
of the body is inspected by viewing it from
the refr, as elevated hairs and patchy
j alopecia may be more obvious from that

Clinical examination of the individual animal

33

angle. All parts of the head including the
nose, muzzle and ears are examined. The
lateral trunk and the extremities are then
examined. The feet of large animals need
to be picked up to examine the inter-
digital clefts and parts of the coronary
bands. The skin of the udder and teats of
cattle, sheep and goats, and horses must
be observed. The ventral aspect of the
body is carefully examined using a source
of light to illuminate the underside of
adult cattle and horses. The external and
internal aspects of the ears, and the
hooves and horns must be examined by
inspection and palpation.

Every centimeter of the skin needs to
be examined for the presence of lesions
in different stages of development. The
visual, tactile and olfactory senses are
used to see, feel and smell the lesions. The
presence or absence of some ectoparasites
can be determined by direct inspection.
For example, lice and ticks of cattle are
usually easily visible. The odor of the skin
in some diseases may be abnormal;
dermatophilosis in cattle is characterized
by a foul and musty odor. Fhrting the hairs
with the fingers or by gently blowing
them is necessary to evaluate the length j
of the hair shafts. Broken hairs, changes j
in hair color and the accumulation of ;
exudative material on hair shafts are 1
noted. The texture and elasticity of the j
skin must be assessed by rolling the skin
between the fingers. Careful digital ,
palpation of the hair coat which appears
normal on visual inspection may reveal j
underlying lesions such as pustules which :
may be covered by the hair coat. In some j
cases, tufts of hairs may be seen protruding 1
through an accumulation of exudate. A '
combination of visual inspection of the !
wool coat of sheep is done carefully and |
systematically by parting the wool coat j
and evaluating the condition of the wool ;
fibers and the underlying skin. The hair
coat should not be clipped, groomed or j
washed before the lesions have been
identified and characterized.

DIAGNOSTIC ULTRASONOGRAPHY

Diagnostic ultrasonography in animals is
the continuation of the clinical examination :

Ultrasonography has developed into a I
valuable imaging technique in almost all
animal species because of the rapid I
development of technically improved j
portable units and their potential use at !
any given location, which is important in
farm animals not being examined in a
veterinary clinic. It is indeed a continuation
of the clinical examination. 1

The ultrasonographic examination is
unique in its patient application because
it is a dynamic examination technique
with no risk to the patient or the sono-
grapher. It is a continuation of the clinical

examination. Ultrasonography is non-
invasive, and well tolerated in unsedated
animals. It enables serial examinations to
monitor the progression of an abnor-
mality or response to treatment. Ultra-
sonography requires considerable skill
and experience to make a diagnosis. Some
practitioners may hesitate before investing
considerable resources in an ultrasound
machine if they feel it will not be used
regularly and if they believe they do not
have enough time for the examination.
Continuing education courses and work-
shops are becoming more common and
they provide excellent training and the
latest concepts. When employed correctly,
ultrasonography is of great benefit to
every veterinary clinician and practitioner
in continuing the clinical examination.
Ultrasonography can be valuable in
examining the contents of cavitary
lesions, synovial cavities, cysts or other
fluid-filled lesions for the presence of
liquid, semisolid or solid contents and/or
effusion. Centesis of synovial cavities or
body cavities, and biopsy of organs such
as liver or kidney are now frequently done
as part of the clinical examination. Ultra-
sonography enables accurate needle
placement following ultrasonographic
examination of the designated structure,
assisting with the measurement of the
distance from the skin surface to the
structure when, for example, a freehand
biopsy technique is to be performed.

The literature on the history of the
development, advances and application of
ultrasound in animals has been reviewed. 2

When a pulse of ultrasound is directed i
into a substance, varying amounts are !
reflected back to the source according to
the material encountered and the return-
ing signal conveys information regarding '
the structures it has penetrated. Real-time i
brightness or'B' mode imaging is currently
the form of ultrasound most commonly
used. Examination of moving structures
such as the heart required a technique
known as time motion or 'M' mode
ultrasound.

During a routine ultrasound examin-
ation, real-time B mode provides infor-
mation regarding the physical form and
structure of tissues, allows subjective
assessment of movement such as peristaltic
contractions within the intestine and
provides an overview that guides the
application of other ultrasound modes.

M mode is now an integral part of
j echocardiographic examinations and all
modem ultrasound machines are equipped
i with this capability.

: The benefits of ultrasound as a

j veterinary diagnostic imaging procedure
j are numerous. 2 Routine examinations
I have no harmful biological effects. It is a
j safe procedure for the animal, the operator

and nearby personnel, allowing it to be
done in any location without the need for
specific safety precautions.

The ability of ultrasound to distinguish
fluid from soft tissue and differentiate
between soft tissues on the basis of their
composition makes it more suited than
radiography for examining soft tissue
structures. Ultrasonography can often
provide information that was previously
only available through exploratory
laparotomy. Ultrasound is limited by its
inability to penetrate gas-filled or bony
structures; therefore 'acoustic windows'
must be found that avoid the inter-
position of bone or gas between the
transducer and the region of interest,
although this can often be achieved by
judicious positioning of the patient.
Transcutaneous examinations in animals
require removal of the hair overlying the
region of interest by clipping, as the beam
cannot penetrate the air trapped between
the hairs.

Examples of the use of ultrasonography
in bovine practice include the diagnosis of
gastrointestinal disease, 3 diseases of the
mammary gland, 4 thoracic disease, 2 splenic
disease, 6 ruptured gall bladder in cows 7
and the blood flow patterns in the com-
mon carotid artery and external jugular
vein for cardiac and blood vessel disease. 8

The use of ultrasonography as a repro-
ductive management aid in dairy cattle
practice represents a major advance in
understanding reproductive biology in
cattle. 9 The literature on the veterinary
ultrasound equipment, imaging the
bovine ovary (ovarian follicles, corpora
lutea, ovarian cysts), the bovine uterus
(early pregnancy diagnosis, early embryonic
loss, identification of cows carrying twins,
determination of fetal sex) and the
diagnostic limitations of ultrasonic imaging
has been reviewed. 9 Because nonpregnancy
can be established 7-14 days earlier after
artificial insemination (AI) using ultra-
sound compared with rectal palpation,
nonpregnant cows can be detected earlier
and returned to AI service, thereby
improving the pregnancy rate through an
increased AI service rate.

The use of ultrasonography to examine
various body systems is described briefly
in their respective chapters in the General
■ Medicine part of the textbook. Readers
are encouraged to consult the publi-
cations listed under Review Literature
and References, and textbooks dealing
with ultrasonography. Short courses and
laboratory workshops are now common-
place and readily available and highly
recommended. The development of
. extension education programs to train
L bovine practitioners is a critical step
j’ toward rapid implementation of this
technology into the dairy industry.

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

REVIEW LITERATURE

Braun U (ed.), Fluckiger M, Kahn W et al. Atlas und
Lehrbuch der Ultraschalldiagnostik beim Rind.
Berlin: Fbrey Buchverlag im Blackwell Wisseshafts-
Verlag, 1997.

Radostits OM, Mayhew IG, Houston DM. Veterinary
clinical examination and diagnosis. London: WB
Saunders, 2000.

Braun U. Ultrasonography in gastrointestinal disease
in cattle. Vet J 2003; 166: 112-124.

King AM. Development, advances and applications of
diagnostic ultrasound in animals. Vet J 2006; 171:
408-420.

Kofler J. Diagnostic ultrasonography in animals -
Continuation of the clinical examination? Vet J
2006; In press.

REFERENCES

1. Kofler J. Vet J 2006; 171:393.

2. King AM. Vet J 2006; 171:408.

3. Braun U. Vet J 2003; 166:112.

4. Flock M, Winter P.Vet J 2006; 171:314.

5. Flock M. Vet J 2004; 167:272.

6. Braun U, SicherD. Vet J 2006; 171:513.

7. Braun U et al. Vet Rec 2005; 156:351.

8. Braun U et al. Am J Vet Res 2005; 66:962.

9. Fricke PM. J Dairy Sci 2002; 85:1918.

Making a diagnosis

The practice of clinical veterinary medicine
consists of two major facets: the making
of a diagnosis and the provision of treat-
ment and control measures. For treatment
and control to be of optimum value the
diagnosis must be as accurate as possible,
so that diagnosis is the crux of all medical
problems.

A diagnosis is the identification of the
disease affecting the patient, and to be
complete should include three parts:

0 The specific cause
0 The abnormality of structure or
function produced by the causative
agent, and which is inimical to normal
body processes

° The clinical manifestation of that
abnormality produced by the
causative agent.

For recording purposes the animal species
should also be included, for example,
'equine Rhodococcus equi pneumonia and
lung abscess'. Many diagnoses fall short
of this objective because of lack of
confirmatory laboratory assistance. So
clinical signs (such as bovine chronic
diarrhea) or necropsy lesions (such as
bovine polioencephalomalacia) are often
used.

DIAGNOSTIC METHODS

At least five distinctly recognizable
methods are used and they are presented
here in order of increasing complexity. As
a general rule the experienced clinician
uses more of the simpler strategies, the
novice clinician more of the complex
ones. This is because the simple method

omits several steps in the clinical reason-
ing process - the sort of appropriate and
safe 'cutting of corners' that it is possible
to carry out with confidence only after
gaining wide experience and after paying
a good deal of attention to assessing one's
own personal competence as a clinician
and especially as a diagnostician.

METHOD 1: THE SYNDROME OR
PATTERN RECOGNITION

In the first few moments of viewing the
patient, e.g. the pain-generated behavior
of a horse with abdominal pain or the
skin lesions of ecthyma in a sheep or
papillomatosis in a cow, the diagnosis is
made instantaneously and reflexly. The
same experience may occur while taking
the history: one may have to rely entirely
on the history in the case of a cow having
an epileptic seizure to be able to diagnose
it. This recognition is based on the
comparison of the subject case and
previous cases in the clinician's memory
and the one is recognized as a replica of
the other. There is no need to seek further
supporting advice and the definitive
diagnosis is made then and there. In the
hands of the wise and experienced clinician
the method is quick and accurate.

METHOD 2: HYPOTHETICO-
DEDUCTIVE REASONING

As soon as the client begins to relate the
presenting signs, usually commencing
with the key clinical sign, the clinician
begins to draw up a short list of diagnostic
possibilities, usually three or four. This is
the process of generating multiple
plausible hypotheses from initial cues.
The clinician then begins to ask questions
and conduct clinical examinations that
test the hypotheses. The questions and
examinations may be directed at support-
ing or discounting the tentative diagnoses
(the confirm/exclude technique) but they
may lead to the addition of more hypo-
theses and the deletion of some others.
(The questions used here are search ones,
aimed at supporting a hypothesis, and are
distinctly different from scanning questions,
which are 'fishing' expeditions looking for
more key signs about which to ask search
questions.) This process of hypothesis and
deduction is continued until one diag-
nosis is preferred to the others. The
original list of hypotheses may be
expanded but not usually to more than
seven, and in the final stages is usually
reduced to two or three. These are then
arranged in order of preference and
become the list of diagnostic possibilities.

In farm animal medicine there is
usually a general absence of both hard
primary data and ancillary data such as
clinical pathology, so that the clinician
may be in the position of having to
provide treatment for two or three

possible illnesses. An example is the
parturition syndrome of recently calved
dairy cows in which the treatment of
subacute mastitis, metritis and acetonemia
is standard procedure because the clinician
is uncertain about which disease is most
accountable for the illness. In the more
resourceful arena of a veterinary teaching
hospital it may still be necessary to
proceed in this way in the first instance
but then to narrow down the list of
hypotheses when additional information
is received from the laboratory. This
polypharmacy approach has a number of
disadvantages, among which are included
the additional expense and the increased
possibility of contamination of food pro-
ducts of animal origin by medications,
especially antibiotics and sulfonamides,
and with resistant strains of bacteria.

One of the important characteristics of
this strategy is the dependence on the
selection of a critical or key clinical sign or
cue on which to base the original hypo-
theses. The selection of the key sign and
additional supporting clinical findings is
done instinctively by experienced clinicians
on the basis of prior experience in similar
situations. For novice clinicians it may be
necessary to examine two or more key
signs.

METHOD 3: THE ARBORIZATION OR
ALGORITHM METHOD

This is really an extension of method 2
but the hypothetico-deductive reasoning
method is formalized and carried out
according to a preplanned program. The
hypothetico-deductive reasoning method
depends on the clinician remembering
and being aware of an all-inclusive list of
diagnostic possibilities in the case under
consideration. Because memory is
unreliable and impressionistic the method
is subject to error by omission. The
arborization or algorithmic method
similarly approaches a listed series of
diagnoses and examines each one in turn
with supporting or disproving questions;
if they pass the proving test they stay in, if
they fail it they are deleted. For example, a
key sign of red urine in a cow promotes
the question: Has the cow had access to
plant substances that color the urine red? If
the answer is no, the next question is: Is
the red color caused by hemoglobinuria or
hematuria? If the answer is hemoglo-
binuria, all the diagnoses on the hematuria
branch of the algorithm are deleted and
the questioner proceeds to the next
question, which will attempt to determine
whether the cow has postparturient
hemoglobinuria or’ any one of a number
of diseases characterized by intravascular
hemolysis.

Provided that the list of possible diag-
noses is complete and is frequently updated

Making a diagnosis

as

as new diagnoses become available - and,
just as importantly, as new ways of sup-
porting or discounting each hypothesis
are added as soon as they are published -
the method works well. These algorithms
are eminently suited to computerization
and can be made available by the supply
of floppy disks or by access to a central
database via a modem, the online data-
base, or dial-up information system.

The arborization method is well suited
to the clinician who has not had the
necessary experience for the memorization
of long lists of potential diagnoses and
the critical tests that confirm or exclude
each of them. Because the algorithms are
likely to include all the recorded diag-
noses that have that particular key sign,
error by omission is not a risk. Thus they
are also valuable to the specialist, who is
less able to afford an omission than the
general practitioner and certainly cannot
really afford to miss even the most
obscure and unlikely diagnosis. Another
major advantage is that they provide a
system of tests that should be performed
and clinical findings that should be
searched for - which is really a form of
clinical protocol, acting as a reminder of

the sequential diagnostic steps to be
taken. The arrangement of the algorithm
represents the clinical reasoning of the
person who designed it and it should
have considerable merit, assuming that
the designer was an expert. This charac-
teristic does arouse the comment that the
method does away with the need for the
clinicians to do their own clinical reason-
ing. That may be so, but the interests of
optimum clinical care of patients are
probably better served by having first-
year interns apply the clinical reasoning
of a specialist and as a consequence
achieve significantly better results.

METHOD 4: THE KEY ABNORMALITY
METHOD

This is a more time-consuming method
than the previous ones and requires that
clinicians rely on their knowledge of
normal structure and function to select
the key abnormality or clinical cue. The
method consists of five steps and is
summarized in Figure 1.1.

Determination of the abnormality of
function present

Disease is abnormality of function which
is harmful to the animal. The first step is

to decide what abnormality of function is
present. There may of course be more
than one and some clinically insignificant
abnormalities may be present, e.g. a
physiological cardiac murmur in a new-
born foal. Definition of the abnormality is
usually in general terms such as paralysis,
state of the alimentary tract, hypoxia,
respiratory insufficiency, nervous shock
and so on. These terms are largely clinical,
referring to abnormalities of normal
physiological function, and their use
requires a foreknowledge of normal
physiology. It is at this point that the pre-
clinical study of physiology merges into
the clinical study of medicine.

The necessary familiarity with the
normal, combined with observation of the
case in hand, makes it possible to deter-
mine the physiological abnormality that
may be, e.g. hypoxia. The next step is to
determine the body system or body as a
whole or organ involved in the production
of the hypoxia.

Determination of the system or body
as a whole or organ affected

Having made a careful physical exam-
ination and noted any abnormalities, it is

Fig. 1.1 Making a diagnosis.

24

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

then possible to consider which body
system or organ is the cause of the
abnormality. In some cases the body as a
whole may be involved. This may not be
difficult with some systems: for example,
hypoxia may be due to failure of the
respiratory or circulatory systems and
examination of these is not difficult.
However, special problems arise when
attempting to examine the nervous system,
the liver, kidney, endocrine glands, spleen
and hemopoietic systems. Here, routine
physical examination by palpation,
auscultation and percussion is not very
rewarding: special ancillary examination
techniques with the aid of a laboratory are
usually necessary. These are described
under special examination methods for
the various systems. As a guiding prin-
ciple, all functions of the organ under
examination should be observed and any
abnormalities noted. For example, if the
integrity of the central nervous system is
to be examined, the clinician would look
for abnormalities of mental state, gait,
posture, muscle and sphincter tone and
involuntary movements, abnormal posture
and paralysis. Knowing the normal
physiological functions of systems, one
looks for aberrations of them.

When only simple physical examin-
ation is available it may be extremely
difficult to choose between two or more
systems as the possible location of the
abnormality. For example, in an animal
that is unable to rise from the recumbent
position it may be difficult to decide
whether the nervous system or the
musculoskeletal system or generalized
weakness from a systemic illness is the
origin of the clinical recumbency. If special
diagnostic techniques and laboratory
evaluations are inconclusive or not avail-
able, it may be necessary to resort to
probability as a guide. For example,
paresis due to diseases of the muscles is
most common in youngcalves, lambs and
foals and generally uncommon in mature
farm animals, with the exception of the
myopathy associated with the downer
cow syndrome in dairy cattle. However,
paresis is common in mature cows
affected with parturient hypocalcemia,
peracute coliform mastitis and acute
diffuse peritonitis.

Determination of the location of the
lesion within the system or organ
affected

The location of the lesion within the body
system involved is not always obvious
and may require special physical and
laboratory examination techniques. For
example, a detailed neurological examin-
ation may be necessary to localize the
lesion in an animal with manifestation of
disease of the nervous system. This may

be combined with radiographic techniques
such as myelography. An exploratory
laparotomy with or without biopsy tech-
niques maybe necessary to determine the
location of an intestinal lesion thought to
be the cause of chronic diarrhea. Endo-
scopy is rapidly becoming standard
practice for the localization of lesions of
the respiratory tract of the horse. Radi-
ography is often necessary to localize
lesions of the musculoskeletal system and
diseases of the feet of horses and cattle.

Determination of the type of lesion

The abnormality observed may be pro-
duced by lesions of different types. In
general, lesions can be divided into
anatomical or physical lesions and func-
tional disturbances. The physical lesions
can be further subdivided into inflam-
matory, degenerative or space-occupying.
These classifications are not mutually
exclusive, as a lesion may be both inflam-
matory and space-occupying: abscesses
in the spinal cord or lung are typical
examples. In these circumstances it is
necessary to modify the diagnosis and say
that such and such a lesion is space-
occupying and may or may not be
inflammatory.

The differentiation between functional
disturbances and physical lesions is often
extremely difficult because the abnor-
malities produced may be identical. For
example, in a case of hypomagnesemia in
a cow there is no physical lesion but
differentiation from the encephalitis of
furious rabies may be impossible. As a
rule, functional disturbances are transient,
often recurrent or fluctuating and are
readily reversible by treatment, whereas
structural lesions cause changes that are
relatively static or at least change slowly
and are affected only gradually by treat-
ment. This is by no means a regular rule:
the acute abdominal pain of intestinal
obstruction usually fluctuates but the
lesion is a physical one, whereas the para-
lysis of parturient paresis in cattle is static
but the disturbance is functional only.

Differentiation between inflammatory,
degenerative and space-occupying lesions
is usually simpler. The latter produce signs
characteristic of pressure on surrounding
organs and can often be detected by
physical means. Inflammatory lesions are
characterized by heat, pain, swelling and
a local or general leukocytosis and, in
severe cases, a systemic toxemia. A total
white blood cell count and differential is a
sensitive but nonspecific test for the
presence of an infection. A leukopenia,
neutropenia and a degenerative left shift
suggests a severe infection. A neutrophilia
and regenerative shift suggests an active
chronic infection. The most common
infections of cattle, which are often not

readily obvious, are in the thoracic and
abdominal cavities (pleuritis, pulmonary
abscesses, pericarditis and peritonitis).
Degenerative lesions produce the same
loss or abnormality of function as lesions
of the other types but are not usually
accompanied by evidence of inflammation
unless they are extensive. If the lesion is
accessible, biopsy should be considered as
a means of determining its nature.

Determination of the specific cause
of the lesion

If in the system involved, the nature of the
abnormality and the type of lesion can be
satisfactorily determined, it then remains
to decide on the specific causative agent.
If, for example, it could be said that a
particular case of paralysis in a calf was
caused by a degenerative lesion of the
musculature, only a few specific etiological
agents would have to be considered to
make a final diagnosis. In many, if not
most cases it is impossible to go beyond
this stage without additional techniques
of examination, particularly laboratory
examinations, and it is a general practice
to make a diagnosis without this confir-
matory evidence because of limitations of
time or facilities.

It is at this stage that a careful history-
taking and examination of the environment
show their real value. It is only by a
detailed knowledge of specific disease
entities, the conditions under which they
occur, the epidemiology and the clinical
characteristics of each disease that an
informed judgment can be made with any
degree of accuracy. If the diagnostic
possibilities can be reduced to a small
number, confirmation of the diagnosis by
laboratory methods becomes so much
easier because there are fewer examin-
ations to be made and confirmation by
response to treatment is easier to assess.
If it is necessary to treat with a great many
drugs serially or in combination to
achieve a cure, the expense is greater and
the satisfaction of both the client and the
veterinarian is diluted in proportion to the
range of treatments. Accuracy in diag-
nosis means increased efficiency, and this
is the final criterion of veterinary practice.

METHOD 5: THE DATABASE METHOD

The basis of this method (also called the
Weed or problem-oriented method, is

to conduct a complete clinical and clinico-
pathological examination of the patient in
order to acquire a comprehensive patient
database. The problems (key signs) in this
database are then matched with the
diagnostic database, in which collections
of signs or syndromes are labeled with
diagnoses, to select the best fit with the
patient\data.

This method also uses the problem-
oriented veterinary medical record

Making a diagnosis

23

system, which is an excellent system for
the daily recording of clinical and labor-
atory data in an orderly, systematic
and consistent manner that can be
easily followed by clinicians and their
colleagues. This system is now used
widely by veterinary teaching hospitals.
The system has four components based
on the four phases of veterinary medical
action:

o Database
° Problem list
0 Initial plans
° Progress notes.

The progress notes are created daily and
divided into four parts known collectively
by the acronym SOAP to designate:

0 S: subjective information
° O: objective data
o A: assessment of problem
° P: plans, which may include
diagnostic, therapeutic or client
education.

The method requires that clinicians be
very painstaking in their examination and
recording. It places great demands on the
time spent by clinicians and clinical
pathologists, on laboratory resources and
on clinical record storage. Much of the data
has no diagnostic significance because the
diagnostic decisions are made largely on
the presence or absence of relatively few
key signs. It also has the disadvantage
that there is a tendency to make the
patient fit a category. It is the opposite of
the key abnormality method, in which
only the signs and other indicants
relevant to the proposed diagnosis are
sought and recorded. Because of its
requirement of time and data recording
and storage this method is not suitable for
use in food animal medicine, where speed
is a vital component of the diagnostic
process. As mentioned earlier, however, it
is an excellent system for the teaching of
clinical veterinary medicine.

The method is really an expanded
version of the hypothetico-deductive
method, where the hypotheses are made
sequentially as further information
becomes available. In the database
method all the hypotheses are pursued in
parallel because all the possible data have
been collected into the patient's database.
The source of error in the method is the
possibility of undue importance being
attached to a chance abnormality in, say,
the clinical biochemistry. If the abnor-
mality cannot be matched to a clinical
sign, it should be weighted downwards in
value or marked for comment only. The
same error may result from inclusion of a
sign that is important, e.g. diarrhea, but
that happens to be present at low
intensity.

INTERPRETATION OF
LABORATORY DATA

WHEN TO COLLECT LABORATORY
DATA

Collection of a full history and perform-
ance of a purposeful physical examination
are the most powerful tools available to
the veterinarian in determining the
nature of an animal's disease and its
likely cause. However, laboratory data,
including results of clinical, biochemical,
hematologic, serologic, radiographic,
electrocardiographic, ultrasonographic
and other examinations, are often
obtained from individual animals or
groups of animals. The reasons for collect-
ing laboratory data can be summarized
as:

° To confirm the presence or cause of a
disease

° To assess the severity of a disease
° To predict the clinical course of a
disease or to determine a prognosis
® To estimate the likely response to
therapy

• To determine the response to therapy
or monitor progression of a disease
0 To satisfy regulatory requirements
0 To determine the disease or immune
status of an animal, herd or flock.

Collection of laboratory data should not
be viewed as a fishing expedition per-
formed in the hope that 'something will
turn up'. The decision to collect laboratory
data should always be made with one or
more of the above aims, with the inten-
tion that the data collected will answer a
particular, clearly stated question. It is
very easy, when faced with a sick animal
with clinical signs that are not clearly
diagnostic or indicative of the organ
system involved, to request a 'serum
biochemical profile' and complete blood
count without having a clear idea of the
usefulness of the information provided by
the results of these tests. While the
usefulness of these tests in most cases is
very clear, the results of the tests are most
informative when used to address a parti-
cular question, for instance: does the
animal have evidence of kidney disease?

A test should never be performed
unless one can anticipate all the likely
results and provide a meaningful inter-
pretation for each. Collecting laboratory
data for the sake of running a test or as an
act of diagnostic desperation is wasteful
of resources and will not, in all likelihood,
contribute to management of the animal
or group of animals. It is more likely that
the results of the test will be uninterpretable
and will muddy the diagnostic picture.

PROPERTIES OF DIAGNOSTIC TESTS

The following properties of a test, and of
the population to which it is applied.

should be known before it is considered
to be reliable:

° The test should be developed and
validated in the population of interest.
Tests developed in one population
might not be valid in an animal frbrn
another population. For instance, tests
developed for use in one species
might not be reliable if used in
another species

0 You should know how accurate the
test is in the situation in which you
intend to use it

0 The specificity of the test, i.e. the
ability of a positive result of the test to
rule in the disease of interest, should
be known. While this is a property of
the test that is usually independent of
the prevalence of the disease in the
population being tested, this might
not always be the case
® The sensitivity of the test, i.e. the
ability of a negative result of the test
to rule out the disease of interest,
should be known. While this is a
property of the test that is usually
independent of the prevalence of the
disease in the population being
tested, this might not always be the
case

° The pre-test likelihood of the disease
in the population should be known.
This permits calculation of post-test
odds of the animal having (positive
predictive value) or not having
(negative predictive value) the
disease for which it is being tested
° The likelihood ratios of the various
test results should be known for the
population of animals being tested
° The reliability of the laboratory

performing the test should be known.
There should be considerable
confidence in the quality control of
the laboratory such that test results
are repeatable and reliable
0 Are the references ranges (values in
animals without the disease or
condition of interest) known and with
what certainty are they known? The
meaning of an abnormal test result
should be clear

0 The test should allow you to rule in or
rule out one of the differential
diagnoses, in the instance in which a
test is being used for diagnostic, as
opposed to monitoring or other
purposes

® All test results should be

interpretable. In other words, all
results should provide information
that will be of use in diagnosis or
monitoring.

* Utility

To be useful, a diagnostic test must
be accurate. An accurate test reliably

26

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

differentiates between normal and diseased
animals, thereby contributing to effective
management of the animal or its disease.
Inaccurate diagnostic tests provide
unreliable data, which in the best scenario
are useless and in the worst scenario
cause mismanagement of the animal or
its disease. The diagnostic accuracy of a
test should be known before it is used
extensively and a test of unknown diag-
nostic accuracy should be assumed to be
inaccurate until proven otherwise.

The usefulness of a test to a veterinarian
depends on a number of factors. Firstly,
the test must be accurate, as discussed
above. Secondly, it should be technically
feasible and reliable, i.e. the test must be
readily performed and its characteristics
(listed above) must be known. A test that
cannot be readily performed has minimal
usefulness and unreliable tests are
inaccurate. For testing of analytes, such as
serum biochemical analysis or serology, it
is important that the analysis yields
results that are accurate and precise.
Laboratory tests that are accurate yield
results that are the same (or very close to)
the true value of the variable being
measured. Precise tests yield results that
have very little variability around the
expected value. Note that a test can be
precise without being accurate, i.e. it has
little variability but yields a value that is
different from the actual value. Tests that
are inaccurate or are highly variable (have
poor precision) are not useful because the
results are unreliable.

Thirdly, the test must have diagnostic
utility in that the results of the test should
enable the veterinarian to make a deci-
sion that will affect the subsequent
management of the animal or its disease.
If the results of the test will not alter the
animal's management or treatment of its
disease nor improve its production or
prognosis, then the test has no diagnostic
utility and should not be performed. The
diagnostic utility depends on the charac-
teristics of the test in the population of
animals being tested. The important
characteristics, which should be known
before the test is widely used, are the
sensitivity and specificity of the test and
the likelihood ratios associated with the
possible results, in the population in
which it will be used. That a test has
sensitivity and specificity implies that
there is a range of values expected in
normal animals, the so-called 'reference
range'.

Reference range (Interval)

An important aspect of evaluating labor-
atory data is to decide whether or not the
result of a test is consistent with the
animal being healthy or diseased. Healthy
animals are assumed to have values

within a certain range, whereas diseased
animals may have values that differ from
that expected in a healthy animal. The
range of values in healthy animals is often
referred to as being the 'normal range'
although, because of the statistical
connotation of this term/reference range'
or 'reference interval' is preferred.

The reference range represents the
range of values of a test that are expected
in a group of healthy animals. Animals
with values outside the reference range
are at increased risk of having the disease,
compared to animals with values within
the reference range. The actual increase in
risk of being diseased depends on the way
in which the reference range was
determined, the sensitivity and specificity
of the test and the prevalence of the
disease in the population from which the
animal was selected. Calculation of likeli-
hood ratios, both positive and negative, is
a useful means of quantitatively assessing
the results of a test.

The reference range for a particular
test is usually developed by collecting
values from a large number of healthy or
'normal' animals and performing a
statistical analysis of the values. For vari-
ables that have a range of possible values
(e.g. serum urea nitrogen concentration),
as opposed to being either present or
absent (e.g. seropositive or seronegative
for antibodies to a disease), the range of
values in normal animals will have a
characteristic spread. For the range of
values of the variable in normal animals,
an upper and a lower value are chosen
that represent the upper and lower limits
of the reference range. These values are
usually chosen to include 95% of the
values from normal animals, calculated as
the mean value for the population of
normal animals plus or minus 2 standard
deviations, or as the 2.5-97.5 percentile
range.

Problems with reference ranges
There are problems with using the
reference range of normal animals to
diagnose diseased animals. Firstly, 5% of
normal animals will have values for the
test that are outside the reference range
and may be incorrectly diagnosed as
being diseased (false positive). Although
a 5% false-positive rate is very low, the
error is compounded when batteries of
tests are run at the same time. This is a
potentially serious problem when inter-
preting data from a serum biochemical
profile analysis, in which 20 or more
analytes may be measured simultaneously
from one animal. The risk of the value of
any one analyte being outside the normal
range is only 5%, but when 20 analytes
are measured simultaneously the chance
of finding one analyte of the 20 with a

value outside the reference range is
almost 66% (100(l-0.95 20 )).

This problem can be mitigated in
several ways. Firstly, serum biochemical
profiles often contain more than one
variable that is indicative of a particular
disorder. If disease affecting a particular
organ system is present, then there
should be appropriate changes in all
variables indicative of disease in this
system. For instance, most serum bio-
chemical profiles measure both serum
creatinine and urea nitrogen concen-
trations. An elevation in the serum urea
nitrogen concentration may be indicative
of renal disease, but if the serum
creatinine concentration is not also
increased, then the likelihood of import-
ant renal dysfunction is much less than if
both analytes were above the reference
range. Secondly, disease may be associ-
ated only with marked increases in value
of the variable such that unusually low
values could be disregarded. For example,
a serum creatinine concentration below
the reference range is very unlikely to
indicate the presence of renal disease, and
a serum creatine kinase activity below the
reference range has almost no diagnostic
value. Thirdly, the extent to which the
variable is outside the reference range
should be considered. A small difference
from the reference range is much less
likely to indicate the presence of disease
than is a much larger difference - calcu-
lation of likelihood ratios is one way of
expressing this effect of variables that are
markedly abnormal.

Another problem with using the
reference range to detect disease is that
not all diseased animals will have a value
for the variable of interest that is outside
the normal range. Some diseased animals
will have values of useful variables that
are within the reference range and these
animals may be falsely diagnosed as not
having the disease (false negative). This
problem can be mitigated by reducing the
size of the reference range, although this
will increase the false-positive rate, or by
measuring other variables that are also
useful in detecting the suspected disease.
For instance, an animal with liver disease
may have a value of the serum activity of
a hepatic enzyme that is within the
reference range suggesting the lack of
liver disease (a false-negative result). How-
ever, the same animal may have marked
increases in serum bilirubin and bile acid
concentrations, findings strongly suggestive
of liver disease.

Sensitivity and specificity

The sensitivity of a test is a measure of the
test's ab(]ity to detect animals that are
diseased "knd its numerical value repre-
sents the proportion of animals with

Making a diagnosis

23

Table 1.3 Me
.and negative

thod for determining sensitivity
tests, positive predictive value

V

i, specificity,- likelihood ratio for posit
and negative predictive value of a te

ive

st

True disease status
Disease present

Disease absent

Test positive

True positive (TP)

False positive (FP)

Test negative

False negative (FN)

True negative (TN)

Sensitivity = (TP/fTP + FN]) x 100

Specificity = (TN/[FP + FN]) x 100

Likelihood ratio positive test = Sensitivity i( 1 - Specificity)

Likelihood ratio negative test = Specif icity/(1 - Sensitivity)

Positive predictive value = TP/(TP + FP)

Negative predictive value = TN/(TN + FN)

the disease that are detected by the test
(Table 1.3). A test with high sensitivity will
detect most diseased animals within a
population.

The specificity of a test is a measure of
the test's ability to detect animals that are
not diseased and its numerical value
represents the proportion of normal
animals detected by the test. A highly
specific test will rule out the disease in
most normal animals. Stated another
way, a negative result for a test with high
sensitivity effectively rules out the disease
being tested for, whereas a positive test
result for a test of high specificity effectively
rules in the disease for which the animal
is being tested.

Sensitivity' and specificity are intrinsic
properties of the test and their values are
not influenced by the likelihood before
the animal is tested that it has the disease
for which it is being tested. The ability of
a test to detect whether an animal has a
particular disease depends on the likeli-
hood that the animal has the disease at
the time it is tested (the prevalence of
disease in the population from which the
animal being tested is drawn) as well as
on the sensitivity and specificity of the
test. The sensitivity and specificity can be
combined to produce a single number,
the likelihood ratio.

Likelihood ratio

The likelihood ratio is an overall measure
of the efficiency of the diagnostic test,
combining both sensitivity and specificity
(Table 1.3) and permitting the calculation
of post-test odds of the disease from the
pre-test odds of disease. The likelihood
ratio is a quality of the test and is not
influenced in most instances by the preva-
lence of the disease in the population. The
likelihood ratio is useful for quantifying
the post-test odds of an animal having
the disease. For instance, in hospitalized
neonatal foals, a positive stall-side test for
failure of transfer of passive immunity has
a likelihood ratio of 4.86. A foal with
pretest probability of having the disease
of 50% that has a positive test (i.e.
indicative of lack of passive immunity)

therefore has a post-test probability of
having the disease of 81%.'

Positive and negative predictive
value

The combined effects on the ability of the
test to correctly detect diseased or healthy
animals of (a) the prevalence of the disease
and (b) the sensitivity and specificity of
the test can be calculated and are called
the positive predictive value (PPV) and
negative predictive value (NPV) respect-
ively. These are important values because
they determine the usefulness of the test
in detecting diseased, or normal, animals.
The positive predictive value is the
likelihood that a positive test is from an
animal with the disease. The negative
predictive value is the likelihood that a
negative test is from an animal that does
not have the disease.

Both the PPV and NPV are inextricably
linked to the prevalence of the disease in
the population being tested. Reports of
the PPV and NPV are therefore only use-
ful for populations of animals similar to
those in which the values of these
variables was determined, especially with
regard to the prevalence of the disease in
the population. The prevalence of the
disease can also be viewed as the prob-
ability that an animal selected at random
from the population has the disease - it is
the pretest probability of disease in the
animal. For a test of given sensitivity and
specificity, the likelihood that a positive

test correctly predicts the presence of
disease (the PPV) increases as the pro-
portion of diseased animals in the
population increases (the disease has
higher prevalence). Conversely, the NPV
increases as the prevalence of the disease
decreases.

The effect of changes in prevalence on
the PPV and NPV of two tests with
differing sensitivities and specificities is
illustrated in Table 1.4. The probability
that either test will detect the presence of
disease in an animal with a high pretest
likelihood of having the disease is very
high. Similarly, the probability that a
negative result is indicative of the absence
of disease in an animal from a population
with very low prevalence of disease is also
very high. Importantly, the ability of a
very good test (sensitivity and specificity
both 95%) to correctly predict the presence
of disease in an animal with a positive test
from a population with a low prevalence
(1% of animals affected) of the disease is
very poor. Applied to an individual
animal, this means that even a very good
test is likely to yield an incorrect result in
an animal that is unlikely to have the
disease.

Conversely, although the test result is
very unlikely to be incorrect, a positive
result in an animal with a very high pretest
probability of having the disease yields
little further information. The test result
does not increase the likelihood of the
animal having the disease by very much.
The diagnostic test has its greatest utility
when the pretest probability of disease is
approximately 50% and the increase in
PPV and NPV is much greater for a test
with higher sensitivity and specificity.

The pre-test probability of disease, and
thus the positive predictive value of the
test, can be increased by selecting animals
to be tested through careful physical
examination and collection of an appro-
priate history. The PPV of a test in an
animal that has signs of the disease being
tested for is much higher than the PPV of
a test in an animal without signs of the
disease. Testing clinically normal animals

•Table. 1 .4 :Effec
Jposit vc tredi ;

' •

-11

Test A

Prevalence or pretest probability PPV (%)

of disease (%)

NPV (%)

Test B
PPV (%)

NPV (%)

1

17

99

1

99

10

67

99

14

92

25

85

98

33

82

50

95

96

60

60

75

98

86

83

31

90

99 t

65

94

12

99

99

19

99

1

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

is more likely to yield false-positive
than true-positive results and such
indiscriminate testing is not wise.

REVIEW LITERATURE

Sackett DL et al. Clinical epidemiology. A basic
science for clinical medicine. Boston: Little. Brown
& Co., 1991: 3-170

Cockcroft P, Holmes M. Handbook of evidence- based
veterinary medicine. Oxford: Blackwell, 2003.

REFERENCE

1. Metzger N etal. JVet Intern Med 2006; 20:382.

COMPUTER-ASSISTED DIAGNOSIS

In the 1980s there was considerable
interest in computer-assisted diagnosis.
The entry of the clinical and laboratory
data from a patient into a computer
program could yield a differential diag-
nosis list of diseases in order of highest to
lowest probability. However, despite over
20 years of activity and interest in the use
of computers for diagnosis, the impact of
computer- assisted diagnosis in medical
practice has been slight. Computerized
programs have been useful in circumscribed
areas such as the differential diagnosis of
abdominal pain in humans and the diag-
nosis and treatment of meningitis. How-
ever, no program developed for use in a
specific localized area of the body has
been successfully adapted for generalized
use. Theoretically, the computer could be
expected to be useful to aid the clinician
with the workup in order to make multiple
and complex diagnoses.

Research on clinical decision-making
has confirmed the importance of creating
the list of differential diagnoses or diag-
nostic hypotheses. A clinician faced with a
diagnostic problem must use clinical
findings to develop a list of possible diag-
noses. With a knowledge of the epi-
demiological and clinical characteristics
of each disease, the veterinarian can
confirm or exclude certain diagnostic
possibilities. Diagnostic acumen depends
on the ability to recognize the most
important clinical abnormalities and to
generate a list of differential diagnoses - a
task that becomes more efficient with
experience.

Specialists can generate many differ-
ential diagnoses in a narrow area of
expertise, but the breadth of knowledge
required in general practice makes it
difficult for generalists to keep current on
rare or unusual conditions. If a disease is
not considered by the clinician faced with
a presenting problem, it is frequently
overlooked as a possibility and may not
be 'stumbled-on' during the diagnostic
process. This problem is complicated in
veterinary education by the common
practice of teaching according to disease
entity. All the nosology of a disease is
presented in a standard format but the

information must then be used in reverse
order in clinical practice: the clinician
generates a list of diseases based on the
history and clinical findings. Textbooks
that feature lists of differential diagnoses
for animals with similar clinical findings
assist in this task, but rapidly become
outdated because of the many major and
minor clinical findings that can be
associated with a disease. The large
storage capacity of computer databases
and the ease of access to stored data
makes the computer useful for handling
this sort of information.

The success of a computer-assisted
diagnosis will depend first on the clinician
determining the important finding or
forceful feature or pivot of the case,
which can be useful in separating possible
look-alike diseases. The second most
important requirement is to know the
propensity for a certain clinical finding to
occur in a disease syndrome. The algorithm
is the center of a computer-aided diag-
nostic system. Statistical algorithms
calculate the most likely diagnosis from
explicit statistical analysis of disease
probabilities and the frequency of clinical
findings in a particular disease. 1 A statistical
algorithm is based on the Bayes theorem.
The posterior probability that an animal
has a given disease can be calculated if
one has access to:

• The incidence (prior probability) of
the disease

• The probability of a given clinical
finding if the animal has the disease

• The probability of the same clinical
finding occurring if the animal has the
disease.

After receiving the data, the computer
uses this theory to calculate the likelihood
of various diseases. However, a major
problem of a Bayesian system is the non-
availability of an order of probabilities of
the incidence of diseases and clinical
findings associated with them. There is a
need in veterinary medicine to generate
comprehensive databases from which the
probabilities of incidence and clinical
finding for each disease can be determined
from actual clinical practice.

In spite of these limitations, some
progress is being made in the develop-
ment of computer-assisted diagnosis in
veterinary medicine. One computer-
assisted diagnostic system for veterinary
medicine was developed at the College of
Veterinary Medicine, Cornell University,
Ithaca, NY. The CONSULTANT program
designed by M. E. White and J. Lewkowicz 2
is available on the Internet at:
http://www.vet.cornell.edu. The Web
version of the CONSULTANT program is
based on the 1996 database. Direct access
to the most current database of

CONSULTANT at the College is possible
using dial-in or telnet.

The data bank contains a description
of several thousand diseases of dogs, cats,
horses, cattle, sheep, pigs and goats. For
each disease, there is a short description,
including information on diagnostic
testing, a list of current references, and a
list of the clinical findings that might be
present in the disease. The clinician enters
one or more of the clinical findings
present in a patient. The computer sup-
plies a list of the diseases in which that
clinical finding or combination of clinical
findings are present. The complete
description can be retrieved for any
disease in the list of differential diagnoses.
The program is available by long-distance
telephone and a modem. A major limi-
tation of the program to date is that the
list of differential diagnoses is not in order
of probability from highest to lowest. This
is because the program does not include
the probability of incidence and clinical
findings for each disease, information
that, as mentioned earlier, is not yet
available.

Experience with the Cornell
CONSULTANT program has shown that
computer-assisted diagnosis is not used
in day-to-day management of routine
cases but is used primarily when faced
with an unusual problem, to provide
assurance that a diagnosis was not over-
looked. Computerized databases also
offer a mechanism for the generalist to
search through a complete list of differ-
ential diagnoses compiled from the
recorded experience of many specialists
and kept current as new information is
published. Practitioners feel that having
access to CONSULTANT is also a signifi-
cant part of continuing education and a
source of references. Experience with a
computer-assisted diagnostic system has
also confirmed the importance of an
accurate history and an adequate clinical
examination. If an important clinical
finding is not detected, or not adequately
recognized - for example, mistaking
weakness of a limb for lameness due to
musculoskeletal pain - the computer
program will be ineffective. Disagreement
between observers about the meaning of
a clinical finding will also continue to be a
problem as computer-assisted diagnosis
becomes more widely used.

At the present time, the most important
service the computer can provide in
making a diagnosis is the generation of a
hypothesis through the generation of a
list of differential diagnoses, and access to
further information. Computers will
probably not be able to make a definitive
etiological diagnosis but they are able to
remind the user of diagnoses that should
be considered and to suggest the collection

Prognosis and therapeutic decision-making

11

of additional data that might have diag-
nostic value.

Prognosis and therapeutic
decision-making

The dilemma of whether or not to
administer a certain drug or perform a
certain operation in an animal patient
with or without an established diagnosis,
or when the outcome is uncertain, is
familiar to veterinarians. Owners of
animals with a disease, or merely a minor
lesion, expect to receive a reasonably
accurate prediction of the outcome and
the cost of treatment, but often consider-
able uncertainty exists about the presence
or absence of a certain disease, or its
severity, because confirmatory diagnostic
information is not available.

The information required for a reason-
ably accurate prognosis includes:

• The expected morbidity and case
fatality rates for the disease

• The stage of the disease

• Whether or not a specific treatment or
surgical operation is available or
possible

• The cost of the treatment.

If success is dependent on prolonged and
intensive therapy, the high cost may be
prohibitive to the owner, who then may
select euthanasia of the animal as the
optimal choice. Veterinarians have an
obligation to keep their clients informed
about all the possible outcomes and the
treatment that is deemed necessary, and
should not hesitate to make strong
recommendations regarding the treat-
ment or disposal of a case. There are also
different levels of outcome, which may
affect the prognosis and therapeutic
decision-making. In the case of breeding
animals, mere survival from a disease is
insufficient and treatment is often not
undertaken if it is unlikely that it will
result in complete recovery and return to
full breeding capacity. Slaughter for
salvage may be the most economical
choice. In other cases, e.g. a pleasure
horse, the return of sufficient health to
permit light work may satisfy the owner.

DECISION ANALYSIS

Veterinarians must routinely make
decisions that have economic con-
sequences for the client and the veteri-
narian. Questions such as whether to
vaccinate or not, whether to treat an
animal or recommend slaughter for
salvage value, whether or not to perform
surgery, or even which surgical procedure
to use to correct a case of left-side dis-
placement of the abomasum, are com-

mon. 3 Many of these questions are
complex, requiring several successive
decisions, and each decision may have
more than one outcome. Clinical deci-
sions are not only unavoidable but also
must be made under conditions of
uncertainty. This uncertainty arises from
several sources and include the following:

• Errors in clinical and laboratory data

• Ambiguity of clinical data and
variations in interpretations

• Uncertainty about the relationships
between clinical information and
presence of disease

• Uncertainty about the effects and
costs of treatment

• Uncertainty about the efficacy of
control procedures such as
vaccination or the medication of feed
and water supplies in an attempt to
control an infectious disease.

The process of selecting a management
plan from a range of options involves a
mental assessment of the available options
and their probable outcomes. Decision
analysis provides a framework for handling
complex decisions so that they can be
more objectively evaluated. Decision
analysis is a systematic approach to
decision-making under conditions of
uncertainty. Because the technique can be
so useful in sorting out complex questions
associated with the treatment and control
of disease in individual animals and in
herds, it is almost certain to become
more commonly used by large-animal
practitioners.

Decision analysis involves identifying
all available choices and the potential
outcomes of each, and structuring a
model of the decision, usually in the form
of a decision tree. Such a tree consists
figuratively of nodes, which describe
choices and chances, and outcomes'. The
tree is used to represent the strategies
available to the veterinarian and to
calculate the likelihood that each out-
come will occur if a particular strategy is
employed. A probability value must be
assigned to each possible outcome, and
the sum of the probabilities assigned to
the branches must equal 1.0. Objective
estimates of these probabilities may be
available from research studies or from a
veterinarian's own personal records or it
may be necessary to use subjective
estimates. The monetary value associated
with each possible outcome is then
assigned, followed by calculation of the
expected value at each node in the tree. At
each decision node the value of the
branch with the best expected value is
chosen and that becomes the expected
value for that node. The expected value
establishes a basis for the decision. An
example of a decision tree without
probability values assigned is shown in
Figure 1 . 2. 4

In the decision tree, choices such as
the decision to use intervention no. 1 or
intervention no. 2 are represented by
squares, called decision nodes. Chance
events, such as favorable or unfavorable
outcomes, are represented by circles
called chance nodes. When several

Favorable

Key
Pi ‘
P 2 -

(1 ~P 2 )

Net value
of income

K-C,

Vn-C ,

v f -c 2

I/ll -Co

Prognosis for a favorable outcome following intervention 1
Prognosis for a favorable outcome following intervention 2
Revenue obtained from a favorable outcome
Revenue obtained from an unfavorable outcome
C-, = Cost of intervention 1
C 2 = Cost of intervention 2

Fig. 1.2 A decision tree for choosing between two interventions. (With
permission from Fetrow J et al. J Am Vet Med Assoc 1985; 186:792-797.]

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

Fig. 1.3 Example of the construction and use of a decision tree. The sources of
probabilities and dollar values are discussed in the text, (a) The skeleton of the
decision tree with a decision (treat Tx versus do not treat) and chance
outcomes (recovery (REC) or spontaneous recovery (SPREC) versus continued
cyst (CYST)), (b) Probabilities and previously calculated outcome values are
placed on the tree, (c) Expected costs of decision alternatives have been
calculated and written in balloons above the chance nodes, (d) At this decision
node, the correct choice is no treatment because it is cheaper
($72.96 v $78.12). Double bars mark the pathway that is not chosen
(treatment). The value $72.96 is then the outcome cost for this decision node.
The value is used in the calculation of the best alternative to the previous
| decision node, as the process is repeated from right to left (not shown).

I (With permission from White ME, Erb HN. Comp Cont Educ Pract Vet 1982;

| 4:S426-S430.)

decisions are made in sequence, the
decision nodes must be placed from left
to right in the same order in which the
decisions would have to be made, based
on information available at that time. The
tree may become very complicated, but
the basic units of choice and chance
events represented by squares and circles
remain the same. Lines, or branches,
follow each node and lead to the next
event. The branches following each
decision node must be exhaustive; for
example, they must include all possible
outcomes, and the outcomes must be
mutually exclusive. 3 After each chance
node there is a probability that an event
occurs. The probabilities following a
chance node must add up to 1.0. The
probabilities are placed on the tree
following the chance node. The expected
outcomes (\/ F and V v in Fig. 1.2) are
entered at the far right of the tree. The
outcomes represent the value that would
result if the events preceding them on the
tree were to take place, and must include
the costs of the intervention.

When a complete tree accurately
representing the problem has been
constructed, the next step is to solve it for
the best decision to follow. This is done by
starting at the right of the tree, where
outcome values are multiplied by the
probabilities of outcome at the preceding
chance node. The figures derived from
this procedure are added together to
obtain the equivalent of a weighted
average value at the chance node, known
as the expected value, which by con-
vention is circled with an oval. This
procedure is repeated from right to left on
the tree at each chance node. When a
decision node is reached when moving
from right to left, the most profitable path
is chosen and a double bar is drawn
across the branches leading to the lesser
cost-effective decisions. When the first
decision node at the left of the tree is
reached, a single path will remain that
leads from left to right and has not been
blocked by double bars. This path repre-
sents the best way to handle the problem
according to the available information,
including the outcome at the end of that
path.

An example of the construction and
use of a decision tree to assist in deciding
at what day postpartum an ovarian cyst
should be treated, as opposed to waiting
for spontaneous recovery, is illustrated in
Figure 1.3.‘ In structuring the problem,
over time, the clinician knows that the
cyst can be treated or left to be treated
later. Retreatment is possible if the first
treatment is ineffective. The structure
must include all alternatives. The other
information needed to solve the problem
includes:

° The incidence or chances of
spontaneous recovery
° The response to treatment, both
initially and following repeated
treatments

0 When the response occurs
0 The cost of treatment and the cost of
the disease. 4

The critical factor in each tree is the
probability value for each possible out-
come.The monetary value of each outcome

can be estimated on a daily basis but,
unless the probability of the outcome can
be assessed as accurately as possible, the
decision analysis will be unreliable.
Decision analysis has been used to
determine the cost-effectiveness of heat
mount detectors, the time at which to
treat bovine ovarian cysts, the effectiveness
of three alternative approaches to
the control of Haemophilus meningo-
encephalitis in feedlot cattle, the

Examination of the herd

31

economically optimal control strategy
among several alternatives for the control
of infection with Brucella ovis in a sheep
flock 5 and the relative merits of testing or
not testing calves entering a feedlot with
a metabolic and cellular profile test as
predictors of performance in the feedlot.
Decision analysis can now be done on
microcomputers which makes the process
highly suitable for assisting the veteri-
narian in daily decision-making.

The details of the steps used in deci-
sion analysis of several different problems
in food-animal practice have been
described and the reader is referred to the
publications for further information . 4
There are some limitations to using
decision analysis in animal health
programs : 6 the technique requires time
and effort, which practitioners are
reluctant to provide unless the benefits
are obvious. The estimates of the prob-
abilities associated with the respective
branches of the tree are seldom readily
available.

A number of techniques that can be
used to derive these probabilities and
incorporate them in decision-making
have been recorded. The rapidly developing
use of analytical veterinary clinical
epidemiology can now provide the tools
to generate the numerical data necessary
to make reliable decisions. There is a need
to apply epidemiological principles to
prospective clinical studies to determine
the most effective therapy or the efficacy
of control procedures for the commonly
occurring economically important diseases
of food-producing animals. The inputs
and outputs of a given strategy may not
have a market value, or the market value
may not be an appropriate measure, or
they may not be tangible or measurable in
the usual monetary units. For example,
the market value of a dairy cow may not
represent the true or real value of the cow
to the farmer. The farmer may consider
the value of the cow in relation to cattle
replacement determinants such as herd
size, the availability of replacements and
the genetic potential of the animal. The
final selection of one option or the other
is usually a complex process that will also
vary from individual to individual depend-
ing on the decision criterion used.

In summary, decision analysis provides
a systematic framework for making rational
decisions about major questions in animal
health and it is hoped that some veteri-
narians will adopt the technique for field
use.

REVIEW LITERATURE

Sackett DL et al. Clinical epidemiology. A basic

science for clinical medicine. Boston: Little, Brown

& Co., 1991: 3-170.

Wilson J. Physical examination. Vet Clin North Am

Food Anim Pract 1992; 8:1-433.

Farver TB. Concepts of normality in clinical
biochemistry. In: Kaneko JJ, Harvey JW, Bruss M
(eds). Clinical biochemistry of domestic animals, 5th
ed. San Diego, CA: Academic Press, 1997: 1-19.

REFERENCES

1. Sackett DL et al. Clinical epidemiology. A basic
science for clinical medicine. Toronto: Little,
Brown & Co., 1985.

2. White ME. J Am Vet Med Assoc 1985; 187:475.

3. Fetrow J et al. J Am Vet Med Assoc 1985: 186:792.

4. White ME, Erb HN. Compend Contin Educ Pract
Vet 1982: 4:S426.

5. Carpenter TE et al. J Am Vet Med Assoc 1987;
190:983.

6. Ngategize PK et al. PrevVet Med 1986; 4:187.

Examination of the herd

The examination of the herd assumes
importance where there are outbreaks of
disease or problems of herd productivity
due to subclinical disease. The purpose of
a herd examination is to define the exact
nature of the problem and to identify
those dysfunctions within the herd
environment that are associated with its
occurrence. The ultimate objective in the
examination of a herd is to establish
strategies for the treatment, correction
and control of the disease problem at the
herd level. This may involve strategies to
increase the resistance of the animals or
strategies that change adverse factors in
the herd environment.

There are a number of ways in which
these objectives can be achieved and they
are not mutually exclusive. The methods
for examination of the herd include:

° Initial definition of the problem to be
examined

° Clinical examination of individual
animals in the herd
0 Analysis of records of performance
and disease

° Examinations of the environment of
the herd

0 Laboratory examination of animal;
nutritional and environmental
sampling

0 Necropsy examinations of dead or
sacrificed animals
° Descriptive and analytical
epidemiological examinations.

Methods for correction of the problem
include:

0 Treatment of individual sick animals
0 Selective or strategic prophylactic
medication of the impacted group
0 Immunoprophylaxis
0 Alterations to the nutrition, the
environment or the management
of the herd or of selected groups
within it.

One, or several, of these methodologies
may be used in dealing with herd prob-

lems depending upon the nature of the
disease under consideration.

Herd examinations can be expensive
and in clinical settings the depth of investi-
gation must be justified by the degree of
economic importance of the problem.
Some diseases are well defined, they are
easily and definitively recognized by
clinical or postmortem examination, their
determinants are well established, and
there are established effective methods for
their control. In these instances a herd
examination in a clinical setting would be
limited to the initial examinations that
establish the diagnosis and to the imple-
mentation of corrective strategies.

Other diseases are less well defined.
There may be several determinants of
their occurrence and consequently all
facets of the examination methods may
be needed to determine the most appro-
priate method for control. It is for this
type of disease that epidemiological
investigations are of particular importance
and, where there is an economic
justification, an in-depth epidemiological
investigation should be considered in
order to determine the appropriate
method of intervention.

APPROACH TO HERD
EXAMINATION

The previous sections have discussed the
approach to clinical examination of the
individual animal and the methods for
determining the presence of system
dysfunction and of reaching a diagnosis
as to cause. Basically, these consist of a
physical examination to assess the func-
tion of each body system coupled with
laboratory or other ancillary diagnostic
methods and information that can assist
in this assessment and in the establish-
ment of cause. In the individual animal,
disease is usually diagnosed and classified
by the system involved and the inciting
agent as, for example, pneumonia associ-
ated with Histophilus somni, myopathy
caused by a deficiency of selenium. Sub-
sequent treatment is based on this knowl-
edge and usually consists of therapy
directed against the cause and therapy
aimed at correcting the system dysfunction.

The approach to the examination
of the herd has a similar logical and
systematic approach but it is obviously
expanded beyond the examination of
individual animals and involves different
systems. It also involves different
approaches to the cause of disease. Herd
examinations are conducted because
there is an outbreak of disease or a prob-
lem of production inefficiency. By defini-
tion this involves a group or a population
of animals. Most outbreaks of disease and
problems of production inefficiency in

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

groups of animals result from faults or
dysfunctions in the complex of inter-
actions that occur within groups of animals
and between the groups of animals and
their management, environment and
nutrition. The characteristics of the group
of animals that are affected thus become
a focus of the examination and the
management, environment and nutrition
are the broad systems that are examined
in relation to this group of animals. In the
examination of the herd one is asking the
following questions:

° What is the disease problem that is
present?

° What are the characteristics of the
animals that are involved?

0 Why has this group of animals
developed the disease?

° Why are they at increased risk in
relation to others within the herd?

° What are the factors in their
management, nutrition or other
environment that have led to this
increased risk?

0 What intervention strategies can be
used to correct the problem?

A major objective of the examination is to
establish a diagnosis of cause. In parti-
cular, the objective is to establish a diag-
nosis of cause that can be altered by an
intervention. The diagnosis of cause in a
herd disease problem is often different
from the diagnosis of cause established in
the examination of an individual. Disease
occurrence in groups of animals is often
multifactorial in cause and the result of
the interaction of several risk factors,
which may be characteristics of the
animals, their environment or of an
inciting agent. In the context of the herd
the cause or 'etiology' of a disease can be
a management fault. In making a diag-
nosis of cause, the clinician establishes
and ranks the major determinants of the
problem from among the various risk
factors.

Examples of multifactorial etiology of
a disease

The examination of an individual animal
that is representative of a group of young
calves with respiratory disease may lead to
a diagnosis of pneumonia associated with
Histophilus somni. The diagnosis of the
cause of the same problem following a
herd examination that evaluates the
numerous risk factors for pneumonia in
calves might be:

• Inadequate ventilation in the calf house

• Failure of adequate passive transfer of
colostral immunoglobulins

• Most probably, a combination of the
above two, plus other additional
factors.

In making a diagnosis of cause, the
clinician establishes and ranks the major
determinants of the problem from among
the various risk factors.

With many diseases one progresses to
an examination of cause in the herd using
knowledge of recognized risk factors for
the disease. These risk factors usually
have a logical relation to the disease being
examined, as with the example of calf
pneumonia. With other diseases the logic
of these relationships may be less apparent.
This occurs particularly with newly
developing or recently recognized diseases,
where the pathogenesis of the disease is
poorly understood but epidemiological
examinations have established certain
relationships that have a causal associ-
ation. The definition of circumstances of
occurrence for a disease can lead to a
method of control even though the cause
of the disease, in the traditional sense, is
not known and the relationship between
the inciting or associated circumstance
and the disease is obscure. A current
example would be the developing recog-
nition of an association between dry cow
nutrition in dairy cattle and metabolic and
infectious diseases that occur early in
lactation.

Example of the control of a disease
without knowledge of its etiological
cause

It is now known that facial eczema in
sheep is a toxicosis from fungal toxins
produced on pastures. However, long
before the toxic nature of this disease was
fully understood, the epidemiological
circumstances of its occurrence were
defined and it was prevented by removing
sheep from pastures that had risk for the
disease during predicted risk periods
factors.

Problems of disease and production
inefficiency encountered in herds can
present a considerable challenge in diag-
nosis and correction. In part this is
because disease in groups or herds is
commonly multifactorial in cause and, for
this reason, in an examination of the herd,
all the factors that influence the behavior
of a disease in that herd assume import-
ance. The obvious approach is a quanti-
tative definition of the disease and a
quantitative examination of the relative
importance of these risk factors. However,
this approach can be difficult in practice.

In clinical settings there is usually no
difficulty in achieving a quantitative
definition of the animals affected and
their characteristics. In large, well-recorded
herds it is usually possible to conduct a
quantitative examination of risk factors if

the records contain information that
relates to them. In small herds, a quanti-
tative examination of the relative import-
ance of risk factors may be limited by low
numbers of animals. Knowledge of risk
factors and their relative importance in
disease causation is improving with
epidemiological research studies that
involve large numbers of animals and
several herds. The role of the clinician in
the approach to a herd disease problem is
to know and to be able to detect these
established influences, to be able to
quantify them where possible, and to be
able to choose from among them those
that are most subject to correction by
intervention from both a practical and an
economic standpoint.

EXAMINATION STEPS

There is no single protocol that can be
used for the examination of the herd as
this will depend both upon the type of
disease problem and the type of herd. For
example the methods of examination that
would be used in the examination and
definition of a problem of ill-thrift in a
flock of weaned lambs would be different
from those used for a problem of lame-
ness in dairy cattle. Most herd investi-
gations will follow certain broad principles
and steps, and these are outlined in
Figure 1.4. A given herd examination
would not necessarily follow all the steps
in this illustration nor would it necessarily
proceed in the exact order given. How-
ever, the general principles apply to most
investigations.

Step 1: Defining the abnormality

It is essential first to define the abnor-
mality in either clinical or subclinical
terms. This definition must be accurate, as
this step of the examination determines
the focus of the examination and the
types of cases that will be included in the
examination and analytical procedures. A
case is defined as an animal or a group of
animals that have the characteristics of
the disease or a defined deviation from
targets of production. With some investi-
gations the problem will have obvious
clinical manifestations and the primary
definition of cases will be made by clinical
examination of affected individuals. With
others the primary complaint may be
lowered production in the absence of
clinical disease. An apparent problem in
production efficiency can be focused by
the examination of records. In many
herds this will prove to be an immediate
major limitation to the investigation
because of a lack of sufficient records on
reproduction, production and associated
management to define the complaint. In
these circumstances the criteria of the
production inefficiency that will be

Examination of the herd

DEFINE THE ABNORMALITY

SUBCLINICAL

by comparison with
STANDARDS OF CLINICAL
NORMALITY

then proceed as in Fig. 1.2 to derive
clinical diagnosis in a number of
individuals, as a specific disease

by comparison with
CLINICOPATHOLOGICAL
STANDARDS
Microbiological,
e.g. quarter infection rate in
mastitis
Radiological,

e.g. epiphyseal closure time
in young horses
Biochemical,
e.g. metabolic profiles in
dairy cows
Serological,

e.g. fa zoonoses such as
tuberculosis

by comparison with
PRODUCTION STANDARDS
by frequent actual
measurement of:
Reproduction,
e.g. intercalving interval,
conception rate
Production,

e.g. annual yield of milk, eggs,
racing speed, acceptability
for sale
Longevity

1

Step 2

DEFINE PATTERN OF OCCURRENCE OF
ABNORMALITY IN THE HERD
in terms of numerical occurrence
relative to subherds based on

TIME

season of year, age
group, stage of
pregnancy, stage
of lactation

NUTRITIONAL
STATUS
existence of
deficiency or
excess status

GENETICS
sire and dam
groups

GENERAL
MANAGEMENT
housing, shearing,
transport,
introductions, etc.

VACCINATION
or other history
of immunity

Step 3

CATEGORIZE ABNORMALITY AS

INFECTIOUS

DISEASE

NUTRITIONAL

DEFICIENCY/EXCESS

INHERITED

ABNORMALITY

MANAGEMENT

ERROR

Step 4

DEFINE ABNORMALITY AND
MAKE HERD DIAGNOSIS
based on and confirmed by

LABORATORY

DIAGNOSIS

RESPONSE TO
TREATMENT

RESPONSE TO
CONTROL
MEASURES

Fig. 1.4 Examination of the herd with the objective of making a diagnosis.

34

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

considered in the examination will need
to be determined and some form of
measurement established.

Step 2: Defining the pattern of
occurrence and risk factors

This step of the examination is often
conducted in conjunction with step 1
above. It has the purpose of defining the
characteristics of the animals that are
affected in the disease problem and that
have been established as cases, and of
determining differences between them, as
individuals or as a group, and the non-
affected animals within the herd. These
differences may be attributes of the
animals themselves or of environmental
influences that affect them.

The initial examination is usually
directed towards the determination of the
characteristics of the animals involved
and the temporal (when) and spatial
(where) patterns of the disease. In general,
the information that allows these exam-
inations is collected at the same time and
consists of such factors as:

° A listing of the cases that have
occurred

° The date when disease was first
observed in each case
o The age, breed and other individual
information for each case, which may
include such information as source,
family association, vaccination history,
previous medication
o Management group membership,
which may be pen membership,
milking string, pastoral group, etc.

° Type of ration and nutritional data
° Management and other

environmental information that is
relevant to the problem.

In order to compute risk group analysis
the number of animals present in both
sick and well groupings must be recorded,
as must be any similarities and differences
in their management and environment.
After the identity of the abnormality has
been established, all the available clinical,
production and laboratory data are
examined according to the affected sub-
groups in the herd and according to time
occurrence, management differences,
nutritional and environmental influences
and factors such as vaccination history.

In most herd examinations the analysis
of these data is restricted to a cross-
sectional study. Prevalence rates within
the various groups are calculated and the
population at risk can be determined.
Animals or groups can be examined as
those with and without disease and those
with and without hypothesized risk
factors, using a 2 x 2 contingency table
generated for each variable. Relative risk,
odds ratios or rate ratios can be calculated

as a measure of association of the variable
with chi-square and Mantel-Haenszel
procedures used for evaluation of the
significance of the risk. This attempts to
determine if any associations exist
between certain groups of animals and
those factors that can influence the
behavior of disease.

In some herds, where there has been
extensive historical recording, it may be
possible to examine the nature of the
problem on the basis of a case-control
study. However, in most herds this will
not be possible because of the paucity of
recording of factors of importance to the
definition of the disease problem. With
problems that are of obvious continuing
importance to the economic viability of
the herd it may be necessary to establish
recording systems that allow a prospective
examination of the problem.

Temporal pattern

The temporal pattern of distribution of a
disease in a population can be of import-
ance in suggesting the type of disease that
is occurring and its possible causes.
Temporal recording and graphing of cases
is of value in indicating possible portals of
entry of an infectious agent or sources of
a toxic influence. For this analysis the
temporal occurrence of the disease is
determined by the collection and graphing
of the time of onset of clinical cases
(hours, days, weeks) and by relating this
information to management or environ-
mental changes.

Generally two types of epidemic curve
are graphed. A point source epidemic
curve is characterized by a rapid increase
in the number of cases over a short period
of time. This type of epidemic curve
occurs when all the animals in a popu-
lation are exposed at the one time to a
common agent. Generally this will be a
poison or a highly infectious agent, with
many animals becoming affected at
approximately the same time and, depend-
ing on the variation in the incubation
period, a sharply rising or a bell-shaped
curve of short time duration. The graph-
ing of a sporadic outbreak suggests the
occasional introduction of a disease agent
into a susceptible population or the
sporadic occurrence of factors suitable to
the clinical manifestation of an endemic
agent, as opposed to the relatively continual
occurrence of an endemic disease.

When the infection has to be trans-
ferred from animal to animal after under-
going multiplication in each, delay results
and the epidemic curve develops a flatter
bell-shaped occurrence of much longer
duration and with varying peaks depend-
ing upon temporal differences in, and
opportunities for, transmission. This is
known as a propagative epidemic.

Whereas the occurrence and identification
of an index case has considerable value in
epidemiological examinations of this
nature, it commonly cannot be identified
in veterinary clinical settings.

Spatial examination

The spatial examination of a disease
problem requires the gathering of infor-
mation on affected and nonaffected
animals in relation to areas of the housing
environment, or pastures, or animal
movements. A cluster of cases associated
with a specific area may indicate the
source of the problem. This is best
analyzed by plotting the frequency of
cases on maps of the environment that
include possible risk factors such as pen
locations within buildings, buildings them-
selves, water sources, pastures, rubbish
dumps, roads, implement storage
areas, etc. When spatial associations are
established, further detailed examination
of the location is indicated.

Step 3: Defining the etiological
group

Following characterization of the abnor-
mality according to groups within the
herd, and having made comparisons of
the prevalence rates between groups, it
may be possible to discern to which
etiological category the abnormality most
logically belongs. In many instances
considerable difficulty maybe encountered
in deciding in which of the general areas
of etiology the major determinant is
located. In so many cases herd problems
are not the result of a single error but are
multifactorial, with several determinants
contributing to a greater or lesser degree,
and the problem may fall in several
categories.

An example might be a problem of
mortality in calves where examinations
have determined that population mortality
rates are highest in the winter period, that
most mortality occurs between 4 days and
1 month of age, that calves that die early
in this period have septicemia, or have
scours associated with rotavirus and
cryptosporidial infections, that the body
condition scores of the calves fall during
the third and fourth weeks of life and that
calves that die later in the time period
appear to die of starvation. Probable
causes include improper feeding of
colostrum, a poor environment leading to
a high infection pressure and possibly
also to excess cold exposure, malnutrition
resulting either from the residual effects
of enteric disease on intestinal absorption
of nutrients or from an inadequate caloric
intake or both. This complex could be
placed in the categories of infectious
disease, nutritional disease and also in the
category of management error; further
definition is the next step.

The use of path models that sum-
marize current knowledge of the causality
of the disease under consideration can
help in this aspect of the herd examin-
ation. Path models specific to the problem
at hand can be constructed and can show
the interrelationships between various
risk factors and give some indication of
the dependence of any one factor on the
occurrence of another. This information
can be used to estimate the relative
contributions of the various etiological
categories and to give guidance as to the
area where intervention is most likely to
be effective.

Step 4: Defining the specific etiology

The final step is to select the probable
most important determinant or combi-
nation of determinants from within one
or more of the general areas and to make
corrective interventions based on this
diagnosis. In many instances the primary
cause may be clear and the correction, be
it alterations in nutrition, alterations in
management, vaccination, etc., can be
made at this stage. In other cases further
prospective examinations may be con-
ducted for a better definition before an
intervention is attempted. In the example
above, failure of passive transfer of colostral
immunoglobulins and inadequate caloric
intake would have been suspect or even
identified as underlying determinants of
the problem. However, with most farm
recording systems there is likely to be no
available data that would help delineate
the specific reasons, and the specific
management deficiencies that require
correction, and so a prospective study
to establish these would need to be
established.

It can be very difficult to obtain a
clearly defined diagnosis of cause of
disease in a herd, because of its complexity,
but the known important relationships
are given for the individual diseases in the
special medicine section. Methods for
practical clinical quantitative assessment
of the level of management expertise or,
more importantly, the intensity with
which it is applied, are not available.
Consequently this must be assessed
qualitatively for most management prac-
tices. Surrogates such as the percentage of
cows presented for pregnancy diagnosis
but not pregnant, bulk tank somatic
count, rates of failure of passive transfer of
colostral immunoglobulins, etc., can give
some indication.

TECHNIQUES IN EXAMINATION
OF THE HERD OR FLOCK

Set out below are some of the techniques
used in examining a group or herd of
animals. Any one or combination of the
techniques may be used at the one time.

Examination of the herd

35

depending on the nature of the problem,
the availability of support facilities such as
diagnostic laboratories and data analysis
laboratories, and their cost.

CLINICAL EXAMINATION

A clinical examination is essential if
clinical illness is a feature of the disease; a
representative sample of animals should
be examined. The importance of this
component of the examination cannot be
overemphasized. Where there is clinical
disease an accurate definition by clinical
examination may lead to a diagnosis of a
disease with known and specific deter-
minants and further examination of the
herd can focus specifically on these
factors. Where clinical examination does
not lead to a finite definition of the cause
of the disease but gives a diagnosis of a
disease of multifactorial determinants, the
examination will still lead to the identifi-
cation of risk factors that need to be
included in the herd examination.

Recording the findings is important
and is greatly assisted by a structured
report form so that the same clinical
features are recorded for each animal.
Commonly, clinically affected animals are
enrolled as cases in an investigation on
the basis of the presence of certain defined
signs or clinical abnormalities and a
recording form aids in this selection. This
is especially important where several
veterinarians in a practice may be involved
in the herd examination over time.

Selection of the animals to be
examined is vital. This should not be left
to the farmer because that selection may
be biased to include the sickest, the
thinnest and the oldest, and not necess-
arily the animals that are representative of
the disease under examination. This is
particularly important if a group of
animals is to be brought from the farm to
a central site for detailed clinical
examination as part of the workup of the
problem. Strict instructions should be
given to the owner to select 10-12
animals as a minimum. The groups
should include eight sick animals, if
possible four advanced and four early
cases, and four normal animals as
controls. If the situation permits it, the
inclusion of animals that can be sacrificed
for necropsy examination is an advantage.
Ideally, unless facilities will not allow it,
the clinical examinations should be on the
farm and the veterinarian should select
the animals for examination.

In outbreaks of disease where there is
mortality, necropsy examination and
associated sampling is an extremely valu-
able investigative and diagnostic tool.
Necropsy examination should not be ?
ignored as the primary method of
establishing a diagnosis of problems of

disease or production inefficiency in
larger herds and flocks. With many
diseases in swine herds and larger sheep
flocks the costs associated with the
sacrifice of a few animals for this purpose
are by far outweighed by the benefits of
an early and accurate diagnosis and the
ability to intervene quickly with corrective
strategies. Even in cattle herds, owners
are willing to sacrifice affected cattle if by
so doing they can facilitate a more accurate
definition of their problem. It must also be
recognized that some diseases cannot be
accurately defined on the basis of their
clinical manifestation and epidemiology
and a necropsy is required as part of the
examination system.

SAMPLING AND LABORATORY
TESTING

Laboratory examination is conducted for
a number of legitimate reasons. It may be
conducted to aid in the establishment of a
diagnosis or it may be conducted follow-
ing the establishment of a diagnosis to aid
in the definition of risk factors or in the
evaluation or the efficacy of treatment
and control strategies.

The validity of laboratory testing in the
investigation of disease is only as good as
the quality and relevance of the samples
that are submitted. The samples submitted
must be appropriate to the question that
is being asked of them. Frequently
samples that can be most conveniently
obtained are not the best for this purpose
and a sampling strategy specifically
directed to the question may need to be
established.

Laboratory analysis of samples is
expensive and should not be undertaken
unless there is a specific objective. Before
submitting samples for examination the
following questions should be asked:

° Is the sampling strategy structured to
answer specific questions or is it a
random 'fishing expedition'?

° Have you established a sampling
strategy that will allow a comparison
of animals in your 'at risk' category
with those believed not at risk for the
disease or the exposure factor?

° Is there a 'gold standard' for the
analysis and its interpretation?

0 What information will be gained from
the results of the laboratory
examination that could not be gained
by other examinations or logically
inferred without these examinations?

0 What are the specific steps to be
taken that depend upon the results of
these examinations, or will the steps
be taken regardless of the results?

This type of questioning of sampling for
laboratory examination may limit it to
situations where it is cost-effective.

16

PART 1 GENERAL MEDICINE ■ Chapter 1: Clinical examination and making a diagnosis

Laboratory examination of samples
taken in association with clinical examin-
ation is usually conducted to help
establish the presence and severity of
organ dysfunction - which generally
cannot establish cause. The value and use
of laboratory examinations in the assess-
ment of organ function is discussed in the
sections in this text that deal with system
diseases. Similarly the nature and value of
sampling to establish the etiological
association of toxic or infectious agents
with disease is discussed under specific
disease headings.

Laboratory testing can also be con-
ducted to determine risk and exposure
factors. When used for this purpose the
sampling strategy must be directed and
should be conducted after the preliminary
diagnosis has been made. It must be
aimed at answering the specific questions j
above, otherwise it will be inordinately >
expensive. An example would be the j
examination of specific feeds that have
been implicated as potential sources for a
toxin following the epidemiological j
examination and risk factor analysis in a
herd where a specific toxicity was
established as the cause of mortality.
Without this prior epidemiological exam-
ination a mass sampling of the herd and
its environment for the presence of the J
toxin would be extremely expensive and I
of limited value. I

At the time of the initial farm visit, it is !
advisable to collect samples that are j
pertinent to the problem and its differ- i
ential diagnosis but are not of primary j
analytical significance in the initial |
definition of the problem. These can be |
stored and, depending upon the results of j
initial laboratory examinations, may be j
discarded or used to further define the j
problem. Duplicates of some samples 1
with storage is often desirable so i
that second thoughts on tests can be I
accommodated. This is particularly ;
important in serological work where the
hindsight may be at a long time interval 1
and a serum bank is most profitable when
one is attempting a retrospective examin- j
ation of prevalence. j

In many ou tbreaks it is usually wise to
collect samples from 'controls' that are j
established specifically to evaluate the
problem under investigation. These may j
be clinically normal animals that have not I
experienced the suspect exposure factor, j
animals that are clinically normal but that [
have been exposed and are possibly in an !
incubation or subclinical stage, and from j
a third group of clinically affected animals, j
This system approximates the protocol for j
the Compton Metabolic Profile, which is j
described in detail in Chapter 28. j

The other consideration is the number j
of animals to be included in each j

sampling group. The sample size required
for the detection of an attribute varies
with the confidence of detection that is
desired, with the size of the population
and the prevalence or frequency of the
attribute in that population. Obviously
there can be no set recommendation even
for one disease. For example, the sample
size required to confirm a diagnosis of
copper deficiency in a group of animals
with overt clinical deficiency disease will
be much smaller than that which is
required to establish a developing defi-
ciency state or the risk for clinical disease
in the face of deficient intakes on pasture.
Unfortunately, cost severely limits the size
of the sample that can be tested in most
circumstances and the small size that is
common can place severe restrictions on
any meaningful interpretation. The com-
monly recommended 10 animals or 10%
of the group would appear to have little
validity in most examinations.

Numerical assessment of
performance

Productivity indexes can be used as
indicators of health; they can also be used
to measure response to treatment or
control measures. More and more they
are being used as guides to husbandry
and management questions to meet the
present-day farmer's concerns with costs
and returns. If recording systems are
present on the farm they can be invaluable
data sources in the investigation of herd
problems with disease. Monitors of pro-
duction efficiency are used extensively in
performance or production management
veterinary practice and are detailed in
texts on that subject in the reference
literature section.

Intervention strategies and response
trials

As the result of a herd examination, a
clinician formulates a hypothesis con-
cerning the disease. This may include
hypotheses on the population of animals
at risk, the determinants of the disease,
the source of the problem and its methods
of transmission or propagation. There
may be sufficient confidence in these
hypotheses that they may result in inter-
vention strategies to correct the problem
without further analysis. In other out-
breaks the hypotheses may be less secure
and may require further examination of
response trials.

Response trials are often used in an
approach to herd disease problems and
problems of production inefficiency. They
have several purposes: they may be used
to establish or confirm a diagnosis, and
when used for this purpose it is usually
because of the difficulty in confirming the
diagnosis by other methods. This may
result from the lack of a suitable labor-

atory test or because the result of the test
is supportive for the diagnosis but not
confirmatory. Response trials can also be
used to determine the degree of inter-
vention that is required and the efficacy of
the level of intervention that has been
used.

Example of reason for response trials

The finding of hypocupremia in a group of
poorly growing calves would support a
diagnosis of growth retardation due to
copper deficiency but does not confirm it,
as calves with normal growth can also be
hypocupremic. The only way to confirm
the association and the diagnosis is to
conduct a response trial with copper
treatment as the variable.

An example of monitoring efficacy of
interventions

Response trials can be used to determine
the degree of intervention that is required
| and the efficacy of the level of intervention
i that has been used. Copper deficiency in
I grazing calves may occur as a simple
j deficiency or as a conditioned deficiency,
i Simple copper deficiency can usually be
: prevented by a single subcutaneous

j treatment of copper glycinate and this may
j protect for several months. On the other
hand, a conditioned copper deficiency may
require treatment every 4-6 weeks.

Some prediction as to the required
treatment frequency can be made by
j pasture element analysis but a response
j trial with 6-week-interval monitoring of
j blood copper concentrations and weight
; gain can monitor the efficacy of the
j treatment that has been decided upon and
I also allow a corrective intervention, if
indicated. In the absence of a treatment
j response trial, a nonresponse due to an
incorrect decision on treatment frequency
j could result in the discarding of the correct
; diagnosis.

There are many limitations to conduct-
; ing response trials in clinical situations in
: private herds and their structure may not
always meet the strict requirements of
j those conducted in research. It is not
1 always possible to establish a controlled
response trial in clinical practice but the
efficacy of intervention strategies should
l still be monitored. The ultimate interest is
in whether the disease or production
j problem is corrected; however, the efficacy
of the individual strategies should be
specifically monitored where possible. In
I the earlier example of calf mortality a
j decision might have been made to change
j the method of feeding colostrum and to
; improve the caloric intake of the calves,
i There qan be various ways that either of
; these changes could be achieved. The
j overall efficacy of these changes will be

Examination of the herd

37

determined by improved survival of
the calves. However, the efficacy of the
colostrum management change in
improving passive transfer should be
determined specifically by measurements
of serum immunoglobulin concentrations
in the serum of a proportion of calves and
the efficacy of caloric improvement by
weight measurements. Should calf
mortality drop, these latter measures are
of limited value but if it does not, then
there are measures of whether the failure
was due to misdiagnosis of the problem
or due to poor efficacy of the suggested
corrective strategies in correcting their
respective target areas.

A diagnosis made on the basis of a
response trial is often presumptive and it
has become customary to couch the
diagnosis in terms of response to a
treatment, for instance, 'selenium-
responsive infertility' in sheep. This is not
a diagnosis in terms of satisfying the
original concepts of Koch's postulates,
although it does satisfy the subsequent
modifications of these postulates that are
now generally accepted and have been
based on a broader interpretation of
disease causation. In populations of
animals, diseases are largely the result of a
number of interacting factors of different
genres, including management, nutrition
and environmental factors, interacting
with traditional agent-causes of disease,
including microbiological and toxic agents.
The answer for the practical problem may
be most economically derived by finding

the cure rather than the cause. This is
especially desirable if that course is cost-
effective and finding the cause is more
expensive than the wastage caused by the
disease.

A simple example would be mortality
in a group of cattle that followed a change
of feed to a more concentrated ration. An
epidemiological examination, including a
temporal examination of cause or deter-
minants, might closely link the mortality
to the change in ration. This should be
sufficient to indicate that the ration
should be withdrawn or its method of
feeding modified. The alternative approach
would be to defer any decision for
correction of the problem until the exact
problem with the ration was established.
This could involve a ration analysis and
an examination for unknown toxic
components. These examinations would
take considerable time, would involve
considerable costs, and could well give no
additional information that would modify
the immediate initial intervention strategy.

The role of the planned animal
health and production program

Properly conducted herd health programs
and planned animal health and pro-
duction programs maintain accurate
records on all matters of production and
health. These are maintained against a
background of epidemiological data,
including number of animals in the herd,
numbers of animals in the reproductive
cycle segment group or age group that are

therefore at risk. In many instances all the
data required to effectively diagnose a
disease or monitor its prevalence are
already at hand in the records of these
herds. It does put the veterinarian and the
farmer in the position of almost being
able to do a herd examination simply by
consulting the records. This approach is
detailed in texts on herd health and pro-
duction medicine.

REVIEW LITERATURE

Kahrs RF. Techniques for investigating outbreaks of
livestock disease. J Am Vet Med Assoc 1978; 73:
101-103.

Blood DC. The clinical examination of cattle. Fbrt 2:
Examination of the herd. In: Proceedings of the 14th
Annual Convention of the AABP, 1981: 14-21.
Cannon AR, Roe RT. Livestock disease surveys. A field
manual for veterinarians. Canberra: Australian
Government Publishing Co., 1982.

Dohoo IR, Waltner-Toews D. Observational studies
and interpretation of results. Comp Cont Educ
PractVet 1985; 7:S605-S613.

Thrushficld MV, Aitken CGG. An introduction to
veterinary observational studies. Edinburgh:
University of Edinburgh Press, 1985: 35.
Thrushfield MV. Veterinary epidemiology. London:
Butterworths, 1986: 165.

Martin SW, Meek AH, Welle berg P. Veterinary
epidemiology, principles and methods. Ames, LA:
Iowa State University Press, 1987: 343.

Lessard PR, Perry BD. Investigation of disease
outbreaks and impaired productivity. Vet Clin
North Am, Food Anim Pract 1988; 4:1-212.

Smith RD.Veterinary clinical epidemiology. A problem
oriented approach. Boston, MA: Butterworth-
Heinemann, 1991: 234.

Radostits OM. Herd health. Food animal production
medicine, 3rd ed. Philadelphia, PA WB Saunders,
2001.

PART 1 GENERAL MEDICINE

General systemic states

HYPOTHERMIA, HYPERTHERMIA,
FEVER 39

Body temperature 39

Hypothermia 40

Hyperthermia (heat stroke or heat
exhaustion) 47

Fever (pyrexia) 49

SEPTICEMIA/VIREMIA 51

TOXEMIA AND ENDOTOXEMIA 53

TOXEMIA IN THE RECENTLY CALVED
COW 60

Postpartum septic metritis in cattle 60

HYPOVOLEMIC, HEMORRHAGIC,
MALDISTRIBUTIVE AND
OBSTRUCTIVE SHOCK 63

ALLERGY AND ANAPHYLAXIS 69

Anaphylaxis and anaphylactic shock 69

Other hypersensitivity reactions 7 1

EDEMA 72

There are several general systemic states
that contribute to the effects of many
diseases. Because the systemic alterations
are common to many diseases they are
considered here as a group in order to
avoid unnecessary repetition. Hyper-
thermia, fever, septicemia and toxemia are
closely related in their effects on the body,
and an appreciation of them is necessary if
they are not to be overlooked in the efforts
to eliminate the causative agent. Likewise,
hypovolemic, hemorrhagic, maldistributive,
obstructive and anaphylactic shock are best
examined together. This chapter will also
present the disturbances of free water,
electrolytes and acid-base balance, and
briefly introduce pain and stress as it relates
to disease. Syndromes of poor perform-
ance, decreased appetite and sudden and
unexpected death are also covered.

Hypothermia,
hyperthermia, fever

Hypothermia, hyperthermia and fever -
characterized by significant changes in
body temperature - are presented here
together, along with an introduction to
thermoregulation mechanisms of the body.

BODYTEM PERATU RE

Farm animals maintain a relatively constant
body core temperature, homeothermy.

DISTURBANCES OF FREE WATER,
ELECTROLYTES AND ACID-BASE
BALANCE 73

Dehydration 74
Acute overhydration (water
intoxication) 76
Electrolyte imbalances 76
Acid-base imbalance 82
Acidemia 84
Alkalemia 86

Naturally occurring combined
abnormalities of free water,
electrolyte and acid-base balance 87

PAIN 102

STRESS 107

LOCALIZED INFECTIONS 110

DISTURBANCES OF APPETITE, FOOD
INTAKE AND NUTRITIONAL
STATUS 112

Polyphagia 1 1 2
Anophagia or aphagia 1 1 2
Pica or allotriophagia 1 1 2

during extreme ranges of thermal environ-
ments. This homeothermic state is
achieved by physiological and behavioral
mechanisms that modify either rates of
heat loss from the body or the rate at
which heat is produced by metabolism of
feed or body energy reserves. For the
body temperature to remain constant in
changing thermal environments, the rate
of heat loss must equal the rate of heat
gain.The body temperature is a reflection
of the balance between heat gain from
the environment (radiation, conduction,
convection) or due to metabolic activity
(maintenance, exercise, growth, lactation,
gestation, feeding) and heat loss to the
environment (radiation, conduction, con-
vection, evaporation) or due to metabolic
activity (milk removal, fecal elimination,
urinary elimination). Absorption of heat
from the environment occurs when the
external temperature rises above that of
the body.

HEAT PRODUCTION

Heat production occurs as a result of
metabolic activity and the digestion of
feed, muscular movement and the main-
tenance of muscle tone. Shivering
thermogenesis is a response to sudden
exposure to cold and is a major contri-
butor to enhanced heat production.
Nonshivering thermogenesis is also
induced by exposure to cold and is the
mechanism in which heat is produced by

Starvation 113

Inanition (malnutrition) 1 1 3

Thirst 114

WEIGHT LOSS OR FAILURE TO GAIN
WEIGHT (ILL-THRIFT) 115

SHORTFALLS IN PERFORMANCE 116

PHYSICAL EXERCISE AND
ASSOCIATED DISORDERS 117

Poor raci ng performance and exercise
intolerance in horses 1 18

Exercise-associated diseases 1 1 9

DIAGNOSIS AND CARE OF
RECUMBENT ADULT HORSES 120

SUDDEN OR UNEXPECTED
DEATH 124

Sudden or unexpected death in single
animals 124

Sudden death in horses 1 24

Sudden or unexpected death in a group
of animals 124

Procedure for investigation of sudden
death 124

the calorigenic effect of epinephrine and
norepinephrine, which are released into
the blood in increased amounts. In the
neonate, heat is produced by the meta-
bolism of brown adipose tissue, which is
present in newborn farm animals and is a
particularly important mechanism of
heat production to prevent neonatal
hypothermia.

HEAT LOSS

Heat is transferred to or from an animal by
the four standard physical phenomena of
convection, conduction, radiation and
evaporation. Convection is a transfer of
heat between two media at different
temperatures, such as the coat surface and
the air. As such, convective heat transfer
depends on the temperature gradient
between the coat surface and air, the surface
area and the air speed over the surface.
Conduction is the transfer of heat between
two media that are in direct contact, such as
the skin and water. Radiation is the
absorption or emission of electromagnetic
radiation at the body surface, and depends
on the skin surface temperature and area.
Evaporative heat transfer is a process
whereby heat is lost by the evaporation of
water, and is dependent on the water vapor
pressure gradient between the epithelial
surface and the environment and the air
f. speed over the surface.

Evaporation occurs by sweating, sali-
vation and respiration, with the relative

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

importance varying between species.
Losses by evaporation of moisture vary
between species depending upon the
development of the sweat gland system
and are less important in animals than in
humans, beginning only at relatively high
body temperatures. Horses sweat pro-
fusely, but in pigs, sheep and European
cattle sweating cannot be considered to
be an effective mechanism of evaporative
heat loss. In Zebu cattle the increased
density of cutaneous sweat glands sug-
gests that sweating may be more import-
ant. Profuse salivation and exaggerated
respiration, including mouth breathing,
are important mechanisms in the dis-
sipation of excess body heat in animals.
The tidal volume is decreased and the
respiratory rate is increased so that heat is
lost but alkalemia due to respiratory
alkalosis is avoided.

BALANCE BETWEEN HEAT LOSS AND
GAIN

The balance between heat gain and heat
loss is controlled by the heat-regulating
functions of the hypothalamus. The
afferent impulses derive from peripheral
hot and cold receptors and the tempera-
ture of the blood flowing through the
hypothalamus. The efferent impulses
control respiratory center activity, the
caliber of skin blood vessels, sweat gland
activity and muscle tone. Heat storage
occurs and the body temperature rises
when there is a decrease in rate and depth
of respiration, constriction of skin blood
vessels, cessation of perspiration and
increased muscle tone. Heat loss occurs
when these functions are reversed. These
physiological changes occur in, and are
the basis of, the increment and decrement
stages of fever.

BREED DIFFERENCES

Differences exist between breeds and
races of cattle in coat and skin characters
that affect heat absorption from solar
radiation and heat loss by evaporative
cooling; differences also exist in the
metabolic rate, which influences the basic
heat load. Interest in this subject has been
aroused by the demands for classes of
animal capable of high production in the
developing countries of the tropical zone.
Detailed information on the physiological
effects of, and the mechanisms of adap-
tation to, high environmental temperatures
are therefore available elsewhere.

These findings are of greater interest in
more temperate climates where the
demand for more economic animal hus-
bandry methods has led to investigation
of all avenues by which productivity
might be increased. Such subjects as the
provision of shelter in hot weather,
the use of tranquilizers to reduce activity,
and therefore heat increment, and the

optimum temperature in enclosed pig
houses are subjects of vital importance to
the farming economy but are not dealt
with in this book because they appear to
have little relation to the production of
clinical illness.

Hypothermia, caused by exposure to
low environmental temperatures, and
hyperthermia (heat stroke or heat
exhaustion), caused by exposure to high
environmental temperatures, are the
major abnormalities of body temperature
associated with extremes of environ-
mental temperatures. Anhidrosis, occur-
ring primarily in horses in hot humid
climates and associated with the inability
to sweat, is described in Chapter 35.

HYPOTHERMIA

Hypothermia is a lower than normal body
temperature, which occurs when excess
heat is lost or insufficient is produced.
Neonatal hypothermia is a major cause of
morbidity and mortality in newborn farm
animals within the first few days of life.
Cold injury and frostbite are presented
under that heading in Chapter 30.

ETIOLOGY

Excessive loss of heat

Exposure to excessively cold air tempera-
tures causes heat loss if increased meta-
bolic activity, shivering and sustained
muscular contraction and peripheral
vasoconstriction are unable to compensate.

Insufficient heat production

Insufficient body reserves of energy and
insufficient feed intake result in insuffi-
cient heat production.

Hypothermia also occurs secondary to
many diseases in which there may be a
decrease in the ability to shiver and
skeletal muscle contraction associated
with decreased cardiac output, decreased
peripheral perfusion and shock. Examples
include parturient paresis, acute ruminal
acidosis (grain overload), and during
anesthesia and sedation, and the reduc-
tion of metabolic activity that occurs in
the terminal stages of many diseases. A
sudden fall in body temperature in a pre-
viously febrile animal, the so-called
premortal fall, is an unfavorable prog-
nostic sign.

Combination of excessive heat loss
and insufficient heat production

A combination of excessive heat loss and
insufficient heat production is often the
cause of hypothermia. Insufficient energy
intake or starvation of newborn farm
animals in a cold environment can be a
major cause of hypothermia. This may not
occur under the same environmental
conditions if the animals receive an
adequate energy intake. Fatal hypothermia
may also occur in other circumstances.

such as in certain breeds of pig (pot-
bellied) following general anesthesia or
sedation with higher doses of azaperone. 1
Mature pot-bellied pigs deprived of feed
and kept outdoors during cooler months
of the year may develop hypothermia,
which would not normally occur in these
conditions if the pigs were receiving
adequate food. 2

EPIDEMIOLOGY
Neonatal hypothermia

Newborn farm animals are prone to
hypothermia in cool environments and
hypothermia is a major cause of neonatal
mortality. The neonates cannot maintain
their rectal temperatures at normal values
during the first few hours after birth
under cold environmental conditions.
Hypothermia and environmental thermo-
regulatory interactions are of particular
importance in piglets and lambs because
of their surface to volume ratio but are
also relevant in calves and sick foals.

At birth, the neonatal ruminant moves
from a very stable thermal environment,
of similar temperature to its core body
temperature, to a variable and unstable
thermal environment that is 10-50°C
colder than its core temperature. The coat
is wet with placental fluids and energy
loss is increased by evaporation and the
low insulative value of a wet coat. The
newborn calf becomes hypothermic in the
first 6 hours after birth and only limited
tissue substrates are available as energy
sources. Neonates also are exposed to a
variety of environmental pathogens against
which they have little specific immunity.
Thus the neonatal period is one of the
most critical to the survival of an animal
and during this period the morbidity and
mortality can be high under adverse
environmental conditions.

The continued emphasis in modern
agriculture on the production of neonates
throughout the year, including times of
inclement weather and limited feed (late
winter and early spring calving in beef
herds in northern climates), the emphasis
on short calving seasons, the use of high
stocking densities, the production of
animals with high muscle growth poten-
tial, which may be associated with an
increased incidence of dystocia resulting
in decreased vitality of newborn animals
at birth, all appear to combine to increase
the incidence of mortality due to hypo-
thermia and related diseases of the
neonate.

In lambs, more than 30% of deaths
occur in the first few days of life and
mortalities may be greater than 10%, with
more than half of the losses due to
hypothermia from either exposure or
starvation. In calves, approximately 50%
of deaths occur within 48 hours of birth

Hypothermia, hyperthermia, fever

41

and most losses are either directly due to,
or follow, dystocial parturitions where still-
births and early postnatal mortality rates
are about 20% compared with less than 5%
in calves bom without dystocia (eutocial). 3

Thermoregulation in neonatal farm
animals

Response to cold stress
Neonatal ruminants, compared with
many altricial neonatal mammals, are
precocial in their development, with well
developed thermoregulatory mechanisms
that allow them to maintain homeothenny
in many environments. 3 Prolonged expo-
sure to heat or cold induces hormonal
and metabolic changes specific to each
stress. This involves secretion of gluco-
corticoid hormones and increased activity
of the sympathetic nervous system
augmented by increased secretion of
catecholamines. The principal metabolic
effect of these increases is greater avail-
ability and utilization of substrates (fat,
glycogen and protein) for catabolism,
with increased production of heat.

Cold-induced thermogenesis
This is achieved by shivering thermo-
genesis in skeletal muscle tissue and non-
shivering thermogenesis in brown adipose
tissue. Shivering thennogenesis consists
of involuntary, periodic contractions of
skeletal muscle. Heat is produced during
contraction of muscle bundles in skeletal
muscle tissue that has increased in tone
as well as in skeletal muscle contracting in
overt tremors. Increased heat production
in neonatal calves in the first several
hours after birth can be significant when
the animals first stand for 10 minutes; this
effect is reproduced later when the calves
are stronger and stand for longer periods.
The principal site of cold-induced non-
shivering thermogenesis in animals is
brown adipose tissue, which is present in
neonatal lambs, kids and calves but not in
piglets. In neonatal lambs, approximately
40% of the thermogenic response during
summit metabolism is attributed to non-
shivering thermogenesis, with the
balance of about 60% attributed to j
shivering thermogenesis.

Control of heat loss

The insulative nature of the external hair
coat and cutaneous tissues to resist non-
evaporative heat loss during cold expo-
sure is critical in maintaining homeothenny.
Total thermal insulation is the sum of
tissue insulation and external insulation.

Tissue insulation. This is the resist-
ance of cutaneous tissue to conductive
heat loss from the body core to the skin
surface. Tissue insulation is influenced by
subcutaneous fat depth, which is minimal
in neonates, and by vasoconstriction.
Tissue insulation increases with age.

External insulation. This is the thermal
resistance of the hair coat and air interface
to radiative, convective and conductive
heat losses from the skin surface to the
environment. External insulation is a
function of length and type of hair coat
and the air interface. When exposed to
dry, cold, still air environmental conditions,
external insulation as a proportion of total
thermal insulation in neonatal calves
ranges from 65-75%. Moisture and mud
in the coat decrease the value of external
insulation; wind and rain can also decrease
external insulation.

The neonate's total thermal resistance
to heat loss is a function of the physical
properties of the skin and hair coat and
the ability to induce vasoconstriction of
cutaneous blood vessels and piloerection
of the hair coat. Neonatal calves are
remarkably cold-tolerant in a dry, still air
environment. The thermal demand of an
outdoor cold environment is a function
of wind and precipitation as well as
ambient temperature.

Conductive heat loss is controlled by
sympathetic regulation of blood vessels
that supply cutaneous tissues, especially
the ears and lower extremities. In response
to cold, vessels constrict, peripheral blood
flow diminishes and heat transfer is
limited. Vasoconstriction of cutaneous
vessels during cold exposure occurs first
in the ears, followed by the lower
extremities and then the skin surrounding
the trunk. Phasic vasodilation in the
skin of the ears and distal extremities at a
point near freezing occurs by the sudden
opening of arteriovenous anastomoses to
permit intermittent warming (called the
hunting reaction). Phasic vasodilation
does not occur on the skin of the trunk.

Thermoregulating mechanisms
! Heat exchange between any homeotherm
and the environment is the result of:

Heat production by metabolism
Insensible heat loss by evaporation of
moisture from the respiratory tract
and skin

Sensible heat transfer by conduction,
convection and radiation.

There is a range in the effective thermal
environment, called the thermoneutral
zone, over which an animal maintains
body temperature with minimal meta-
bolic effort. Within this zone, body tem-
perature is maintained primarily by
varying blood flow to the body surface,
piloerection of the hair coat, behavioral
and postural changes. These responses
adjust the physical processes of heat
transfer to balance the body's heat pro- i
duction. The lower limit of the thermo- S'
neutral zone - the lower critical j
temperature - is the minimum tempera- j

ture that an animal can tolerate without
actually increasing its rate of metabolic
heat production to maintain thermal
balance. 4 The lower critical temperature of
an animal is determined by the animal's
ability to resist heat loss (thermal
insulation) and the animal's resting,
thermoneutral heat production through
metabolism. An increase in thermal
insulation or an increase in thermoneutral
metabolic rate decreases the lower critical
temperature, improving cold tolerance.

Estimates of lower critical tempera-
tures of calves during the first day of life
are not available but some estimates for
older calves include 13°C for 2-day-old
Ayrshire calves and 8-10°C for dairy and
crossbred calves at 1-8 weeks of age. In
lambs, estimates are 37°C and 32°C for
light (2 kg) and heavy (5 kg) birth weights
immediately after birth while still wet
with amnionic fluid, and 31°C and 22°C
when these lambs are more than 1 day
old. 4

Older cattle are much more cold
tolerant, with lower critical temperatures
of 0°C for 1-month-old calves and -36°C
for finishing feedlot cattle. At the lower
border of the cold zone is the cold lethal
limit - the ambient temperature below
which the calf is unable to generate suffi-
| cient heat to offset heat losses required to
I maintain thermal balance, and at which
j hypothermia begins. Prolonged periods
I of exposure below the cold lethal limit will
i result in death. The cold lethal limit also can
i be defined as the ambient temperature
below which heat loss exceeds the
animal's summit or maximal metabolism.

Because published values for lower
critical temperatures assume still air, dry
clean coats, standard radiation and a
standing animal given a maintenance
level of feeding, there are limitations
i to their use. Insulation of extremities
| decreases, and heat loss increases, at
j temperatures below freezing. Thus some
j lower critical temperatures for cattle are
| too low, which means that neonates may
j be affected by cold temperatures not
j normally considered harmful. External
j insulation can change because of changes
: in air velocity and long-wave radiation,
j Behavioral changes of animals may occur
! to minimize heat loss. For example,
j animals may orient towards the wind to
j decrease their profile, and they may seek
I shelter, huddle and change their posture.
Solar radiation varies throughout the
daylight hours depending on the quantity
of cloud. In general, radiation balance is
positive in the day, while at night, when
the skies are clear, the radiation balance is
usually negative. Heat production varies
i with the time of day, time since the last
meal and physical activity. Rain will often
depress intake of feed and illness and

42

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

hypothermia severely depress feed intake,
whereas cold stimulates intake.

Heat production

Heat produced by metabolism varies
directly with the level of feed intake. The
more an animal eats, the greater the heat
increment of feeding. Animals subjected
to cold will increase their feed intake if
given the opportunity. In adults, propor-
tionate dry matter increases of up to 35%
are typical. This increased feed intake is
accompanied by decreased retention time
in the intestine and a decrease in
digestibility of approximately 2.5 g/kg per
8°C decrease in environmental tempera-
ture. Heat is also generated from physical
activity. When newborn calves stand for
the first time and are able to stand for
10 minutes, the energy expenditure is
increased proportionately 30-100%. As
calves become stronger and are able to
stand for more than 30 minutes, heat
production increases by 40%.

Cold thermogenesis

The major source of heat in cold thermo-
genesis, whether it is induced by either
shivering thermogenesis or by non-
shivering thermogenesis, is lipid. Glycogen
is also important for maximum metabolic
rates and for lipid metabolism. For the
neonate, in the first 24 hours there is little
digestion of colostral proteins and little
catabolism of amino acids.

Shivering thermogenesis. This is the
most obvious sign of increased heat pro-
duction of cold thermogenesis.

Nonshivering thermogenesis. Func-
tional brown adipose tissue is present in
newborn calves, lambs and kids, and its
primary function is to generate heat by
nonshivering thermogenesis. The release
of norepinephrine during cold exposure
in neonatal ruminants stimulates increased
blood flow to brown adipose tissue.
Thyroid hormones also have an essential
role in regulating cold thermogenesis.
Glucocorticoids are essential for cold
thermogenesis through the mobilization
of lipid and glycogen to supply energy
substrates. Large deposits of brown
adipose tissue are present in the abdomi-
nal cavity (perirenal), around large blood
vessels and in the inguinal and pre-
scapular areas. In calves, 20 g/kg body
weight (BW) may be present and in lambs
from well-fed ewes, 6 g/kg BW. At
parturition, marked changes occur in both
the neonate's supply and demand for
nutrients. In utero the fetal ruminant is
provided with high levels of carbohydrate
and low levels of fat, whereas after birth it
is provided with colostrum high in fat and
low in carbohydrate. Before colostrum is
fed, the neonatal ruminant depends on
mobilization of tissue glycogen and lipids
to provide energy substrates for basal

metabolism as well as thermogenesis in
shivering muscle tissue and in brown
adipose tissue. The major sources of energy
substrates for thermogenesis in neonatal
ruminants include glycogen and lipid
in liver and muscle because protein
catabolism is minimal during the early
postnatal period.

Summit metabolism. This is the
maximal rate of metabolism which occurs
in response to cold without a decline in
body temperature. The time for which
summit metabolism can be maintained is
usually short, e.g. a few minutes in
neonatal lambs. It is approximately five
times resting metabolic rate and is associ-
ated with increased sympathetic activity
and development of metabolic acidosis
and increased plasma concentrations of
glucose, glycerol, free fatty acids and
lactate. Prepartum hypoxia is likely
associated with postpartum depression
of sympathetic nervous activity and of
thermogenic responses to cold.

Birth weight and summit meta-
bolism. The principal factor which deter-
mines an animal's resting, thermoneutral
metabolism is body size. In newborn
animals, thermoneutral metabolic rates
and summit metabolic rates are pro-
portional to W 1 rather than W 075 , which
means that summit metabolism per unit
of W is similar for all neonates regardless
of size, but lightweight animals have more
surface area per unit of W than heavy-
weight neonates. Therefore, lightweight
neonates have a lower summit metabolic
rate per unit of surface area and, as a
consequence, lightweight neonates will be
less cold-tolerant than heavyweight
neonates. Summit metabolism can be 33%
higher in a 55 kg newborn calf compared to
a 32 kg calf. Thus lightweight neonates
have a more difficult time maintaining
thermal balance during cold stress because
of a lower cold-induced thermogenic rate
per unit of skin surface area than heavier
animals. This, in part, explains the higher
incidence of neonatal mortality in smaller
piglets and lambs, and in smaller calves
born to first-calf heifers, and even to
mature cows.

Factors affecting cold thermogenesis
Several factors affect the ability of the
newborn calf to avoid hypothermia.
Prompt activation of thermogenic mechan-
isms must occur immediately after birth
when the demand for heat production is
usually highest. The development of
functional brown adipose tissue must
occur in fetal life in order to enable calves
to have maximal nonshivering thermo-
genesis during the early postnatal period.
Most of the functional brown adipose
tissue is deposited in late gestation in
lambs and calves.

Ambient temperature and nutrition
during pregnancy can affect cold thermo-
genesis of lambs. Maternal cold exposure
by winter shearing of sheep increases
lamb birth weight independent of changes
in prepartum feed intake. Lambs from
cold-exposed (winter sheared) ewes were
15% heavier at birth, and had 21% more
perirenal adipose tissue that was 40%
more thermogenically active than lambs
from unshorn ewes. Thus newborn lambs
from cold-exposed ewes were more cold-
tolerant. Acute cold exposure during late
gestation increases glucose supply to the
fetus, which stimulates insulin secretion
which in turn promotes fetal growth;
recruitment and proliferation of brown
adipose tissue occurs to enhance cold
tolerance of the newborn lamb. There is
some evidence that prepartum exposure
of pregnant cows to a cold environment
may result in heavier calf weights.

Malnutrition of the dam during late
gestation. This can adversely affect
neonatal calf survival. Prepartum energy
restriction beginning at day 90 of gestation
of ewes can also reduce the proportional
weight of perirenal adipose tissue and
reduce the nonshivering ability of new-
born lambs. The influence of prepartum
nutritional restriction on cold thermo-
genesis in newborn calves is unknown
but prepartum protein restriction during
the last trimester reduced thermoneutral
thermogenic rates by 12% without affect-
ing birth weights, resulting in an estimated
increase in the lower critical temperature.
Maternal malnutrition also adversely
affects the availability of energy substrates
required by the neonate for cold thermo-
genesis. Nutritional restriction of pregnant
ewes reduces total body lipid in fetal
lambs but not muscle or liver glycogen.
Thus, nutritional restriction of the fetus
impairs cold tolerance of the neonate by
reducing body substrate reserves available
for cold thermogenesis and reduces
nonshivering thermogenic capabilities.

European or British breeds of cattle are
also more cold-tolerant and more adap-
table to temperate climates, whereas
Zebu cattle are more adaptable to sub-
tropical climates because of greater heat
tolerance. 4 The lack of cold tolerance of
the newborn Bos indicus calf is associated
with a higher mortality rate in purebred
Brahman herds in the USA. These calves
are less cold-tolerant and more susceptible
to the weak calf syndrome.

Postnatal changes in cold thermogenesis
As calves and lambs grow during the
early postnatal period, heat loss per unit
of body weight declines because of
improveci. thermal insulation and a decrease
in the ratio of skin surface area to body
weight. Nonshivering thermogenesis

Hypothermia, hyperthermia, fever

43

decreases during the first month of age in
lambs and calves, which is associated
with a decrease in summit metabolism.
This coincides with the conversion of
brown adipose tissue to white adipose
tissue by about 10 days after birth. Post-
natal exposure to cold delays the dis-
appearance of brown adipose tissue,
which enhances cold tolerance of the
lamb and calf by delaying the normal
decline in nonshivering thermogenesis.

Risk factors for neonatal
hypothermia

Calves

Beef calves born outdoors during cold
weather are susceptible to hypothermia.
Wind, rain and snow decrease the level of
insulation and increase the lower critical
temperature. Dairy calves born indoors
are not usually exposed to cold environ-
ments that cause hypothermia. Hypo-
thermia (<37°C) has been recognized in
calves reared outdoors in cold climates
and in some calves affected with enteritis. 3

Dystocia can affect cold thermogenesis.
During a normal delivery, fetal hypoxemia
may occur, causing anaerobic glycolysis,
the production of lactic acid and a mixed
respiratory-metabolic acidosis that the
calf can usually compensate for within
hours after birth. In prolonged dystocia, a
metabolic acidosis may occur, which will
inhibit nonshivering thermogenesis and
impair cold tolerance immediately after
birth. Dystocia may result in a weak calf
that has weak teat-seeking activity, a poor
suck reflex and a poor appetite for col-
ostrum, resulting in colostrum deprivation
and hypogammaglobulinemia.

Colostrum supplies passive immunity
to the calf and the nutrients to meet
energy demands during the immediate
postpartum period. In order for the calf to
maintain thermal balance during cold
exposure, it is critical that the calf ingests
colostrum early to provide enough energy
reserves to sustain cold thermogenesis.
Thus it is important that newborn calves
consume adequate colostrum to ensure
adequate passive immunity and to aid in
the maintenance of thermal stability
during the early postnatal period when
rates of heat loss are greatest. The limited
availability of energy substrates from body
reserves also requires that adequate
quantities of colostrum are ingested during
long periods of cold exposure, especially
in neonatal calves at higher risk for
developing hypothermia. The thermo-
neutral maintenance requirements of a
40 kg calf can be met with about 2.4 L of
cow colostrum; an additional 125 mL of
colostrum are required to supply the
energy requirements for every 1°C decrease
in effective environmental temperature
below the lower critical temperature. 3

Young calves to be reared for veal are
usually transported for 1-2 days during
the first 2 weeks of life. These calves are
prone to cold stress because they are very
young and are being fed at a low level
directly after transport. Veal calves arriving
in a veal calf unit are dependent on body
reserves to meet their energy requirement
because of limited feed allowances, and
ambient temperatures should not be
below 14°C immediately after arrival, to
prevent extra mobilization of energy
reserves. 5 The thermal requirements of
these calves are higher during standing
than during lying and the provision of
bedding that stimulates lying will have a
positive effect on thermal requirements. 6

Survival of beef calves born in the USA
can be influenced by ambient temperature. 7
Calving late in spring, compared with
earlier calving during cold winter months,
results in a decreased mortality, especially
in calves born to 2-year-old dams.

Lambs

Cold exposure resulting in hypothermia is
a primary cause of lamb mortality, as seen
when large numbers of lambs die during
or soon after periods of a few hours of low
temperatures (<5°C) with wind and rain,
or after prolonged rain. Deaths in 'bad'
weather cannot necessarily be attributed
with certainty to exposure as a primary
cause, because lambs debilitated for other
reasons, such as starvation, are highly
susceptible to chilling and conditions
such as low birth weight, birth injury and
sparse hair coat all predispose lambs to
cold exposure; under less harsh conditions
such lambs may survive.

Colostrum intake is also critical in
lambs. Under field conditions in the UK it
is estimated that lambs require 180-210 mL
colostrum per kg BW in the first 18 hours
after birth to provide sufficient energy
substrate for heat production. 3 This
colostral requirement exceeds that for
adequate transfer of colostral immuno-
globulins. The thermoneutral and summit
metabolic rates are much higher in lambs
fed colostrum compared with unfed
lambs at 4-5 hours of age. The increased
metabolic rates are attributed to increased
availability of energy substrates from
colostrum: plasma concentrations of
glucose and non-esterified free fatty acids
are doubled from birth to 4 hours of age
in colostrum-fed lambs but remain
unchanged in colostrum-deprived lambs.

The heaviest losses in Australian sheep
flocks, which occur in the form of
'outbreaks' when the weather is very bad,
are due to hypothermia. The high
mortality rates in newborn lambs due to
the effects of cold exposure and starvation 1 f
occur because many of these lambs are
born during the late winter and early

spring, when adverse conditions are most
likely to occur. This is also true in the
northern USA and Canada.The lambs are
often born outdoors in unprotected pens
designed to accommodate a large number
of ewes. Under these circumstances, the
lambs may be severely cold-stressed
because the ambient air temperatures
outside and within the lambing sheds are
often 15°C or less, which is considerably
lower than the critical temperatures
described for heavy- (32°C) and light-
weight (37°C) lambs. Cold- stressed lambs
often become hypothermic because of
excessive heat loss from exposure to
inclement weather and because of heat
production due to severe hypoxia at birth
or to starvation. 8 Factors that further
increase the susceptibility of lambs to
hypothermia include:

® Lambs from ewes in poor condition
® Lambs from young or aged ewes
® Lambs from multiple births
o Lambs from dystocias
■ Lambs with a low birth weight or

born prematurely

° Breed differences in susceptibility to

cold

® Length of the birthcoat
® Wetting of the birthcoat
® Exposure to wind.

The effects of experimental cold stress
(0°C and -10°C) on pregnant ewes during
the last weeks of gestation and their
lambs of up to 3 days of age have
been examined. 9 In general, ewes were
unaffected by treatment. Cold-induced
changes in lambs included physical
weakness, depression and poor nursing
response. Serum concentrations of glucose
and insulin decreased and cortisol
increased. The mortality rate was 40% in
stressed lambs and 10% in lambs kept at
the warmer temperatures. 9 Cold-exposed
lambs had reduced amounts of adipose
tissue in perirenal areas and extensive
subcutaneous hemorrhages and edema in
the distal portions of the thoracic and
pelvic limbs.

Wetness of the fleece is amajorfactor
in determining whether or not lambs
become hypothermic. Wet lambs suffer a
reduction in coat insulation, primarily as a
result of reduced coat depths, but this
effect is small compared with the increase
in evaporative heat loss which occurs as a
result of wetting. Lambs exposed to
experimental air movement from a fan
produce more body heat than those in
still air, and differences in resistance to
cold stress between single and twin lambs
are largely caused by the corresponding
differences in body weight and coat
depth.

The relative importance of environ-
mental and maternal factors is not easy to

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

determine. Inclement weather kills many
lambs, probably more than would other-
wise die, but principally those that are at
risk because of reduced vigor - dependent
upon poor preceding nutrition - or
because of poor mothering - itself as
dependent on poor nutrition of the ewe
as on her inherited lack of mothering
ability. The vigor of the lamb, principally
manifested as 'sucking drive', is reduced
by lack of reward, so that a vicious cycle is
created if the ewe will not stand. Vigor is
also greatly reduced by cold discomfort,
giving inclement weather two points at
which it influences lamb survival rates.
The lamb dies of hypothermia and
inanition.

Piglets

At birth, the newborn piglet experiences a
sudden and dramatic 15-20°C decrease in
its thermal environment. Because the
newborn pig is poorly insulated, main-
tenance of homeothermia depends almost
exclusively on its capacity to produce
heat. Unlike most other mammals the
newborn pig does not possess brown
adipose tissue. 10 Consequently, neonatal
pigs are assumed to rely essentially on
muscular thermogenesis for thermo-
regulatory purposes. Newborn pigs shiver
vigorously from birth because it is the
main heat-producing mechanism and the
thermogenic efficiency of shivering
increases during the first 5 days of life. 10

Thermoregulation in the newborn
piglet is important in the first 2 days. 11
Metabolic heat production and rectal
temperature increase and the develop-
ment of adequate thermal insulation
helps to withstand the effects of a cold
environment. Body reserves are important
for the piglet to survive in the first few
hours and glycogen and fat reserves are
utilized as major energy substrates for heat
production within the first 12-24 hours.
Thus ingestion of colostrum is crucial.
Coldness impairs the development of
thermostability and induces hypothermia,
which diminishes the vigor of the piglet
and reduces colostrum intake and
immunoglobulins. Thus the need for a
high ambient temperature for piglets in
the first several days of life.

Foals

Newborn foals that are premature, dys-
mature or affected with neonatal mal-
adjustment syndrome cannot maintain
their rectal temperatures at normal values
during the first few hours after birth
under the environmental conditions
usually encountered within foaling boxes
in the UK. 12 Their overall mean metabolic
rate is about 25% below the mean value
for recumbent healthy foals.

This difference in resting metabolic rate
affects the lower critical temperature - the

air temperature below which heat loss
exceeds resting heat production. The
lower critical temperature for healthy
foals is estimated to be about 10°C and
for sick foals is about 24°C. When wet
with amniotic fluid, the lower critical tem-
perature probably will be much higher.
Covering these foals with rugs and
providing thermal radiation using radiant
heaters would increase the lower critical
temperature.

Premature foals are the most com-
promised compared to dysmature and
those with neonatal maladjustment
syndrome. They have small body masses,
the lowest rates of metabolism and the
lowest rectal temperature. Premature
foals are also likely to be deficient in
energy reserves and thermal insulation, in
addition to immaturity of organ systems,
which could limit further energy avail-
ability. Colostrum intake is also crucial
to their survival.

Post-shearing hypothermia in sheep

Sudden unpredicted summer rainfall can
cause high mortality due to hypothermia
in newly shorn sheep. 13 A fall in body
weight in the period immediately
preceding shearing is another major risk
factor. It is estimated that in Australia
0.8 million sheep die annually during the
first 14 days after shearing and many of
the deaths are associated with cold, wet,
windy weather. Overall, crude mortality
rates can range from 12-34% for sheep up
to 28 days after shearing. In outbreaks in
Australia in January the mean tempera-
ture can be 10°C, with a high rainfall and
high wind velocity, accounting for a wind
chill factor (a function of temperatures,
rain and wind velocity). Other factors that
increase heat loss include sunshine versus
cloud, and the depth of the wool cover.
The speed of the wind at the location of
the animals varies greatly depending on
the presence of protective windbreaks
such as trees.

Cold environments and animal
production

Farm animals maintain a relatively con-
stant body core temperature during
exposure to the extreme range of thermal
environments experienced in countries
such as Canada. 14 The severity of the
winter is particularly challenging.
Homeothermy is achieved by physio-
logical and behavioral mechanisms that
modify either rates of heat loss from the
body or the rate at which heat is produced
by metabolism of feed or body energy
reserves. Despite the extremely cold
temperatures that occur in most of the
agricultural regions of Canada, the effec-
tive severity of extremely cold tempera-
tures is reduced because of the dryness of
the frozen environment and the effective

external insulation of the animal's hair
coat. The influence of wind can add to
cold stress and the provision of shelter
from wind by natural tree shelter belts or
manmade structures such as porosity
fences is required.

Prolonged exposure to cold results in
subtle adaptation of hormonal and meta-
bolic responses. Acclimatization to cold
and winter conditions generally has little
long-term effect on energy metabolism
but increases thermal insulation and
appetite. During prolonged exposure of
cattle and sheep to cold environments
down to -10 to -20°C there is a reduction
in the apparent digestibility of the diet. 14
To offset the lowered digestibility, the
animals would accordingly need to con-
sume more feed to achieve a similar
digestible energy intake when kept out-
doors during winter than if they were
kept in a heated barn.

PATHOGENESIS

Sudden exposure of neonatal animals at
birth and during the first few days of life
to cold ambient temperature results in
subnormal body temperature, shivering
and decreased cardiac output, heart rate
and blood pressure. This results in muscular
weakness and mental depression, respir-
atory failure, recumbency and a state of
collapse and, eventually, coma and death.
The entire body, especially the extremities,
becomes cold and the rectal temperature
is below 37°C and may drop to 30°C in
neonates. Cold injury or frostbite of the
extremities may occur in extremely cold
conditions. Nonshivering induced thermo-
genesis may occur, resulting in depletion
of brown adipose tissue deposits. The
neurological signs of convulsions seen in
some cases of hypothermia have not been
adequately explained. 15 The nervous signs
observed in piglets with an inadequate
intake of milk and exposed to cold
environmental temperature are probably
due to a marked hypoglycemia.

In newborn lambs carbohydrate and
lipid are the major energy substrates for
heat production because protein catabolism
is minimal during the first day after
birth. 16 Liver glycogen concentrations
increase markedly during the last few
days before normal parturition. The
amount of liver and skeletal muscle
glycogen available in the newborn lamb
at birth determines how long it can avoid
hypoglycemia and hypothermia if not fed.
The amount of lipid present in the new-
born lamb can also affect the duration of
the glycogen reserves. In growth-retarded
lambs, lipid availability is decreased and
glycogen exhaustion occurs earlier than
normakSuch lambs are highly susceptible
to hypothermia but this can be minimized
by the early ingestion of colostrum, which

Hypothermia, hyperthermia, fever

45

is rich in lipid and extends the availability
of glycogen.

Deaths are the result of excessive body
cooling due to low temperature, driving
winds and starvation. Wetness may or
may not be involved. The starvation
results indirectly from poor mothering by
the ewe, either because she is a poor
mother, because the weather interferes
with mothering or because the lamb is
weak owing to poor antepartum nutrition.
These lambs often walk after birth but at
postmortem examination there is little to
see. They may have sucked but there is
little digestion and the intestine on the
recumbent side is flaccid. There are also
subcutaneous hemorrhages of the limbs
and depletion of brown fat stores.

Hypothermia secondary to other
diseases is due to failure of the thermo-
regulation mechanism and is usually
accompanied by varying degrees of shock
and the inability to invoke shivering
thermogenesis.

CLINICAL FINDINGS

A decrease in body temperature to below
37°C represents hypothermia for most
farm animal species. Weakness, decreased
activity, cold extremities and varying
degrees of shock are common. Bradycardia,
weak arterial pulse and collapse of the
major veins are characteristic. The mucous
membranes of the oral cavity are cool and
there is a lack of saliva.

Neonatal hypothermia

Body temperatures may be as low as 35°C
in neonatal calves, piglets, lambs and
foals exposed to a cold environment
within hours after birth or follow-
ing 12-24 hours of profuse diarrhea
accompanied by marked dehydration and
acidosis. However, acute dehydration
in a thermoneutral environment is
accompanied by a mild increase in rectal
temperature. In the early stage of hypo-
thermia, affected animals may be
shivering and trembling and the skin of
•their extremities and ears feels cool to
touch. Hypothermic piglets will attempt
to huddle together, are lethargic, do not
suck and eventually become recumbent
and die. Hypothermic calves exposed to a
cold environment will assume sternal
recumbency, lie quietly, will have a weak
suck reflex and will die in a few hours. In
later stages, further weakness leading to
coma is common. Tire mucous mem-
branes of the oral cavity are cool and may
be dry. The heart rate is commonly slower
than normal and the intensity of the heart
sounds decreased. Death is common
when the body temperature falls below
35°C but field observations indicate that
the temperature may fall below 30°C and
animals still survive if treated intensively.

Shorn sheep hypothermia

Sheep with hypothermia associated with
recent shearing and inclement weather
have a range of body temperatures from
35-38°C. They huddle in tight groups and
the animals that cannot maintain sufficient
heat will become weak, recumbent and die
within a few hours. They may be found in
lateral or sternal recumbency, with their
heads back over their shoulders. Palpebral
reflexes are decreased, skin and extremities
are cold, mucous membranes are pale to
white and generalized weakness similar
to circulatory collapse is common.

Hypothermia secondary to other
diseases

The hypothermia secondary to other
diseases is usually not marked and there
are clinical findings related to the under-
lying illness. Hypothermia is common in
diseases such as milk fever in cattle but
returns to normal within a few hours after
successful treatment with calcium salts.
Successful treatment of the primary
disease will usually return the tempera-
ture to within the normal range.

CLINICAL PATHOLOGY

Clinical pathological examinations are
usually not done because the diagnosis is
frequently obvious and the variability
in biochemical changes make them of
limited value in reaching a diagnosis of
hypothermia. The serum concentrations
of glucose, non-esterified fatty acids and
immunoglobulins are commonly reduced,
and hypoglycemia may be profound. How-
ever, the glucose concentration depends
on the level of starvation that coexisted
with the hypothermia. In starvation-
induced depletion of body lipid and
glycogen reserves, there is a depression in
cold thermogenesis and subsequent
hypothermia. In neonatal calves and
lambs with hypothermia caused by
excessive heat loss during short cold
exposure, the serum concentrations of
glucose, non-esterified fatty acids and
immunoglobulins may be at adequate
levels. Hemoconcentration, azotemia and
metabolic acidosis may occur.

Necropsy findings

Lesions associated with hypothermia
depend on the duration and severity of
the hypothermia. Fatal hypothermia in
lambs and calves is characterized by an
absence of lesions. A relative absence of
milk in the abomasum is common.
Experimental cold stress may result in
subcutaneous edema of the ventral body
wall and subcutaneous edema and
hemorrhages of the extremities. Marked
reductions in the amount of perirenal
adipose tissue may be obvious. However,
intense cold exposure of short duration
may cause death of calves with no signifi-

cant changes in the visual appearance of
perirenal, pericardial or cardial adipose
tissue depots.

TREATMENT

Hypothermic newborn lambs

A system for the detection and treatment
of hypothermia in newborn lambs can
improve the survival rate. 17 Most lambs
become hypothermic within 5 hours or at
more than 12 hours after birth. Hypo-
thermia in the first 5 hours of life is most
commonly caused by a high rate of heat
loss from the wet newborn lamb, whereas
a depressed rate of heat production con-
sequent to starvation is the most common
cause in the older lamb. Twin and triplet
lambs are more susceptible to hypothermia
than singles because of lower body
energy reserves; the ewe takes longer to
lick diy two or three lambs, and the milk
requirement of two or three lambs is
higher than that of a single lamb and
starvation is more likely.

Using an electronic thermometer, the
body temperature of any weak or suspect
lamb is taken. 18 Lambs of any age with
mild hypothermia (37-39°C) are dried off
if necessary to reduce heat loss, given ewe
or cow colostrum by stomach tube and
placed in a sheltered pen with the ewe.
Lambs less than 5 hours of age with
severe hypothermia (<37°C) are dried off
and given an intraperitoneal injection of
20% glucose at a temperature of 39°C. A
large lamb (>4.5 kg) is given 50 mL, a
medium lamb (3.0-4.5 kg) 35 mL and a
small lamb (<3.0 kg) 25 mL. Hypothermic
lambs are then placed in warming pens,
measuring 2 x 2 m and made of hori-
zontally laid straw bales, two bales high.
The pen is divided horizontally into two
chambers by a sheet of weld mesh upon
which the lambs lie. Warm air, at 38-40°C,
is blown into the lower chamber from a
domestic heater, and a sheet of polythene
fitted over the entire pen retains the heat.
When the lamb's temperature reaches
37°C, it is removed from the warmer and
immediately fed ewe or cow colostrum by
stomach tube at a rate of 50 mL/kg BW.
Any lamb that is vigorous and able to
suck is returned to its ewe in a sheltered
pen and monitored over the next several
hours. Colostrum can be hand milked
from the ewe after administration of
oxytocin.

The immersion of hypothermic lambs
in water at 38°C can result in the recovery
to an euthermic state in about 28 minutes
at a reduced expense in metabolic effort
by lambs. However, this requires extra
Jabor and lambs must be quickly dried,
'otherwise the heat loss is exaggerated
after removal from water because of the
wet fleece.

46

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Hypothermic newborn calves

Clinical management of hypothermic
newborn calves is similar to that of lambs.
Supplemental heat must be provided
immediately. Rewarming can be done
in small, enclosed boxes bedded with
blankets and heat provided by infrared
heat lamps. Colostrum or milk should be
warmed to 40°C and intubated using an
esophageal feeder. Fluids given intra-
venously must be warmed; one practical
method requires submersion of the
intravenous line in a sustained source of
warm water. Intravenous dextrose (1 mL
of 50% dextrose/kg BW) should be
routinely administered to all hypothermic
calves because most have moderate to
severe hypoglycemia. This dosage rate of
50% dextrose will increase the serum
glucose concentration of the calf by
approximately 100 mg/dL, assuming that
the extracellular fluid space is 50% of the
calf's body weight. The rectal temperature
should be taken every 30 minutes during
treatment to assess progress.

A more aggressive rewarming technique
involves the repeated administration of
warm (40°C) 0.9% NaCl enemas via a
flexible soft tube; a 20-30F Foley catheter
works well in this regard when it is
advanced through the anus and the bulb
inflated to maintain the catheter in the
rectum. Rectal fluid should be aspirated
before infusing additional fluid volumes
via the Foley catheter in order to
maximize the warming ability of enema
fluids. Use of enema fluids as part of the
rewarming protocol makes it more
difficult to monitor the increase in body
temperature. Whether immersion of hypo-
thermic calves in water at 38-40°C is
beneficial has not been determined, but
immersion presents practical difficulties.

Hypothermic newborn foals

The clinical management of sick foals that
are prone to hypothermia is presented
below under Control.

Hypothermic newborn piglets

Hypothermic piglets must be placed in a
warming box with a heat lamp and
treated with intraperitoneal adminis-
tration of glucose for the hypoglycemia.
The subject is presented in additional
detail in Chapter 3.

CONTROL

Control and prevention of hypothermia is
dependent on providing the necessary
surveillance at the time of parturition in
animals being born in cold environments.
Early recognition and treatment of animals
with diseases leading to hypothermia is
also necessary.

Lambs and calves

Prevention of hypothermia in calves
depends on the planning and implemen-

tation of effective management strategies
that will limit the risk factors known to
predispose newborn calves to hypothermia
and starvation. Management strategies to
prevent hypothermia from excessive heat
loss are most important in the first
24 hours after birth. They include
changing the calving season to a warmer
time of the year to minimize exposure to
severe weather. Measures to minimize
excessive heat loss include providing a
dry, draft-free environment for calving and
lambing. Providing a protective shelter for
beef cow/calf pairs for calving and during
the first week after birth can reduce
mortality from hypothermia. In extensive
beef cow/calf herds, calf huts large enough
for 8-10 calves provide excellent shelter
from wind, rain and snow.

The provision of adequate surveillance
and assistance at the time of lambing or
calving is necessary to minimize the
incidence of dystocia and its consequences
for the neonate. The ingestion of ade-
quate quantities of colostrum, beginning
as soon after birth as possible, is important
in order to provide immunoglobulins and
energy sources for the neonate.

Piglets

The newborn piglet requires an adequate
intake of colostrum within a few hours
after birth, continued intake of milk after
the colostral period, a warm external
environment of 30-34°C for at least the
first 3 days of life (with heat lamps) and
protection from traumatic injuries such as
crushing by the sow. Sows do not
instinctively remove the amniotic fluid
from the surface of piglets; it is removed
by contact with other surfaces or by
evaporation. Smaller than normal or
weak piglets should be dried manually to
minimize excessive heat loss. Cross-
fostering is used when gilts or sows have
large litters that they cannot nurse
adequately.

Sick foals

Sick foals are prone to hypothermia but
cold stress can be reduced by good
management procedures, including the
following; 12

0 The foal should be housed in an
environment with minimal drafts, in
which the air temperature is
controlled at a steady value, set
according to the foal's needs. Air
temperature should be at, or a few
degrees above, the lower critical
temperature. This temperature may
exceed 24°C for a sick, uncovered,
recumbent foal. Radiant heaters are
useful but should not be placed too
close to the foal

0 Excessive moisture should be
removed from the foal's hair coat

immediately after birth. A sick foal
that cannot increase its metabolic rate
is particularly susceptible to cold
stress when wet with amniotic fluid 19

0 Additional insulation with foal rugs
and leg bandages will reduce heat
loss from the dry body surface. The
dry sick foal needs an additional
10 mm of insulation for each 10°C
decline in air temperature below
24°C. Because sick foals are
recumbent, they should lie on a
heated pad or on thick bedding
material to minimize heat loss by
conduction to the floor

0 Energy intake should be sufficient to
sustain resting metabolism and can be
given by the oral or parenteral route

• Frequent monitoring of both rectal
and air temperature, as well as energy
intake, will assist in the diagnosis of
thermal stress, so that appropriate
action can be taken. A lack of
shivering does not indicate an
absence of cold stress.

REVIEW LITERATURE

Close WH. Thermoregulation in piglets: environmental
and metabolic consequences. In: Neonatal
survival and growth. Occasional Publications No.

15. London: British Society of Animal Production,
1992: 25.

Rowan TG. Thermoregulation in neonatal ruminants.
In: Neonatal survival and growth. Occasional
Publication No. 15, British Society of Animal
Production, 1992: 13-24.

Christopherson RJ. Overcoming climatic constraints.
In: Martin J (ed.) Animal production in Canada.
Edmonton, Alberta: University of Alberta Press,
1993: 173-190.

Carstens GE. Cold thermoregulation in the newborn
calf. In: Perinatal mortality in beef herds. Vet Clin
North Am, Food Anim Pract 1994; 10: 69-106.

REFERENCES

1. Duran O.Vet Rec 1997; 140:240.

2. Arbuckle JBR. Vet Rec 1995; 136:156.

3. Rowan TG. In: Varley MA, ed. Neonatal survival
and growth. Occasional Publication No. 15.
Penicuik: British Society of Animal Production,
1992: 13-24.

4. Carstens GE.Vet Clin North Am FoodAnim Pract
1994; 10:69.

5. Schrama JW et al. J Anim Sci 1993; 71:1761.

6. Schrama JW et al. J Anim Sci 1993; 71:3285.

7. Azzam SM et al. J Anim Sci 1993; 71:282.

8. Hancock RD et al. Trop Anim Health Prod 1996;
28:266.

9. Olson DP et al. CanVet J 1987; 28:181.

10. Berthon D et al. J Therm Biol 1994; 19:413.

11. Close WH. In: \forley MA, ed. Neonatal survival and
growth. Occasional Publication No. 15. Penicuik:
British Society of Animal Production, 1992: 25.

12. OuseyJC etal.Vet J 1997; 153: 185.

13. Glass MH, Jacob RH. AustVet J 1992; 69:142.

14. Christopherson RJ. In: Martin J (ed.) Animal
production in Canada. Edmonton, Alberta:
University of Alberta Press, 1993: 173.

15. Green SL. Equine Vet Educ 1994; 6:44.

16. Mellor DJ, Cockburn F. Q J Exp Physiol 1986;
71:361.

17. Eales^FA et al.Vet Rec 1984; 114:469.

18. Eales ?A et al.Vet Rec 1982; 110:118.

19. McArthur AJ, Ousey JC. J Therm Biol 1996; 21:43.

Hypothermia, hyperthermia, fever

47

HYPERTHERMIA (HEAT STROKE
OR HEAT EXHAUSTION)

Hyperthermia is the elevation of body
temperature due to excessive heat pro-
duction or absorption, or to deficient heat
loss, when the causes of these abnor-
malities are purely physical. Heat stroke
(heat exhaustion) is the most commonly
encountered clinical entity.

ETIOLOGY

The major causes of hyperthermia are the
physical ones of high environmental
temperature and prolonged, severe
muscular exertion, especially when the
humidity is high, the animals are fat, have
a heavy hair coat or are confined with
inadequate ventilation, such as on board
ship or during road transportation. Fat
cattle, especially British beef breeds, can
be overcome by the heat in feedlots.
Brahman cattle in the same pen may be
unaffected. Angora goats are much more
sensitive to high environmental tempera-
tures than sheep, especially when they are
young. 1 The original concept of sunstroke
as being due to actinic irradiation of the
medulla has now been discarded and all
such cases are now classed as heat stroke.

High environmental temperature

The upper border of the thermoneutral
zone - the upper critical temperature -

is the effective ambient temperature
above which an animal must increase
heat loss to maintain thermal balance.
The upper critical temperature in sheep
with a light wool coat on board ship
appears to be 35°C (95°F) at a humidity of
33-39 mmHg (4.4-5. 2 kFh) vapor pressure.
Differences between breeds of animal in
their tolerance to environmental high
temperatures, exposure to sunlight and
exercise are important in animal manage-
ment and production. Water buffalo have
been shown to be less heat-tolerant than
Shorthorn steers, which were less tolerant
than Javanese Banteng and Brahman
crossbreds - the last two appear to be
equally tolerant. The differences appear to
be at least partly due to capacity to increase
cutaneous evaporation under heat stress.

There are similar differences in heat
tolerance between lactating and non-
lactating cows; lactating animals show
significantly greater increases in rectal
temperature and heart and respiratory
rates when the environmental tempera-
ture is raised. This is primarily a result of
the greater dry matter intake and heat of
fermentation in dairy- tattle that must be
dissipated. Heat stress is therefore an
important production-limiting disease
when dairy cattle are kept in conditions of
high heat and humidity.

Rested, hydrated horses are well able
to maintain homeothermy in the hottest

environmental conditions. Their most
efficient mechanism in ensuring that
body temperature is kept low is their
capacity for heavy sweating.

Other causes of hyperthermia

0 Neurogenic hyperthermia - damage
to hypothalamus, e.g. spontaneous
hemorrhage, may cause hyperthermia
or poikilothermia

0 Dehydration - due to insufficient
tissue fluids to accommodate heat
loss by evaporation
8 Excessive muscular activity - e.g.

strychnine poisoning
8 Miscellaneous poisonings, including
levamisole and dinitrophenols
° Malignant hyperthermia in the
porcine stress syndrome
0 Hyperkalemic periodic paresis in
horses

• Fescue toxicity in ruminants and
horses

° Cattle with hereditary bovine
syndactyly

0 Administration of tranquilizing drugs
to sheep in hot weather
“ Specific mycotoxins, e.g. Claviceps
purpurea, Acremonium coenophialum,
the causes of epidemic hyperthermia.
Bovine idiopathic hyperthermia in
cattle in Australia may be due to
Claviceps purpurea 2
° Iodism

° Sylade (possibly) poisoning.

PATHOGENESIS

The means by which hyperthermia is
induced have already been described. The
physiological effects of hyperthermia are
important and are outlined briefly here.

Unless the body temperature reaches a
critical point, a short period of hyper-
thermia is advantageous in an infectious
disease because phagocytosis and
immune body production are facilitated
and the viability of most invading organ-
isms is impaired. These changes provide
justification for the use of artificial fever to
control bacterial disease. However, the
metabolic rate may be increased by as
much as 40-50%, liver glycogen stores are
rapidly depleted and extra energy is
derived from increased endogenous
metabolism of protein. If anorexia occurs
because of respiratory embarrassment
and dryness of the mouth, there will be
considerable loss of body weight and lack
of muscle strength accompanied by
hypoglycemia and a rise in nonprotein
nitrogen.

There is increased thirst due in part to
dryness of the mouth. An increase in
heart rate occurs due directly to the rise in
blood temperature and indirectly to the
fall in blood pressure resulting from
peripheral vasodilatation. Respiration
increases in rate and depth due directly to

the effect of the high temperature on the
respiratory center. An increased respir-
atory rate cools by increasing salivary
secretion and the rate of air flow across
respiratory epithelial surfaces, thereby
increasing the rate of evaporative cooling.
Urine secretion is decreased because of
the reduced renal blood flow resulting
from peripheral vasodilatation, and
because of physicochemical changes in
body cells that result in retention of water
and chloride ions.

When the critical temperature is
exceeded, there is depression of nervous
system activity and depression of the
respiratory center usually causes death by
respiratory failure. Circulatory failure also
occurs, due to myocardial weakness, the
heart rate becoming fast and irregular. If
the period of hyperthermia is unduly
prolonged, rather than excessive in
degree, the deleterious effects are those of
increased endogenous metabolism and
deficient food intake. There is often an
extensive degenerative change in most
body tissues but this is more likely to be
due to metabolic changes than to the
direct effects of elevation of the body
temperature.

CLINICAL FINDINGS

An elevation of body temperature is the
primary requisite for a diagnosis of hyper-
thermia and in most species the first
observable clinical reaction to hyper-
thermia occurs when the rectal tempera-
ture exceeds 39.5°C (103°F). In most
instances the temperature exceeds 42°C
(107°F) and may reach 43.5°C (110°F). An
increase in heart and respiratory rates,
with a weak pulse of large amplitude,
sweating and salivation occur initially,
followed by a marked absence of sweat-
ing. The animal may be restless but soon
becomes dull, stumbles while walking
and tends to lie down.

In the early stages there is increased
thirst and the animal seeks cool places,
often lying in water or attempting to
splash itself. When the body temperature
reaches 41°C (106 °F) respiration is labored
and general distress is evident. Beyond
this point the respirations become shallow
and irregular, the pulse becomes very
rapid and weak and these signs are
usually accompanied by collapse, con-
vulsions and terminal coma. Death occurs
in most species when the core tempera-
ture exceeds the normal value by approxi-
mately 5°C (8°F). Abortion, may occur if
the period of hyperthermia is prolonged
and a high incidence of embryonic
mortality has been recorded in sheep that
were 3-6 weeks pregnant. In cattle,
breeding efficiency is adversely affected
T by prolonged heat stress and in intensively
housed swine a syndrome known as

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

summer infertility, manifested by a
decrease in conception rate and litter size
and an increase in anestrus, occurs during
and following the hot summer months in
most countries. Sudden exposure of cattle
that are acclimatized to cold temperatures
-20°C; -4°F) to warmer temperature
(20°C; 68°F) results in heat stress. The
respiratory rate may increase from 20 to
200 breaths/min within 1 hour, the heart
rate will increase by 10-20 beats/min and
the temperature will undergo an increase
of 0.5-1. 0°C (33-34°F). The respiratory
rate is the most practical indicator of heat
stress, and a respiratory rate above
70 breaths/min indicates that animals are
suffering heat stress. It is not uncommon
in hot humid climates to see cattle open-
mouth breathing with respiratory rates
exceeding 80 breaths/min during periods
of heat stress. In summary, the pro-
gression of changes in cattle with heat
stress is increased respiratory rate,
rectal temperature and heart rate,
followed by decreased urine concen-
tration (due to increased water intake)
and finally decreased appetite and milk
production.

Affected horses are fatigued and have
profound fluid and electrolyte losses,
characterized by hypotonic dehydration
due to excessive sweating. The resultant
clinical signs include decreased perform-
ance, depression, weakness, increased
heart and respiratory rates, and marked
increases in rectal temperature (usually
exceeding 42°C). Because of the hypo-
natremia, affected horses may lose the
stimulus to drink, thereby exacerbating
their dehydration. In advanced cases, the
skin is dry and hot because sweating is
impaired. Hyperthermic horses that have
been participating in an endurance event
may have synchronous diaphragmatic
flutter as a result of hypocalcemia and
metabolic alkalosis. Coma and death can
occur in extreme cases of hyperthermia
that are not identified and treated until
the condition is advanced.

CLINICAL PATHOLOGY

No important clinicopathological change
is observed in simple hyperthermia.
However, horses with advanced hyper-
thermia typically have hyponatremic
dehydration and azotemia. Horses with
synchronous diaphragmatic flutter are
typically hypocalcemic.

Necropsy findings

At necropsy there are only poorly defined
gross changes. Peripheral vasodilatation
may be evident, clotting of the blood is
slow and incomplete, and rigor mortis
and putrefaction occur early. There are no
constant or specific histopathological
changes.

TREATMENT

The presence of adequate drinking water
is essential and together with shade and
air movement is of considerable assist-
ance when multiple animals are exposed
to high air temperature.

If treatment of individual animals is
necessary because of the severity or
duration of the hyperthermia, affected
animals should be immediately placed in
the shade and hosed on the midline of
the back with cold water so that their
coats are saturated. Fans should be
immediately placed in front of the animal
to promote evaporative cooling, and
cooled water, with and without added
electrolytes, should be made available for
the animal to drink. In severe cases of
hyperthermia where large volumes of
water are not available, very cold water
(2-8°C) should be applied and imme-
diately scraped off because the water
becomes warm almost immediately. The
application of very cold water does not
induce a clinically relevant degree of
peripheral vasoconstriction and has not
been associated with clinically relevant
side effects. Water applied by hose does
not need to be scraped off because heat is
conducted to the applied water stream.
Placement of wet sheets or towels over
the head or neck is not recommended as
they provide unneeded insulation.

The rectal temperature should be
monitored frequently during cooling, and
water application should be stopped
when the rectal temperature has returned
to normal. Because affected animals may
not be interested in or capable of
drinking, the intravenous administration
of fluids such as 0.9% NaCl is indicated in
animals that are weak, recumbent or
dehydrated. Horses often need 20-40 L of
intravenous fluids over the first few hours
of treatment. Horses with synchronous
diaphragmatic flutter should be treated
with intravenous calcium.

Fluids can also be administered orally
to horses, but care should be taken to
ensure that gastrointestinal motility is not
impaired. A practical oral electrolyte
solution is obtained by dissolving 20 g of
table salt (NaCl) and 20 g of Litesalt
(NaCl and KC1) in 5 L of water; this
provides 107, 28, and 132 mmol/L of
sodium, potassium and chloride, respect-
ively. Five L of this fluid can be
administered to an adult horse each hour
by nasogastric tube.

CONTROL

Shade alone is a most important factor in
maintaining the comfort of livestock and
preventing heat stress. Shade reduces the
heat gain from solar radiation and can be
provided by trees or artificially by roofs or
shades made from cloth or artificial

material. Shades should be placed over
feed and where the producer wants the
animals to spend their time. The efficiency
of metal shades can be increased by
painting metal shades white on the
topside and black on the underside. A
north-south orientation will permit
drying under the shades as the shaded
area moves throughout the day; this may
be helpful in decreasing the incidence of
coliform mastitis if sprinklers are used
under the shades and cattle prefer to lie
under the shades than in freestalls.

In dairy and feedlot cattle, the following
measures should be taken to manage
heat stress:

• Provide cool clean water and plenty of
trough space for drinking

• Use shades and intermittent sprinkler
systems (wet time of 1-2 min with an
adequate dry off time of 20-30 min);
continuous application of water
increases the local humidity and
decreases the effectiveness of
evaporative cooling

• Enhance airflow by fans or by
providing mounds for cattle to stand
on

• Adjust rations and feed a larger
percentage of the ration in the
evening when it is cooler

• Minimize handling during periods of
greatest heat stress

• Select cattle based on breed and coat
characteristics, and house the most
susceptible cattle (heavy, black) on
east-sloping lots with the most shade.

In exercising horses, periodic rests in the
shade with fans and water sprinklers and
maintaining a normal hydration status can
be very helpful in preventing heat stress.
Monitoring the heart rate is a useful and
practical method of assessing the degree of
heat stress in horses, in that heart rates
remain elevated for a longer period of time
in horses undergoing heat stress.

If animals have to be confined under
conditions of high temperatures and
humidity, the use of tranquilizing
drugs has been recommended to reduce
unnecessary activity. However, care is
needed because blood pressure falls and
the animals may have difficulty losing
heat if the environment is very hot, and in
some cases may gain heat. Chlorpromazine,
for example, has been shown to increase
significantly the survival rate of pigs
exposed to heat and humidity stress.

REVIEW LITERATURE

Stokka GL, Smith J, Kuhl G, Nichols D. Compend
Contin Educ PractVet 1996; S296-S302.

Foreman JH.The exhausted horse syndrome. Vet Clin
North Am Equine Pract 1998; 14:205-219.
Guthrie AJ, Lund RJ. Thermoregulation. Base
mecli'anisms and hyperthermia. Vet Clin North
Am Equine Pract 1998; 14:45-59.

Hypothermia, hyperthermia, fever

49

REFERENCES

1. McGregor B. AustVet J 1985; 62:349.

2. JessepTM et al. AustVet J 1987; 64:353.

FEVER (PYREXIA)

Fever is an elevation of core body
temperature above that normally main-
tained by an animal and is independent
to the effects of ambient conditions on
body temperature. It is important to
realize that fever is a combination of
hyperthermia and infection or inflam-
mation that results from an elevated set-
point for temperature regulation.

ETIOLOGY

Fevers may be septic, the more common
type, or aseptic, depending on whether or
not infection is present.

Septic fevers

These include infection with bacteria,
viruses, protozoa or fungi as:

• Localized infection such as abscess,
cellulitis, empyema

• Intermittently systemic, as in
bacteremia, endocarditis

• Consistently systemic, as in
septicemia.

Aseptic fevers

• Chemical fevers, caused by injection
of foreign protein, intake of
dinitrophenols

• Surgical fever, due to breakdown of
tissue and blood

® Fever from tissue necrosis, e.g.
breakdown of muscle after injection
of necrotizing material

• Severe hemolytic crises
(hemoglobinemia)

• Extensive infarction

• Extensive necrosis in rapidly growing
neoplasms such as multicentric
lymphosarcoma in cattle

• Immune reactions - anaphylaxis,
angioneurotic edema.

PATHOGENESIS

Most fevers are mediated through the
action of endogenous pyrogens produced
by granulocytes, monocytes and macro-
phages. The most important and best
known endogenous pyrogen is
interleukin-1, produced by monocytes
and macrophages. The febrile response is
initiated by the introduction of an
exogenous pyrogen to the body.
Exogenous pyrogens include pathogens
such as bacteria, viruses, bacterial
endotoxins, antigen-antibody complexes,
hemoglobinemia in a hemolytic crisis,
and many inorganic substances. In hyper-
sensitivity states, soluble antigen-
antibody complexes may act as mediators.
One of the most potent exogenous
pyrogens is the lipopolysaccharide of
Gram-negative bacteria.

Endogenous pyrogens

Endogenous pyrogens are proteins
released from monocytes and, to a lesser
extent, lymphocytes. These proteins were
originally designated as monokines and
lymphokines respectively, but are now
more commonly referred to under the
more general term of cytokines. One of
the pyrogenic cytokines is interleukin-1,
formerly known as lymphocyte activating
factor. Interleukin-1 stimulates
T- lymphocyte proliferation in the presence
of antigen and thereby enhances the
immune response. The mediators between
endogenous pyrogen and the hypo-
thalamus appear to be prostaglandins and
the level of calcium in the hypothalamus
appears to regulate its activity.

Interleukin-1 initiates fever by inducing
an abrupt increase in the synthesis of
prostaglandins, particularly prostaglandin
E 2 , in the anterior hypothalamus. The
elevated prostaglandin levels in the hypo-
thalamus raise the thermostatic set point
and induce the mechanisms of heat
conservation (vasoconstriction) and heat
production (shivering thermogenesis)
until the blood and core temperature are
elevated to match the hypothalamic set
point.

Prostaglandin precursors are believed
to be the chemical mediators of fever
according to the following sequence:

1. Endogenous pyrogens cause the
release of arachidonic acid, with
subsequent synthesis of
prostaglandins

2. Arachidonic acid breakdown products
modulate the hypothalamic
thermoregulatory mechanism,
resulting in an increase in the set
point value

3. Prostaglandin synthetase-inhibitor
antipyretics lower fever by blocking
the synthesis of prostaglandins or
prostaglandin precursors from
arachidonic acid.

A cytokine known as tumor necrosis
factor (TNF) -a reproduces many of the
physiological derangements observed in
septic shock and mediates many of the
deleterious effects of Gram-negative
bacterial infection, including fever.

In addition to their pyrogenic activity,
cytokines mediate the acute phase
response, which is a term now being
used to describe the reaction of animals to
pathogen invasion, tissue injury,
immunological reactions and inflam-
matory processes. During the acute phase
response, the liver increases the synthesis
of certain proteins, whereas albumin
synthesis is reduced. Haptoglobins,
fibrinogen, ceruloplasmin and proteinase
inhibitors have been examined in cattle
with the acute phase response. 1 In this

response, the serum iron concentration
decreases during fever, which inhibits the
growth of certain bacteria that require
iron. Blood concentrations of zinc also
decrease, with a simultaneous increase in
serum copper concentrations. 2 Measure-
ment of acute phase proteins may provide
a basis for monitoring the severity of
some infections and act as an aid in
making a diagnosis. The concentration of
fibrinogen can be a useful addition to
routine hematological determination in
animals. 3

The physiological mechanisms involved
in the production of fever after stimu-
lation by pyrogens must be matured or
sensitized by previous exposure to
pyrogen. Injection of pyrogens into new-
born lambs does not cause fever but
subsequent injections do.

Effect of pyrogens on the
hypothalamus

The effect of bacterial and tissue pyrogens
is exerted on the thermoregulatory center
of the hypothalamus so that the thermo-
static level of the body is raised. The
immediate response on the part of organs
involved in heat regulation is the
prevention of heat loss and the increased
production of heat. This is the period of
increment, or chill, which is manifested
by cutaneous vasoconstriction, resulting
coldness and dryness of the skin and an
absence of sweating. Respiration is
reduced and muscular shivering occurs,
while urine formation is minimal. The
extremities are cold to the touch and the
rectal temperature is elevated and
the pulse rate increased. When the period
of heat increment has raised the body
temperature to a new thermostatic level
the second period of fever, the fastigium,
or period of constant temperature,
follows. In this stage the mechanisms of
heat dissipation and production return to
normal. Cutaneous vasodilatation causes
flushing of the skin and mucosae, sweat-
ing occurs and may be severe, and
diuresis develops. During this period
there is decreased forestomach motility in
ruminants, metabolism is increased
considerably to maintain the body tem-
perature, and tissue wasting may occur.
There is also an inability to maintain a
constant temperature when environ-
mental temperatures vary.

When the effect of the pyrogenic sub-
stances is removed, the stage of
decrement, or fever defervescence,
appears and the excess stored heat is
dissipated. Vasodilatation, sweating and
muscle flaccidityare marked andthe body
temperature falls. The fall in body tem-
perature after the initial rise is accompanied
by a decline in plasma zinc and plasma
total iron concentrations. If the toxemia

50

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

accompanying the hyperthermia is suffi-
ciently severe, the ability of tissues to
respond to heat production or conser-
vation needs may be lost and as death
approaches there is a precipitate fall in
body temperature.

Febrile response

The febrile response, and the altered
behavior that accompanies it, are thought
to be part of a total mechanism generated
to conserve the resources of energy and
tissue being wasted by the causative
infection. The febrile response has major
effects on immune mechanisms. Endo-
genous pyrogens stimulate T-cell prolifer-
ation. The increased body temperature
causes increases in leukocyte mobility,
leukocyte bactericidal and phagocytic
activities, lymphocyte transformation, and
also enhances the effects of interferon
and interleukin -1.

Some possible adverse effects of fever
include anorexia, which can lead to
excessive catabolism if prolonged. Rarely,
extremely high fevers can result in
disseminated intravascular coagulation
and effects on the central nervous system
that may lead to convulsions.

CLINICAL FINDINGS

The effects of fever are the combined
effects of hyperthermia and infection or
inflammation. There is elevation of body
temperature, an increase in heart rate
with a diminution of amplitude and
strength of the arterial pulse, hyperpnea,
wasting, oliguria often with albuminuria,
increased thirst, anorexia, scant feces,
depression and muscle weakness. The
temperature elevation is always moderate
and rarely goes above 42°C (107°F).

The form of the fever may vary. Thus
the temperature rise may be:

° Transient

° Sustained, without significant diurnal
variation

° Remittent, when the diurnal variation
is exaggerated

- 1 Intermittent, when fever peaks last for
2-3 days and are interspersed with
normal periods

c Atypical, when temperature variations
are irregular.

A biphasic fever, consisting of an initial
rise, a fall to normal and a secondary rise,
occurs in some diseases, e.g. in strangles
in the horse and in erysipelas in swine.
The outstanding example of intermittent
fever in animal disease is equine infec-
tious anemia.

In farm animal practice the most
common cause of a fever is the presence
of an inflammatory process such as
pneumonia, peritonitis, mastitis, ence-
phalitis, septicemia, viremia and the like.
The clinical abnormalities that are typical

of the particular disease must be detected
and differentiated in the process of making
a diagnosis. In the absence of physical
causes of hyperthermia, the presence of a
fever indicates the presence of inflam-
mation, which is not always readily
apparent. A fever of unknown origin
occurs commonly in farm animals and
requires repeated clinical and laboratory
examinations to elucidate the location
and nature of the lesion.

In horses, a fever of unknown origin
is characterized by prolonged, unexplained
fever associated with nonspecific findings
such as lethargy, inappetence and weight
loss. In a series of horses with fever of
unknown origin, the cause was found to
be infection in 43%, neoplasia in 22%,
immune-mediated in 7% and miscel-
laneous diseases in 19%. The cause
remained undetermined in 10%. 4

The magnitude of the fever will vary
with the disease process present and it is
often difficult to decide at what point the
elevated temperature is significant and
represents the presence of a lesion
that requires specific treatment. This is
especially true when examining groups of
animals with nonspecific clinical findings
including an elevated temperature. The
typical example is a group of feedlot cattle
affected with depression, inappetence,
dyspnea and fever ranging from
39.5-40. 5°C. The suspected disease may
be pneumonic pasteurellosis but it may
be impossible to make that diagnosis
based on auscultation of the lungs of all
the affected animals. Some of the animals
may have a fever of unknown origin from
which they will recover in a few days
and specific therapy is not required.
Under these circumstances and based
on clinical experience, the tendency
is to make a diagnosis of 'acute
undifferentiated bovine respiratory
disease' or 'undifferentiated fever' in
animals with a temperature > 40.5°C for
2 days in succession. This emphasizes the
need to select an upper threshold value
that indicates a clinically and physio-
logically significant fever.

CLINICAL PATHOLOGY

There are no clinicopathological findings
that are specific for fever. The hemogram
will reflect the changes associated with
the cause of the fever. Inflammation is
characterized by marked changes in the
total and differential leukocyte count
characteristic for each disease. A wide
variety of tests can be performed to
identify the location and nature of the
lesion causing the fever. The most com-
monly used include:

* Microbiologic testing of blood samples
° Analysis of serous fluids from body

cavities

0 Cerebrospinal fluid analysis
G Milk sample analysis
° Reproductive tract secretion analysis
° Joint fluid analysis
0 Biopsies

° Exploratory laparotomy.

Medical imaging may be necessary to
detect deep abscesses.

Necropsy findings

The necropsy findings will be charac-
teristic of the individual disease process
and are commonly characterized by vary-
ing degrees of peracute, acute and chronic
inflammation depending on the severity
of the disease, the length of illness and
whether or not treatment had been given.
In the case of longstanding fevers the
above findings are still characteristic but
they may fluctuate in severity daily or
over longer periods.

Fever must be differentiated from
hyperthermia due to a physical cause
such as heat stroke or exhaustion or
malignant hyperthermia. In fever of
unknown origin, the history, physical
examination, laboratory findings and
epidemiological setting should be
reviewed. Localizing clinical findings may
provide a clue to the body system or
organ involved. Common inflammatory
processes include:

° Abscesses of the peritoneum,
pleura and lungs
° Septic metritis
0 Endocarditis
0 Polyarthritis
° Pyelonephritis.

Many animals are placed in the category
of fever of unknown origin because the
veterinarian overlooks, disregards or
rejects an obvious clue. No algorithms or
computer-assisted diagnostic programs
are likely to solve the diagnostic chal-
lenge. In order to improve the diagnostic
accuracy, veterinarians will have to work
harder. This requires obtaining a detailed
history, repeated physical examinations,
reconsideration of the epidemiological
characteristics of the affected animal,
requesting consultations from colleagues,
and the investment of time to consider
the diagnosis and the circumstances.

TREATMENT
Antimicrobial agents

The most important aspects of the clinical
management of fever should be directed
at its cause. The main objective is to
identify and treat the primary disease.
Antimicrobial agents are indicated for the
treatment of bacterial infections. The
selection of antimicrobial, the route of
administration and the duration of treat-
ment dfepend on the cause of the
infection, its severity and the accessibility

Septicemia/viremia

51

of the lesion to the drug. The use of
antimicrobial agents to prevent secondary
bacterial infections in animals with viral
diseases (e.g. viral interstitial pneumonia)
is controversial and of doubtful benefit.

In animals with a fever of unknown
origin, broad-spectrum antimicrobial
agents seem rational. However, blind
therapy is not recommended because it
may lead to drug toxicity, superinfection
due to resistant bacteria, and interference
with subsequent accurate diagnosis by
cultural methods. In addition, the fall of
the temperature following treatment may
be interpreted as a response to therapy,
with the conclusion that an infectious
disease is present. If such a trial is begun
the response should be monitored daily
to determine effectiveness and continued
efforts should be made to determine the
cause of the fever. In some cases it may be
necessary to surgically remove by drain-
age techniques the source of the infection
located in abscesses or body cavities such
as the pleural cavity.

Antipyretics

Since fever ordinarily does little harm and
usually benefits the animal's defense
mechanism, antipyretic agents are rarely
essential and may actually obscure the
effect of a specific therapeutic agent or of
the natural course of the disease. If the
fever is high enough to cause discomfort
or inappetence, or is so high that death
due to hyperthermia is possible, then
nonsteroidal anti-inflammatory drugs
(NSAIDs) should be administered. Most
NSAIDs, such as flunixin meglumine, are
inhibitors of prostaglandin synthesis and
act centrally to lower the thermoregulatory
set point. Rectal temperatures start to
decline within 30 min of parenteral
NSAID administration but usually do not
completely return to within the normal
physiological range.

REVIEW LITERATURE

Dinarello CA. Interleukin-1 and the pathogenesis of
the acute phase response. N Engl J Med 1984;
311:1413-1418.

McMillan FD. Fever: pathophysiology and rational
therapy. Comp Cont Educ Pract Vet 1985;
7:845-855.

Eckersall PD, Conner JG. Bovine and canine acute
phase proteins. Vet Res Commun 1988; 12:169-178.

REFERENCES

1. Eckersall PD, Conner JG. Vet Res Commun 1988;
12:169.

2. Auer DE et al. Vet Rec 1989; 124:235.

3. Hawkey CM, Hart MG. Vet Rec 1987; 121:519.

4. MairTS et al. Equine Vet J 1989; 21:260.

Septicemia/viremia

Septicemia is the acute invasion of the
systemic circulation by pathogenic bacteria
accompanied by sepsis or septic shock

with possible bacterial localization in
various body systems or organs if the
animal survives. Septicemia is a common
cause of morbidity and mortality in
newborn farm animals which have not
received a sufficient quantity of colostrum
in the first 24 hours after birth. Bacteremia
is different from septicemia in that
bacteremia is not accompanied by sepsis
or septic shock. The difference between
septicemia and bacteremia is one of
degree. In bacteremia, bacteria are pre-
sent in the bloodstream for only transitory
periods and do not produce clinical signs;
for example, a clinically unimportant
bacteremia probably occurs frequently
after rectal examination or other mani-
pulations in which mucosa is disturbed.
In septicemia, the pathogen is present
throughout the course of the disease and
is directly responsible for initiation of the
disease process.

Viremia is the invasion of the systemic
circulation by pathogenic viruses with
localization in various body tissues and in
which the lesions produced are charac-
teristic of the specific virus. Many infections
associated with rickettsias, protozoa and
fungi are also spread hematogenously
throughout the body but do not initiate a
systemic inflammatory response syndrome.

ETIOLOGY

Many different infectious agents can
result in septicemia or viremia. Some of
the notable examples of septicemias and
viremias are outlined below.

All species

Anthrax, pasteurellosis and salmonellosis
are found in all species of food animal.

Neonatal septicemias

Neonatal septicemias are caused most
commonly by Gram-negative bacteria.

Calves

Bacteremia and septicemia are often
associated with Escherichia coli and
Salmonella spp. E. coli is most frequently
isolated from the blood of calves 1 but
Gram-positive infections may be found in
10% of septicemic calves and polymicrobial
infections in 28%. 2 Calf septicemia is
infrequently caused by an Actinobacillus-
suis- like bacteria 3 Thirty percent of severely
ill calves with or without diarrhea are
bacteremic, with the risk of bacteremia
being higher in calves with failure of
transfer of colostral immunoglobulins. 1,4,5

Piglets

Septicemia due to E. coli is possible, also
septicemia with localization in the joints,
endocardium and meninges associated
with Streptococcus suis type 1.

Foals

Septicemia with localization associated
with E. coli, Actinobacillus equuli, Klebsiella

pneumoniae, a-hemolytic Streptococcus,
and Salmonella spp. are seen.

Lambs

Septicemia associated with E. coli occurs
most frequently.

Cattle

Histophilus somni, Pasteurella multocida,
Mannheimia haemolytica, Pasteurella
(Yersinia) pseudotuberculosis, acute and
chronic infections with bovine virus
diarrhea virus and bovine malignant
catarrh are encountered.

Sheep (young lambs)

Histophilus somni is the main pathogen.

Pigs

Hog cholera and African swine fever
viruses and Erysipelothrix insidiosa are
encountered.

Horses, donkeys, mules

African horse sickness andM. haemolytica
infection are implicated.

Secondary septicemias

The principal cause of death in subacute
radiation injury is septicemia resulting
from loss of leukocyte production because
of injury to bone marrow. Septicemia may
also result when there is a congenital
defect in the immune system or when
immunosuppression occurs in older
animals as a result of corticosteroid
therapy or toxin such as bracken.

EPIDEMIOLOGY

Systemic infections associated with
bacteria, viruses, rickettsia, protozoa and
other pathogens occur in animals of all
ages and under many different circum-
stances.The epidemiological characteristics
for each entity are presented under each
disease described in this book. The risk
factors for each infectious disease are
categorized according to:

° Animal risk factors
0 Environmental risk factors
0 Pathogen risk factors.

For example, colostrum-deprived new-
born animals are highly susceptible to
septicemia. 6 Failure of transfer of passive
immunity in foals is defined by serum
IgGj levels of < 400 mg/dL; partial failure
of transfer of passive immunity between
400 and 800 mg/dL. Serum IgG concen-
trations of > 800 mg/dL are less frequently
associated with sepsis in foals and this is
considered the threshold concentration
for prophylaxis in foals.

PATHOGENESIS

Two mechanisms operate in septicemia:
the exotoxins or endotoxins produced
by the infectious agents initiate a pro-
's found toxemia and high fever because of
their initiation of the release of host
mediators and because of the rapidity

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

with which the agents multiply and
spread to all body tissues (see also
Toxemia and Shock. The clinical
manifestations are the result of the effect
of the pathogens on monocytes and
lymphocytes, which initiate the systemic
inflammatory response syndrome.
TNF-a is associated with clinical
septicemia in newborn foals 7 and calves, 8
with plasma TNF-a concentration being
associated with the severity of clinical
signs.

Localization of certain pathogens
occurs in many organs and may produce
severe lesions in animals that survive the
toxemia. Direct endothelial damage and
hemorrhages may also be caused. The
same general principles apply to a
viremia, except that toxins are not pro-
duced by viruses. It is more likely that the
clinical manifestations are the result of
direct injury of the cells invaded by the
virus. Transplacental infection can
occur, resulting in fetal mummification,
abortion, or infection of the fetus that
may be carried to term.

Disseminated intravascular
coagulation

Disseminated intravascular coagulation
(DIC) is common in severe septicemic
disease, especially that which terminates
fatally. It is initiated by vascular injury
with partial disruption of the intima,
caused by the circulation of foreign
materials such as bacterial cell walls,
antigen-antibody complexes and endo-
toxin, with subsequent platelet adherence
and the formation of platelet thrombi.
Once coagulation proceeds, the initial
hypercoagulable state changes to hypo-
coagulation, as clotting factors and
platelets are consumed. The activation of
the fibrinolysis system can be a major
cause of the hemorrhagic diathesis present
in this syndrome.

CLINICAL FINDINGS

The major clinical findings in septicemia
are fever, cardiovascular dysfunction
and shock, and submucosal and sub-
epidermal hemorrhages that are usually
petechial and occasionally ecchymotic.
The hemorrhages are best seen under the
conjunctiva and in the mucosae of the
mouth and vulva. Tachycardia, tachypnea
and shock-induced organ dysfunction
with cardiovascular hypotension, myo-
cardial asthenia and respiratory distress
may occur in severe cases if the pathogen
initiates the release of the host mediators,
causing the systemic inflammatory
response syndrome (SIRS). These fea-
tures are described under Toxemia and
Shock.

Specific signs may occur as the result
of localization of the infection in joints,
heart valves, meninges, eyes or other

organs. The clinical findings characteristic
of each disease in which septicemia and
viremia occur are presented under each
disease heading in this book.

Neonatal septicemia

Neonatal septicemia is common in all
farm animal species from a few hours up
to several days of age. The following
features are common:

° Recumbency
° Depression

° Absence or marked depression of the
suck reflex
° Dehydration
0 Fever
0 Diarrhea

0 Injected or congested mucous
membranes
• Weakness
° Rapid death.

Colostrum-deprived foals are commonly
very ill and become comatose and die
within several hours. Localized infections
in the joints and lungs are frequent in
foals that survive for several days. Septic
polyarthritis is common and is charac-
terized by heat, pain, synovial distension
and lameness. Pneumonia is often observed
and is characterized by dyspnea and
abnormal lung sounds. The survival rate
of foals with confirmed septicemia in one
series was 70%. 9

In calves under 30 days of age with
septicemia clinical findings can include
evidence of shock with cold extremities,
dehydration, weak pulse, prolonged capil-
lary refill time, weakness and recumbency. 2
Findings indicative of localization include
ophthalmitis, neurological abnormalities,
omphalophlebitis and polyarthritis.

Clinical sepsis score
A clinical sepsis score for the early
diagnosis of septicemia in newborn foals
has been evaluated and validated. 10 It
should be recognized that application of
such scoring systems is statistically
flawed, as it assigns equal weights to
predictors and equal weights to change in
severity within a given predictor. Never-
theless, such sepsis scores have been
adopted by some and do have the value of
facilitating the identification of neonates
at risk for being septicemic. A score for
predicting bacteremia in neonatal dairy
calves from 1-14 days of age has also
been suggested to predict clinically
whether a sick calf has bacteremia. 11 The
calves are scored according to degrees of
hydration status, fecal appearance,
general attitude, appearance of scleral
vessels and umbilical abnormality.
However, the sensitivity, specificity and
positive predictive value are too low to be
of diagnostic value. 5

CLINICAL PATHOLOGY
Blood culture

Isolation of the causative bacteria from the
bloodstream should be attempted by
culture. Ideally, blood cultures should be
obtained just before the onset of fever and
from a major vein or any artery. The
standard is three blood cultures or animal
inoculation at the height of the fever. A
minimum of 10 mL of blood (preferably 30
mL) should be collected anaerobically after
aseptic preparation of the venipuncture site
by clipping and scrubbing with povidone
iodine scrub. Blood samples should be
inoculated into a broth medium with the
ratio of blood to broth being 1.10 to 1:20, 12
and the culture bottles should be examined
for growth daily for up to a week. 13 Growth
is manifest as turbidity and possibly by the
presence of hemolysis.

Hemogram

The presence of leukopenia or leuko-
cytosis is an aid in diagnosis and the type
and degree of leukocytic response may be
of prognostic significance.

Plasma fibrinogen concentrations may
be increased. 2 Consumption coagulopathy
is detected by falling platelet counts,
prothrombin and fibrinogen values, and
also by the presence of fibrin degradation
products.

Immunoglobulin status

Low levels of serum protein and
immunoglobulins are associated with
failure of transfer of colostral immuno-
globulins in newborn farm animals with
consequent septicemia due, most com-
monly, to Gram-negative bacteria.

Serology

Serological tests are available for most
infectious diseases described in this book.

Necropsy findings

The lesions will reflect the specific disease
causing the septicemia. Subserous and
submucosal hemorrhages may be present,
together with embolic foci of infection
in various organs accompanied by the
lesions typical of the specific pathogen.

TREATMENT

The principles of treatment are similar to
those described for the treatment of
toxemia, fever and shock, and treatment
should focus on broad-spectrum anti-
microbial agents and general supportive
measures. For neonatal septicemia the
provision of a source of immunoglobulins
by plasma or blood transfusion is necess-
ary when there is failure of transfer of
passive immunity. Whether such treat-
ment alters the mortality rate is uncertain.
Intensive care of the newborn with
septicemia,,is described in Chapter 3.
The frequency of bacteremia (approxi-
mately 30%) is sufficiently high in calves

Toxemia and endotoxemia

53

with diarrhea that are severely ill (as
manifest by reduced suckle reflex,
> 6% dehydration, weakness, inability to
stand, or clinical depression) that affected
calves should be routinely treated for
bacteremia, with emphasis on treating
potential E. coli bacteremia. 1,4,5 Strict
hygienic precautions to avoid spread of
infection are also necessary.

REFERENCES

1. Fecteau G et al. Can Vet J 1997; 38:95.

2. Aldridge BM et al. J Am Vet Med Assoc 1993;
203:1324.

3. DeBey BM et al. JVet Diagn Invest 1996; 8:248.

4. Lofstedt J et al. J Vet Intern Med 1999; 13:81.

5. Constable PD. JVet Intern Med 2004; 18:8.

6. Robinson JA et al. EquineVet J 1993; 25:214.

7. Morris DD, Moore JN. J Am Vet Med Assoc 1991;
199:1584.

8. Basoglu A et al. J Vet Intern Med 2004; 18:238.

9. Raisis AL et al. AustVet J 1996; 73:137.

10. Brewer BD, Koterba AM. EquineVet J 1988; 20:18.

11. Fecteau G et al. CanVet J 1997; 38:101.

12. Kasari TR, Roussel AJ. Compend Contin Educ
Pr act Vet 1989; 11:655.

13. Hariharan, H. et al. CanVet J 1992; 33:56.

Toxemia and endotoxemia

Toxemia is a clinical systemic state caused
by widespread activation of host defense
mechanisms to the presence of toxins
produced by bacteria or injury to tissue
cells. Toxemia does not include the diseases
caused by toxic substances produced by
plants or insects or ingested organic or
inorganic poisons. Theoretically, a diag-
nosis of toxemia can be made only if
toxins are demonstrable in the blood-
stream. Practically, toxemia is often diag-
nosed when the syndrome described
below is present. In most cases there is
contributory evidence of a probable source
of toxins, which in many cases are
virtually impossible to isolate or identify.

The most common form of toxemia in
large animals is endotoxemia, caused by
the presence of lipopolysaccharide cell-
wall components of Gram-negative
bacteria in the blood, and characterized
clinically by abnormalities of many body
systems. Because of the overwhelming
importance of endotoxemia in large
animals with Gram-negative bacterial
infections, the focus of this discussion will
be on endotoxemia. The abnormalities of
endotoxemia include:

° Marked alterations in
cardiopulmonary function
° Abnormalities in the leukon

(neutropenia and lymphopenia) and
thrombocytopenia that may lead to
coagulopathies

° Increased vascular permeability
° Decreased organ blood flow and
metabolism, leading to heart and
renal failure

° Decreased gastrointestinal motility
» Decreased perfusion of peripheral
tissues, leading to shock
• The need for intensive and complex
therapy

° A high case fatality rate.

Current therapeutic regimens are only
moderately successful.

Gram-negative bacteria such as E. coli,
Salmonella spp., Pasteurella spp. and
Histophilus somni, as examples, cause
many diseases of ruminants in which
endotoxemia is common. 1 Varying degrees
of severity of toxemia occur in diseases
such as mastitis, peritonitis, pneumonia
and pleuritis, pericarditis, septic metritis,
septicemia of neonates, myositis,
meningoencephalitis and some enteritides.
Endotoxemia is also one of the commonest
causes of death in horses affected with
gastrointestinal disease due to a physical
obstruction causing strangulation and
ischemic necrosis.

ETIOLOGY OF TOXEMIA AND
ENDOTOXEMIA

Toxins can be classified as antigenic or
metabolic.

Antigenic toxins

These are produced by bacteria and to a
lesser extent by helminths. Both groups of
pathogens act as antigens and stimulate
the development of antibodies. Antigenic
toxins are divided into exotoxins and
endotoxins.

Exotoxins

These are protein substances produced by
bacteria that diffuse into the surrounding
medium. They are specific in their
pharmacological effects and in the anti-
bodies that they induce. The important
bacterial exotoxins are those produced by
Clostridium spp., for which commercial
antitoxins are available. They may be
ingested preformed, as in botulism, or
produced in large quantities by heavy
growth in the intestines, such as in
enterotoxemia, or from growth in tissue,
as in blackleg and black disease.

Enterotoxins

These are exotoxins that exert their effect
principally on the mucosa of the intestine,
causing disturbances of fluid and electro-
lyte balance. The most typical example is
the enterotoxin released by enterotoxigenic
E. coli, which causes a hypersecretory
diarrhea in neonatal farm animals.

Endotoxins

The endotoxins of several species of
Gram-negative bacteria are a major cause
of morbidity and mortality in farm
animals. The endotoxins are lipo-
polysaccharides found in the outer wall of
the bacteria. Endotoxins are released into
the immediate surroundings when the

bacteria undergo rapid proliferation with
production of unused sections of bacterial
cell wall or, most commonly, when the
bacterial cell wall breaks. Endotoxin gains
access to the blood when there is a severe
localized infection, such as a coliform
mastitis in dairy cattle, or a disseminated
infection, such as coliform septicemia in
newborn calves.

Gram-negative bacteria are present in
the intestinal tract as part of the normal
microflora and endotoxins are also
present. The endotoxins are not ordinarily
absorbed through the intestinal mucosa
unless it is injured, as in enteritis or more
particularly in acute intestinal obstruc-
tion. Ordinarily, small amounts of endo-
toxin that are absorbed into the circulation
are detoxified in the liver but, if hepatic
efficiency is reduced or the amounts of
toxin are large, a state of endotoxemia
is produced. Endotoxins may also be
absorbed in large amounts from sites
other than intestine including the mam-
mary gland, peritoneum, abscesses and
other septic foci, or from large areas of
injured or traumatized tissue. The best
known endotoxins are those of E. coli,
which have been used extensively as
models for experimental endotoxemia,
and Salmonella spp.

The most common causes of endo-
toxemia in horses are associated with
diseases of the gastrointestinal tract
including colitis, intestinal strangulation
or obstruction and ileus. 2 Complications
associated with foaling and grain over-
load are also common causes.

Metabolic toxins

These may accumulate as a result of
incomplete elimination of toxic materials
normally produced by body metabolism,
or by abnormal metabolism. Normally,
toxic products produced in the alimentary
tract or tissues are excreted in the urine
and feces or detoxified in the plasma and
liver. When these normal mechanisms are
disrupted, particularly in hepatic dys-
function, the toxins may accumulate
beyond a critical point and the syndrome
of toxemia appears. In obstruction of the
lower alimentary tract there may be
increased absorption of toxic phenols,
cresols and amines that are normally
excreted with the feces, resulting in the
development of the syndrome of auto-
intoxication. In ordinary circumstances in
monogastric animals these products of
protein putrefaction are not absorbed by
the mucosa of the large intestine but when
regurgitation into the small intestine occurs
there may be rapid absorption, apparently
because of the absence of a protective
‘f barrier in the wall of the small intestine.

In liver diseases, many of the normal
detoxification mechanisms, including

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

oxidation, reduction, acetylation and con-
jugation with such substances as glycine,
glucuronic acid, sulfuric acid and cysteine,
are lost and substances which are
normally present in insufficient quantity
to cause injury accumulate to the point
where illness occurs. The production of
toxins by abnormal metabolism is taken to
include the production of histamine and
histamine-like substances in damaged
tissues. Ketonemia due to a dispropor-
tionate fat metabolism, and lactic acidemia
caused by acute ruminal acidosis (grain
overload), are two common examples of
toxemia caused by abnormal metabolism.

PATHOGENESIS OF ENDOTOXEMIA

The specific effects of the particular
bacterial exotoxins and metabolic toxins
are presented in the relevant sections of
specific diseases in the Special Medicine
section of this book. The principles of the
effects of bacterial endotoxemia will be
presented here.

The total toxic moiety of the lipo-
polysaccharide molecule is generally
similar regardless of the bacterial source.
Endotoxemia results in an extraordinary
array of pathophysiological effects,
involving essentially all body systems. Of
the endotoxins produced by bacteria most
is known of those produced by E. coli.

Endotoxins are normally present in
the intestine and although the intestinal
mucosa provides a highly efficient barrier,
limiting transmural movement of endo-
toxins, small quantities are absorbed into
the portal blood. These endotoxins are
removed by the liver and do not reach the
peripheral blood. In hepatic failure the
level of endotoxins in plasma is increased.
Significantly greater quantities of endo-
toxins escape the intestine when the
mucosal barrier is disrupted by intestinal
ischemia, trauma, ionizing radiation,
bacterial overgrowth, reduced luminal pH
or inflammatory intestinal disease 3 These
conditions not only temporarily over-
whelm Ihe capacity of the liver to remove
endotoxin from the portal circulation but
also allow transmural movement of
endotoxins into the peritoneal cavity from
which they reach the peripheral blood.

Endotoxemia may also occur when
Gram-negative bacteria gain access to
tissues and/or blood. Most of these
organisms liberate endotoxin during rapid
growth and gain access to the blood from
primary foci of systemic or superficial
tissue infections. An example is coliform
septicemia in newborn farm animals. Once
the endotoxins gain access to the blood,
they are removed from the circulation by
the mononuclear phagocyte system,
and the response of these phagocytes to
the lipopolysaccharides determines the
severity of the clinical illness.

Biochemical mediators

Endotoxins do not cause their effects via
direct toxic effect on host cells but rather
induce the production of soluble and cell-
bound mediators from a broad range of
host cells, including endothelial and
smooth muscle cells, polymorphonuclear
granulocytes, platelets, thrombocytes and
cells of the monocyte/macrophage lineage.
These cells release a series of phlogistic
biochemical mediators, which include
cytokines, platelet-activating factor, throm-
boxane A 2 , prostaglandins, leukotrienes,
proteinases, toxic oxygen metabolites and
vasoactive amines. Macrophages become
highly activated for enhanced secretory,
phagocytic and cidal functions by the
lipopolysaccharide. The cytokines derived
from the macrophages are responsible for
many of the pathophysiological con-
sequences of endotoxemia. Pulmonary
intravascular macrophages are the most
important producers of cytokines in large
animals.

Animals have evolved to recognize
and respond to the lipopolysaccharide of
Gram-negative bacteria. Although lipo-
polysaccharide may directly injure the
host tissue, many of its effects are
indirectly mediated through inappropriate
activation of host defense mechanisms,
culminating in multiple-organ dys-
function and failure. Importantly, the
response to endotoxin can be attenuated
with certain substances. Experimentally,
the use of detergents, such as a nonionic
surfactant, can attenuate the response of
the horse given endotoxin. 4 The literature
on the pathophysiological effects of endo-
toxemia and Gram-negative bacteremia in
swine has been reviewed. 5

There is a large individual variability in
the response to endotoxin administration,
with much of the variability still being
unexplained. Circulating lipopoly-

saccharide forms complexes in plasma
with high density lipoproteins or a unique
plasma protein termed lipopoly-
saccharide-binding protein (LBP) and
bound lipopolysaccharide is cleared from
plasma within a few minutes by fixed and
circulating macrophages in the bovine
lung and liver that recognize the
lipopolysaccharide-LBP complex. The
lipopolysaccharide-LBP complex binds to
a membrane-bound receptor (mCD14)
on mononuclear cells via a secreted
linking protein called MD-2 and then
attaches to a toll-like receptor 4 (TLR4)
on the mononuclear cell membrane; the
lipopolysaccharide-LBP-mCD14-MD-2
complex is then internalized and lipo-
polysaccharide is thought to be destroyed
in the process. Internalization of lipopoly-
saccharide activates the intracellular
signaling pathway via nuclear factor
kappa B (NF-kB), which translocates to

the nucleus and causes the transcription
of many cytokine genes and release of
proinflammatory cytokines, of which
TNF-ct, interleukin-1 and interleukin-6
are the most important. Some of the
genes activated include those that code
for cyclooxygenase 2 (COX-2, the inducible
form of cyclooxygenase), inducible nitric
oxide (iNOS), endothelial adhesion
molecules, which promote the adhesion
of neutrophils to endothelial surfaces, and
chemokines.

The plasma concentrations of the
arachidonic acid metabolites, throm-
boxane A 2 and prostacyclin, increase in
several species during endotoxemia, and
these eicosanoids are probably responsible
for the hemodynamic abnormalities caused
by endotoxin. Endotoxin initiates cellular
events that activate a cell- membrane
enzyme known as phospholipase A 2 .
Activation of this enzyme leads to the
hydrolysis of membrane-bound phospho-
lipids; arachidonic acid is released from
the phospholipid portion of damaged
mammalian cell membranes. 6 The enzyme
cyclooxygenase converts arachidonic acid
into intermediate endoperoxides, which
are substrates for the formation of pros-
taglandins, thromboxane and prostacyclin,
by specific synthetases. Platelets are the
principal source of thromboxane, which
acts as a potent vasoconstrictor and
induces platelet aggregation. Most
prostacyclins are synthesized in vascular
endothelial cells and cause vasodilation
and inhibit platelet aggregation. The
generalized endotoxin-induced pro-
duction of cyclooxygenase products may
contribute to the multisystemic organ
dysfunction, shock and disseminated
coagulopathy that culminates in death.

TNF-ct is released by macrophages
early in the course of endotoxemia and
circulating TNF-a activity correlates with
the severity and outcome of disease.
Infusion ofTNF induces an endotoxemic-
shock-like syndrome and TNF-a
blockade confers marked protection
against the effects of Gram-negative
sepsis and lipopolysaccharide adminis-
tration. Experimentally, pretreatment of
horses with monoclonal antibody to
TNF-a can reduce the hematological and
clinical effects of endotoxin-induced TNF
activity 7 and interleukin-6 activity can be
reduced by neutralization of TNF-a. 8
Interleukin-1 release is proinflammatory
and leads to pyrexia and the hepatic acute
phase response. Interleukin -6 contributes
to the hepatic acute phase response and
promotes B-lymphocyte proliferation.
Interleukin-6 may have value as a
prognostic indicator, as its plasma con-
centration appears to be a better predictor
of mortality in humans than TNF-a or
interleukin-1.

Toxemia and endotoxemia

55

The systemic effects of endotoxemia
can be demonstrated experimentally by
parenteral injection of purified endotoxin,
TNF-a or interleukin-1. In naturally
occurring disease, however, the total
effect includes those of bacterial toxins
plus those of mediators produced by
tissues in response to the toxins, and the
counterbalancing effects of anti-
inflammatory molecules that are also
secreted during sepsis, such as
interleukin-4, interleukin-10, interleukin-
11, interleukin- 13, and soluble CD14
receptors. The pathophysiological effects
of endotoxemia associated with Gram-
negative bacteria are summarized here
according to their effects on various body
systems or functions.

Cardiopulmonary function

The hemodynamic effects of endotoxemia
are manifested in two phases. 9 In the
early stages, heart rate and cardiac output
commonly increase, although systemic
blood pressure remains near or slightly
less than normal. This is known as the
hyperdynamic phase of endotoxemia.
Oxygen demands of peripheral tissues are
increased during the hyperdynamic phase,
resulting in compensatory mechanisms
that increase blood flow in an attempt to
meet the increased metabolic demands.
However, despite the absolute increase in
cardiac output and oxygen delivery
during this hyperdynamic phase, blood
flow still may be inadequate to meet the
needs of tissues in a hypermetabolic state.
During the hyperdynamic state, affected
animals hyperventilate and have decreased
capillary refill time and red, congested
mucous membranes. Microcirculatory
shunting of blood continues in organs
such as the gastrointestinal tract and
kidney. Ischemia of intestinal mucosa is
manifested clinically by ileus and diarrhea
may occur. Decreased renal perfusion will
result in decreased urine output.

With uncontrolled endotoxemia, the
hyperdynamic phase progresses to the
hypodynamic phase of shock. Changes
include decreased cardiac output, systemic
hypotension, increased peripheral resist-
ance and decreased central venous return.
Hypothermia, rapid irregular pulses,
prolonged capillary refill time, pale to
cyanotic mucous membranes, acidemia
and hypoxemia provide clinical evidence
of this advanced stage of endotoxemia.
The skin and extremities are cool. Severe
pulmonary edema and increasing pul-
monary hypertension occur. In horses,
administration of endotoxin at high
dosages can induce circulatory shock with
increased heart rate, decreased cardiac
output and stroke volume, and con-
comitant increases in peripheral vascular
resistance. The slow intravenous infusion

of low dosages of endotoxin into conscious
horses results in pulmonary hypertension
without causing hypotensive, hypo-
volemic shock. 10 Intestinal vasoconstriction
occurs as part of the compensatory
response to endotoxemia following slow
infusion of low dosages of endotoxin.

Infusion of endotoxin into swine
induces widespread changes including
intense pulmonary vasoconstriction
and hypertension, bronchoconstriction,
increased vascular permeability, hypo-
volemia, systemic hypotension, pulmonary
edema, hypoxemia, granulocytopenia and
thrombocytopenia. 5 The vascular changes
in endotoxemia include increased vascular
permeability, changes in vascular tone
and microvascular obstruction. Increased
capillary permeability promotes trans-
mural movement of albumin and other
colloids, which carry water to the interstitial
space. The result is hypoalbuminemia,
hypoproteinemia, interstitial edema,
pulmonary edema, relative hypovolemia,
decreased return to the heart and further
decreases in cardiac output. Arterial and
arteriolar vasoconstriction develops in the
systemic and pulmonary circulations.
Prolonged infusion of endotoxin into
sheep causes systemic hypotension,
pulmonary hypertension and acute lung
injury with progressive respiratory
failure. 11

Endotoxemia causes an acute and
severe neutropenia, which precedes
neutrophilia and hemoconcentration.
Neutropenia is due mainly to leukocyte
margination and sequestration; persist-
ence of severe neutropenia is a poor
prognostic indicator. Hemoconcentration
is due to movement of fluid from the
vascular to extravascular spaces. Endotoxin
administration causes an immediate
accumulation, margination and activation
of leukocytes in the microcirculation,
particularly in the alveolar capillaries. This
is followed by degranulation and leuko-
cyte migration into the interstitium and
endothelial cell damage. Pulmonary
sequestration of neutrophils is preceded
by endotoxin uptake by pulmonary intra-
vascular macrophages, indicating that the
pulmonary macrophage response is
pivotal to the subsequent inflammatory
response. Leukopenia appears to be an
immediate response to endotoxin adminis-
tration, and is observed as early as 5 min
after infusion. The rebound leukocytosis is
caused by humoral effects on the bone
marrow; a neutrophil-releasing factor
that promotes release of neutrophils from
bone marrow, and macrophage-colony-
stimulating factor, which stimulates
granulopoiesis. Colostrum-fed calves
have a greater neutrophilia in response tos.
endotoxin than colostrum-deprived calves,
possibly because of absorption of a

granulopoietic factor from colostrum.
Endotoxemia also induces a lymphopenia
that is secondary to the release of endo-
genous corticosteroids and redistribution
of lymphocytes from peripheral blood
and the spleen to lymphatic tissue.

Thrombocytopenia is consistently
observed after endotoxin administration,
but occurs later than neutropenia, although
it is sustained for a longer period of time.
Endotoxin affects platelet function by a
number of different mechanisms.

Hemostatic system

Endotoxins cause endothelial injury
directly or indirectly, and thereby expose
subendothelial collagen and tissue
thromboplastin, initiating the intrinsic
and extrinsic coagulation cascades,
respectively. 3 Endotoxin can initiate the
coagulation cascade directly by activation
of factor XII or by inducing platelet
release of thromboxane and other pro-
coagulant substances. Endotoxin may
induce coagulopathy indirectly by
endothelial damage with secondary factor
XII activation, or through the effects of
complement activation. Macrophages and
leukocytes have been shown to release a
procoagulant substance in response to
endotoxin, which functions similarly to
factor VII and may also have a role in
perpetuating coagulopathy in endotoxemia
via the extrinsic pathway.

Disseminated coagulopathy is the
cause of diffuse microvascular thrombosis
and eventual organ failure subsequent to
endotoxemia. The experimental injection
of endotoxin can cause diffuse micro-
thrombosis in multiple or organ systems.
The principal clinical finding of DIC in
horses is petechial and/or ecchymotic
hemorrhages on mucous membranes and
sclerae with a tendency to bleed from
venepuncture sites. Spontaneous epistaxis
or prolonged hemorrhage after nasogastric
intubation may also occur. The result of
exaggerated thrombin formation during
DIC is widespread fibrin deposition in the
microcirculation causing circulatory
obstruction and organ hypoperfusion that
may lead to ischemic necrosis and failure.
The ultimate consequences are multiple
organ failure and death.

Thermoregulation

Bacterial endotoxins are potent stimu-
lators of macrophage interleukins, which
belong to a family of polypeptides
functioning as key mediators of various
infectious, inflammatory and immuno-
logical challenges to the host. Interleukin-1
induces fever, an increase in the number
and immaturity of circulating neutrophils,
muscle proteolysis through increased
prostaglandin E 2 production, hepatic
acute phase protein production, and

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

reduced albumin synthesis. Interleukin-1
participates in the acute phase response,
which is characterized by fever, hepatic
production of acute phase proteins,
neutrophilia and procoagulant activity. 9

Endotoxins commonly cause a fever
followed by hypothermia. Serum
interleukin -6 concentrations are lower in
endotoxin-induced colostrum- deprived
foals and take longer to reach peak levels
compared to colostrum-fed foals. 12 The
higher and more rapid concentrations in
colostrum-fed foals may be part of a
resistance factor in equine neonates.
Interleukin-6 plays a key role in host
defense, regulating antigen-specific
immune responses, hematopoiesis, cellular
differentiation and the acute phase
reaction subsequent to an inflammatory
insult. Serum TNF-oi responds in a similar
pattern in colostrum-deprived and
colostrum-fed foals given endotoxin
and the mean rectal temperature in
colostrum-deprived foals is significantly
less than in colostrum-fed foals. 12

Gastrointestinal function

Endotoxemia can cause a profound
inhibition of gastrointestinal motility,
including the stomach, small and large
intestine. Postoperative ileus is a frequent
and serious complication of equine colic
surgery and there is a good correlation
between the incidence of ileus and the
presence of ischemic intestine. Low doses
of endotoxin infused into ponies
produced profound disruption of normal
fasting intestinal motility patterns, with
an inhibition of gastric contraction ampli-
tude and rate, left dorsal colon contraction
product and small-colon spike rate. 13 In
the small intestine, there is an increase in
abnormally arranged regular activity and
a decrease in irregular activity. Experi-
mental endotoxemia in the horse causes
cecal and proximal colonic hypomotility
(ileus) by a mechanism involving
a-adren ergic receptors, which is reversible
by yohimbine. 14 Numerous mediators
may interact with the sympathetic nervous
system to induce this effect.

The administration of endotoxin to
adult dairy cows can reduce the frequency
of reticulorumen contractions; this is
caused by endotoxin-induced mediators 15
and the effect can be abolished by flunixin
meglumine. Endotoxemia also decreases
the abomasal emptying rate in cattle and
is suspected to play a role in the develop-
ment of left displaced abomasum.

Carbohydrate metabolism

The effects on carbohydrate metabolism
include a fall in plasma glucose concen-
tration, the rate and degree varying with
the severity of endotoxemia, a dis-
appearance of liver glycogen and a
decreased glucose tolerance of tissues so

that administered glucose is not used
rapidly. Endotoxic shock can result in
lactic acidemia and both hyper- and
hypoglycemic responses. Hyperglycemia
occurs early and transiently in endotoxic
shock, is accompanied by increased rates
of glucose production and is dependent
on mobilization of hepatic glycogen.
Hypoglycemia is very common in pro-
longed or severe endotoxemia. Experi-
mental infusion of endotoxin into sheep
results in transient hyperglycemia associ-
ated with increased hepatic glucose
production followed by hypoglycemia
3-8 hours later, when hepatic glucose
production decreases. Sympathetic acti-
vation occurs early in endotoxemia and is
probably responsible for the initial
hyperglycemia and glycogenolysis. Blood
pyruvate and lactate concentrations
I increase as a result of poor tissue per-
| fusion and the anaerobic nature of tissue
metabolism. By extrapolation from the
known pathogenesis of endotoxic shock
in horses, it is likely that the resulting
accumulation of lactate has significant
effects in causing mental depression and
j poor survival.

I

| Protein metabolism

! There is an increase in tissue breakdown
! (catabolism) and a concomitant increase
i in serum urea nitrogen concentration. The
| changes observed include alterations in
j individual plasma amino acid concen-
5 trations, increased urinary nitrogen
' excretion and increased whole-body
j protein turnover. The time-course changes
| in the concentrations of plasma amino
| acids and other metabolites during and
| after acute endotoxin-induced fever in
| mature sheep have been described. Rapid
; and extensive changes occur in the
| patterns of tissue protein metabolism in
I the ruminant in response to endotoxin
administration, and these changes may
S contribute to economic losses incurred
! during infectious disease outbreaks. There
I is also an alteration in the aminogram (the
; relative proportions of the amino acids
■ present in blood) and the electrophoretic
I pattern of plasma proteins. The globulins
[ are increased and albumin decreased as
' part of the acute phase reaction.

j Mineral metabolism

i Negative mineral balances occur. These
| include hypoferremia and hypozincemia
j as part of the acute phase reaction as the
i animal attempts to sequester these
j microminerals from invading bacteria, but
i blood copper concentrations are com-
| monly increased concurrently with an
| increase in blood ceruloplasmin levels.

j Reproduction and lactogenesis

j Endotoxemia can cause pregnancy failure
j in domestic animals, particularly when

pregnancy is corpus-luteum-dependent.
In horses and cattle, experimentally
induced endotoxemia causes an immediate
and pronounced release of prostaglandin
F 2a . The intravenous administration of
endotoxin may influence luteal function
by the activation of the arachidonic acid
cascade, by a direct effect of prostaglandin
F 2a on the corpus luteum. The adminis-
tration of endotoxin to mares pregnant
21-35 days results in a decrease in
progesterone and fetal death, which can
be prevented by daily treatment with a
progesterone compound. 16 Similar results
have been produced in pregnant dairy
cows during the first 150 days of lactation,
and coliform mastitis in the first 5 months
of lactation is becoming an increasingly
important cause of early embryonic death
and return to estrus. The uterus of the
early postpartum cow is capable of
absorbing endotoxin, which may provoke
changes in the serum concentrations of
prostanoids 17 and is thought to contribute
substantially to the systemic signs of toxic
metritis in cows. Endotoxin has a negative
effect on the genital functions of the ram;
the changes in luteinizing hormone (LH)
and testosterone are similar to those seen
after heat-induced stress.

In recently farrowed swine with the
mastitis-metritis-agalactia syndrome, it is
suggested that the endotoxin from the
mammary glands affected with mastitis
may be important in the pathogenesis of
the agalactia.

Combined effects on body systems

The combined effects of the hypo-
glycemia, hyper L-lactatemia and acidemia
I interfere with tissue enzyme activity and
reduce the functional activity of most
tissues. Of these factors, acidemia is
probably the most important in adult
animals; in neonates glucose levels are
probably as important as acidemia
because profound hypoglycemia is more
commonly encountered in neonatal
animals. Experimental endotoxemia in
calves at 24-36 hours of age causes severe
hypoglycemia, lactic acidemia and hypo-
tension commonly associated with
moderate to severe sepsis. 18 The myo-
cardium is weakened, the stroke volume
decreases and the response to cardiac
stimulants is diminished. There is
dilatation and in some cases damage to
capillary walls, so that the effective
circulating blood volume is decreased;
this decrease, in combination with
: diminished cardiac output, leads to a fall
I in blood pressure and the development of
circulatory failure. The resulting decline in
the perfusion of tissues and oxygen
! consumption contributes greatly to the
[ animal's decline and to the clinical signs,
i such as the dark red coloration of the oral

Toxemia and endotoxemia

3S

mucosa. Respiration is little affected
except in so far as it responds to the
failing circulation.

There is decreased liver function, and
the damage to renal tubules and glomeruli
causes a rise in blood nonprotein nitrogen
and the appearance of albuminuria. The
functional tone and motility of the ali-
mentary tract is reduced and the appetite
fails; digestion is impaired, with consti-
pation usually following. A similar loss of
tone occurs in skeletal muscle and is
manifested by weakness and terminally
by prostration.

Apart from the effects of specific toxins
on the nervous system, such as those
of Closiridium tetani and Clostridium
botulinum, there is a general depression of
function attended by dullness, depression
and finally coma. Because of the suspected
role of E. coli in the etiology of edema
disease of swine, it is noteworthy that
some of the characteristic nervous system
lesions of that disease are missing
from experimentally induced porcine
colitoxicosis. Changes in the hemopoietic
system include depression of hemo-
poiesis and an increase in the number of
leukocytes - the type of cell that increases
often varying with the type and severity of
the toxemia. Leukopenia may occur but is
usually associated with aplasia of the
leukopoietic tissue associated with viruses
or specific exogenous substances such as
radioactive materials. Most of these
pathophysiological effects of endotoxicosis
have been produced experimentally, and
it is apparent that very small amounts of
endotoxin can contribute greatly to the
serious effects of intestinal disease,
especially in the horse.

Endotoxin tolerance

The repeated administration of lipo-
polysaccharide results in attenuation of
the host response, known as endotoxin
tolerance. This refractoriness to endotoxin-
mediated effects comprises two phases.
Early phase tolerance is transient, occurs
within hours or days and is not associated
with anti-endotoxin antibody production.
Late phase tolerance requires several days
to develop and is long lasting, antigen
specific and the result of antibody pro-
duction. By this mechanism it is possible
for individual animals to survive a dose of
endotoxin lethal to the nontolerant
individual. Experimentally, horses develop
endotoxin tolerance following sequential
sublethal infusions of endotoxin. 19

Hypersensitivity

A secondary effect produced by some
toxins is the creation of a state of
hypersensitivity at the first infection so
that a second infection, or administration
of the same antigen, causes anaphylaxis
or an allergic phenomenon such as

purpura hemorrhagica. Also, a generalized
Schwartzmann reaction can be induced in
pigs by an injection of E. coli endotoxin,
especially if there are two injections
properly spaced (in time). Pigs on a
vitamin-E-deficient diet are much more
severely affected than pigs on a normal
diet. Vitamin E is protective; selenium
is not.

Other infectious toxins

In mycoplasmosis ( Mycoplasma mycoides
var. mycoides), at least part of the toxic
effect is attributable to galactans con-
tained in the toxins. These have a notice-
ably local effect in causing hemorrhages
in alveolar ducts and pulmonary vessel
walls so that pulmonary arterial blood
pressure rises as systemic blood pressure
falls. Later lesions are pulmonary edema
and capillary thrombosis, which are
characteristic of the natural disease of
pleuropneumonia. Disseminated intra-
vascular coagulation is also a charac-
teristic of the lesions associated with the
toxin of Pseudomonas spp.

CLINICAL FINDINGS OF TOXEMIA
AND ENDOTOXEMIA
Acute toxemia

The clinical findings of acute toxemia in
most nonspecific toxemias are similar. The
syndrome varies with the speed and
severity of the toxic process but the
variations are largely of degree. De-
pression, anorexia and muscular weak-
ness are common in acute endotoxemia.
Calves do not suck voluntarily and may
not have a suck reflex. Scant feces are
common but a low-volume diarrhea may
also occur. The heart rate is increased and
initially the intensity of the heart sounds
is increased, but later as the toxemia
worsens the intensity may decrease. The
pulse is weak and rapid but regular. A
fever is common in the early stages of
endotoxemia but later the temperature
may be normal or subnormal. In neonatal
calves, foals and lambs a fever may not
occur because of failure of thermo-
regulation or deprivation of colostrum.
Terminally, there is muscular weakness to
the point of collapse and death occurs in
a coma or with convulsions.

Endotoxemia

When toxin formation or liberation into
the circulation is rapid and the toxicity of
the toxin high enough, the onset of
cardiovascular collapse is rapid enough to
cause a state of 'toxic' or 'septic' shock.
The remarkable clinical findings are:

o Severe peripheral vasodilatation

with a consequent fall in blood

pressure

Pallor of mucosa

Hypothermia
» Tachycardia

• Pulse of small amplitude
° Muscle weakness.

The syndrome is discussed also in the
section on Shock. Endotoxemia is most
commonly associated with bacteremia or
septicemia due to infection with Gram-
negative organisms, especially E. coli.

The clinical findings of severe endo-
toxemia include:

° Depression

° Hyperthermia followed by
hypothermia

° Tachycardia followed by decreased
cardiac output

° Decreased systemic blood pressure
° Cool skin and extremities
o Diarrhea

o Congested mucosae with an increased
capillary refill time
° Muscular weakness, leading to
recumbency.

Renal failure is common and is charac-
terized by anuria. If DIC develops, it is
characterized by petechial and ecchymotic
hemorrhages on mucous membranes and
sclerae with a tendency to bleed from
venepuncture sites.

Chronic toxemia

Lethargy, separation from the group,
inappetence, failure to grow or produce
and emaciation are characteristic signs of
chronic toxemia.

Localized infection

With localized infections there are, in
addition to the general signs of toxemia,
the clinical effects of the space occupation
by the lesion. These are presented under
Localized infections.

CLINICAL PATHOLOGY OF

ENDOTOXEMIA

Hematology

Changes in total and differential leuko-
cyte numbers occur in endotoxemia.
Leukocytosis and neutrophilia occur with
mild endotoxemia and leukopenia,
neutropenia and lymphopenia increase in
severity and duration with increasing
severity of endotoxemia. Endotoxin-
induced rebound neutrophilia may occur
and is attributed to an accelerated release
of neutrophils from the bone marrow
reserve into the circulation through
generation of the neutrophil releasing
factor.

In experimental sublethal endotoxemia
in foals 3-5 days of age, there is
leukopenia followed by leukocytosis,
hypoglycemia, increased prothrombin
time and partial thromboplastin time, and
mild hypoxemia. 20

Serum biochemistry

A low plasma glucose concentration, high
i serum urea concentration (nonprotein

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

nitrogen), and a low serum albumin and
total protein concentration are usually
present in acute endotoxemia. Decreased
albumin and total protein concentrations
are in response to increased capillary
permeability, whereas the azotemia
reflects a decreased glomerular filtration
rate. Adult herbivores have a mild
hypocalcemia, hypomagnesemia and
hypokalemia, and hypophosphatemia, 21
which most likely reflects inappetence
and decreased gastrointestinal tract
motility.

In more chronic toxemic states, a high
serum total protein concentration, with
globulins noticeably increased on electro-
phoretic examination, is more common.

Endotoxin

Endotoxin can be detected in the whole
blood of horses using a whole blood
hemagglutination inhibition assay. 22
However, sensitivity, specificity and
predictive values are not high enough to
be of routine use.

NECROPSY FINDINGS OF TOXEMIA
AND ENDOTOXEMIA

Gross findings at necropsy are limited to
those of the lesion that produces the
toxin. Microscopically, there is degener-
ation of the parenchyma of the liver, the
glomeruli and tubules of the kidney and
of the myocardium. There may also be
degeneration or necrosis in the adrenal
glands.

TREATMENT OF ENDOTOXEMIA

The principles of treatment of endotoxemia
or septic shock include: 1) removal of the
foci of infection; 2) administration of anti-
microbial agents with a Gram-negative
spectrum; 3) aggressive fluid and electro-
lyte therapy to combat the relative hypo-
volemia, hypoglycemia, and electrolyte
and acid-base disturbances; and 4)
NSAIDs or glucocorticoids for the
inhibition of products of the cyclo-
oxygenase pathway. These four treat-
ments are routinely applied. Other treat-
ments that may be applied in selected
cases include the administration of
inotropic agents or vasopressors, intra-
venous or intramjimmaiy administration
of polymyxin B, and hyperimmune
plasma containing antibodies directed
against core lipopolysaccharide antigens.
Fbtential therapeutic agents under investi-
gation (such as pentoxifylline, dimethyl
sulfoxide, tyloxapol and insulin) cannot
be currently recommended for treating
endotoxemic animals.

Endotoxemic or septic shock occurs
when the animal is overwhelmed by an
infection or endotoxemia. This is a complex
disease that requires a rapid and compre-
hensive treatment plan, including the
following.

Removal of foci of infection

Removal of endotoxin before it can be
absorbed is an important cornerstone of
treatment in foals and calves with
omphalophlebitis, horses with ischemic
or necrotic bowel and lactating dairy
cattle with coliform mastitis.

Antimicrobial agents
Bactericidal Gram-negative anti-
microbial agents are always indicated
whenever there is evidence of septicemia
or a localized infection causing endo-
toxemia.The choice and route of adminis-
tration will depend on the pathogens
suspected of causing the infection and
endotoxemia and the site of infection. The
speed of kill of Gram-negative bacteria
may be an important clinical issue, as
antimicrobial agents with a rapid kill
(such as moxalactam) can produce a bolus
release of endotoxin into the blood
stream by punching multiple holes in the
bacteria, causing a rapid explosion of the
bacteria due to osmotic fluid shifts and
bolus release of endotoxin. Antimicrobial
agents that alter the cell wall of Gram-
negative bacteria can theoretically pro-
duce a bolus release of endotoxin when
administered to animals with Gram-
negative septicemia. On this basis,
P-lactam antibiotics effective against Gram-
negative bacteria should theoretically be
avoided, however, clinical experience has
not indicated deleterious effects following
administration of p-lactam antibiotics.
Moreover, coadministration of amino-
glycosides blocks the potential bolus
release of endotoxin by p-lactam
antibiotics. 23 However, it is clinically
prudent to ensure that whenever anti-
microbial treatment is initiated in endo-
toxemic animals, that NSAIDs are
administered concurrently.

Aggressive fluid therapy

The intravenous infusion of large quan-
tities of fluids and electrolytes is a
high priority in the management of
endotoxemia 24 Maintenance of peripheral
perfusion is essential to any therapeutic
regimen for treatment of endotoxic shock.
Large volumes of isotonic fluids have
been standard practice. Lactated Ringer's
solution or other balanced electrolyte
solution must be given by intravenous
infusion over several hours. A beneficial
response is noted by the following:

° Correction of peripheral
vasoconstriction

0 Restoration of an acceptable pulse
quality

° Return of urine output
° Increase in the central venous
pressure

0 Restoration of arterial blood pressure
0 Restoration of cardiac output

® Restoration of oxygen delivery to

acceptable levels. 24

It may be necessary to deliver fluids in
amounts equivalent to 0.5-1.0 times the
estimated blood volume of the animal
over a period of several hours. Glucose
should always be included in the infusion
fluids because hypoglycemia, increased
glucose utilization and inappetence are
usually present.

Hypertonic solutions

The use of hypertonic saline, 7.5% NaCl,
may enhance tissue perfusion and decrease
the volume of subsequent fluids required
for a beneficial response. 25 Experimentally,
the use of hypertonic saline in sublethal E.
coli endotoxemia in mature horses was
associated with a more effective cardio-
vascular response than was an equal
volume of isotonic saline solution.
Cardiac output is increased and peripheral
vascular resistance is decreased compared
to results for isotonic saline controls.
Hypertonic saline rapidly expands the
plasma volume and increases preload by
acting as an effective osmotic agent in the
extravascular compartment, causing a
translocation of fluid from the intra-
cellular space and gastrointestinal tract.

Hypertonic sodium bicarbonate is
widely used for the initial treatment of
metabolic acidosis in endotoxemic adult
horses. However, in horses with experi-
mental endotoxemia, hypertonic sodium
bicarbonate did not normalize blood pH,
and it increased blood L-lactate concen-
trations and caused hypokalemia, hyper-
natremia and hyperosmolality 26

Nonsteroidal anti-inflammatory
drugs

Nonsteroidal anti-inflammatory drugs
(NSAIDs) have been in general use for
the treatment of endotoxemia because of
their analgesic, anti-inflammatory and
antipyretic properties. NSAIDs suppress
production of thromboxane and prosta-
glandins and reduce the acute hemo-
dynamic response to endotoxemia.
Although NSAIDs are routinely admin-
istered to endotoxemic animals, a large-
scale study in humans with severe sepsis
failed to demonstrate an effect of
ibuprofen on mortality, despite improve-
ment in a number of clinical indices and
decreased production of arachidonic acid
metabolites. 27

Flunixin meglumine is the NSAID
most commonly used in the treatment of
endotoxemia in horses and cattle 28 and
remains the NSAID of choice for treating
this condition. Flunixin meglumine is a
potent inhibitor of cyclooxygenase and its
action on this enzyme to inhibit
the synthesis of eicosanoids such as
prostaglandin E 2 may explain the anti-

Toxemia and endotoxemia

59

inflammatory action of the drug. Flunixin
meglumine also modulates the acute
hemodynamic changes and hyper
L-lactatemia commonly seen during endo-
toxemia, which may increase survival rate.
Endotoxin-stimulated production of
thromboxane B 2 (a metabolite of throm-
boxane) and prostaglandin Fi a are blocked
by flunixin meglumine at 0.25 and
0.10 mg/kg respectively, 29 which resulted
in a widespread clinical use of an 'anti-
endotoxemic' dose of 0.25 mg/kg. How-
ever, the term 'anti-endotoxemic effect'
should be discouraged as it is misleading,
and a dose rate of 1.1 mg/kg BW every
12 hours is recommended in horses. Care
should be taken to ensure adequate
hydration in endotoxemic animals receiving
multiple doses of flunixin meglumine.
Flunixin meglumine is usually given
intravenously or intramuscularly in cattle at
1. 1-2.2 mg/kg BW every 24 hours. 30 The
oral administration of flunbin meglumine
at 2.2 mg/kg BW prior to experimentally
induced endotoxemia in cattle exerted an
effect equal to that after intravenous
administration by minimizing the fever and
prostaglandin F 2a metabolite concentration
induced by the endotoxin administration.
However, flunixin meglumine did not
prevent the decrease in peripheral
mononuclear cells and polymorphonuclear
leukocytes seen after endotoxin adminis-
tration. The bioavailability of flunixin
meglumine in cattle ranges from 53-60%
in cattle and 80-86% in horses. 30

Flunixin meglumine was superior to
prednisolone and dimethylsulfoxide in
providing protection and mitigating the
effects of experimental endotoxemia in
calves but was only partially protective
against the hypotension and hyper
L-lactatemia and failed to alter the hypo-
glycemic effect. 31 Although flunixin
meglumine is the most widely used
NSAID in endotoxemia, there is little
experimental evidence demonstrating its
efficacy over other NSAIDs. Ketoprofen,
flunixin meglumine, ketorolac and
phenylbutazone have been compared for
treating experimental endotoxemia in
calves. 32 Each drug modified the response
to endotoxin but none was clearly superior
to the others in modulating the clinical
signs. Phenylbutazone given to calves at
5 mg/kg BW/day intravenously for 5 days
suppressed the clinical response to
experimental endotoxin in neonatal
calves with progressively increasing
amounts of endotoxin until large amounts
were given. 32 There were no significant
differences between ketoprofen and
flunixin meglumine in in vitro studies of
the effects of the drugs on equine peri-
pheral blood monocytes. 33 An interesting
finding in adult dairy cows with
experimentally induced endotoxemia was

that flunixin meglumine and phenyl-
butazone delayed the plasma clearance of
endotoxin by 2-3 and 6-12 times
respectively, 34 suggesting that both
NSAIDs may prolong the clinical signs of
endotoxemia in cattle, possibly by inter-
fering with hepatic metabolism. The clinical
significance of this finding is unknown.

Glucocorticoids

Glucocorticoids (corticosteroids) have
been used extensively in the past for the
treatment of endotoxemia and shock. The
rationale for the use of glucocorticoids
includes:

® Organelle and cell-membrane
stabilization

• Improved cellular metabolism and
gluconeogenesis

• Improved microcirculation

® Decreased production of endogenous
toxins such as myocardial depressant
factor

® Decreased leukocyte activation and
degranulation

° Minimal reticuloendothelial
depression and histologic organ
damage. 24

The corticosteroids most commonly used
in endotoxic shock were hydrocortisone,
prednisolone, methylprednisolone and
dexamethasone. However, these corti-
costeroids have been most beneficial
therapeutically when given as a pre-
treatment in experimental situations.
Published evidence, based on controlled
clinical trials, that corticosteroids are
efficacious in naturally occurring cases
of endotoxemic shock in farm animals
appears to be lacking.

Glucocorticoids improve capillary
endothelial integrity and tissue perfusion,
decrease activation of complement and
the clotting cascade, decrease neutrophil
aggregation, stabilize lysosomal mem-
branes, protect against hepatic injury and
improve survival rate. However, there are
concerns about their use in septicemic
animals because they may cause
immunosuppression. Large doses are
required, which are cost-prohibitive in
farm animals where they are used most
commonly in acute cases and in doses
such as 1 mg/kg B W of dexamethasone
intravenously every 24 hours. It is
currently believed that glucocorticoids, if
they are to be clinically effective, must be
given as early as possible to endo-
toxemic animals. Glucocorticoids are less
frequently administered to endotoxemic
animals as a result of a number of studies
supporting the use of NSAIDs.

Inotropic agents and vasopressors

Critically ill neonates and adults may
require the administration of positive

inotropic agents and vasopressor agents.
Inotropic agents increase cardiac con-
tractility, thereby increasing cardiac
output and oxygen delivery. Vasopressor
agents increase systemic arterial blood
pressure. Inotropic and vasopressive
agents are usually administered for short
periods of time during anesthesia or
recovery from anesthesia.

Dobutamine (0.5-1.0 pg/kg BW/min
in adults and 1-3 pg/kg BW/min in
neonates) is the inotropic agent of choice. 33
Dobutamine should be diluted in 0.9%
NaCl, 5% dextrose or lactated Ringer's
solution and the dose carefully titrated
by monitoring heart rate and rhythm
and blood pressure. Norepinephrine
(0.01-1 pg/kg BW/min) is the vasopressor
agent of choice in hypotensive animals
that have not responded to intra-
venous fluid loading or dobutamine. 33
Norepinephrine should be diluted in 5%
dextrose and the dose titrated as there
is marked individual variability in the
response to norepinephrine administration.

Polymyxin B

Polymyxin B is a cationic antibiotic that
has an appropriate charge distribution to
stoichiometrically bind to the lipid A
moiety of lipopolysaccharide. Parenteral
administration of antimicrobial doses of
polymyxin can lead to nephrotoxicity,
neurotoxicity and ototoxicity but lower,
non -nephrotoxic doses are effective in
ameliorating the effects of endotoxin in
horses. Specific endotoxin binding agents
such as intravenous polymyxin B are
therefore theoretically of benefit and have
shown efficacy in endotoxemic horses
when administered at a recommended
dose of 5000 U/kg administered at
8-12-hour intervals 36,37 but definitive
efficacy studies have not been completed
in endotoxemic calves or horses with
naturally acquired endotoxemia. In parti-
cular, because the efficacy of polymyxin B
is focused against circulating lipo-
polysaccharide before it is bound to
lipopolysaccharide binding protein, it is
currently believed that polymyxin B, like
glucocorticoids, must be given as early as
possible to endotoxemic animals if they
are to be clinically effective. Attractive
features of polymyxin B are its shelf life
and ease of storage, ease of adminis-
tration (intravenous bolus) cost and
8-12-hour duration of effect. 37

Antiserum

Hyperimmune serum is commercially
available for the treatment of endo-
toxemia in the horse. The rationale is that
anti-lipid A antibodies bind circulating
lipopolysaccharide, thereby preventing
the subsequent inflammatory cascade.
However, on theoretical grounds it is
difficult for an antibody to competitively

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

inhibit the strong binding affinity
and high specificity between lipopoly-
saccharide and lipopolysaccharide binding
protein. There are also difficulties with
spatial hindrance between immunoglobulin
(Ig)G and the R-core subtraction of
lipopolysaccharide that contains lipid A. It
is therefore difficult to believe that
antiserum against core lipopolysaccharide
antigens will ever be therapeutically
successful in animals with naturally
acquired endotoxemia, and large-scale
studies in septic humans have failed to
observe a decrease in mortality following
the administration of hyperimmune core-
lipopolysaccharide plasma. However, the
administration of antiserum has many
theoretical advantages separate from
those of endotoxin neutralization, and it
may be that plasma transfusion alone is
beneficial.

The use of antiserum to the rough
mutant of £. coli 0111:B4(J-5) as a
treatment of experimental or naturally
acquired endotoxemia has been demon-
strated in some, but not all, studies in
adult horses 38 ' 39 but not in foals and
calves. 40 One study in foals indicated that
administration of hyperimmune serum
resulted in a worsening of the clinical
signs and augmented release of TNF-a
and interleukin-6. 41 Antiserum does
not appear as rational a treatment
for neutralizing circulating lipopoly-
saccharide as polymyxin B and, for this
reason, the administration of hyper-
immune serum should probably be
reserved for animals that fail to improve
after polymyxin B administration.

Anticoagulants

Disseminated intravascular coagulation
(hypercoagulative states) can be treated
with heparin in an attempt to impair
intravascular coagulation. Much of the
knowledge regarding DIC in endo-
toxemia has been extrapolated from
species other than large animals, and there
is little objective infonnation available to
guide the clinical use of anticoagulants in
endotoxemic large animals. Instead, the
focus of treatment should be aggressive
intravenous fluid administration in order
to maximize microcirculation.

CONTROL OF ENDOTOXEMIA

The hallmarks of a control program are to
decrease the risk or prevent neonatal
septicemia, institute early and aggressive
treatment of Gram-negative bacterial
infections and ensure prompt surgical
removal of ischemic and damaged intes-
tine. Vaccines based on core lipo-
polysaccharide antigens are widely used
in North America to decrease the
incidence and severity of Gram-negative
mastitis in lactating dairy cows (see Ch. 15)
and Gram-negative infections in pigs, but

similar vaccination protocols have not been
developed for horses, small ruminants and
New World camelids, which are also at
risk of endotoxemia.

REVIEW LITERATURE

Morris DD. Endotoxemia in horses. A review of
cellular and humoral mediators involved in its
pathogenesis.] Vet Intern Med 1991; 5:167-181.
Cullor JS. Shock attributable to bacteremia and
endotoxemia in cattle: clinical and experimental
findings. J Am Vet Med Assoc 1992; 200:
1894-1902.

Olson NC, Kruse-Elliott KT, Dodam JR. Systemic and
pulmonary reactions in swine with endotoxemia
and Gram-negative bacteremia. J Am Vet Med
Assoc 1992; 200:1870-1884.

Roy M. Sepsis in adults and foals.Vet Clin North Am
Equine Pract 2004; 20:41-61.

Southwood LL. Postoperative management of the
large colon volvulus patient. Vet Clin North Am
Equine Pract 2004; 20:167-197.

Sykes BW, Furr MO. Equine endotoxemia - a state of
the art review of therapy. Aust Vet J 2005;
83:45-50.

REFERENCES

1. Cullor JS. J Am Vet Med Assoc 1992; 200:1894.

2. Shuster R et al. J Am Vet Med Assoc 1997; 210:87.

3. Morris DD. J Vet Intern Med 1991; 5:167.

4. Longworth KE et al. Am J Vet Res 1996; 57:1063.

5. Olson NC et al. J Am Vet Med Assoc 1992;
200:1870, 1884.

6. Bottoms GD, Adams HR. J Am Vet Med Assoc
1992; 200:1842.

7. Cargile JL et al. Am J Vet Res 1995; 56:1451.

8. Cargile JL et al. Am J Vet Res 1995; 56:1445.

9. Green EM, Adams HR. J AmVet Med Assoc 1992;
200:1834.

10. Clark ES et al. Equine Vet J 1991; 23:18.

11. Fferkowski SZ et al. J Appl Physiol 1996; 80:564.

12. Robinson JA et al. Am J Vet Res 1993; 54:1411.

13. KingJN, Gerring EL. Equine Vet J 1991; 23:11.

14. Eades SC, Moore JN. Am J Vet Res 1993; 54:581.

15. Eades SC. J Dairy Sci 1993; 76:414.

16. Gossett KA et al. J Am Vet Med Assoc 1990;
51:1370.

17. Gilbert RO et al. Theriogenology 1990; 33:645.

18. GerrosTC et al. Can J Vet Res 1995; 59:34.

19. Allen GK et al. Equine Vet J 1996; 28:269.

20. Daels PF et al. Am I Vet Res 1991; 52:282.

21. Toribio RE et al. J Vet Intern Med 2005; 19:223.

22. Smith NL J Equine Vet Sci 1993; 13:433.

23. Bentley AP et al. Am J Vet Res 2002; 63:660.

24. Haskins SC. J AmVet Med Assoc 1992; 200:1915.

25. Tyler JW et al. Ana J Vet Res 1994; 55:278.

26. LeGrand EK. J Am Vet Med Assoc 1990; 197:454.

27. Bernard GR et al. New Engl J Med 1997; 336:912.

28. Moore JN, Morris DD. J AmVet Med Assoc 1992;
200:1903.

i 29. Semrad SD et al. Equine Vet J 1987; 19:201.

! 30. Odensvik K, Magnusson U. Am J Vet Res 1996;
l 57:201.

| 31. Semrad SD. Am J Vet Res 1993; 54:1517.
j 32. Semrad SD. Am J Vet Res 1993; 54:1339, 1511.

! 33. Jackman BR et al. Can J Vet Resl994; 58:138.

34. Haubro Andersen P et al. JVet Med A 1996; 43:93.

35. Corley KIT. Vet Clin North Am Equine Pract
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36. Parviainen AK et al. Am JVet Res 2001; 62:72-76.

37. Barton MH et al. Equine Vet J 2004; 36:397.

38. Garner HE et al. Equine Pract 1988; 10:10.

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40. BoosmanR et al.Vet Rec 1990; 127:11.

41. Durando MM et al. Am JVet Res 1994; 55:921.

Toxemia in the recently
calved cow

A special occurrence of toxemia of major
importance in food-animal practice is that
caused by several diseases in the period
immediately after calving in the dairy cow.
The syndrome is characterized clinically by
lack of appetite, marked reduction in milk
yield, reduced ruminal and intestinal
activity, dullness, lethargy and a fever. The
term 'parturition syndrome' is often used
but is not recommended because its
general adoption could dissuade clinicians
from seeking more accurate identification
of the component disease.

The diseases commonly included in
the broad category of periparturient
toxemia are:

0 Acetonemia

° The fat cow syndrome and pregnancy
toxemia
° Mastitis
° Peritonitis
° Septic metritis.

A brief account of septic metritis in cattle
is provided here because of the common
occurrence of septic metritis and the
profound nature of the systemic signs of
illness in affected cattle. All the other
diseases are described under their respec-
tive headings in this book.

POSTPARTUM SEPTIC METRmS IN
CATTLE

Postpartum septic metritis occurs pri-
marily in dairy cows within 2-10 days of
parturition and is characterized clinically
by severe toxemia and a copious, foul-
smelling uterine discharge, with or without
retention of the fetal membranes.

ETIOLOGY

The etiology is multifactorial. It is assumed
that a combination of impaired neutrophil
function, abnormal postpartum uterine
j involution, often with retained fetal
membranes, and infection of the uterus
precipitates the disease. A mixed bacterial
flora is common, which includes organisms
j such as Arcanobacterium (Actinomyces or
[ Corynebacterium) pyogenes, Bacteroides spp.,
j Fusobacterium necrophorwn; these com-
| monly predominate as a mixed flora in
j cows with retained placenta and post-
! partum metritis, 1,2 particularly after 5-7
! days post partum. Other observations
j found that £. coli predominates in cows
I with retained placenta, 3 particularly in the
; first 5-7 days post partum. Staphylococcus
| spp., Streptococcus spp.. Pseudomonas
j aeruginosa, Proteus spp. and occasionally
: Clostridium spp. are also present; the
: last can occasionally result in tetanus if
! C. tetani proliferates.

Toxemia in the recently calved cow

61

EPIDEMIOLOGY

The disease occurs in cows of all ages but
is most common in mature dairy cows
within 2-4 days of parturition. Factors
strongly associated with an increased
incidence of metritis include:

a Large herds
o Dystocias

o Retained fetal membranes
o Overconditioning or

underconditioning of cows. 4

Septic metritis is most common in cows
with fetal membranes retained for more
than 24 hours following parturition.
Several cause and effect relationships
have been implicated for retained placenta
in cattle, 5 with impaired neutrophil func-
tion being the most likely underlying
cause.

Retention of fetal membranes is
associated most commonly with abortion,
dystocia and multiple births. The most
commonly used definition is the presence
of fetal membranes 12 hours or more
following parturition but retention for
more than 6-8 hours is the time limit set,
particularly in older cows. 5 Approximately
10% of dairy cows have retained fetal
membranes for longer than 6 hours after
parturition. 6 The incidence between herds
ranges from 3 to 27%. In single calvings
the incidence is about 10%; in twin
calvings 46%. Metritis occurs in about
50% of cows with retained placenta, and
metritis is 25 times more likely to occur
with retained placenta than without.
Other less common risk factors for
retained placenta include:

Old age

Increased gestation length

Hormone-induced parturition

Fetal anasarca

Uterine prolapse

Fetotomy.

The factors that are associated with reten-
tion of the placenta are indirectly associ-
ated with the development of postpartum
metritis. The forceful removal of retained
placenta, particularly in the first 4 days
post partum, is also considered to be a
major predisposing factor to septic
metritis. Recent work indicates that the
fundamental cause of retained placenta is
impaired neutrophil function, whereby
the ability of the maternal immune
system to recognize the placenta as
'foreign' tissue is impaired. 7 In other
words, retained placenta is an indication
of an impaired immune system.

Uncomplicated cases of retained fetal
membranes in cattle have no significant
effect on subsequent fertility and the
calving-to-conception interval. However,
the calving-to-conception interval is
significantly increased in cows that develop

clinical metritis as a sequel to retained
fetal membranes. Vitamin E and selenium
deficiency, placentitis and vitamin A
deficiency have also been suggested as
factors.

PATHOGENESIS

Failure of normal uterine involution
combined with retention of the fetal
membranes and infection of the uterus
with a mixed bacterial flora results in
acute metritis and a severe toxemia. There
is diffuse necrosis and edema of the
mucosa and wall of the uterus. There is
marked accumulation of foul-smelling
fluid in the uterus and enlargement of the
uterus. Absorption of toxins results in
severe toxemia, particularly in fat cows,
which may develop irreversible fatty
degeneration of the liver.

CLINICAL FINDINGS

Affected cows become acutely anorexic
and toxemic within 2-10 days after
parturition. There is a marked drop in
milk production.The temperature is usually
elevated, in the range 39.5-41. 0°C, but may
be normal in the presence of severe
toxemia. The heart rate is usually elevated
and may range from 96-120 beats/min.
The respiratory rate is commonly
increased to 60-72 breaths/min and the
breath sounds may be louder than
normal. Rumen contractions may be
markedly depressed or absent. A foul-
smelling fluid diarrhea may occur. Mild to
moderate dehydration is common because
affected cows do not drink normally.

Retention of the fetal membranes is
common, and manual examination of the
vagina reveals the presence of copious
quantities of foul-smelling, dark brown to
red fluid containing small pieces of
placenta pooled in the vagina. When the
fetal membranes are retained and pro-
taiding through the cervix, the hand can
usually be inserted through the cervix and
! into the uterus. Manual exploration of the
uterine cavity will usually reveal the state
of adherence of the fetal membranes.
Often the fetal cotyledons are firmly
attached to the maternal caruncles, but
occasionally they have separated from the
caruncles and the placenta can be
removed by simple traction.

Rectal examination usually reveals that
the uterus is large, flaccid and lacks the
longitudinal ridges that indicate invo-
lution. In large cows the enlarged, flaccid
uterus may be situated over the pelvic
brim extending into the ventral part of the j
j abdomen and thus may not be easily
1 palpable and examined. This is an import-
ant finding because the fetal membranes
; may be fully retained in the uterus and no
| evidence of their presence may be
: detectable on examination of the vagina
t and the cervix, which may be almost

closed, making examination of the uterus
impossible.

The presence of viscid, nonodorous
mucus in the cervix and anterior part of the
vagina usually, but not always, indicates
that the fetal membranes have been
expelled. When evidence of a retained
placenta and septic metritis cannot be
found on examination of the reproductive
tract, either by rectal palpation or vaginal
examination, and if the history indicates
some uncertainty about the disposition of
the placenta, a retained placenta and septic
metritis should be considered until proven
otherwise. Persistent toxemia, tachycardia
(100-120 beats/min), anorexia and rumen
stasis that cannot be explained by any
other disease should arouse suspicion of
septic metritis until proved otherwise.

Tenesmus occurs most commonly
when the fetal membranes are retained
and this causes irritation in the vagina.
Manual examination of the vagina may
also stimulate tenesmus.

The course of the disease varies from
2-10 days. Those cases with retained fetal
membranes may be toxemic and not
return to normal appetite until the mem-
branes are fully expelled, which may take
up to 10 days. Necrotic pieces of placenta
may be passed for 10-14 days after
treatment is begun.

CLINICAL PATHOLOGY
Hematology

A leukopenia, neutropenia and degener-
ative left shift occur in acute cases and the
degree of change parallels the severity of
the disease and reflects the absorption of
endotoxin from the uterine lumen.

Vaginal/uterine fluid
Samples of fluid from the vagina and
uterus reveal a mixed bacterial flora
including E. coli, Proteus spp., A. pyogenes,
Staphylococcus spp. and Streptococcus spp.,
with the predominant bacteria varying
mainly with time since parturition. In
; general, E. coli predominates in the first
! 5 days after parturition, whereas A.

| pyogenes and F. necrophorum predominate
! after the first 5 days in cattle with retained
1 placenta. 8,9 Uterine lochia of cattle with
! retained placenta had a much higher
i endotoxin concentration in the first 2 days
i post partum than did lochia of healthy
j cattle or cattle that had undergone a
dystocia but did not have retained
j placenta. Endotoxin was not detected in
the plasma of cattle with high lochial
endotoxin concentrations, indicating
effective systemic clearance. 8

Other samples and tests
j Ketonuria may occur in animals that are
i overconditioned and mobilize excessive
L quantities of depot fat, resulting in
ketosis. Liver function tests reveal a

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

decrease in liver function, which may be
irreversible in excessively fat cows.

NECROPSY FINDINGS

The uterus is enlarged, flaccid and may
contain several liters of dark brown, foul-
smelling fluid with decomposed fetal
membranes. The uterine mucosa is
necrotic and hemorrhagic and the wall of
the uterus is thickened and edematous. In
severe cases, fibrin may be present on the
serosal surface of the uterus. The liver
may be enlarged and fatty and there is
usually mild degeneration of the myo-
cardium and kidneys.

The fat cow syndrome

This is characterized by excessive body
condition, anorexia to inappetence,
ketonuria, a marked loss in milk pro-
duction, decreased rumen movements
and delayed involution of the uterus. The
temperature is usually normal but the
heart and respiratory rates may be
increased. The prognosis is poor in cows
that are totally anorexic; those that are
inappetent will usually recover after
5-7 days of supportive therapy.

Acute diffuse peritonitis

This may occur in cows within a few days
postpartum and is characterized by
anorexia, toxemia, a spontaneous grunt
or one that can be elicited by deep
palpation, rumen stasis, fever and the
presence of an inflammatory exudate in
the peritoneal fluid.

Peracute and acute mastitis

This occurs in cows within a few days
after parturition and is characterized by
severe toxemia, swelling of the affected
quarters and abnormal milk.

TREATMENT
Conservative therapy

Uncomplicated cases of retained fetal
membranes without any evidence of
clinical toxemia usually do not require
parenteral or intrauterine treatment. The
placenta will usually be expelled within
4-6 days. Cows with retained fetal mem-
branes and tenesmus should be examined
vaginally to ensure that there is no
evidence of injury to the vagina or cervix.
In cows with tenesmus, if the placenta is
detached and loose it should be removed
by careful traction. Forceful removal of the
placenta should be avoided.

Antimicrobial agents

Cows with retained fetal membranes but
without systemic illness should be
monitored but treatment with anti-
microbial agents is not indicated. Antibiotic
treatment with oxytetracycline (10 mg/kg
BW, daily) before placental shedding
delays detachment of the placenta; this
finding is consistent with the concept that
intrauterine bacterial infection facilitates
placental detachment. 9

Cows with retained fetal membranes
complicated by septic metritis and
toxemia should be treated with anti-
microbial agents daily for several days or
until recovery occurs. Death can occur in
untreated animals. Because of the mixed
bacterial flora in the postpartum uterus
with a retained placenta, broad-spectrum
antimicrobials are recommended. Intra-
muscular procaine penicillin (22 000 U/kg
BW every 24 h), subcutaneous ceftiofur
(2.2 mg/kg BW every 24 h), intramuscular
ampicillin (10 mg/kg BW) and intravenous
oxytetracycline (11 mg/kg BW every 24 h)
are commonly administered for several
days until recovery is apparent. 10 ' 11
Ceftiofur increases the cure rate and milk
yield, and decreases rectal temperature,
when administered to dairy cows with
fever and vaginal discharge or dystocia. 12
Subcutaneous administration of ceftiofur
(1 mg/kg BW) achieved concentrations of
ceftiofur derivatives in uterine tissue and
lochial fluid that exceeded the reported
minimal inhibitory concentrations for
common metritis pathogens. 13 Ampicillin
increased the pregnancy rate and
decreased the cure rate, compared to
ceftiofur, in cattle that were also treated
with intrauterine ampicillin and
cloxacillin! 4 In general, oxytetracycline
use should be confined to the first
5-7 days post partum when E. coli pre-
dominates, as it is likely to be ineffective
against A. pyogenes in the endometrium.
Oxytetracycline at 30 mg/kg BW intra-
venously as a single dose in cows with
retained fetal membranes resulted in
concentrations of the antimicrobial in
uterine secretions, placenta and cotyledon
for 32-36 hours. 15 Two intramuscular
injections of oxytetracycline at 25 mg/kg
BW resulted in lower peak concen-
trations, but these were maintained for
144 hours. Parenteral oxytetracycline
appears to decrease endotoxin pro-
duction, as indicated by the severity
of leukopenia in cattle with retained
placenta. 9

In severely affected cases, large
amounts of balanced isotonic crystalloid
fluids, electrolytes and glucose by
continuous intravenous infusion may be
necessary and often result in a marked
beneficial response within 24-48 hours.
The uterus should always be examined by
palpation per rectum and vaginally to
determine the degree of uterine invo-
lution, the thickness of the uterine wall,
the volume of the uterus, the nature of the
luminal contents and the degree of
attachment of the placenta to the
cotyledons. This can be done daily to
assess progress. Uterine fluids should be
drained by creating a siphon, if suffi-
ciently liquid in nature, although care
must be taken to ensure that the tube
does not penetrate a friable uterine wall.

If parenteral antimicrobial and supportive
therapy is provided the placenta will
invariably be expelled within 6-8 days
and usually within 4-6 days. The use of
antimicrobial agents must be accompanied
by appropriate withdrawal periods for the
milk produced by treated animals. 16

Intrauterine medication

The necessity for intrauterine medication
is controversial. There is limited evidence,
if any, that the intrauterine infusion of
antimicrobial agents with or without lytic
enzymes and estrogens has any beneficial
effect in the treatment of postpartum
septic metritis. Nevertheless, a wide
variety of antimicrobial agents have been
used for intrauterine medication for
retained placenta and metritis in cows,
although in general, P- lactam- resistant
antibiotics should be administered
because the uterine lumen can contain
P-lactamase-producing bacteria. Intra-
uterine infusion of 0.5 g of the first-
generation cephalosporin cephapirin
improved the reproductive performance,
but only when administered after 26 days
in milk. 17,18 Intrauterine infusion of 1 g of
the third -generation cephalosporin
ceftiofur in 20 mL of sterile water once
between 14 and 20 days of lactation had
no effect on reproductive performance
but decreased the risk of culling and
increased the time to culling. 19 Tetracycline
products (5-6 g) are commonly used but
should be administered as a powder
dissolved in an appropriate volume of
0.9% NaCl, as vehicles such as propylene
glycol can irritate the endometrium.
Infusion of oxytetracycline decreases
lochial odor and the incidence of fever in
cattle with retained placenta. 20 In cattle
with retained placenta, intrauterine
administration of a povidone-based
oxytetracycline solution (5 g daily until
expulsion) combined with fenprostalene
(1 mg subcutaneously) did not alter the
time to detachment of the placenta but
increased the frequency of pyometra; 21
this finding was consistent with the
concept that intrauterine bacterial infection
facilitates placental detachment. 9 Milk
from cows treated by intrauterine infusion
of antimicrobial agents should be dis-
carded for an appropriate period of time
in order to avoid illegal residues. 16

Intrauterine administration of anti-
septics (povidone iodine, chlorhexidine,
hypertonic saline) has been done but
studies demonstrating efficacy are lacking.

Ancillary treatment and control

Portions of retained placenta protruding
from the vagina should be wrapped in a
plastic rectal sleeve to minimize wicking
of fecal bacteria after defecation, although
this supposition has not been verified.
Alternatively, protruding remnants of

placenta can be excised, although this
may prolong to the time to expulsion
because the decreased weight may
interfere with traction on the remaining
placenta in the uterine lumen. Complete
manual removal is often requested by
the producer but is not recommended
because studies have not demonstrated
its efficacy.

The infusion of collagenase solution
(200 000 U dissolved in 1 L of 0.9% NaCl
containing 40 mg calcium chloride and
sodium bicarbonate) into the umbilical
arteries within 12 hours of parturition is
an effective treatment for retained placenta.
Collagenase injection therefore provides
an effective method for preventing septic
metritis in cattle with retained placenta.
However, the collagenase solution is
expensive, not widely available and the
technique is difficult in some animals
because of difficulty in identifying intact
umbilical arteries for injection. As a result,
collagenase injection is rarely performed in
clinical veterinary practice. The efficacy of
umbilical artery infusion with antimicrobial
agents has not been adequately evaluated.

Ecbolic drugs have been proposed for
the prevention and treatment of retained
placenta in cattle. These include pros-
taglandins, ergot derivatives, oxytocin
and P 2 - adrenoceptor antagonists. 22 The
rationale for their use is that they stimu-
late uterine contractions and physically aid
in the expulsion of the fetal membranes. In
general, the consensus is that they are
ineffective after the diagnosis of a
retained placenta is recognized. However,
their use may be effective if used immedi-
ately after calving. In particular, the
frequent intramuscular administration of
oxytocin appears to provide the most
effective means of preventing metritis,
with a recommended protocol of 20 IU
every 3 hours for postpartum days 0-3, 30
rU every 2 hours for postpartum days 4-6
and 40 IU every 2 hours for postpartum
days 7-10 23 A large study found that intra-
muscular injection of oxytocin (30 IU)
immediately after parturition and 2-4 hours
later decreased the incidence of retained
placenta and the calving-to-conception
interval. 24 Fenprostalene at 1 mg sub-
cutaneously, 25 mg dinoprost trome-
thamine intramuscularly, or 20 IU oxytocin
given to a large number of dairy cows in
five commercial dairy herds did not
reduce the incidence of retained fetal
membranes or improve reproductive
performance. 6 A detailed review failed to
identify any evidence supporting the use
of estrogen or prostaglandins in the first
7-10 days post partum. 23

The finding that retained placenta can
be caused by neutrophil dysfunction at
calving 7 provides the basis for epi-
demiological evidence that deficiency of
trace minerals or vitamins (such as

Hypovolemic, hemorrhagic, maldistributive and obstructive shock

63

selenium and vitamin E) is associated
with an increased incidence of retained
placenta. In regions deficient in seleni m,
supplementation of the diet up to 0.3 ppm
can decrease the incidence of retained
placenta in herds that are fed a total mixed
ration. Selenium can also be administered
by intraruminal boluses or parenteral
administration of vitamin E/selenium
preparations during the dry period.

IDENTIFICATION OF AFFECTED COWS

Cows affected with retained placenta
and metritis should be identified and
recorded in the records system and
examined 30-40 days after parturition for
evidence of further complications such as
pyometra.

REVIEW LITERATURE

Laven RA, Peters AR. Bovine retained placenta:
etiology, pathogenesis and economic loss.Vet Rec
1996; 139:465-471.

Peters AR, Laven RA. Treatment of bovine retained
placenta and its effects. Vet Rec 1996;
139:535-539.

Frazer GS. Hormonal therapy in the postpartum cow -
days 1 to 10 - fact or fiction? AABP Proc 2001;
34:109.

REFERENCES

1. Bekana M et al. Acta Vet Scand 1996; 37:251.

2. Cohen RO et al. J Vet Med B 1996; 43:193.

3. Ziv G et al. Israel J Vet Med 1996; 51:63.

4. Kaneene JB, Miller R. Prevent Vet Med 1995;
23:183.

5. Laven RA, Peters AR. Vet Rec 1996; 139:465.

6. Stevens RD, Dinsmore RP. J Am Vet Med Assoc
1997; 211:1280.

7. Kimura K et al. J Dairy Sci 2002; 85:544.

8. Dohmen MJW et al. Theriogenology 2000;
54:1019.

9. Konigsson K et al. Reprod Dom Anim 2001; 36:247.

10. Bretzlaff KN et al. Am J Vet Res 1983; 44:764.

11. Smith BI et al. J Dairy Sci 1998; 81:1555.

12. Zhou C et al. J Am Vet Med Assoc 2001; 219:805.

13. Okker H et al. J Vet Pharmacol Ther 2002; 25:33.

14. Drillich M et al. J Dairy Sci 2001; 84:2010.

15. Cohen RO et al. Israel J Vet Med 1993; 48:69.

16. Dinsmore RP et al. J Am Vet Assoc 1996; 209:1753.

17. Leblanc SJ et al. J Dairy Sci 2002; 85:2237.

18. McDougall S. New Zealand Vet J 2001; 49:150.

19. Scott HM et al. J Am Vet Med Assoc 2005;
226:2044.

20. Callahan CJ et al. Bovine Pract 1988; 23:21.

21. Stevens RD et al. J Am Vet Med Assoc 1995;
207:1612.

22. Peters AR, Laven RA. Vet Rec 1996; 139:535.

23. Frazer GS. AABP Proceedings 2001; 34:109.

24. Mollo A et al. Anim Reprod Sci 1997; 48:47.

Hypovolemic, hemorrhagic,
maldistributive and
obstructive shock

Etiology Shock due to a reduction
in venous return (circuit failure) secondary
to hypovolemia, hemorrhage, mal-
distribution of blood or obstruction to
venous return

Clinical findings Depression and
weakness, subnormal temperature,
elevated heart rate with weak thready
pulse, cold skin and extremities, prolonged
capillary refill time. Progressive
development without aggressive fluid
therapy and collapse and death from
irreversible shock

Clinical pathology Increased blood or
plasma L-lactate concentration, decreased
venous oxygen tension, evidence of
multiple organ dysfunction. Decreased
central venous pressure, low mean arterial
blood pressure terminally. Changes in heart
rate, activity level and blood or plasma
L-lactate concentration indicate the efficacy
of treatment

Necropsy findings None specific for
hypovolemic or maldistributive shock; the
source of hemorrhage may be apparent in
hemorrhagic shock
Diagnostic confirmation Clinical
signs, blood or plasma L-lactate
concentrations, venous oxygen
tension

Treatment Aggressive fluid therapy
based on intravenous isotonic crystalloid
solutions and possibly colloid solutions.

Blood transfusion or stroma-free
hemoglobin administration for
hemorrhagic shock. Initial treatment by
rapid infusion with small-volume
hypertonic saline sol^ti^nPfS^s'a^pid but
transient resuscit3tTve"affdcI /)m|tjlPicr<^hial
agents and nomsfe^draal anti-inflamnjatqry
drugs in maldi^fritative shock due to \\
endotoxemiq / V

<! ., Acv. W, I

ETIOLOGY \U

The circulatory s>

(the heart) and a
Circulatory shock can result from abnor-
mal functioning of the pump or circuit, or
both. It is clinically very important to
differentiate pump failure (cardiogenic
shock due to acute or chronic heart failure)
from circuit failure, because the diag-
nosis and treatment of cardiogenic shock
is vastly different to that of circuit shock.
Cardiogenic shock is covered in detail
in Chapter 8, whereas circuit failure is
addressed in the following section.

Circuit failure occurs whenever the
cardiac output is reduced below a critical
point because of inadequate venous
return to the heart. There are four main
ways that circuit failure occurs:

0 Hypovolemic shock occurs when
there is a reduction in circulating
blood volume due to plasma or free
water loss

8 Hemorrhagic shock occurs when
there is a reduction in circulating
blood volume due to rapid blood
loss

° Maldistributive shock occurs
when there is a reduction in
circulating blood volume due to
increased capillary permeability,
Dooline of blood in canacitance

>• //

' <4 /'

stefnigonsistg 0f aj'ump

cfctouCthe. va^dulature) .

64

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

vessels (such as the veins in the
splanchnic circulation), or pooling
of plasma is a large third space
such as the thoracic or abdominal
cavities

° Obstructive shock occurs when
there is an acute reduction in venous
return due to a mechanical
obstruction, such as pericardial
tamponade or pulmonary
artery thrombosis. Obstructive
shock is extremely rare in large
animals.

Regardless of the initiating cause for
circuit failure and inadequate venous
return, tissue hypoperfusion results,
leading to impaired oxygen uptake and
anaerobic metabolism. The end result
of inadequate tissue perfusion is the
development of multiple organ failure,
L- lactate acidemia, and strong ion
(metabolic) acidosis, manifest as the
hypodynamic stage of shock. Hypo-
volemia and poor tissue perfusion results
in cold extremities, elevated heart rate, a
weak thready pulse, decreased capillary
refill times and altered mental status.
Cardiac arrhythmias may occur because
of myocardial ischemia and electrolyte
and acid-base disturbance. There is
anorexia and gastrointestinal stasis. Signs
of renal failure include anuria or oliguria
and azotemia.

Common causes of circuit failure in
large animals are as follows.

Hypovolemic shock

0 Fluid loss and dehydration, such as in
neonatal calf diarrhea and burn injury,
especially when fluid loss is severe
and rapid

0 Fluid loss into the gastrointestinal
tract due to acute intestinal
obstruction.

Hemorrhagic shock

Acute hemorrhage with loss of 35% or
more of total blood volume, equivalent to
an acute blood loss of 2.8% of body
weight (assuming blood volume is 8% of
body weight) will lead to clinical signs of
severe hemorrhagic shock. In contrast,
acute hemorrhage with loss of less than
10% of total blood volume (equivalent to
an acute blood loss of less than 0.8% of
body weight) produces minimal detect-
able clinical changes.

Traumatic injury or spontaneous rupture
of large blood vessels are the common
reasons for acute hemorrhage. Any sort of
minor surgical wound, e.g. castration,
dehorning, may lead to excess hemorrhage
where there is a hemorrhagic tendency
due to defects of clotting. Some of the
more common causes of hemorrhagic
shock areas follow.

Cattle and sheep

° Spontaneous pulmonary hemorrhage
associated with caudal vena caval
syndrome

° Abomasal ulcer, sometimes
originating from a bovine viral
leukosis lesion (cattle)

0 Enzootic hematuria with bleeding
from a bladder lesion (cattle)

° Pyelonephritis with bleeding from a
renal lesion (cattle)

0 Intra-abdominal hemorrhage as a
result of arterial aneurysm, possibly
associated with copper deficiency
(cattle)

° Laceration of arteries in the wall of
the vagina as a result of dystocia
0 Ruptured middle uterine artery during
prolapse or torsion of uterus
0 Cardiac tamponade due to rupture of
coronary artery or ventricular
chamber, rupture of aorta
(see Chapter 1)

0 Rupture of liver associated with
dystocia in lambs, and in older lambs
possibly associated with vitamin E
deficiency.

Horses

° Ethmoidal hematoma 1
° Exercise -induced pulmonary
hemorrhage 2

0 Rupture of the middle uterine, utero-
ovarian (especially right side) or iliac
artery associated with parturition,
more commonly in aged mares 3
0 Nasal bleeding from hemorrhage into
the guttural pouch, from carotid or
maxillary arteries with guttural pouch
mycosis or associated with rupture of
the longus capitis muscle following
trauma 11

• Rupture of mesenteric arteries

secondary to strongyle larval migration
0 Splenic hematoma 5 or rupture
following blunt trauma
° Rupture of liver with hyperlipemia
° Hemangioma, hemangiosarcoma and
other neoplasia

° Ftersistent bleeding from the vulva in
association with ulcerated varicose
veins on the dorsal wall of the vagina 6
0 Congenital venous aneurysm (rare). 7

Pigs

0 Esophagogastric ulceration
0 Proliferative hemorrhagic enteropathy
° Rupture of liver in hepatosis dietetica
° Congenital neonatal bleeding, e.g.
umbilical hemorrhage.

Maldistributive shock

0 Endotoxemia in neonatal septicemia,
salmonellosis, coliform mastitis in
lactating dairy cattle, toxic metritis in
cattle

° Septic shock due to Gram-positive
bacterial septicemia 8-10

® Too sudden reduction of pressure in a
body cavity, e.g. by rapid withdrawal
of ascitic fluid.

Obstructive shock

° Pericardial tamponade.

PATHOGENESIS
Hypovolemic shock

When cardiac output falls as a result of
decreased venous return, the carotid and
aortic baroreceptors stimulate the sym-
pathetic nerves and adrenal medulla to
release catecholamines resulting in
vasoconstriction in vessels with alpha-
adrenergic receptors. 8,11 Vasoconstriction
leads to decreased renal perfusion,
which activates the renin-angiotensin-
aldosterone system, thereby inducing
sodium and water retention. The decrease
in renal perfusion can result in renal
ischemia and nephrosis if the ischemia is
sufficiently severe and prolonged (see
Chapter 11). Hypovolemia also stimulates
the release of antidiuretic hormone
(vasopressin). There is contraction of the
spleen and venous capacitance vessels, an
increased peripheral vascular resistance
and an increase in heart rate in an
attempt to maintain cardiac output and
blood perfusion through the coronary and
cerebral blood vessels.

Water shifts from the interstitial space
to the vascular space in response to the
contraction of precapillary arterioles. In
the initial stages of hypovolemic failure
the primary signs are those of interstitial
fluid depletion and dehydration, with dry
mucous membranes, sunken eyes and
decreased skin turgor. Peripheral vaso-
constriction in the face of continued
hypovolemia and falling cardiac output
results in the opening of arteriovenous
shunts and decreased perfusion of organ
systems, with resultant damage from
hypoxia and tissue acidosis and the
development of clinical signs of peripheral
vascular failure and shock. Arterial blood
pressure falls terminally, and a decrease
in mean arterial pressure indicates a
complete lack of cardiovascular reserve.
The rate at which hypovolemia develops
profoundly affects the outcome because
compensatory mechanisms are more
readily overcome by acute than chronic
changes.

Hemorrhagic shock

The major effects of hemorrhage are loss
of blood volume (hypovolemic shock),
loss of plasma protein (decreased plasma
oncotic pressure), and loss of erythrocytes
(decreased oxygen-carrying capacity).

With acute and severe hemorrhage,
the rapid loss of blood volume results in
hypovolemic shock and the loss of
erythrocytes in anemic anoxia. The
combination of these two factors is

termed hemorrhagic shock and is often
fatal. With less severe hemorrhage, the
normal compensatory mechanisms,
including release of blood stored in the
spleen and liver and the withdrawal of
fluid from the tissue spaces, may maintain
a sufficient circulating blood volume, but
the anemia is not relieved and the oncotic
pressure of the blood is reduced by
dilution of residual plasma protein. The
resulting anemia and edema are repaired
with time provided the blood loss is
halted.

Maldistributive shock

In normal animals the healthy intestinal
mucosa is an effective barrier to the
absorption of endotoxin that is present in
the gut and the small amounts of endo-
toxin that are absorbed into the portal
blood are cleared by the liver and do not
reach the systemic circulation. When the
integrity of the intestine is compromised
by factors such as ischemia, trauma or
inflammation, sufficient endotoxin can be
absorbed to overwhelm the clearance
mechanisms of the liver, and endotoxin
may also leak to the peritoneal cavity and
thereby gain access to the systemic circu-
lation. Endotoxin can also be absorbed
from sites of local infection, as with
diffuse peritonitis, coliform mastitis and
toxic metritis, or released from Gram-
negative bacteria in the blood stream.
Intestinal mucosal integrity is lost in the
terminal stages of circulatory shock due to
tissue hypoxia, and endotoxin trans-
location from the intestinal tract is
markedly increased in the terminal stages
of shock, independent of the initiating
cause.

Endotoxin and other bacterial toxins
cause direct endothelial damage. 11 Endo-
toxin also activates macrophages and
neutrophils provoking the release of a
multitude of inflammatory mediators,
including TNF, interleukin-1, interleukin-
6 and platelet activating factor, which lead
to endothelial damage, leaky vessels,
hypotension and vasculitis and eventually
decreased intravascular volume. 12 In-
adequate perfusion of tissue with appro-
priately oxygenated blood impedes
oxidative cellular metabolism and leads to
the release of arachidonic acid, which is
metabolized by the cyclooxygenase
pathway to yield prostaglandins and
thromboxane A 2 or by the lipoxygenase
pathway to yield leukotrienes. 13,14 These
eicosanoids are potent vasoactive
compounds. They can act locally or be
carried in the circulation to act at distant
sites to further adversely affect vascular
reactivity and vascular permeability. 11
Endotoxin itself also provokes increased
synthesis and release of eicosanoids 13 and
many of the early effects of endotoxin are

Hypovolemic, hemorrhagic, maldistributive and obstructive shock

65

mediated by these metabolites of
arachidonic acid. 15

A further consequence to tissue hypoxia
is damage to endothelium with exposure
of collagen; tissue thromboplastin
can initiate the intrinsic and extrinsic
coagulation cascades, leading to damage
to other organ systems and further
complications from the development of
DIC, 11 which may be central to the
development of irreversible shock.

In the early hyperdynamic stage of
endotoxemia and sepsis there is an
increased oxygen demand by peripheral
tissue and an increase in heart rate and
cardiac output with pulmonary and
systemic vasoconstriction. 16 Pulmonary
hypertension increases transvascular fluid
filtration in the lung and pulmonary
edema can develop when hypertension is
accompanied by increased vascular
permeability. 17 There is hypoxemia and,
despite the increase in cardiac output,
blood flow may be inadequate to meet
the needs of tissue in a hypermetabolic
state. 11 The late hypodynamic stage of
endotoxemia and sepsis is characterized
by decreased venous return, cardiac
contractility, cardiac output and mean
arterial pressure.

Obstructive shock

In severe pericardial tamponade, the
rapid increase in pericardial fluid volume
impedes diastolic filling of the heart and
therefore results in decreased cardiac
output. A similar response occurs in
advanced traumatic reticulopericarditis in
cattle that have ingested a wire; however,
in the latter condition the obstruction is
slow to develop.

CLINICAL FINDINGS

Depression, weakness and listlessness are
accompanied by a fall in temperature to
below normal. The skin is cold and skin
turgor is decreased. The mucosae are pale
gray to white and dry, and capillary refill
time is extended beyond 3-4 s.

There is an increase in heart rate to
120-140 beats/min in horses and cattle,
with abnormalities of the pulse including
small and weak pressure amplitudes (a
'thready' pulse). Cardiac arrhythmias are
present terminally. Venous blood pressure
is greatly reduced in hypovolemic and
hemorrhagic shock and the veins are
difficult to raise. Arterial blood pressure,
measured either directly by arterial punc-
ture or by indirect oscillometric methods,
is decreased terminally and fails to
provide an early indicator of the severity
of the circulatory failure.

Anorexia is usual but thirst may be
evident and there is anuria or oliguria.
Nervous signs include depression, list-
lessness and obtusion, and coma in the
terminal stages.

During the early hyperdynamic
stage of maldistributive shock the tempera-
ture is normal or elevated, mucous mem-
branes are injected and brick-red in color,
there is tachycardia but normal capillary
refill time, and the extremities (particularly
ears) are cool to the touch. Whereas these
signs are not specific for shock, the
recognition of this stage in animals that
are at risk for maldistributive shock, such
as the neonate or animals with early signs
of acute intestinal accident, can allow the
early institution of therapy, which will
frequently result in a better outcome than
therapy instituted when the later stages of
shock are manifest.

Therapeutic reversal of maldistributive
shock in its later stages is difficult. In
contrast, circulatory failure that is a result
of hypovolemic or hemorrhagic shock is
relatively easily treated and can be
successfully reversed even at stages of
profound depression.

CLINICAL PATHOLOGY

The use of clinical pathology is directed at
determining the cause and severity of shock
and at monitoring the effectiveness of
therapy. Volume expansion and restoration
of tissue perfusion will usually correct
acid-base and strong ion (metabolic)
acidosis in the majority of animals with
shock and abnormalities are addressed
once fluid balance is established. 18

Examination of the blood for hematocrit
and plasma protein concentration are
valuable in indicating the magnitude of the
blood loss in hemorrhagic shock and
provide a clinically useful index to the
progress of the disease. However, there can
be a delay in the fall of the hematocrit
following hemorrhage for up to 4-6 hours
because splenic contraction temporarily
augments circulating red cell numbers. The
hematocrit and plasma protein concen-
trations usually fall to their lowest levels
12-24 hours following hemorrhage, and
determination at this time provides a
clinically useful index of the amount of
blood lost. Signs of a regenerative
response (increased hematocrit, presence
of reticulocytes, increased red blood cell
volume) should be seen within 4 days of an
acute hemorrhage in ruminants and pigs
but cannot be used as a guide in the horse.
In general, the hematocrit increases by 1%
per day following acute hemorrhage in
ruminants.

Abdominocentesis, thoracocentesis
and ultrasound are used to identify sites
of internal bleeding. Thrombocyte and
clotting factor examinations are indi-
cated in cases in which unexplained
spontaneous hemorrhages occur.

Monitoring in shock

Clinical parameters of heart rate, pulse

character, mucous membrane color,

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

temperature of the extremities (particularly
the ears) and activity level provide
extremely useful guides to the efficacy of
treatment when performed serially over
time. The single most valuable index is the
heart rate, although, in animals housed in
a stable ambient temperature, peripheral
skin temperature is also a useful clinical
guide but not during rapid intravenous
fluid administration because a thermal lag
of at least 30 minutes before increased
blood and heat flow to the periphery is
manifest as an increase in skin surface
temperature. 19 Blood or plasma L-lactate
concentration and venous oxygen ten-
sion provide the most useful measures of
the adequacy of oxygen delivery and
tissue perfusion, and therefore the efficacy
of treatment. These two laboratory
parameters are much more infonnative
than measurement of central venous
pressure or mean arterial blood
pressure, and blood pressure measure-
ment is discussed mainly for historical
interest.

Blood or plasma L-lactate concen-
tration, preferably measured in arterial
blood or blood from a large vein such as
the jugular vein, provides an indication of
prognosis and an even more valuable
serial measure of the efficacy of treat-
ment. In general terms, plasma L-lactate
concentrations are normally less than
1.5 mmol/L and fluctuate slightly depend-
ing on diet and time since feeding.
Plasma L-lactate concentrations of more
than 4 mmol/L indicate the presence of
widespread anaerobic metabolism and
the need for aggressive therapy, and
plasma L-lactate concentrations above
10 mmol/L are associated with a high
mortality in humans, pigs and horses. 20
Blood L-lactate concentrations are increased
in cows with abomasal volvulus
(3.8 mmol/L; 21 7.3 mmol/L; 22 4.8 mmol/L 23 );
however, blood lactate concentration did
not provide an accurate prognostic indi-
cator for survival. In general, it is the
change in plasma L-lactate concen-
tration after initiation of therapy that
provides the most useful guide to treat-
ment. In particular, failure to decrease the
plasma L-lactate concentration despite
aggressive and appropriate therapy is a
poor prognostic sign.

Venous blood oxygen tension (PoJ,
preferably measured in a large vein such
as the jugular vein, provides an indication
of the adequacy of oxygen delivery and is
a useful guide to the efficacy of treatment.
In general terms, venous Po 2 is normally
35-45 mmHg, arterial Po 2 is normally
90 mmHg and the difference between the
venous and arterial Po 2 depends on the
amount of oxygen extracted by tissues.
Whenever tissues receive inadequate
blood flow and therefore oxygen delivery.

their oxygen extraction ratio increases,
resulting in a greater difference between
arterial Po 2 and venous Po 2 and a lower
value for venous Po 2 . Venous Po 2 below
30 mmHg indicates inadequate oxygen
delivery and the need for aggressive
therapy; hemoglobin in erythrocytes or
stroma free solution in hemorrhagic
shock, plasma volume expansion in
hypovolemic and maldistributive shock. A
venous Po 2 below 25 mmHg indicates
severe abnormalities in oxygen delivery,
and venous Po 2 below 20 mmHg indi-
cates impending death. Aggressive resusci-
tation should always increase venous Po 2
to more than 40 mmHg, and failure to
substantially increase venous Po 2 despite
aggressive and appropriate therapy is a
poor prognostic sign.

Central venous pressure (CVP) is
another measure of hypovolemia but
individual measurements can be mis-
leading and serial measurements should
be used. By definition, central venous
pressure can only be measured by a
catheter placed in a blood vessel within
the thorax (typically the cranial vena
cava), as this permits measurement of
negative values for central venous pressure.
'Central venous pressure' is frequently
measured in the jugular vein through a
short intravenous catheter; this pressure
is more correctly termed jugular venous
pressure and, because it cannot be
negative, is of much less clinical value
than measuring CVP in shocked animals.
The normal CVP of the standing horse
referenced to the point of the shoulder
(scapulohumeral joint) is 12 ± 6 cmH 2 0
(1.2 ± 0.6 kPa) and is markedly influenced
by factors such as head position and
excitement. 24 In contrast, the normal CVP
of a standing calf is 0.6 ± 0.8 cmH 2 0 (0.06
±0.08 kPa), with only a small decrease in
CVP to -1.9 ± 1.0 cmH : 0 (0.19 ± 0.10 kPa)
being present in hypovolemic calves that
were severely dehydrated (14% body
weight). 25 A general rule of thumb in
horses is to administer fluids as long as the
CVP remains below 2 cmH 2 0 (0.2 kPa),
and to immediately discontinue fluid
administration whenever CVP exceeds
15 cmH 2 0 (1.5 kPa). The main clinical
utility of CVP measurement is ensuring
that volume overload is not occurring.

Mean arterial blood pressure is an
insensitive but specific method for deter-
mining the severity of shock and the
efficacy of therapy, in that mean arterial
blood pressure only decreases in the
terminal stages of shock, indicating a
complete lack of cardiovascular reserve.

NECROPSY FINDINGS

In hemorrhagic shock there is extreme
pallor of all tissues and a thin watery
appearance of the blood may be

accompanied by large extravasations of
blood if the hemorrhage has been
internal. Where the hemorrhage has been
chronic, anemia and edema are charac-
teristic findings. In obstructive shock
there is a large increase in pericardial fluid
(usually blood), or the presence of a large
thrombus in the cranial or caudal vena
cava or pulmonary circulation, or evidence
of severe abdominal distension (such as
in ruminal tympany). There are no specific
findings in hypovolemic or maldistributive
shock, although in maldistributive shock
the capillaries and small vessels of the
splanchnic area may be congested and
there may be evidence of pulmonary
edema. With death from septic shock the
major findings relate to the changes
associated with the infectious disease.
Dehydration is evident in animals dying
from hypovolemic shock.

DIFFERENTIAL DIAGNOSIS

Circulatory failure due to a circuit
abnormality can be diagnosed when there
is no detectable primary cardiac
abnormality, and when a primary cause
such as hemorrhage, dehydration, or
endotoxemia is known to be present.
Ideally, endotoxemic or septic shock should
be diagnosed in its early hyperdynamic
stage and aggressively treated at this
stage. This requires a knowledge of the
risks for shock with various conditions in
each of the animal species. Hypovolemic,
hemorrhagic, or maldistributive shock
should be anticipated:

• In septicemic disease, especially of the
neonate

• In acute localized infections

• With intestinal disease, but especially
with those in the horse that have acute
intestinal accident as part of the
differential diagnosis

• When severe trauma occurs

• Where there is severe fluid loss for any
reason

• Where decompression of an area is to
be practiced (i.e. removal of fluid from a
body cavity)

• When there is to be a significant surgical
procedure.

TREATMENT
Identification of cause

The identification and, if possible, the
immediate elimination of the precipitating
cause of the shock is important in cases
where circulatory failure is initiated by
conditions that are amenable to surgical
correction. Prompt surgical intervention
coupled with aggressive fluid therapy may
save an animal, whereas delaying surgery
until shock is advanced is almost always
followed by fatality. This requires a full
clinical examination and often ancillary
laboratory examination to accurately
identify the cause.

Hypovolemic, hemorrhagic, maldistributive and obstructive shock

67

The identification of cause will also
give some indication of the likelihood of
success in treatment. In general there is
greater success in the treatment and
management of hypovolemic and hemor-
rhagic shock, especially if treatment is
instituted early in the clinical course.
Effective treatment and management of
maldistributive shock is less successful
unless the sepsis can be controlled and
the source of the endotoxemia eliminated.

Hypovolemic and maldistributive
shock

The rapid administration of intravenous
fluids is the single most important
therapy in animals with hypovolemic or
maldistributive shock. The goal is to
increase venous return and thereby restore
circulatory function and tissue perfusion.
Crystalloid solutions (fluids that contain
electrolytes) and colloid solutions (fluids
that increase the plasma oncotic pressure
and expand plasma volume) can be used.
The general principles and practice of
fluid therapy are extensively discussed in
the section on disturbances of free water,
electrolytes and acid-base balance.

Isotonic crystalloid solutions
These are the least expensive and most
commonly used treatment for hypo-
volemic and maldistributive shock in
large animals. Balanced electrolyte solu-
tions, such as lactated Ringer's solution,
are preferable to 0.9% NaCl solutions. 26
Fluids for the restoration of the extra-
cellular fluid volume must contain
sodium but glucose solutions (fluids that
provide free water when the glucose is
metabolized) are not indicated in the
treatment of shock. Large volumes of
isotonic crystalloid fluids are required.
There is no set dose and each case needs
to be assessed individually; an initial
administration of 100 mL/kg by rapid
intravenous infusion is not unusual and
50 mL/kg is probably the minimum.
Isotonic crystalloid solutions expand the
interstitial fluid volume and promote
urine flow; however, beneficial responses
are absent shortly after the cessation of
fluid administration unless the syndrome
is resolved. 17,27

More fluids are administered as required
on the basis of clinical response and the
monitoring measures discussed above; in
general this involves continuous intra-
venous infusion during the clinical course.
In calves, ruminants and horses the re-
establishment of adequate tissue perfusion
by intravenous fluid therapy can often be
sustained by oral administration of large
volumes of electrolyte solutions. 28

The disadvantages of the use of
isotonic crystalloid solutions are the large
volume required for treatment, the
requirement for repeated treatment, and a

sustained increase in pulmonary artery
pressure with the risk for production of
pulmonary edema in animals with mal-
distributive shock due to endotoxemia. 29
Moreover, the delivery of large volumes of
isotonic fluid to large animals takes time
and is difficult to accomplish in the field.
This has led to the widespread use of
small-volume hypertonic saline solu-
tions for the initial resuscitation of
shocked animals. The intravenous adminis-
tration of small volumes of hypertonic salt
solutions results in a transcompartmental
and transcellular shift of fluid into the
vascular compartment, with an increase
in the circulating volume, cardiac con-
tractility and stroke volume and an
increase in blood pressure with a reduc-
tion in peripheral and pulmonary vascular
resistance. 17,26,27,29,30 However, there is
little improvement in renal function, the
improvement in hemodynamic function
is very short-lived and their use must be
followed by intravenous isotonic crystalloid
fluids.

Hypertonic saline solution
This has been used successfully in fluid
therapy of hypovolemic, maldistributive
and hemorrhagic shock and is of value for
the rapid resuscitative effect and the
lower risk for induction of pulmonary
edema in animals with endotoxemia 27,29-31
Small volumes (4-5 mL/kg) of hypertonic
saline (7.2%, 2400 mosmol/L) are infused
intravenously over 4-5 min. Too rapid an
infusion will result in vasodilation and
death and too slow an infusion will
diminish the resuscitative effect. There is a
risk of phlebitis if there is perivascular
deposition of hypertonic fluid.

Colloids

The intravenous administration of colloid
solutions (dextran, gelatin polymers,
hexastarch) induces a more sustained
increase in plasma volume than crystalloid
solutions and smaller volumes are required
for therapy, but colloid solutions are
expensive and are rarely used in cattle
and occasionally used in horses, with the
exception of blood transfusion. Colloid
solutions also have a risk for the induc-
tion of pulmonary edema 28 and may also
increase risk for coagulopathy. 11 For
horses, equine plasma is available
commercially but is expensive. The use of
hypertonic saline in combination with
colloids or infusions containing albumin
gives a more sustained response and
hypertonic saline-dextran solution
(2400 mosmol/L sodium chloride with 6%
Dextran-70) at a dose of 5 mL/kg is more
effective than hypertonic saline alone. 17,31

Hemorrhagic shock B

The source of the hemorrhage should be :
determined and the cause corrected. The

other immediate concern is to replenish
the blood volume and a decision must be
made if this will be with fluids, whole
blood or stroma-free hemoglobin solu-
tions. Blood transfusion replaces all
elements of the blood and in cases of
severe hemorrhage blood transfusion is
the most satisfactory treatment. However,
a decision for blood transfusion should
not be made lightly as the procedure is
time-consuming, costly and carries some
risk. 32 The collection of blood for trans-
fusion and its administration is covered in
detail in Chapter 9. The decision to use
whole blood in addition to fluids for
treatment is based on the need to replace
erythrocytes. The hematocrit can be a
guide, in combination with clinical
assessment, if the hemorrhage started at
least 4 hours previously. With acute
hemorrhage (<4h), transfusion is indi-
cated solely on the basis of the severity of
clinical signs.

In the period immediately following
hemorrhage a hematocrit of 20% is indi-
cative of a significant loss of erythrocytes
and the hematocrit should be monitored
over the next 24-48 hours. If there is a fall
to less than 12%, a transfusion of blood is
indicated, but a stable packed cell volume
(PCV) between 12% and 20% is not
usually an indication for transfusion. 33

Blood should be administered intra-
venously with an in-dwelling catheter
through an in-line filter. Administration
of the blood at too rapid a rate may cause
overloading of the circulation and acute
heart failure, particularly in animals with
both circuit and pump failure. A gallon
(4.5 L) of blood usually requires an hour
to administer to a cow and comparable
rates in the smaller species are advisable;
and an infusion rate of 10-20 mL/kg/h is
recommended for the horse, 32 with faster
rates (40 mL/kg/h) for foals. 33

Hypertonic saline solution is
recommended in the initial treatment of
hemorrhagic shock and has been shown
to be effective in the treatment of
experimental hemorrhagic shock in large
animals. 17,18,24 Hypertonic saline can be of
particular value to the ambulatory clinician,
as this therapy can be used in emergency
situations for the initial resuscitation of
cases of hemorrhagic shock pending
transfusion. 17,18 A further advantage to
the ambulatory clinician is the ease of
portability of this fluid. The use of hyper-
tonic saline is contraindicated where the
hemorrhage has not been controlled, as
its use in these cases will result in more
protracted bleeding.

Drugs to assist coagulation and arrest
hemorrhage are used in some cases but
there is limited information on their
efficacy. Aminocaproic acid (10 g in 1 L of
saline for an adult horse, administered

68

PART T GENERAL MEDICINE ■ Chapter 2: General systemic states

intravenously) has been recommended 34
for the management of hemoperitoneum
in the horse. Formalin has traditionally
been used to control hemorrhage and
10-30 mL of buffered neutral formalin in
500 mL of saline administered rapidly
intravenously through an intravenous
catheter has been recommended for the
control of postparturient hemorrhage in
mares. 35 Ergonovine maleate, 1-3 mg
intramuscularly at 3-hour intervals has
also been used to control hemorrhage in
the postparturient mare. 36

Animals should be kept quiet and in a
dark stall to minimize excitement and the
risk of further hemorrhage. Analgesic
drugs should be given with hemorrhagic
disease where there is pain, such as
rupture and hemorrhage of the broad
ligament of the uterus.

Obstructive shock

The source for the obstruction should be
identified and specific remedies applied.
This is a rare cause of shock in large
animals.

Ancillary treatment

A large number of drugs have been
shown to influence various components
of the inflammatory response in septic
shock but none has been shown to alter
the eventual outcome and the inter-
ference of one aspect of the inflammatory
cascade triggered by endotoxin should
not be expected to improve overall
survival. 11 The specific treatment of
maldistributive shock has been discussed
earlier.

Corticosteroids

There is considerable controversy over the
use of corticosteroids in shock. Experi-
mental studies have shown that they may
have value in the prevention of mal-
distributive shock but for this to occur
corticosteroids must be given prior to the
bacterial or endotoxin challenge. There is
little evidence that they are of value in the
treatment of hypovolemic, hemorrhagic
or maldistributive shock in animals once
clinical signs have developed. 11,26,37,38
Despite this, corticosteroids are frequently
used in the treatment of shock in
animals. 26 The dose that is used is con-
siderably higher than that used for other
indications, for example a dose of
1-2 mg/kg BW of dexamethasone
intravenously.

Cyclooxygenase inhibitors
The use of cyclooxygenase inhibitors such
as flunixin meglumine (0.25 mg/kg BW)
and ketoprofen (0.5-2.2 mg/kg BW) has
attractions in that they inhibit the pro-
duction of the vasoactive prostaglandins
and thromboxane A 2 . This may not be
entirely advantageous as the alternate
path of metabolism of arachidonic acid is

to leukotrienes, which are also potent
mediators of inflammation. Treatment of
horses with endotoxemia with cyclo-
oxygenase inhibitors does result in a
better maintenance of blood pressure and
tissue perfusion but does not influence
the eventual mortality. 11 Tirilazad
mesylate suppresses eicosanoid pro-
duction and TNF activity and has been
shown to be of benefit in the treatment of
experimental endotoxemia in calves. 39

Antibiotic therapy

With maldistributive shock the appro-
priate antibiotic therapy should be
immediately instituted. Antibiotic therapy
will not counteract the immediate effects
of endotoxin and may theoretically
increase the release of endotoxin in the
short term but this should not be a
contraindication to antibacterial therapy.
Pending the result of bacterial culture and
susceptibility testing a broad-spectrum
bactericidal antibiotic, or a combination of
antibiotics to achieve a broad spectrum,
should be used. Gram-negative septicemia
in calves or foals, or acute-diffuse
peritonitis, must be treated with anti-
biotics as well as by aggressive fluid
therapy if there is to be any chance of
survival.

Vasoconstrictors and vasodilators
The administration of vasoconstrictors
and vasodilators in cases of shock
remains problematic unless the patient's
cardiovascular status is accurately known
and can be continuously monitored.
In general, their use is not currently
recommended. The administration of a
vasoconstrictor substance in a case of
low-pressure distributive shock might
seem rational because blood pressure
j would be elevated but it could reduce
j tissue perfusion still further, a- Adrenergic
| blockers improve tissue perfusion and
I cardiac function once the circulating
i blood volume has been restored but if
| hypotension is already present it will
i be further exacerbated. 40 Dopaminergic
| agonists may be useful in the early stages
! of maldistributive shock as long as
j monitoring is adequate. 26 This is seldom
] possible in large animal ambulatory
j practice and their use in large animals is
: confined to referral hospitals.

i Immunotherapy

Immunotherapy with antibody directed
against the core lipopolysaccharide
i antigens of Gram-negative bacteria may
be of value in the therapy or prevention of
j shock produced by endotoxin in some
I diseases but not in others. Immuno-
| therapy has shown some promise in the
i treatment of shock associated with
experimental endotoxemia in horses but
none for the control of maldistributive

f

shock associated with Gram-negative
sepsis in the neonate. 41-43 Hyperimmune
serum is available commercially and may
be indicated in those cases where
endotoxemia is a risk, in which case it is
given before the onset of severe signs. 44
Vaccination with these antigens has
proved of value in the reduction of clinical
disease produced by endotoxemia and in
a reduction of the occurrence of endotoxin-
induced shock associated with Gram-
negative mastitis in cows, although it
does not reduce the occurrence of infec-
tion of the udder. 45,46

REVIEW LITERATURE

Wagner AE, Dunlop Cl. Anesthetic and medical
management of acute hemorrhage during
surgery. J Am Vet Med Assoc 1993; 203:40-45.

Durham AE. Blood and plasma transfusions in horses.

Equine Vet Educ 1996; 8:8-12.

Constable PD. Hypertonic saline. \fet Clin North Am
Food Anim Pract 1999; 15:559-585.

Constable PD. Fluids and electrolytes. Vet Clin North
Am Food Anim Pract. 2003; 19:1-40.

Roy M. Sepsis in adults and foals. Vet Clin North Am
Equine Pract 2004; 20:41-61.

Sykes BW, Furr MO. Equine endotoxemia - a state of
the art review of therapy. Aust Vet J 2005;
83:45-50.

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Allergy and anaphylaxis

69

33. Durham AE. EquineVetEduc 1996; 8 : 8 .

34. Jeffery SC. Vet Med 1996; 91:850.

35. Hooper RN et al.Vet Med 1994; 89:57.

36. Rossdale PD. Equine Vet Educ 1994; 6:135.

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38. Ewart K et al. Am J Vet Res 1985; 46:140.

39 . Semrad SD, Dubielzig R. Can J Vet Res 1994;
58:67.

40. Hardie EM, Krues-Elliott K. J Vet Intern Med
1990; 4:306.

41. Spier SJ et al. Circ Shock 1989; 28:235.

42. Morris DD et al. Am JVet Res 1986; 47:544.

43. Morris DD et al. Am JVet Res 1986; 47:2554.

44. Murray R. In Practice 1998; 20(2):88.

45. Hogan JS et al. J Dairy Sci 1992; 75:78.

46. Cullor JS. J Am Vet Med Assoc 1992; 200:1894.

Allergy and anaphylaxis

When exposure of an animal to an
antigen produces a state of increased
reactivity of the animal's tissues to that
antigen, a state of specific immune
responsiveness is achieved. In most
animals these responses are defensive
and beneficial but, on occasion, they can
be detrimental to the host. In these cases
a state of hypersensitivity is said to exist,
which is clinically recognizable as allergy.
When the reaction is sudden and
clinically severe it is called anaphylaxis
and if sufficiently severe it may result in
anaphylactic shock.

There are a number of immune
reactions that can be harmful to tissues
but in large animals the immediate
hypersensitivity reactions, especially
those that result in severe anaphylaxis,
pulmonary (potentially recurrent airway
obstruction (RAO) horses) and derma-
tological diseases (such as Queensland
itch) are most important. There are other
immediate hypersensitivity reactions that
should be noted. They include isoimmune
erythrolysis of foals - a specific cytotoxic
hypersensitivity - and the more general-
ized formation of circulating immune
complexes, which cause vasculitis, throm-
bosis, hemorrhage and consequent tissue
damage. Purpura hemorrhagica is prob-
ably the best example.

There are four major mechanisms for
the induction of a hypersensitivity
response. They are classified as types I- IV
based on the immune mechanism that
elicits the disease state . 1 Types I-III are
antibody-mediated responses to antigen
and include such conditions as systemic
anaphylactic shock (type I), autoimmune
hemolytic anemia (type II) and the local
Arthus reaction (type III). Type IV hyper-
sensitivity is caused by the induction of
sensitized T lymphocytes and thus has a
cell-mediated mechanism . 1

TYPE I

In immediate hypersensitivity reactions

the antigen, or allergen, reacts with

antibody, which may be either circulating
or cell-bound, to set in train a series of
complex biochemical and pharmacological
reactions that culminate in the release of
pharmacologically active mediators. There
are a number of recognized mediators
and the importance of any one varies with
the host species and possibly the nature
of the hypersensitivity reaction. In general
they act to contract smooth muscle and
increase capillary permeability. These
agents may act immediately at the site of
antigen-antibody reaction or they may be
carried in the blood to produce effects in
susceptible tissues at sites remote from
the primary focus. The difference in
manifestation of acute, immediate-type
hypersensitivity reactions between species
appears to depend largely on differences
in the tissue site of antibody binding and
the distribution of susceptible smooth
muscle, as well as differences in the major
pharmacological mediators of the reaction.
The high incidence of atopic hyper-
sensitivity with familial predisposition seen
in humans and dogs does not occur in
large animals.

The literature on immunoglobulin -E-
mediated hypersensitivity in food-
producing animals has been reviewed
and the details are available . 1

Immunological injury in the absence of
significant release of pharmacological
mediators also occurs but it is rarely
approached from the clinical standpoint
as a primary allergy and is generally
considered in the disease complex in
which it is occurring. The anemia and
glomerulitis that accompany equine
infectious anemia is an example. Serum
sickness is rare in large animals.

TYPE II

Autoimmune reactions are uncommon
in farm animals. They contribute to the
formation of spermatic granulomas.
Isoimmune hemolytic anemia and
thrombocytopenic purpura could be
considered as examples and are dealt
with elsewhere under those headings.

TYPE III

Arthus-type reaction or the Arthus
phenomenon is the development of an
inflammatory lesion, with induration,
erythema, edema, hemorrhage and
necrosis, a few hours after intradermal
injection of antigen into a previously
sensitized animal producing precipitating
antibody; it is classed as a type III
hypersensitivity reaction in the Gell
and Coombs classification of immune
responses. The lesion results from the
precipitation of antigen-antibody com-
plexes, which causes complement acti- j
vation and the release of complement '!
fragments that are chemotactic for
neutrophils; large numbers of neutrophils

infiltrate the site and cause tissue
destruction by release of lysosomal
enzymes.

TYPE IV

Cell-mediated or delayed hyper-
sensitivity is of importance in ' the
tuberculin and other long-term skin
sensitivity tests, but similar delayed
reactions to topically applied antigens are
not common in farm animals. Queensland
and sweet itch are probably examples.
Delayed hypersensitivity reactions may
contribute to the pathology of many
diseases such as mycoplasmal pneumonia
in swine, but those are considered clinically
under their initiating etiology.

TREATMENT

The treatment of allergic states is by the
use of functional antagonists which have
opposing effects to those of the allergic
mediators, and the specific pharmacological
antagonists, especially antihistamines and
corticosteroids. The functional antagonists
include the sympathomimetic drugs,
those related to epinephrine and, to a less
extent, the anticholinergic drugs. Of the
sympathomimetic drugs there is a choice
between those with an alpha-response
(vasoconstriction and maintaining vascular
permeability) and those with a beta-
response (bronchodilatory and cardiac-
stimulatory). Of the pharmacological
antagonists, antihistamines have very
limited usefulness, being effective only
when the allergic mediator is histamine,
the corticosteroids have very wide
applicability, and the NSAIDs, including
acetylsalicylic acid, phenylbutazone and
meclofenamic acid, all inhibit prostaglandin
synthesis and thus reduce inflammation.

ANAPHYLAXIS AND
ANAPHYLACTI C SHOCK

Anaphylaxis is an acute disease caused by
antigen-antibody reaction. If severe it
may result in anaphylactic shock.

ETIOLOGY

Most commonly, severe anaphylactic
reactions are seen in farm animals follow-
ing the parenteral administration of a
drug or biological product . 1 Other routes
of entry of the allergen, such as via the
respiratory or gastrointestinal tract, may
also result in anaphylactic reactions. The
reaction may occur at the site of exposure
or in other areas.

In general the reaction is due to
sensitization to a protein substance
entering the bloodstream and a second
exposure to the same substance. In
veterinary practice such incidents are not
uncommon, although the sensitizing
substance cannot always be isolated.

Although severe anaphylactic reactions
occur usually after a second exposure to a

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

f

sensitizing agent, reactions of similar
severity can occur with no known prior
exposure. In large- animal practice this is
most likely to occur after the injection of
sera and bacterins, particularly hetero-
logous sera and bacterins in which
heterologous serum has been used in the
culture medium.

Hypersensitivity reactions are some-
times observed at a higher incidence than
normal in certain families and herds of
cattle.

Anaphylactic reactions can occur in the
following circumstances:

® Repeated intravenous injection of
biological preparations such as
glandular extracts

• Repeated blood transfusions from the
same donor

• Repeated injections of vaccines, e.g.
those against foot-and-mouth disease
and rabies

® Rarely, after a first injection of a
conventional drug such as penicillin,
usually procaine or benzathine
penicillin, or a test agent such as
bromsulfalein. The reaction is
reminiscent of'serum sickness'in
humans because there has been no
known previous exposure to the
product, but occurs much earlier. It
may in fact be immediate and is
usually within a few hours after
injection

° Similar rare occurrences after the
injection of lyophilized Brucella
abortus strain 19 vaccine and
Salmonella vaccine. These, like the
preceding group, are really
anaphylactoid reactions because there
has been no apparent previous
exposure to the sensitizing antigen
° Assumed anaphylactic reaction to
ingested protein occurs in animals at
pasture or in the feedlot
° Cows, especially Channel Island
cattle, may develop anaphylaxis when
milking is stopped because the cows
are being dried off - severe urticaria
and respiratory distress occur
18-24 hours later

• A systemic reaction after Hypoderma
spp. larvae are killed in their
subcutaneous sites may be
anaphylactic, but is more likely to be a
toxic effect from breakdown products
of the larvae

• Anaphylactic like reactions can be
produced experimentally in calves by
injecting the endotoxin-like extract of
ruminal contents. Acute toxemia
develops about 30 minutes later, but
an anaphylactic reaction occurs when
the same extract is injected 15 days
later. This response is more correctly
termed endotoxemic shock.

PATHOGENESIS

Anaphylactic reactions occur as the result
of antigen reacting with circulating or
cell-bound antibody. In humans and dogs
a specific class of reaginic antibody, IgE,
has been identified and has particular
affinity for fixed tissue mast cells. 1 The
tissue distribution of mast cells in part
accounts for the involvement of certain
target organs in anaphylactic reactions in
these species. Homocytotropic antibody
has been detected in farm animals but the
classes of antibody involved in anaphylactic
reactions have not been fully identified
and are likely to be diverse. Anaphylactic
antibodies may be transferred via
colostrum.

Antigen-antibody reactions occurring
in contact with, or in close pro>«mity to
fixed tissue mast cells, basophils and
neutrophil leukocytes result in the
activation of these cells to release
pharmacologically active substances that
mediate the subsequent anaphylactic
reaction. These substances include
biogenic amines such as histamine,
serotonin and catecholamines; vasoactive
polypeptides such as kin ins, cationic
proteins and anaphylatoxins; vasoactive
lipids such as prostaglandins and slow
reacting substance of anaphylaxis (SRS-A);
and others. Knowledge of the type and
relative importance of pharmacological
mediators of anaphylaxis in farm animals
rests with studies of severe anaphylactic
reactions that have been induced experi-
mentally, but it is likely that these
mediators are also of significance in less
severe reactions. From these studies it
appears that histamine is of less import-
ance as a mediator in farm animals than
in other species and that prostaglandins
and SRS-A are of greater importance.
Bradykinin and 5-hydroxytryptamine
(5-HT) are also known to act as mediators
in cattle but the reactions in all species are
complex and involve a sequence of
mediator effects.

In the horse, there are four phases in
the development of the anaphylactic
response. The first is acute hypotension
combined with pulmonary arterial
hypertension 2-3 minutes after the injec-
tion of the triggering agent; it coincides
with histamine release. In the second
phase, blood plasma 5-HT levels rise,
and central venous blood pressure
rises sharply at about 3 minutes and
onward. The third phase commences at
about 8-12 minutes, and is largely reflex
and manifested by a sharp rise in
blood pressure, and alternating apnea
and dyspnea. Finally, there is a second
and more protracted systemic hypo-
tension due to prostaglandin and SRS-A
influence which persists until the return
to normality.

In cattle, there is a similar diphasic
systemic hypotension with marked
pulmonary venous constriction and pul-
monary artery hypertension. An increase
in mesenteric venous pressure and
mesenteric vascular resistance causes
considerable pooling of blood on the
venous side of the mesenteric vessels. In
both cattle and horses these reactions
are accompanied by severe hemo-
concentration, leukopenia, thrombo-
cytopenia and hyperkalemia.

Sheep and pigs also show a largely
pulmonary reaction.

In horses and cattle the marked
changes in vascular tone coupled with
increased capillary permeability, increased
secretion of mucous glands and broncho-
spasm are the primary reactions leading
to the development of severe pulmonary
congestion, edema and emphysema and
edema of the gut wall. Death is due to
anoxia.

Less severe reactions are also depen-
dent upon the effect of mediators on
capillary permeability, vascular tone and
mucous gland secretion. The major
manifestation depends on the distri-
bution of antibody-sensitized cells and of
susceptible smooth muscle in the various
organs. In cattle, reactions are generally
referable to the respiratory tract but the
alimentary tract and skin are also target
organs. Sheep and pigs show largely a
pulmonary reaction and horses manifest
changes in the lungs, skin and feet.

Sensitization of a patient requires
about 10 days after first exposure to the
antigen, and persists for a very long time:
months or years.

CLINICAL FINDINGS
Cattle

In cattle, initially there is a sudden onset
of severe dyspnea, muscle shivering and
anxiety. In some cases there is profuse
salivation, in others moderate bloat and
yet others diarrhea. After an incompatible
blood transfusion, the first sign is often
hiccough. Additional signs are urticaria,
angioneurotic edema and rhinitis. Muscle
tremor may be severe and a rise in
temperature to 40.5°C (105°F) may be
observed. On auscultation of the chest
there may be increased breath sounds,
crackles if edema is present, and
emphysema in the later stages if dyspnea
has been severe. In most surviving cases
the signs have usually subsided within
24 hours, although dyspnea may persist if
emphysema has occurred.

In natural cases the time delay after
injection of the reagin intravenously is
about 15-20 min but in experimentally
induced cases a severe reaction may be
evident within 2 min and death within
7-10 min of the injection. Clinical signs

Allergy and anaphylaxis

71

include collapse, dyspnea, wild paddling,
nystagmus, cyanosis, cough and the
discharge of a creamy, frothy fluid from
the nostrils. Recovery, if it occurs, is
complete in about 2 hours.

Sheep and pigs

In sheep and pigs, acute dyspnea is
common. Laminitis also occurs rarely in
ruminants.

Horses

In the horse, naturally occurring
anaphylactic shock is manifested by
severe dyspnea, distress, recumbency and
convulsions. Death may occur within less
than 5 min but it usually requires about
an hour. Laminitis and angioneurotic
edema are also common signs in the
horse. Experimentally induced anaphylaxis
may be fatal but not in such a short time.
Within 30 min of injecting the reagin the
horse is showing anxiety, tachycardia,
cyanosis and dyspnea. These signs are
followed by congestion of conjunctival
vessels, increased peristalsis, fluid diarrhea,
generalized sweating and erection of the
hair. If recovery occurs it is about 2 hours
after the incident began. Death, if it
occurs, takes place about 24 hours after
the injection.

Pigs

In pigs, experimentally produced ana-
phylactic shock can be fatal within a few
minutes, with systemic shock being
severe within 2 min and death occurring
in 5-10 min. The disease appears to occur
in only one phase, in contrast to the four
fairly distinct states in horses. Labored
respiration, severe cyanosis, vomiting and
edema of the larynx, stomach and
gallbladder are the usual outcome. 9

CLINICAL PATHOLOGY

Blood histamine levels may or may not be
increased and few data are available on
blood eosinophil counts. Tests for sensi-
tivity to determine the specific sensitizing
substance are rarely carried out for
diagnostic purposes but their use as an
investigation tool is warranted. Serological
tests to determine the presence of
antibodies to plant proteins in the diet
have been used in this way.

Some significant changes occur during
immediate anaphylaxis in cattle and
horses but whether they have diagnostic
importance is uncertain. There is a
marked increase in packed cell volume, a
high plasma potassium concentration and
a neutropenia.

NECROPSY FINDINGS

In acute anaphylaxis in young cattle and
sheep the necropsy findings are confined
to the lungs and are in the form of severe
pulmonary edema and vascular engorge-
ment. In adult cattle there is edema and

emphysema without engorgement. In
protracted anaphylaxis produced experi-
mentally in young calves, the most
prominent lesions are hyperemia and
edema of the abomasum and small
intestines. In pigs and sheep pulmonary
emphysema is evident and vascular
engorgement of the lungs is pronounced
in the latter. Pulmonary emphysema
and widespread petechiation in the horse
may be accompanied by massive edema
and extravasations of blood in the wall
of the large bowel. There may also be
subcutaneous edema and lesions of
laminitis.

DIFFERENTIAL DIAGNOSIS

• A diagnosis of anaphylaxis can be made
with confidence if a foreign protein
substance has been injected within the
preceding hour, but should be made
with reservation if the substance
appears to have been ingested.

• Characteristic signs as described above
should arouse suspicion and the
response to treatment may be used as a
test of the hypothesis.

• Acute pneumonia may be confused
with anaphylaxis, but there is usually
more toxemia and the lung changes are
more marked in the ventral aspects; in
anaphylaxis there is general involvement
of the lung.

TREATMENT

Treatment should be administered
immediately; a few minutes' delay may
result in the death of the animal.
Epinephrine is the most effective treat-
ment for anaphylaxis and anaphylactic
shock. Epinephrine administered intra-
muscularly (or one-fifth of the dose given
intravenously) is often immediately effec-
tive, the signs abating while the injection
is being made. Corticosteroids potentiate
the effect of epinephrine and may be given
immediately following the epinephrine.
Antihistamines are in common use but
provide variable results due to the presence
of mediators other than histamine. Atropine
is of little value.

The identification of mediators other
than histamine in anaphylactic reactions
in farm animals has led to studies of the
effectiveness of drugs more active against
these mediators than antihistamines.
Acetylsalicylic acid, sodium meclofenamate
and diethylcarbamazine have all shown
ability to protect against experimentally
induced anaphylaxis in cattle and horses
and warrant trial in anaphylactic reactions
in these species. One of the important
clinical decisions, especially in horse
practice, is to decide whether an animal is
sufficiently hypersensitive to be at risl^
when being treated. An acute ana-
phylactic reaction, and even death, can

occur soon after intravenous injection of
penicillin into a horse. In suspect cases it
is customary to conduct an intradermal or
a conjunctival test for hypersensitivity
with a response time of about 20 minutes,
but these tests have their limitations. The
types of sensitivity are not necessarily
related and there is no sure relationship
between anaphylactic sensitivity and
either skin (or conjunctival) sensitivity or
circulating antibody, and the test often
gives false negatives. The reason why
some animals develop systemic hyper-
sensitivity and some develop cutaneous
hypersensitivity does not appear to
be related to the nature of the reagin
but may be related to the size of the
sensitizing dose.

OTHER HYPERSENSITIVITY
REACTIONS

These reactions include anaphylaxis of a
less severe degree than anaphylactic
shock and cases of cell-mediated delayed
hypersensitivity. The resulting clinical
signs vary depending on the tissues
involved, but are usually localized and
mild.

ETIOLOGY

Exposure to any of the etiological agents
described under anaphylaxis may result
in this milder form of hypersensitivity.
Exposure may occur by injection, by
ingestion, by inhalation or by contact with
the skin.

PATHOGENESIS

In anaphylactic reactions the clinical signs
may depend on the portal of entry. Thus
ingestion may lead to gastrointestinal
signs of diarrhea, inhalation to con-
junctivitis, rhinitis, and laryngeal and
bronchial edema. Cutaneous lesions can
result from introduction of the reagin via
any portal. They are usually manifested by
angioedema, urticaria or a maculopapular
reaction. All the lesions result from the
liberation of histamine, serotonin (5-HT)
and plasma kinins as in anaphylactic
shock.

CLINICAL FINDINGS

In ruminants inhalation of a sensitizing
antigen may cause the development of
allergic rhinitis. On ingestion of the
sensitizing agent there may be a sharp
attack of diarrhea and the appearance of
urticaria or angioneurotic edema; in
ruminants mild bloat may occur. Contact
allergy is usually manifested by eczema.
In farm animals the eczematous lesion is
commonly restricted to the skin of the
lower limbs, particularly behind the
pastern, and at the bulbs of the heels, or
to the midline of the back if the allergy is
due to insect bites. In many cases of
allergic disease the signs are very transient

2

PART 1 GENERAL MEDICINE ■ Chapter 2 : General systemic states

and often disappear spontaneously with-
in a few hours. Cases vary in severity from
mild signs in a single system to a systemic
illness resembling anaphylactic shock. On
the other hand, cases of anaphylaxis may
be accompanied by local allergic lesions.

DIFFERENTIAL DIAGNOSIS

The transitory nature of allergic mani-
festations is often a good guide, as are the
types of lesion and sign encountered. The
response to antihistamine drugs is also a
useful indicator. Skin test programs as
applied to humans should be utilized
when recurrent herd problems exist. The
differential diagnosis of allergy is dis-
cussed under the specific diseases listed
above.

TREATMENT

A combination of epinephrine, anti-
histamines and corticosteroids is usually
highly effective. Skin lesions other than
edema may require frequent local appli-
cations of lotions containing antihistamine
substances. Continued exposure to the
allergen may result in recurrence or
persistence of the signs. Keeping the
animals indoors for a week often avoids
this, probably because the allergen occurs
only transiently in the environment. Hypo-
sensitization therapy, as it is practiced in
human allergy sufferers, may ha ve a place in
small animal practice but is unlikely to be
practicable with farm animals.

REVIEW LITERATURE

Black L. Hypersensitivity in cattle, Pt 1. Mechanism of
causation; Pt 2. Clinical reactions; Pt 3. Mediators
of anaphylaxis. Vet Bull 1979; 49:77, 303.

Gershwin LJ. Immunoglobulin E-mediated hyper-
sensitivity in food-producing animals. Vet Clin
North Am Food Anim Pract 2001; 17:599-619.

REFERENCE

1. Gershwin LJ. Vet Clin North Am Food Anim Pract
2001; 17:599.

Edema

ETIOLOGY

Edema results from four causes: increased
hydrostatic pressure in capillaries and
veins due to chronic (congestive) heart
failure or obstruction to venous return;
decreased plasma oncotic pressure;
increased capillary permeability in
endotoxemia, part of the allergic response,
vasculitis and damage to the vascular
endothelium; or obstruction to lymphatic
flow.

Increased hydrostatic pressure

" Symmetric ventral edema in chronic
(congestive) heart failure, symmetric
pulmonary edema in acute heart
failure

» Generalized edema in enzootic
calcinosis of cattle

Etiology Increased hydrostatic pressure
(chronic (congestive) heart failure or
obstruction to venous return), decreased
plasma oncotic pressure
(hypoalbuminemia), increased capillary
permeability (endotoxemia) or decreased
lymphatic drainage (obstruction to lymph
flow) result in accumulation of fluid in the
interstitial space

Clinical findings Pitting, cool, usually
dependent, subcutaneous swelling and
fluid accumulation in peritoneal and
pleural cavities. Distribution of edema
varies with animal species
Clinical pathology Hypoalbuminemia
except with obstruction to venous return
or lymph flow. Examinations aimed at
establishing the organ principally
responsible for edema formation
(commonly heart, kidney, gastrointestinal
tract, and liver) and at the cause of the
organ failure

Necropsy findings Fluid accumulation
in tissues and body spaces. Specific
changes with cause
Diagnostic confirmation Clinical
findings coupled with clinical pathology
Treatment Diuretics (furosemide) and
colloid replacement fluid therapy using
blood, plasma, or plasma volume
expanders. Correction of specific cause

° Local symmetric ventral edema in
udder edema in late pregnancy from
compression of veins and lymphatics
by the developing mammary gland
(and possibly the enlarging fetus and
uterus), causing mammary or ventral
edema in cows (particularly heifers),
mares and occasionally ewes. 1
Sodium and potassium intakes and
cation-anion differences in the diet
contribute to the severity of udder
edema. 2 Edema resolves 5-10 days
following parturition
-- Local edema by compressive lesions
on veins (as in thymic
lymphosarcoma with compression of
the cranial vena cava) 3 draining other
anatomic locations

° Local edema in portal hypertension
due to hepatic fibrosis causing ascites
(rare in large animals).

Decreased plasma oncotic pressure

Decreased total protein concentration in
plasma, and particularly decreased
plasma albumin concentration, will result
in symmetric ventral edema. Hypo-
albuminemia is more important than
hypoglobulinemia in inducing edema
formation because albumin provides the
largest contribution to plasma oncotic
pressure. Hypoalbuminemia can result
from increased loss (due to blood-
sucking parasites or across the gastro-
intestinal tract, kidneys or into a large
third space such as the pleural or peritoneal

cavities), decreased production (as in
chronic hepatic failure) or decreased
intake:

° Chronic blood loss, especially in
heavy infestations with blood-sucking
parasites such as Strongylus sp. in the
horse. Fasciola sp. in ruminants,
Haemonchus sp. in ruminants of all
ages, especially goats, and
Bunostomum sp. in calves
° Protein-losing gastroenteropathies as
in Johne's disease and amyloidosis in
adult cattle, right dorsal colitis in
horses; heavy infestation with
nematode parasites in ruminants,
particularly Ostertagia sp. in young
cattle and cyathostomiasis in horses
° Glomerulonephropathies, such as
amyloidosis in adult cattle, inherited
glomerulonephritis in Finnish
Landrace lambs

o Chronic liver damage causing failure
of plasma protein synthesis (rare and
terminal in large animals)

® Terminally in prolonged malnutrition
with low dietary protein intakes, e.g.
ruminants at range in drought time.

Increased capillary permeability

° Increased capillary permeability due
to endotoxemia

° Allergic edema as in urticaria and
angioneurotic edema caused by local
liberation of vasodilators
° Toxic damage to vascular endothelium
or vasculitis - in anthrax, gas
gangrene and malignant edema in
ruminants, edema disease of pigs,
mulberry heart disease in pigs, equine
viral arteritis, equine infectious
anemia, purpura hemorrhagica in
horses, and heartwater (cowdriosis) in
ruminants.

Obstruction to lymphatic flow

» Part of the edema caused by tumors
or inflammatory swellings is
lymphatic obstruction. Extensive fluid
loss also originates from
granulomatous lesions on serous
surfaces. Ascites or hydrothorax may
result

0 Congenital in inherited lymphatic
obstruction edema of Ayrshire and
Hereford calves

o Sporadic lymphangitis (bigleg) of
horses

o Edema of the lower limbs of horses
immobilized because of injury or
illness.

PATHOGENESIS

Edema is the excessive accumulation of
fluid in the interstitial space of tissue caused
by a disturbance in the mechanism of
fluid interchange between capillaries, the
interstitial space and the lymphatic
vessels. At the arteriolar end of the

Disturbances of free water, electrolytes and acid-base balance

73

capillaries the hydrostatic pressure of the
blood is sufficient to overcome its oncotic
pressure and fluid tends to pass into the
interstitial space. At the venous end of
the capillaries the position is reversed and
fluid tends to return to the vascular
system. The pressure differences are not
great, but there is a large area for exchange,
and a small increase in hydrostatic
pressure or a small decrease in oncotic
pressure leads to failure of the fluid to
return to the capillaries.

Increased fluid passage into the
interstitial space can also occur where
there is increased vascular permeability
due to vascular damage. Under these
circumstances, fluid accumulates in the
interstitial space when the fluid flux
across the endothelium is greater than the
ability of the lymphatic system to drain it.
Alternatively, capillary hydrostatic pressure,
oncotic pressure and vascular permeability
might be normal, but fluid and vascular
permeability can accumulate in the
interstitial space when lymphatic drain-
age is occluded.

Edema of the lower limbs of immo-
bilized horses ('filling') is usually ascribed
to poor lymphatic or venous return due to
inactivity of the 'foot pump'. Lower limb
edema in horses may also be related to
changes in the hematocrit and plasma
protein concentration in the distal limb
vasculature as a result of inactivity.

CLINICAL FINDINGS

Accumulation of edematous transudate in
subcutaneous tissues is referred to as
anasarca, in the peritoneal cavity as ascites,
in the pleural cavities as hydrothorax and
in the pericardial sac as hydro-
pericardium. Anasarca in large animals is
usually confined to the ventral wall of the
abdomen and thorax, the brisket and, if
the animal is grazing, the intermandibular
space because of the large hydrostatic
pressure gradient between the sub-
mandibular space and heart. Inter-
mandibular edema may be less evident in
animals housed such that they do not
have to lower their heads to feed. Edema
of the limbs is uncommon in cattle, sheep
and pigs but occurs in horses quite
commonly when the venous return is
obstructed or there is a lack of muscular
movement. Hydrothorax is not common
with generalized edema and is usually an
indication of an obstructive intrathoracic
lesion. Local edema of the head in the
horse is a common lesion in African horse
sickness and purpura hemorrhagica.

Edematous swellings are soft, pain-
less and cool to the touch, and pit on
pressure. In ascites there is distension of
the abdomen and the fluid can be
detected by a fluid thrill on tactile per-
cussion, fluid sounds on succussion and

by paracentesis. A level top line of fluid
may be detectable by any of these means.
In the pleural cavities and pericardial sac
the clinical signs produced by the fluid
accumulation include restriction of
cardiac movements, embarrassment of
respiration and collapse of the ventral
parts of the lungs. The heart sounds and
respiratory sounds are muffled, and the
presence of fluid may be ascertained by
percussion and thoracocentesis or peri-
cardiocentesis.

More localized edemas cause more
localized signs: pulmonary edema is
accompanied by respiratory distress and
in some cases by an outpouring of froth
from the nose; cerebral edema is mani-
fested by severe nervous signs of altered
mentation. A not uncommon entity is a
large edematous plaque around the
umbilicus in yearling horses. The plaque
develops rapidly, causes no apparent
illness and subsides spontaneously after
about 7 days. Thrombophlebitis is a
common cause of localized edema,
particularly of the head in horses and
cattle with thrombophlebitis of both
jugular veins. Head edema usually occurs
in affected animals only when there is
rapid and complete occlusion of both
jugular veins by thrombophlebitis; a
slower rate of jugular vein occlusion
permits development of collateral veins
for venous drainage of the head.

CLINICAL PATHOLOGY

Cytological examination of a sample of
fluid reveals an absence of inflammatory
cells where edema is the result of increased
hydrostatic pressure, decreased plasma
oncotic pressure (hypoalbuminemia),
increased vascular permeability or obstruc-
tion to lymphatic flow. Thoracocentesis or
abdominocentesis is useful to differentiate
the causes of fluid accumulation, in
conjunction with measurement of serum
albumin concentration and central venous
pressures.

Examinations should always be directed
towards determining the mechanism for
hypoalbuminemia; in particular, the renal
and gastrointestinal systems and liver are
examined for evidence of disease and
altered function. In general, the serum
albumin concentration is usually less than
15 g/L in animals with generalized edema
due to decreased plasma oncotic pressure.
Generalized edema should always be
expected whenever serum albumin con-
centration is less than 10 g/L.

NECROPSY FINDINGS

The nature of the accumulation of fluid in
most cases is obvious on gross post-
mortem examination but the determination
of the cause of the disease that has
resulted in hypoalbuminemia may require
further histological and cultural exam-

ination. Necropsy findings for the specific
diseases where edema is a feature are
given in the individual disease sections.

DIFFERENTIAL DIAGNOSIS

• Rupture of urethra or bladder for
differentiation of ascites

• Peritonitis or pleuritis for accumulation
of fluid in abdominal or pleural cavities

• Cellulitis for local edema

TREATMENT

The treatment of edema should be aimed
at correcting the cause, whether it is
increased hydrostatic pressure, decreased
plasma oncotic pressure, increased endo-
thelial permeability, or obstruction to
lymphatic drainage. Chronic (congestive)
heart failure may need to be treated with
digoxin and thrombophlebitis of the
jugular veins may need specific treatment
(see Ch. 8). Hypoalbuminemia may
require the administration of plasma or
plasma substitutes, although this is only a
short-term measure and is expensive.
Parasitic gastroenteritis requires adminis-
tration of the appropriate anthelmintic,
obstructive edema requires removal of
the physical cause, and increased per-
meability edema requires resolution of
the cause of endothelial damage.

Ancillary nonspecific measures include
restriction of the amount of salt in the diet
and the use of diuretics. Diuretics may
relieve the effects of pressure temporarily
but the primary cause needs to be
addressed for a satisfactory outcome.
Aspiration of edema fluid is rarely success-
ful and is not routinely recommended.
Aspiration usually provides temporary
relief because the fluid rapidly accumulates.

REFERENCES

1. Block E. J Dairy Sci 1994; 77:1437.

2. Al-Ani FK.Vestweber JGE.Vel Bull 1986; 56:763.

3. Alexander AN et al. J Vet Intern Med 1996; 10:275.

Disturbances of free water,
electrolytes and acid-base
balance

There are many diseases of farm animals
in which there are disturbances of body
fluids (free water), electrolytes and acid-
base balance. A disturbance of body water
balance in which more fluid is lost from
the body than is absorbed results in
reduction in circulating blood volume and
in dehydration of the tissues. In contrast,
the rapid ingestion of large quantities of
water can lead to overhydration (water
: intoxication).

Electrolyte imbalances occur com-
monly as a result of loss o f electrolytes,

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

shifts of certain electrolytes or relative
changes in concentrations due to loss of
water. Common electrolyte imbalances
include hyponatremia, hypokalemia,
hypocalcemia and hypochloremia.

Acid-base imbalances, either
acidemia or alkalemia, occur as a result
of the addition of acid and depletion of
alkali reserve, or the loss of acid with a
relative increase in alkali reserve.

Under most conditions, the above
disturbances of fluid and electrolyte
balance will occur simultaneously, in
varying degrees, depending on the initial
cause. Each major abnormality will be
described separately here with emphasis
on etiology, pathogenesis, clinical path-
ology and treatment. However, it is
important to remember that actual disease
states in animals in which treatments
with fluids and electrolytes are contem-
plated are rarely caused by single abnor-
malities. In most cases it is a combination
of dehydration together with an electro-
lyte deficit, and often without a disturbance
of the acid-base balance, that necessitates
treatment.

DEHYDRATION

ETIOLOGY

There are two major causes of dehydration:

° Inadequate water intake
« Excessive fluid loss.

Deprivation of water, a lack of thirst due
to toxemia, and the inability to drink
water as in esophageal obstruction, are
examples of dehydration due to in-
adequate water intake. The most common
cause of dehydration is when excessive
fluid is lost. Diarrhea is the most common
reason for excessive fluid loss, although
vomiting, polyuria and loss of fluid from
extensive skin wounds or by copious
sweating may be important in sporadic
cases. Severe dehydration also occurs in
acute carbohydrate engorgement in
ruminants, acute intestinal obstruction
and diffuse peritonitis in all species, and
in dilatation and volvulus of the abo-
masum. In most forms of dehydration,
deprivation of drinking water being an
exception, the serious loss, and the one
that needs correction, is not the fluid but
the electrolytes (Fig. 2.1).

The ability to survive for long periods
without water in hot climates represents a
form of animal adaptation that is of some
importance. This adaptation has been
examined in camels and in Merino sheep.
In the latter, the ability to survive in dry,
arid conditions depends on a number of
factors, including insulation, the ability to
carry water reserves in the rumen and
extracellular fluid space, the ability to
adjust electrolyte concentrations in
several fluid locations, the ability of the
kidney to conserve water and the ability

to maintain the circulation with a lower
plasma volume. Dehydrated mammals in
hot environments can save water by
reducing the rate of panting and sweating
and regulating body temperature above
hydrated levels. Sweating is a significant
avenue of evaporative heat loss in goats
when they are hydrated and exposed to
high ambient temperatures above 40°C.

Observations of drinking behavior of
cattle transported to the abattoir indicate
that those animals that had been sold in
livestock markets prior to arrival at the
abattoir are more thirsty and more tired
than cattle sent directly from farms. 1 This
indicates inadequate water intake and
dehydration.

PATHOGENESIS

Two factors are involved in the patho-
genesis of dehydration:

° Depression of tissue water content
with resulting interference in tissue
metabolism

0 Reduction in the free water content of
blood.

The initial response to negative water
balance is the withdrawal of fluid from
the tissues and the maintenance of
normal blood volume. The fluid is drained
primarily from the intracellular and
interstitial fluid spaces. Essential organs
including the central nervous system,

Fig. 2.1 Etiology and pathogenesis of dehydration.

heart and skeleton contribute little and
the major loss occurs from connective
tissue, muscle and skin. The loss of fluid
from the interstitial and intracellular
spaces results in loss of skin elasticity,
dryness of the skin and mucosa, and a
reduction and retraction of the eyeball
(enophthalmia) due to reduction in the
volume of the postorbital fat deposits. In
the goat, total body water may be reduced
as much as 44% before death occurs.

The secondary response to continued
negative water balance is a reduction in
the fluid content of the blood causing a
reduction in circulating blood volume
(volume depletion) and an increase in
the concentration of the blood (hemo-
concentration). Because of the hemo-
concentration, there is an increase in the
viscosity of the blood, which impedes
blood flow and may exacerbate peripheral
circulatory failure. The loss in circulating
blood volume also contributes to the
mental depression of dehydrated animals,
which is also due to varying degrees of
acidemia and toxemia depending on the
cause of the dehydration. In deprivation
of water and electrolytes or in deprivation
of water alone or inability to consume
water in an otherwise normal animal (e.g.
esophageal obstruction), the dehydration
is minimal because the kidney compensates
effectively by decreasing urine output and
increasing urine osmolality. In addition,
water is preserved by reduced fecal output
and increased absorption, which results in
dehydration of the contents of the rumen
and large intestine, which in turn results
in dry, scant feces.

In calves with acute diarrhea there is
increased fecal output of water compared
to normal calves but the total water losses
are not much greater than in normal
calves. In the diarrheic calf the kidney
compensates very effectively for fecal
water loss, and the plasma volume can be
maintained if there is an adequate oral
fluid intake. Urine excretion decreases,
the urine becomes progressively more
concentrated and the renal insufficiency
may accentuate pre-existing acidemia
and electrolyte imbalance, hence the
importance of restoring renal function.
The newborn calf is able to concentrate
urine at almost the same level as the
adult. This illustrates the importance of
oral fluid and electrolyte intake during
diarrhea to compensate for continuous
losses. However, it is possible for meta-
bolic acidosis to occur in diarrheic calves
and goat kids that are not dehydrated. 2,3

Goats are more sensitive to water
deprivation during pregnancy and
lactation than during anestrus. Water
deprivation for 30 hours causes a marked
increase in the plasma osmolality and
plasma sodium concentration in pregnant

Disturbances of free water, electrolytes and acid-base balance

75

and lactating goats. Pregnant and
lactating goats drink more than goats in
anestrus.

The dehydration in horses used for
endurance rides is hypotonic, in which
both sodium and water are lost through
sweating. This may account for the lack of
thirst in some dehydrated horses with the
exhaustion syndrome. Weight losses of
10-15 kg/h may occur in horses exercising
in high environmental temperatures
exceeding 32°C (89°F) and a horse
weighing 450 kg can lose 45 L of fluid in
a 3-hour ride.

Dehydration exerts important effects
on tissue metabolism. There is an increase
in breakdown of fat, then carbohydrate
and finally protein, to produce water of
metabolism. The increased endogenous
metabolism under relatively anaerobic
conditions results in the formation of acid
metabolites and the development of
metabolic acidosis. Urine formation
decreases because of the restriction of
renal blood flow and this, together with
the increased endogenous metabolism,
causes a moderate increase in blood levels
of nonprotein nitrogen. 4 The body
temperature may increase slightly initially
- dehydration hyperthermia - because of
insufficient fluid to maintain the loss of
heat by evaporation. The onset of sweating
in steers after exposure to high environ-
mental temperatures has been shown to
be delayed by dehydration.

Dehydration may cause death, especially
in acute intestinal obstruction, vomiting
and diarrhea, but it is chiefly a contri-
butory cause of death when combined
with other systemic states, such as
acidosis, electrolyte imbalances, toxemia
and septicemia.

CLINICAL FINDINGS

The first and most important clinical
finding in dehydration is dryness and
wrinkling of the skin, giving the body
and face a shrunken appearance. The eyes
recede into the sockets and the skin
subsides slowly after being picked up into
a fold. The dehydration is usually much
more marked if water and electrolyte
losses have been occurring over a period
of several days. Peracute and acute losses
may not be obvious clinically because
major loss will have occurred from the
intravascular compartment and only
minor shifts have occurred from the
interstitial spaces. Sunken eyes and
inelastic skin are not remarkable clinical
findings of dehydration in the horse.

The best indicator of hydration status
in calves has been demonstrated to be the
degree of recession of the eye into the
orbit. Hydration status is assessed by -
gently rolling the lower eyelid out to its
normal position and estimating the

distance of eye recession in millimeters.
This distance is multiplied by 1.7 to
provide an estimate of the degree of
dehydration as a percentage of euhydrated
body weight. 5 The second best indicator
of hydration status in calves is the
elasticity of the skin of the neck and
lateral thorax, which are assessed by
pinching the skin between the fingers,
rotating the skin fold 90° and noting the
time required after release of the skin fold
for the skin fold to disappear (normally
< 2 s). The elasticity of the skin fold on the
upper or lower eyelid is a poor indicator
of hydration status in calves and is not
recommended. The best methods for
assessing hydration status in adult cattle
and other large animals has not been
determined but it is likely that eye
recession and skin tent duration in the
neck region provide the most accurate
and sensitive methods for estimating
hydration status.

In diarrheic calves, the severity of
dehydration, hypothermia and metabolic
acidosis are associated with the degree of
mental depression. 6 The combined effects
of acidemia and dehydration also contri-
bute to hypothermia.

Loss of body weight occurs rapidly in
dehydration and muscular weakness and
inappetence or anorexia are common. In
horses deprived of water for 72 hours
there is a mean body weight loss of about
15%, and 95% of the animals have a urine
specific gravity of 1.042, a urine osmolality
of 1310 mosmol/kg and a urine osmolality/
serum osmolality ratio of 4:14. Prerenal
azotemia also develops.

The degree of thirst present will
depend on the presence or absence of
other diseases causing an inflammatory
response or endotoxemia. In primary
water deprivation, dehydrated animals
are very thirsty when offered water. In
dehydration secondary to enteritis associ-
ated with severe inflammation, acidemia
and electrolyte imbalance, there may be
no desire to drink. Horses that become
dehydrated in endurance rides may refuse
to drink and the administration of water
by oral intubation and enemas may be
necessary. In cattle on pasture and
deprived of water for up to 9 days and
then given access to water, there will be
staggering, falling, convulsions and some
death - signs similar to salt poisoning in
pigs. Experimental restriction of the water
intake in lactating dairy cattle for up to
4 days may reduce milk yield by 75% and
decrease body weight by 14%. A 10%
reduction in water intake causes a drop in
milk production that may be difficult to
detect. Behavioral changes are obvious:
cows spend considerable time licking the
water bowls. In cold climates, cattle are
often forced to eat snow as a source of

’6

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

water. The snow must be soft enough so
that it can be scooped up by the cattle and
3-5 days are necessary for the animals to
adjust to the absence of water and
become dependent on snow. During this
time there is some loss of body weight.
Lactating ewes relying on snow as a
source of free water reduce their total
water turnover by approximately 35%.

CLINICAL PATHOLOGY

Dehydration is characterized by an
increase in the packed cell volume
and total serum protein concentration,
although the latter response may be
modified by the presence of severe
enteritis, peritonitis, or proteinuria.

REFERENCES

1. Jarvis AM et al. Appl Anim Behav Sci 1996; 50:83.

2. Tremblay RRM, Butler DG. Can Vet J 1991; 32, 308.

3. Lorenz I. Vet J 2004; 168:323.

4. Groutides CP, Michell AR. BrVet J 1990; 146:205.

5. Constable PD ct al. J Am Vet Med Assoc 1998;
212:991.

6. Naylor JM.CanVetJ 1989; 30:577.

ACUTE OVERHYDRATION (WATER
INTOXICATION)

Synopsis .AHAA <>

Etiology Rapid ingestion of large
quantities of water

Epidemiology Access to water by thirsty
calves, or calves that have been marginally
deprived of water for some time

Clinical findings Dark red urine,
weakness and depression

Clinical pathology Hemoglobinuria,
hemoglobinemia, hypo-osmolality,
hyponatremia, hypochloremia
Necropsy findings Hemoglobinuria and
renal cortical necrosis
Diagnostic confirmation
Epidemiological, presence of hyponatremia
and hypochloremia; rule out other causes
of intravascular hemolysis
Treatment Time, possibly intravenous
hypertonic saline but usually too late to be
effective

The rapid ingestion of large amounts of
water by young calves with normal serum
sodium concentrations may result in
intravascular hemolysis, hemoglobinemia
and hemoglobinuria. In contrast, water
ingestion in hypernatremic animals may
result in cerebral edema but does not
produce hemoglobinuria. The cerebral
edema syndrome is described in sodium
chloride poisoning. Water intoxication
(acute overhydration) is described here.

ETIOLOGY

The ingestion of excessive quantities of
water when animals are very thirsty may
result in overhydration, which is also
called water intoxication. The primary
cause of acute overhydration is a rapid

decrease in the osmolality of the small
intestinal contents, which are normally
isotonic to plasma. Such a rapid decrease
in luminal osmolality occurs within
5 minutes of water ingestion 2 because
thirsty calves close their esophageal
groove when drinking. This results in a
large volume of water in the abomasum,
which is subsequently emptied into the
duodenum. Free water rapidly moves
from the small intestinal lumen into the
intravascular compartment because of
the large surface area for absorption in
the small intestine and development of an
osmotic gradient between the small
intestinal lumen and intestinal capillary
bed. The end result is a rapid decrease in
plasma osmolality and expansion and
rupture of erythrocytes, leading to intra-
vascular hemolysis, hemoglobinemia,
hemoglobinuria, hyponatremia, hypo-
chloremia and a decrease in plasma protein
concentration from preingestion values.

EPIDEMIOLOGY

The syndrome has been reported from
several countries but is uncommon.
Calves 2-4 months of age are most
commonly affected but the disease is also
recorded in adult cattle, 1 sheep 3 and
pygmy goats. 4 Water intoxication occurs
in calves in normal husbandry systems
when animals that have had limited
access to water are suddenly given free
access. Commonly water intoxication
occurs when calves previously fed a milk
replacer diet but no other fluid, or weaned
calves that have been on a starter diet but
limited water, are turned out to pasture or
to yards where water is freely available.
Calves that are not fed supplementary salt
or that have lost salt as a result of severe
exercise or high environmental tempera-
tures may be at higher risk 5 but the
syndrome also occurs where salt has not
been restricted. The majority of calves
show clinical signs within minutes to
hours of access to water.

The condition has been reproduced in
l calves by gavage with water at 12% of
, body weight. 6

CLINICAL FINDINGS

j Hemoglobinuria as a result of intra-
i vascular hemolysis is prominent and
i there may be a moderate to severe
\ hemolytic anemia. Dark red urine is
\ passed shortly following access to water,
j Additional signs include tachycardia and
| hypothermia if the temperature of the
j water ingested is below body tempera-
i ture. Affected animals are usually depressed
I and weak.

CLINICAL PATHOLOGY

Hemoglobinuria and hemoglobinemia
are evident and there is hypo- osmolality,
hyponatremia and hypochloremia. 5 Serum

total protein and albumin concentration
may be decreased but are usually within
the normal range because animals are
usually mildly dehydrated and thirsty
before ingesting large volumes of water.

Postmortem findings

There is marked pallor of the carcass and
renal cortical necrosis due to hemo-
globinemic nephrosis may be evident
histologically. 7

DIFFERENTIAL DIAGNOSIS

Other causes of intravascular hemolysis
and hemoglobinuria.

TREATMENT

Treatment of affected animals is usually
not attempted as the hypo-osmotic lysis
has already occurred when clinical signs
are manifest and serum osmolality is
usually gradually increasing as the distal
convoluted tubules eliminate excessive
free water. Hypertonic saline (7.2% NaCl,
5 mL/kg BW over 5 min intravenously)
is usually administered to correct the
hyponatremia and hypochloremia but
treatment is not necessary in mild cases.
Case fatality is low and hemoglobinuria
persists for only a few hours.

CONTROL

Water intoxication does not occur com-
monly and can be avoided by preventing
thirsty animals from having unlimited
access to water. Calves should have free
access to water by the end of the first
week of life.

REVIEW LITERATURE

Angelos SM, van Metre DC. Treatment of sodium
balance disorders: water intoxication and salt
toxicity.Vet Clin North Am Food Anim Pract 1999;
15:609-618.

REFERENCES

1. Bianca W. BrVet J 1970; 126:121.

2. ShimizuY et al. Jpn J Vet Sci 1979: 41:583.

3. Abdelrakim Al et al. Rev d'Elevage Med Vet Pay
| Trop 1985; 38:180.

| 4. Middleton JR et al. J Vet Intern Med 1997; 11:382.

i 5. Gilchrist F. CanVetJ 1996; 37:490.

| 6. Slalina L et al. Vet Med Prague 1993; 38:459.
j 7. Njoroge EM et al. Onderstepoort J Vet Res 1997;
64:111.

i

| ELECTROLYTE IMBALANCES

! Most electrolyte imbalances are due to a
I net loss of electrolytes associated with
i diseases of the alimentary tract. Sweating,

| exudation from burns, excessive salivation
I and vomiting also result in electrolyte
I losses, but are of minor importance in
| farm animals, with the exception of
i sweating, in the horse and dysphagia in
| ruminants. The electrolytes of major con-
| cern are sodium, chloride, potassium,

Disturbances of free water, electrolytes and acid-base balance

77

calcium and phosphorus. Losses of bicar-
bonate are presented under acid- balance
imbalance.

HYPONATREMIA

Sodium is the most abundant ion in the
extracellular fluid and is chiefly responsible
for the maintenance of osmotic pressure
of the extracellular fluid. The most com-
mon cause of hyponatremia is increased
loss of sodium through the intestinal tract
in enteropathies (Fig. 2.2). This is parti-
cularly marked in the horse with acute
diarrhea and to a moderate extent in
calves with acute diarrhea. The sodium is
lost at the expense of the extracellular
fluid. In calves with acute diarrhea due to
enterotoxigenic E. coli the sodium con-
centration of the intestinal fluid secreted
in response to the enterotoxin is similar to
that of plasma, and hyponatremia usually
occurs (hypotonic dehydration). Animals
affected with diarrhea of several days'
duration continue to lose large quantities
of sodium and the hyponatremia may
become severe. Hyponatremia can become
severe when sodium-free water or 5%
dextrose are used as the only fluid therapy
in animals already hyponatremic. Hypo-
natremia can also occur in animals with
proximal tubular dysfunction.

Hyponatremia causes an increase in
the renal excretion of water in an attempt
to maintain normal osmotic pressure,
which results in a decrease in the extra-

cellular fluid space, leading to a decreased
circulating blood volume, hypotension,
peripheral circulatory failure and ultimately
renal failure. Muscular weakness, hypo-
thermia and marked dehydration are
common findings.

Isotonic dehydration occurs when
there is a parallel loss of sodium and
water. Hypertonic dehydration, which
is uncommon, occurs when there is a loss
or deprivation of water with minor losses
or deprivation of sodium. Hypertonic
dehydration can occur in animals that are
unable to consume water because of an
esophageal obstruction. The dehydration
in isotonic and hypertonic dehydration is
mild compared to the marked clinical
dehydration that can occur in hypotonic
dehydration accompanied by marked loss
of water and concentration of the extra-
cellular space (Fig. 2.3).

There are no clinical signs that are
characteristic of hyponatremia. There is
usually dehydration, muscular weakness
and mental depression, which occur with
other disturbances of both water and
electrolytes and with acid-base imbalance.
Similarly, there are no clinical signs
characteristic of hypochloremia. However,
hyponatremia affects the osmotic pressure
of the extracellular fluid, and hypochloremia
promotes the reabsorption of bicarbonate
and further development of alkalosis.
Polyuria and polydipsia occur in cattle
with dietary sodium chloride deficiency.

HYPOCHLOREMIA

Hypochloremia occurs as a result of an
increase in the net loss of the electrolyte
in the intestinal tract in acute intestinal
obstruction, dilatation and impaction and
volvulus of the abomasum and in enteritis
(Fig. 2.4). Normally a large amount of
chloride is secreted in the abomasum by
the mucosal cells in exchange for bicar-
bonate, which moves into the plasma. The
hydrogen, chloride and potassium ions
secreted in gastric juice are normally
absorbed by the small intestine. Failure of
abomasal emptying and obstruction of
the proximal part of the small intestine
will result in the sequestration of large
quantities of chloride, hydrogen and
potassium ions which leads to a hypo-
chloremic, hypokalemic metabolic
alkalosis. A severe hypochloremia can be
experimentally produced in calves by
feeding them a low chloride diet and daily
removal of abomasal contents. Clinical
findings include anorexia, weight loss,
lethargy, mild polydipsia and polyuria. A
marked metabolic alkalosis occurs, with
hypokalemia, hyponatremia, azotemia
and death.

HYPOKALEMIA

Hypokalemia may occur as a result of
decreased dietary intake, increased renal
excretion, abomasal stasis, intestinal
obstruction and enteritis, and repeated
administration of corticosteroids with

Fig. 2.2 Etiology and pathogenesis of hyponatremia.

pgi PARTI GENERAL MEDICINE ■ Chapter 2: General systemic states

Fig. 2.3 Types of dehydration.

Fig. 2.4 Etiology and pathogenesis of hypochloremia.

mineralocorticoid activity (Fig. 2.5). The
prolonged use of potassium-free solu-
tions in fluid therapy for diarrheic animals
may result in excessive renal excretion of
potassium and hypokalemia. Alkalosis
may result in an exchange of potassium
ions for hydrogen ions in the renal
tubular fluid, resulting in hypokalemia.
Hypokalemia can cause muscle weak-
ness, prolonged unexplained recumbency,
inability to hold up the head, anorexia,
muscular tremors and, if severe enough,
coma. The treatment of ketosis in
lactating dairy cows with multiple
dosages of isoflupredone, a glucocorticoid
with some mineralocorticoid activity, can

cause hypokalemia and recumbency, with
a high case fatality rate. 1

The most common occurrence of
hypokalemia in ruminants is in diseases
of the abomasum that cause stasis and
the accumulation of fluid in the abo-
masum. Potassium becomes sequestered
in the abomasum along with hydro-
gen and chloride, resulting in hypo-
kalemia, hypochloremia and metabolic
alkalosis.

Metabolic alkalosis and hypokalemia
in cattle are often accompanied by
muscular weakness and paradoxic aciduria.
Hypokalemia causes muscle weakness by
lowering the resting potential of mem-

branes, resulting in decreased excitability
of neuromuscular tissue. Thus, the
differential diagnosis of the animal with
muscle weakness should always include
hypokalemia.

Hypokalemia and alkalosis also are
often directly related because of the renal
response to either. Hypokalemia from
true body deficits of potassium will cause
decreased intracellular concentration of
this ion. The intracellular deficit of
potassium and excess of hydrogen will
cause hydrogen secretion into the urine
when distal sodium reabsorption is
required. This situation exists in metabolic
alkalosis, where sodium bicarbonate

Disturbances of free water, electrolytes and acid-base balance

79

Fig. 2.5 Etiology and pathogenesis of hypokalemia.

reabsorption in the proximal nephron is
decreased because of the excess of plasma
bicarbonate. Distal nephron avidity for
sodium is increased to protect extra-
cellular fluid volume, and the increased
distal sodium reabsorption is at the
expense of hydrogen secretion, although
it is contrary to the need of acid retention
in the presence of alkalosis. In other
words, the kidney prioritizes maintenance
of plasma volume above that of acid-base
balance, presumably because respiratory
compensation can usually keep blood pH
within the normal physiological range.
Because electroneutrality of extracellular
fluid must be maintained by reabsorbing
an equivalent charge of cations and
anions, the reabsorption of chloride and
of bicarbonate in the kidneys are inversely
proportional to each other. Thus, with
excess trapping of chloride in the
abomasum, the kidneys will compensate
for the resulting hypochloremia by
increasing bicarbonate reabsorption,
which may proceed until metabolic
alkalosis develops.

The treatment of hypochloremic,
hypokalemic alkalosis requires correction
of extracellular fluid volume and sodium
and chloride deficits with 0.9% NaCl
infusions and oral KC1. Providing ade-
quate chloride ion allows sodium to be
reabsorbed without bicarbonate. Increased
proximal reabsorption of sodium will
decrease distal acid secretion because less

sodium is presented to the distal nephron.
As less bicarbonate is reabsorbed and less
acid secreted, the metabolic alkalosis is
resolved. Specially formulated solutions
containing potassium are necessary in
cases of severe hypokalemia and small-
intestinal obstruction.

Hypokalemia also occurs following
treatment of the horse affected with
metabolic acidosis and hyponatremia,
and probably reflects whole-body
potassium depletion. Horses used for
endurance rides may be affected by
hypokalemia, hypocalcemia and alkalosis
due to loss of electrolytes during the
competition. Synchronous diaphragmatic
flutter also occurs, which may be the
result of the electrolyte imbalance
(particularly hypocalcemia) causing
hyperirritability of the phrenic nerve.

Since potassium is the major intra-
cellular cation, the measurement of
plasma or serum potassium is not a
reliable indication of whole-body
potassium status. Extremely low levels or
high levels are usually indicative of a
potassium imbalance, often associated
with other electrolyte and acid-base
imbalances. In severe alkalosis, for
example, potassium leaves the extra-
cellular space and becomes concentrated
in the cells. This may result in low serum
potassium levels when, in fact, there
might not be potassium depletion of the
body. Conversely, in severe metabolic

acidosis of calves with acute diarrhea, the
potassium leaves the cells and moves into
the extracellular fluid. This results in
hyperkalemia in some cases where the
body potassium is normal or even
decreased. When changes occur in the
concentration of intracellular and extra-
cellular potassium, the ratio of intra-
cellular to extracellular potassium may
decrease by as much as 30-50%, which
results in a decrease in the resting
membrane potential. This is thought to be
the explanation for the effects of hypo-
kalemia and hyperkalemia on muscle
function.

The potassium concentration of red
blood cells may be a more accurate
indicator of whole-body potassium deficit
in diarrheic horses and provides a basis
for a calculated oral dose of potassium
chloride in horses with diarrhea, which is
a safe therapeutic procedure.

Potassium should be administered
intravenously or orally. The intravenous
route is used only for the initial treatment
of recumbent ruminants with severe
hypokalemia and rumen atony, as it is
much more dangerous and expensive
than oral treatment. The most aggressive
intravenous treatment protocol is an
isotonic solution of KC1 (1.15% KC1),
which should be administered at less than
3.2mL/kg per hour, equivalent to a
maximal delivery rate of 0.5 mEq of K + /kg
BW per hour. Higher rates of potassium

80

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

administration run the risk of inducing
hemodynamically important arrhythmias,
including ventricular premature complexes
that can lead to ventricular fibrillation and
death. A less aggressive intravenous
treatment is an isotonic equimolar
mixture of NaCl (0.45% NaCl) and KC1
(0.58% KC1), and the least aggressive
intravenous treatment is the addition of
10 mmol of KC1/L of Ringer's solution,
which will increase the solution osmolarity
to 329 mosmol/L. Clinical experience with
oral administration of KC1 has markedly
decreased the number of adult ruminants
treated with intravenous KC1.

Oral administration of potassium is
the method of choice for treating
hypokalemia. Inappetent adult cattle
should be treated with 30-60 g of feed
grade KC1 twice with a 12-hour interval,
with the KC1 placed in gelatin boluses.
Adult cattle with severe hypokalemia
(< 2.5 mEq/L) should initially be treated
with 120 g of KC1, followed by two 60 g
KC1 treatment at 8-hour intervals, for a
total 24-hour treatment of 240 g KC1.
Higher doses have been administered to
dairy cows but these are accompanied by
diarrhea, and oral administration of 0.58 g
KCl/kg BW was toxic in 6-month-old
Holstein calves, manifest by excessive
salivation, muscular tremors of the legs
and excitability, and a peak plasma [K + ] of
9.0 mEq/L. Extrapolating this toxic dose in
normokalemic calves to hypokalemic
600 kg cows suggests that a daily dose of
240 g KC1 approaches the upper limit of
safety. The recommended doses are
empirical but are effective in rapidly
increasing serum [K + ] and [CL], Inappetent
horses often have whole-body potassium
depletion and would benefit from supple-
mentary dietary potassium (25-50 g/d KC1).

HYPERKALEMIA

Hyperkalemia is not as common in farm
animals as hypokalemia, occurring most
commonly in severe metabolic acidosis.
The classic description for the develop-
ment of hyperkalemia in metabolic
acidosis involves a purported redistribution
of potassium from the intracellular space
to the extracellular space because a large i
proportion of the excess hydrogen ions j
are buffered intracellularly. Thus potassium j
is supposedly exchanged with hydrogen ;
ions across the cell membrane in order to i
maintain electroneutrality. A more likely j
mechanism is that metabolic acidosis is ;
accompanied by acidemia and a decreased j
intracellular pH; during intracellular ;
acidosis the function of all enzyme i
systems is decreased. As a direct result of i
the intracellular acidosis, the Na-K- |
ATPase activity is decreased, with !
potassium leaving the cell down its i
concentration gradient.

Hyperkalemia is potentially more life-
threatening than hypokalemia. Hyper-
kalemia (when over 7-8 mmol/L) has a
profound effect on cardiac function. There
is usually marked bradycardia and
arrhythmia and sudden cardiac arrest may
occur. The electrocardiogram (ECG)
changes in experimentally induced
hyperkalemia in the horse have been
described. The changes include four
successive stages as hyperkalemia
increased. There was a widening and
lowering of amplitude followed by inver-
sion and disappearance of the P wave, an
increase in the amplitude of the T wave,
an increase in the QRS interval, with
some irregularity in the ventricular rate,
and periods of cardiac arrest that became
terminal or were followed by ventricular
fibrillation. The minimum plasma
potassium concentration required to
induce ECG changes was 6-7 mmol/L
and severe cardiotoxic effects occurred at
levels between 8-11 mmol/L. The effects
of hyperkalemia on the ECG are exacer-
bated by the presence of hyponatremia.

Hyperkalemia has traditionally been
treated by intravenous administration of
sodium bicarbonate, glucose, insulin and
sometimes calcium. Hypertonic saline is
just as effective as is hypertonic sodium
bicarbonate in decreasing hyperkalemia
and hyperkalemia-associated brady-
arrhythmias, as a result of sodium-induced
intracellular movement of potassium,
extracellular volume expansion and the
strong ion effect of increasing the serum
concentration of a strong cation. The
long-held myth regarding the need to
administer glucose and insulin to 'drive'

I potassium into the cells during hyper-
I kalemia needs to be re-evaluated. Calcium
| counteracts the effect of hyperkalemia on
j the resting membrane potential by
increasing the threshold potential to a
higher value, thereby returning an appro-
priate difference between resting and
threshold potentials. Calcium can be
administered intravenously at 0.2-0.4 mL
of a 23% calcium gluconate solution/kg
BW. The focus of treatment in hyper-
kalemia should be correction of acidemia,
plasma volume expansion and increasing
the serum sodium concentration. Glucose
and insulin are not routinely needed to
correct hyperkalemia.

Hyperkalemic periodic paralysis
occurs in heavily muscled Quarterhorse.
Affected horses become weak, may stand
base-wide and are reluctant to move.
Sweating commonly occurs and
generalized muscle fasciculations are
apparent. Affected horses remain bright
and alert but may yawn and do not eat or
drink. Some horses become recumbent
and may appear to be in a state of
flaccidity. Attacks may occur in a rest

period following exercise or at random.
During the episode the serum potassium
concentration is elevated by up to twofold
and returns to normal values when the
animal recovers. Treatment consists of
sodium bicarbonate, hypertonic saline or
5% dextrose given intravenously, possibly
with insulin.

HYPOCALCEMIA

Hypocalcemia or milk fever may occur in
recently calved mature dairy cows that
have been inappetent or anorexic for a
few days. Hypocalcemia can be due to a
reduction in dry matter intake because of
illness or it may be the earliest stages of
hypocalcemic parturient paresis. The
clinical findings include anorexia, mild
tachycardia with a reduction in
the intensity of the heart sounds and
occasionally an arrhythmia, a decrease in
the frequency and amplitude of rumen
contractions or complete ruminal stasis,
and a decrease or complete absence of
feces, which may last from 6-36 hours if
untreated.

Hypocalcemia cases often mimic
intestinal obstruction and create problems
in the differential diagnosis. Affected
cattle may not exhibit any evidence of
muscular weakness and the detection of
the hypocalcemic state can be elusive. The
total serum calcium concentrations range
from 1. 5-2.0 mmol/L and the response to
intravenous therapy is usually good,
although recovery may require several
hours before the appetite returns to nor-
mal and feces are passed.

Calcium should be administered by
the intravenous, subcutaneous, or oral
route. Calcium gluconate and calcium
borogluconate are the preferred forms for
intravenous and subcutaneous adminis-
tration because CaCl 2 causes extensive
necrosis and sloughs of tissue when
administered perivascularly. Compared to
calcium gluconate, calcium borogluconate
! has improved solubility and shelf life,
i Plasma ionized calcium concentrations
are increased to a greater extent following
| CaCl 2 treatment when high equimolar
I solutions of CaCl 2 and calcium gluconate
I are administered, leading to more cardiac
j arrhythmias during CaCl 2 administration.

1 A typical treatment to an adult lactating
! dairy cow with periparturient hypocalcemia
j is 500 mL of 23% calcium borogluconate
\ by slow intravenous injection with cardiac
! auscultation, this provides 10.7 g of
| calcium. Although the calculated calcium
\ deficit in a recumbent periparturient dairy
! cow is 4 g calcium, additional calcium
i should be provided to overcome the
I continued loss of calcium in milk. A field
j study comparing the effectiveness of
[ different 5 doses of calcium for treating
| periparturient milk fever determined that

9 g of calcium was superior to 6 g. A good
rule of thumb for administering 23%
calcium borogluconate solutions (2.14 g
calcium/100 mL) to cows with periparturent
hypocalcemia is therefore to administer
1 mL/kg BW. There do not appear to be
any clinically important advantages to
slow administration of the solution over
6 h, when compared to 15 min. 2

The normal cardiac response to intra-
venous calcium administration is an
increase in the strength of cardiac con-
traction and a slowing of the heart rate.
Intravenous administration is continued
until the first arrhythmia is detected (a
bradyarrhythmia such as a prolonged
pause); the rate of intravenous adminis-
tration is then slowed until a second
arrhythmia is detected, at which time
intravenous administration is discontinued
and the remainder of the solution is
placed subcutaneously over the lateral
thorax. This treatment method titrates the
calcium dose required for each animal.
Auscultation of the heart is an absolute
requirement during treatment: visual
monitoring of the jugular pulse at the
base of the neck does not allow the early
detection of bradyarrhythmias, making it
more likely that the cow will receive a
toxic and possibly lethal dose of calcium.
The maximum safe rate of calcium
administration in cattle is 0.07 mEq of
Ca 2+ /kg BW/min, which is equivalent to
0.065 mL 23% calcium borogluconate/kg
BW/min. For a 500 kg normocalcemic
dairy cow, this corresponds to a maximum
safe rate of administration of 33 mL/min.
Typical rates of administration through a
14-gauge needle are 50 mL/min; this rate
of administration is safe for cows
with hypocalcemia, provided that cardiac
auscultation is performed during
administration.

Subcutaneous administration of

calcium solutions has been practiced for
many years. To facilitate absorption, it is
preferable to administer no more than
125 mL at a site. A 14-gauge needle is
placed subcutaneously over the lateral
thorax, 125 mL is administered, the
needle is redirected and another 125 mL
is administered. The process is then
repeated on the other side of the cow.
Although the effectiveness of sub-
cutaneous administration of calcium has
been documented in healthy normal
cows, there do not appear to be any
reports documenting the rapidity by
which subcutaneous calcium is absorbed
by cows with periparturient hypocalcemia.
Subcutaneous administration of calcium
gluconate is not recommended in
recumbent cows because poor peripheral
blood flow is suspected to lead to slow
absorption from the subcutaneous site.
Calcium chloride is not recommended for

Disturbances of free water, electrolytes and acid-base balance

81

subcutaneous administration because of
extensive tissue damage; the addition of
dextrose to the administered calcium is
also not recommended because it
increases the tonicity of the solution and
propensity for bacterial infection and
abscessation. Rectal calcium adminis-
tration is not recommended because it
causes severe mucosal injury and tenesmus
but does not increase plasma concen-
trations of calcium.

Oral administration of calcium has
also been practiced for many years,
usually by ororuminal intubation of calcium
borogluconate solutions designed for
parenteral administration. Over the past
decade there has been increased interest
in improving the efficacy of oral calcium
formulations. The results of a number of
studies indicate that oral calcium salts are
effective at increasing plasma calcium
concentration; orally administered calcium
is absorbed by a dose-dependent passive
diffusion process across ruminal epithelium
and a dose-independent calcium-binding
protein mechanism in the small intestine
that is modulated by vitamin D. Rapid
correction of hypocalcemia by oral
calcium administration is predominantly
by passive ruminal diffusion, as small
intestinal absorption is too slow to be of
clinical value.

Two calcium formulations are currently
recommended for oral administration to
ruminants; CaCl 2 and calcium pro-
pionate, but most commercially available
products contain 50 g of CaCl 2 . Calcium
chloride has the advantage of low cost
and low volume (because of its high
solubility), but CaCl 2 can severely damage
the pharynx and esophagus in ruminants
with reduced swallowing ability, can lead
to necrosis of the forestomach and
abomasum when administered in high
doses, and can lead to aspiration
pneumonia when administered as a
I drench. Calcium propionate has the
advantage that it is less irritating while
I providing a gluconeogenic substrate
I (propionate), but the disadvantages of l
\ higher volumes and cost. Oral calcium j
: solutions should only be administered to :

; cattle that have normal swallowing i
j ability, precluding their administration to '
j animals with advanced clinical signs of i
i hypocalcemia. Higher plasma calcium j
j concentrations are obtained more quickly !
| when calcium solutions are drenched j
j after administration of vasopressin to )
induce esophageal groove closure, or
when the calcium solution is administered
as a drench instead of ororuminal intu-
bation. Calcium solutions are suspected
! to have a higher likelihood of aspiration
pneumonia than calcium gels (with a
consistency similar to toothpaste),
although this supposition does not appear

to have been verified. Commercially avail-
able formulations of calcium gels contain
50 g of CaCl 2 and increase plasma calcium
concentrations within 30-60 minutes and
for at least 6 hours. Retreatment at 12-hour
intervals (if needed) therefore appears
indicated and provide 100 g of CaCl 2 and
37 g of calcium over 24 hours, but more
aggressive treatment protocols are not
recommended.

HYPOPHOSPHATEMIA

Hypophosphatemia also occurs in cattle
under conditions similar to those of
hypocalcemia. A decrease in feed intake
or alimentary tract stasis will result in a
decrease in serum inorganic phosphate.
Acute recumbency in lactating dairy cattle
may be associated with marginal
phosphorus deficiency, 3 although a cause
and effect relationship between hypo-
phosphatemia and recumbency has
not been established. 4 However, many
inappetent and weak cows have marginal
hypophosphatemia and clinically appear
to benefit from normalization of their
plasma concentration of phosphate. As
such, it is currently recommended that
ruminants with marked hypophosphatemia
and signs of illness should be treated with
phosphorus-containing solutions.

Almost all commercially available
intravenous solutions for treating hypo-
phosphatemia use phosphite (P0 2 2 ') or
hypophosphite (P0 3 3- ) salts as the
source of phosphorus because these salts
are very soluble, even in the presence of
calcium and magnesium. However, the
phosphorus in phosphite and hypo-
phosphite is unavailable to mammals,
meaning that the vast majority of
'phosphate'-containing solutions have no
efficacy in treating hypophosphatemia.
Instead, the monobasic mono-
phosphate form of sodium phosphate
(NaH 2 P0 4 ) should be administered. The
pH of the solution should be mildly acidic
(pH 5.8) to maintain phosphate solubility
in cold weather but is not needed in warm
ambient temperatures. A recommended
treatment to an adult lactating dairy cow
with severe hypophosphatemia is 300 mL
of 10% NaH 2 P0 4 (monohydrate) solution
by slow intravenous injection; this
provides 7 g of phosphate and increases
plasma phosphate concentrations for at
least 6 hours. Human enema formulations
that contain a mixture of monobasic
sodium phosphate monohydrate and
dibasic sodium phosphate heptahydrate
in a buffered solution have also been
administered to cattle with hypo-
j phosphatemia but are not recommended.

\ This human enema solution is extremely
| hypertonic and must therefore be diluted
before administration. A major drawback
i with intravenous administration of

PART I GENERAL MEDICINE ■ Chapter 2: General systemic states

phosphate solutions is that they should
not be administered within 2 hours of
intravenous calcium administration,
because of concerns that calcium-
phosphate precipitates may be formed in
the plasma of cattle with treatment-
induced hypercalcemia and hyper-
phosphatemia. This has traditionally been
evaluated by calculating the calcium-
phosphorus product, whereby metastatic
calcification may occur if the product of
serum calcium concentration and serum
phosphate concentration (both in mg/dL)
exceeds 70.

Hypophosphatemia is more safely
treated by administration of oral mono-
sodium phosphate, and this is the
preferred method of administration in
ruminants with rumen motility. Oral
administration also results in a more
prolonged increase in plasma phosphorus
concentration. Recommended dose is
200 g of feed grade monosodium phos-
phate (contains 50 g of phosphate)
administered in gelatin boluses, drench,
or by ororuminal intubation. Phosphorus
in other feed grade minerals (such as
bone meal or dicalcium phosphate) is
poorly available and is not recommended
for the treatment of hypophosphatemia.

HYPOMAGNESEMIA

Magnesium is usually administered
parenterally only when a ruminant exhibits
clinical signs of hypomagnesemia. Treat-
ment of hypomagnesemia is more
dangerous (to the animal and clinician)
and less satisfying than treatment of
periparturient hypocalcemia; the response
to treatment is much slower in hypo-
magnesemia presumably because mag-
nesium concentrations must be normalized
in cerebrospinal fluid, which turns over at
approximately 1% per minute.

Treatment of hypomagnesemia has
historically used 25% Epsom salts solu-
tion (magnesium sulfate heptahydrate;
MgS0 4 .6H 2 0); this solution concen-
tration was selected because it provided
approximately 1 mmol of magnesium per
liter. It should be noted that 25% Epsom
salts solution is markedly hypertonic
(2028 mosmol/L). A typical treatment for
an adult cow has been slow intravenous
administration (over at least 5 min) of
100 mL of the 25% Epsom salts solution,
this provides 2.5 g of magnesium (25 mg
of magnesium/mL of solution). More
recently, hypomagnesemia has been
treated using commercially available
combined calcium and magnesium solu-
tions; 500 mL of these solutions typically
contain 1.6-2. 7 g of magnesium in the
form of a borogluconate, chloride or
hypophosphite salt. Although the calcu-
lated extracellular deficit in a cow with
hypomagnesemia is 2 g of magnesium.

we should provide additional magnesium
to correct presumed intracellular defi-
ciencies and to overcome the anticipated
urinary loss of magnesium. Combined
calcium and magnesium solutions are
preferred for intravenous administration
to 25% Epsom salts solution because
ruminants with hypomagnesemia fre-
quently have hypocalcemia, and hyper-
calcemia provides some protection against
the toxic effects of hypermagnesemia.
Moreover, administration of solutions
containing magnesium as the only cation
increases the risk of developing cardiac
and respiratory failure during treatment.
The maximum safe rate of administration
of magnesium in cattle is 0.08 mEq Mg 2+ /kg
BW per minute, which is equivalent to
0.04 mL 25% Epsom salts/kg BW per
minute. For a 500 kg beef cow with hypo-
magnesemia, this corresponds to a
maximum safe rate of administration of
20 mL/min.

Magnesium-containing solutions (such
as 25% Epsom salts solution) can also be
administered subcutaneously, although
this frequently leads to necrosis of the
skin, particularly when 50% Epsom salts
solution is administered. Only combined
calcium and magnesium solutions should
therefore be administered subcutaneously.

The oral bioavailability of magnesium
is low and much lower than that of
calcium. Accordingly, oral administration
of magnesium is not recommended for
the treatment of hypomagnesemia, but is
essential for the prevention of hypo-
magnesemia. Magnesium absorption
from the rumen is facilitated by volatile
fatty acids but decreased by potassium
and the ammonium ion.

Rectal administration may be the only
practical and safe method for treating a
convulsing hypomagnesemic beef cow.
After evacuating the rectal contents, an
enema containing 60 g of Epsom salts
(magnesium sulfate heptahydrate) or
magnesium chloride in 200 mL of water
can be placed in the descending colon
(and not the rectum) and the tail held down
for 5 minutes; this increases plasma mag-
nesium concentrations within 10 minutes.
However, enema solutions can be pre-
maturely evacuated, eliminating the
chance for therapeutic success, and some
degree of colonic mucosal injury is
expected because of the high osmolarity
of 30% solutions (approximately
2400 mosmol/L). The safety of this treat-
ment protocol does not appear to have
been evaluated, although a 50 mL enema
of a 30% MgCl 2 .6H 2 0 solution rapidly
and effectively increased serum magnesium
concentration in 7-10-week-old calves and
relieved clinical signs of hypomagnesemia.

Oral administration of magnesium
hydroxide and magnesium oxide excess-

ively alkalinizes the rumen and can create
a severe metabolic alkalosis (strong ion
alkalosis), as absorption of magnesium
leads to hypermagnesemia and increased
plasma strong ion difference. Because oral
administration of sodium bicarbonate
causes expansion of the plasma volume
and creates a metabolic alkalosis (strong
ion alkalosis) without hypermagnesemia,
it is likely that oral sodium bicarbonate is
a more effective treatment for grain over-
load in ruminants.

REVIEW LITERATURE

Angelos SM, van Metre DC. Treatment of sodium
balance disorders: water intoxication and salt
toxicity .Vet Clin North Am Food An im Pract 1999;
15:609-618.

Goff JP. Treatment of calcium, phosphorus, and
magnesium balance disorders. Vet Clin North Am
Food Anim Pract 1999; 15:619-640.

Sweeney RW. Treatment of potassium balance
disorders. Vet Clin North Am Food Anim Pract
1999; 15:609-618.

Constable PD. Fluids and electrolytes. Vet Clin North
Am Food Anim Pract 2003; 19:1-40.

REFERENCES

1. Seilman ES et al. J Am Vet Med Assoc 1997;
210:240.

2. Braun U et al. Vet Rec 2004; 154:336.

3. Gerlof f BJ, Swenson EP. J Am Vet Med Assoc 1996;
208:716.

4. Metzner M, Klee W. Tier Umschau 2005; 60:13.

ACID-BASE IMBALANCE

The pH of mammalian blood is main-
tained within the normal range of
7.35-7.45 by its buffer systems, of which
hemoglobin is the most important,
because it has the greatest buffering
capacity. However, because the blood
hemoglobin concentration is regulated on
the basis of oxygen delivery instead of
acid-base balance, and because rapid
changes in hemoglobin concentration
occur only with marked changes in
hydration status or splenic contraction
associated with exercise, the bicarbonate
system has traditionally been considered
to be the most important buffer. Other
buffers in blood are plasma proteins and
phosphate. The addition of relatively large
amounts of acid or alkali to the blood is
necessary before its buffering capacity is
exhausted and its pH changed. Changes
from normal acid-base balance towards
alkalemia or acidemia occur commonly in
sick animals and make a significant
contribution to the observed clinical signs.

The traditional approach for assess-
ing acid-base balance focuses on how
plasma carbon dioxide tension (PCO 2 ),
plasma bicarbonate concentration
([HC0 3 “]), the negative logarithm of the
apparent dissociation constant (pKj') for
plasma carbonic acid (H 2 C0 3 ), and the
plasma solubility of C0 2 (S) interact to
determine plasma pH. This relationship
is most commonly expressed as the

Disturbances of free water, electrolytes and acid-base balance

83

Henderson-Hasselbalch equation: pH

= pK/ + log([HC0 3 “]/S x Pc O 2 ). The
evaluation of acid-base balance using the
Henderson-Hasselbalch equation has
historically used pH as an overall measure
of acid-base status, Pco 2 as an indepen-
dent measure of the respiratory
component of acid-base balance, and
extracellular base excess, actual HC0 3 “
concentration or standard HC0 3 “ as a
measure of the nonrespiratory (also called
metabolic) component of acid-base
balance.

When using the traditional Henderson-
Hasselbalch approach, four primary
acid-base disturbances can be dis-
tinguished: respiratory acidosis (increased
Pco 2 ), respiratory alkalosis (decreased
Pco 2 ), metabolic acidosis (decreased
extracellular base excess or actual HC0 3 “
concentration) and metabolic alkalosis
(increased extracellular base excess or
actual HC0 3 “ concentration). The anion
gap is easily calculated from the results of
serum biochemical analysis and is used to
determine whether unmeasured anions are
present. The Henderson-Hasselbalch
equation has a long history of use and
remains widely and routinely used in the
clinical management of acid-base dis-
orders. These advantages should not be
overlooked. The principal disadvantage of
the Henderson-Hasselbalch equation is
that it is more descriptive than mechanistic,
decreasing the value of the approach in
explaining the cause of acid-base changes
during disease. This is because the
Henderson-Hasselbalch equation fails
to distinguish between the effects of
independent and dependent variables on
plasma pH.

Actual plasma HC0 3 " concentration

in units of mmol/L is not measured
but calculated using the Henderson-
Hasselbalch equation and measured
values for pH and Pco 2 , whereby:

[HCOf] = S x Pco 2 x 10'^-^

The values for pK/ and S at 37°C are
6.12 and 0.0307/mmHg respectively for
normal mammalian plasma. The equation
at 37°C is therefore:

[HCOf] = 0.0307 x Pco 2 x

Because actual HC0 3 “ concentration is
calculated from pH and Pco^ it can never
provide an independent measure of the
nonrespiratory component of an acid-
base disturbance. A primary decrease in
Pco 2 (respiratory alkalosis) at normal pH
always is accompanied by a decrease in
plasma HC0 3 “ concentration (which
would be interpreted as a metabolic
acidosis). Likewise, a primary increase in
Pco 2 (respiratory acidosis) at normal pH
always produces an increase in plasma
HC0 3 “ concentration (which would be

interpreted as a metabolic alkalosis). In
both cases, the actual HC0 3 “ concen-
tration is dependent upon the pH and
Pco 2 , thereby providing no additional
information as to the cause of the
acid-base imbalance than that obtained
by knowledge of the pH and Pco 2 . It is
therefore illogical to use actual HC0 3 “
concentration to define the non-
respiratory (metabolic) component of an
acid-base disturbance.

The current use of actual HC0 3 "
concentration in the evaluation of acid-
base status results from Van Slyke's work
in 1924, where pH and total C0 2 (which
is highly correlated with actual [HC0 3 “])
could be measured more accurately than
Pco 2 .This led to the graphical depiction of
the curvilinear HC0 3 -pH relationship,
the so-called Davenport diagram, to
represent acid-base disturbances. With
the later development of accurate and
practical laboratory methods in the 1950s
to measure Pco^ acid-base derangements
were graphically depicted as approxi-
mately linear log(Pco 2 )-pH relationships.
This development led directly to the base
excess concept.

The normal range of plasma bicar-
bonate in large animals is 24-30 mmol/L
(this should be compared to the normal
range in humans, which is 22-24 mmol/L).
In mild metabolic acidosis the bicar-
bonate concentration is in the range of
20-24 mmol/L, moderate metabolic
acidosis is 14-18 mmol/L, and in severe
cases the values are below 10 mmol/L and
carry a grave prognosis. The levels of
Pco 2 , Po 2 , plasma bicarbonate and blood
pH can be used to detennine the degree
of compensation, if any, which has taken
place. In metabolic acidosis there may be
a compensatory decrease in Pco 2 due to
hyperventilation; in metabolic alkalosis
there may be an increase in Pco 2 due to
hypoventilation. In respiratory acidosis
due to severe pneumonia the arterial Po 2
will be markedly decreased.

The base excess value directly
expresses the amount (usually expressed
in units of mEq/L) of strong base (or acid)
added per liter of blood or plasma, when
the normal mean base excess value is
arbitrarily fixed at zero. As such, the base
excess is defined as the amount of strong
acid (such as HC1) needed to titrate the
pH of 100% oxygenated human blood to
7.40 at 37°C and at a Pco 2 of 40 mmHg.
By definition, the normal base excess
value for humans is 0 mEq/L (range is
-2 to +2 mEq/L), and a base excess of
more than +2 mEq/L indicates metabolic
alkalosis, whereas a value of less than
-2 mEq/L (negative base excess value or
base deficit) reflects metabolic acidosis.
The normal range of base excess in
large animals is 0-6 mmol/L.

Mathematical formulas and nomo-
grams are available to calculate base
excess from measured pH, Pco 2 and
blood hemoglobin concentration. Base
excess is usually expressed as BE ecf (also
called standard base excess or in vivo
base excess). Extracellular base excess is
the preferred measurement as this
formulation provides the best clinical
estimate of the required mmol/L of
HC0 3 “ required to correct metabolic
acidosis, as it assumes a fixed hemoglobin
concentration of 5 g/dL. Clearly, the BE ecf
value will be incorrect when applied to
animals with anemia or polycythemia;
however, the error introduced by this
approximation is small and usually
clinically insignificant.

Most blood gas analyzers calculate
base excess in units of mEq/L using
Siggaard -Andersen's empirical equation
derived from his nomogram with hemo-
globin concentration [Hb] and actual
HC0 3 ~ concentrations in mmol/L:

BE U ood = (1 - 0.023 x [Hb]) x

([HCOf] - 24.4 + (7.7 + 2.3 x [Hb])

x (pH -7.40)),

which is equivalent to the following
expression when [Hb] = 3.1 mmol/L =
5 g/dL:

BEecf = 0.93 x ([actual HCOf] -

24.4 + 14.83 x (pH -7.40)).

The calculated BE ecf value assumes
normal serum protein concentration
(7.2 g/dL) and therefore provides an
inaccurate estimate of the magnitude of a
metabolic acidosis or alkalosis in domestic
animals with hypoproteinemia or hyper-
proteinemia. The ability of extracellular
base excess (BE ecf ) and actual HC0 3 “
concentration to accurately characterize
the metabolic component of acid-base
status has been controversial for many
years, although BE ecf has advantages
compared to actual HC0 3 “ concentration.
The major advantages of the base excess
approach are that BE ecf is theoretically
related to strong ion difference and is
independent of respiratory activity. On
this basis, when using the traditional
Henderson-Hasselbalch approach to
acid-base balance, the recommended
approach is to use pH as an overall index
of acid-base status, Pco 2 as an index of
the respiratory component and standard
(in vivo) base excess as an index of the
nonrespiratory (metabolic) component.

The strong ion approach to acid-base
balance provides a revolutionary method
to assess acid-base balance that is
becoming more widely adopted. This
strong ion approach differs in three
■ii important areas from the tra-
ditional bicarbonatecentric application of
the Henderson-Hasselbalch equation:

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

1) acid-base balance is examined using a
systems approach; 2) a clear conceptual
distinction is made between dependent
variables (such as pH and [HC0 3 ~]) and
the independent variables; and 3) the
effects of protein concentration on acid-
base balance are considered.

The strong ion approach reduces the
chemical reactions in plasma to that of
simple ions in solution. This assumption
can be made because the quantitatively
important plasma cations (Na + , K + , Ca 2+ /
Mg 2 ^ and anions (CF, HC0 3 ~, protein,
lactate, sulfate, ketoacids) bind each other
in a salt-like manner. Plasma ions (such
as Cu 2+ , Fe 2+ , Fe 3+ , Zn 2+ , Co 2+ and Mn 2+ )
that enter into oxidation-reduction
reactions, complex ion interactions and
precipitation reactions are not categorized
as simple ions but are assumed to be
quantitatively unimportant in deter-
mining plasma pH, primarily because
their plasma concentrations are low.

Simple ions in plasma can be differ-
entiated into two main types, nonbuffer
ions (strong ions or strong electrolytes)
and buffer ions. Strong ions are fully
dissociated at physiological pH and
therefore exert no buffering effect. Strong
ions do, however, exert an electrical effect
because the sum of completely dissociated
cations does not equal the sum of
completely dissociated anions. Stewart
termed this difference the strong ion
difference (SID). Because strong ions do
not participate in chemical reactions in
plasma at physiological pH, they act as a
collective positive unit of charge.

In contrast to strong ions, buffer ions
are derived from plasma weak acids and
bases that are not fully dissociated at
physiological pH. The conventional dis-
sociation reaction for a weak acid (HA),
conjugate base (A“) pair is:

HA ^ - — H + + A~

and, at equilibrium, an apparent weak
acid dissociation constant (K a ) can be
calculated adopting the accepted con-
vention regarding hydrated solutes as K a
= [H + ][A“]/[HA], Fora weak acid to act as
an effective buffer, its pK a (defined as the
negative logarithm of the weak acid
dissociation constant K a ) lies within the
range of pH ± 1.5.

Conceptually, the buffer ions can be
subdivided into volatile buffer ions (HC0 3 ~)
and nonvolatile buffer ions (non-HC0 3 ~).
Bicarbonate is considered separately
because this buffer system is an open
system in arterial plasma; rapid changes
in carbon dioxide tension and hence
arterial plasma HCO^ concentration can
be readily induced through alterations in
respiratory activity. In contrast, the non-
HC0 3 ~ buffer system is a closed system
containing a fixed quantity of buffer.

Another important physiological dis-
tinction between these two buffer
systems is that an open buffer system
such as HC0 3 ~ can be effective beyond
the limits of pH = pKa ± 1.5. Finally, it
should be appreciated that HC0 3 ~ is a
homogeneous buffer ion while the non-
volatile buffer ion (A“) represents a
diverse and heterogeneous group of
plasma buffers (albumin, globulin and
phosphate) that is being modeled as a
single buffer. Another assumption in
Stewart's strong ion model is that HA and
A" do not take part in plasma reactions
that result in the net destruction or
creation of HA or A“. This is because
when HA dissociates, it ceases to be HA
(therefore decreasing plasma [HA]) and
becomes A“ (therefore increasing plasma
[A - ]). The sum of [HA] and [A~] (called
Atot) therefore remains constant through
conservation of mass, whereby: [A XOT ] =
[HA] + [A“] .

In summary, the strong ion approach
assumes that plasma ions act as either
strong ions, volatile buffer ions (HC0 3 ~)
or nonvolatile buffer ions (A“). Plasma
therefore contains three types of charged
entity: SID, HC0 3 ~ and A“. The require-
ment for electroneutrality dictates that at
all times the SID equals the sum of
bicarbonate buffer ion activity (HC0 3 ~)
and nonvolatile buffer ion activity (A'),
such that: SID - HC0 3 - A“ = 0. This
equation obviously assumes that all
ionized entities in plasma can be classified
as either a strong ion (SID), a volatile
buffer ion (HC0 3 ~) or a nonvolatile buffer
ion (A“).

An equation relating plasma pH to
three independent variables (Pco 2 ,
SID, A tot ) and three constants (K a , K 1; S)
has been developed based on these
assumptions. The most important factors
that determine plasma pH are Pco 2 , SID
and the concentrations of individual
nonvolatile plasma buffers (albumin,
globulins, phosphate). A change in any
one of these variables will produce a
direct and predictable change in plasma
pH. Using the strong ion approach, six
primary acid-base disturbances can be
distinguished, instead of the four pri-
mary acid-base disturbances (respiratory
acidosis, respiratory alkalosis, metabolic
acidosis, metabolic alkalosis) differentiated
when using the traditional Henderson-
Hasselbalch approach. The strong ion
approach indicates that acidemia results
from an increase in Pco 2 and nonvolatile
buffer concentration, or from a decrease
in SID. Alkalemia results from a decrease
in P C 0 2 and nonvolatile buffer concen-
tration, or from an increase in SID. The
unmeasured strong anion concentration
is quantified by calculating the strong ion
gap (SIG).

ACIDEMIA

ETIOLOGY

The traditional Henderson-Hasselbalch
approach to acid-base balance indicates
that general causes of nonrespiratory
(metabolic) acidosis can be divided
into three categories on the basis of
pathogenesis (Fig. 2.6):

° Excessive loss of base (bicarbonate)

0 Accumulation of endogenous or
exogenous acid

0 Combination of both of the above
processes.

For comparison, the strong ion approach
indicates that general causes of non-
respiratory (metabolic) acidosis can be
divided into two categories: strong ion
acidosis due to a decrease in strong
cation concentration (hyponatremia) or
increase in strong anion concentration
(hyperchloremia, hyper L-lactatemia,
hyper D-lactatemia, ketoacidosis), and
nonvolatile buffer ion acidosis due to
an increase in albumin, globulin and
phosphate concentration.

Some common specific causes include
acute diarrhea in newborn animals, acute
enteritis in adult cattle and horses and
carbohydrate engorgement in ruminants
and horses. Metabolic acidosis without
dehydration, which is probably due to
hyper D-lactatemia, has been described in
neonatal goat kids 1 and neonatal calves. 2
Respiratory acidosis also occurs where
there is retention of carbon dioxide in the
blood as a result of interference with normal
respiratory exchange. Thus pneumonia,
severe pulmonary emphysema, depression
of the respiratory center and left-sided
heart failure may all be accompanied by
respiratory acidosis. Metabolic acidosis
occurs in the newborn at the time of
parturition if this is prolonged and diffi-
cult. It is also common in shock with
peripheral circulatory failure and anaerobic
oxidation. A decrease in renal excretion of
acid in renal insufficiency or renal failure
also contributes to a metabolic acidosis.
The administration of excessive quantities
of acidifying solutions for the treatment of
metabolic alkalosis also may cause
acidosis. Acute intestinal obstruction in
the horse is commonly accompanied by
metabolic acidosis, whereas in other
species alkalosis occurs, at least initially.

PATHOGENESIS

The traditional Henderson-Hasselbalch
approach indicates that metabolic acidosis
is characterized by a low arterial blood pH
and a reduced plasma bicarbonate con-
centration, following the loss of bicarbonate
or the addition of hydrogen ions. Extra-
and intracellular buffering and respiratory
compensation minimize the change in

Disturbances of free water, electrolytes and acid-base balance

85

Weakness, lassitude, terminal coma.
Tachycardia. Decrease in blood
pressure and pulse amplitude

Bradycardia, arrhythmia

Fig. 2.6 Etiology and pathogenesis of acidema.

pH until the kidney can excrete sufficient
hydrogen ions to correct the acid-base
imbalance. 3 In general, the body will
tolerate a pH range of 7. 0-7. 6, although
survival has been reported at pH values
beyond these limits for short periods,
particularly in neonatal animals with
diarrhea.

Acidemia generally depresses cardiac
contractility and cardiac output in the
denervated heart. In the intact animal,
however, activation of the sympathetic
nervous system in response to acidemia
causes increased cardiac contractility,
increased heart rate and increased cardiac
output. In acidemia, the myocardial

response to catecholamines is not
depressed until the blood pH is decreased
to below 7. 0-7.1. 4 The increased carbon
dioxide tension of the blood and deple-
tion of bicarbonate causes an increase in
the depth and then the rate of respiration
by stimulation of the respiratory center
(Kussmaul breathing). However, when
hypovolemic shock is severe enough,
there is often depressed respiratory func-
tion, resulting in the additional accumu-
lation of hydrogen ions, and so the acidemia
is accentuated.

Acidemia causes varying degrees of
depression of the central nervous system
and muscular weakness. 1,5 Central nervous

abnormalities may develop in neonatal
foals that develop severe respiratory
compromise, resulting in hypoxemia and
hypercapnia, because of the reduced
ability of the cerebrospinal fluid to buffer
acid-base changes. 6 Carbon dioxide
concentration within the central nervous
system (CNS) may have an effect on
respiratory rate, neurotransmitter activity,
CNS activity, cerebral blood flow and
cerebral extracellular fluid volume. If the
blood-CSF and brain-CSF interfaces in
the neonate are immature and unable to
adequately compensate for vascular
1 changes in C0 2 , the hypercapnia may
contribute to the CNS abnormalities that

86

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

are often seen in sick newborn foals. The
increased cerebral blood flow may be
associated with cerebral edema, resulting
in the depression of cerebral activity
observed in these sick foals.

The increased urinary excretion of
acids in acidosis also causes polyuria,
which may be sufficiently severe to cause
dehydration or accentuate concomitant
dehydration.

CLINICAL FINDINGS

The major clinical manifestation of meta-
bolic acidosis is mental depression and
varying degrees of muscular weakness.
Newborn calves and goat kids with
metabolic acidosis are depressed, weak
and reluctant to suck. 3 In severe acidemia,
affected animals may be in lateral
recumbency and appear to be in a state of
coma. The depth and rate of respirations
may be increased because of the increased
Pco 2 . Respiratory compensation is normally
evident when the bicarbonate level is
diminished to 50% of normal. Calves
affected with severe acidemia and
dehydration due to acute diarrhea may be
unable to compensate because of

depressed respiratory function. Their
respiratory rate will be much slower and
the depth of respiration much more
shallow than normal. There is usually
tachycardia, which becomes worse as the
acidosis becomes more severe, and the
amplitude of the pulse and blood
pressure both decrease. A concomitant
hyperkalemia will cause bradycardia,
heart block, sudden collapse and rapid
death. This is particularly evident when
animals with acidosis and hyperkalemia
are transported and handled for treat-
ment. The increased muscular activity
appears to accentuate the abnormalities
and sudden death is not uncommon.
Weakness, lassitude and terminal coma
are frequent observations.

A syndrome of metabolic acidosis with
minimal signs of dehydration or diarrhea
has been described in calves from
1-4 weeks of age. 2,7 Affected calves are
depressed, weak and ataxic, and the suck
and menace reflexes may be weak or
absent. Some calves appear comatose. On
succussion of the abdomen fluid-splashing
may be audible, which suggests that the
syndrome may be related to diarrhea,

which most of the calves may have had
but from which they appeared to recover.
The same abnormality has also occurred
in goat kids with no apparent history of
previous diarrhea. 1 The abnormal labor-
atory findings include a reduced venous
blood pH, Pco 2 and bicarbonate ion
concentration, marked hyper D-lactatemia,
elevated blood urea nitrogen, increased
anion gap and a neutrophilic leukocytosis
with a left shift. Many of the clinical signs
appear to be primarily the consequence of
hyper D-lactatemia. 2 The intravenous
administration of 2. 5-4. 5 L of isotonic
(1.3%) sodium bicarbonate solution, the
amount depending on the severity of the
condition, 7 is necessary.

ETIOLOGY AND PATHOGENESIS

Alkalemia is caused by an increased
absorption of alkali, excessive loss of acid
or a deficit of carbon dioxide (Fig. 2.7).
Abomasal atony due to dilatation, impac-
tion or torsion of the abomasum is one of
the commonest causes of alkalemia in
cattle. There is continuous secretion of

ALKALEMIA

Fig. 2.7 Etiology and pathogenesis of alkalemia.

hydrochloric acid and potassium into the
abomasum, with failure of evacuation of
the abomasal contents into the duo-
denum for absorption. Sequestration of
hydrochloric acid and potassium occurs in
the abomasum, along with reflux into the
rumen, all of which results in a hypo-
chloremic, hypokalemic alkalosis. In
metabolic alkalosis, potassium will shift
from the extracellular to the intracellular
space, resulting in a hypokalemia when in
fact there may not be depletion of total
body potassium. In cattle with metabolic
alkalosis there is a paradoxical aciduria,
which is not well understood but may be
due to severe electrolyte depletion placing
limits on the kidney to regulate acid-base
balance. Paradoxic aciduria must be dif-
ferentiated from postparturient aciduria,
which has been reported to occur in dairy
cows.

Metabolic alkalosis has been recorded
in cows with severe coliform mastitis but
the pathogenesis is unknown. 8

CLINICAL FINDINGS

The clinical findings of alkalosis are not
characteristic enough to be recognized
reliably. Alkalosis results in slow, shallow
respirations in an attempt to preserve
carbon dioxide. Muscular tremors and
tetany with tonic and clonic convulsions
may occur because of depression of the
ionized fraction of serum calcium.
Hyperpnea and dyspnea may also occur
in the terminal stages.

REVIEW LITERATURE

Constable PD. Clinical assessment of acid-base
status: strong ion difference theory .Vet Clin North
Am Food Anim Pract 1999; 15:447-471.

Constable PD. Clinical assessment of acid-base status:
comparison of the Henderson-Hasselbalch and
strong ion approaches. Vet Clin Path 2000;
29:115-128.

Constable PD. Fluids and electrolytes. Vet Clin North
Am Food Anim Pract 2003; 19:1 — 40.

REFERENCES

1. Tremblay RRM, Butler DG. Can Vet J 1991; 32:308.

2. Lorenz I.Vct J 2004; 168:323.

3. Lunn DP, McGuirk SM. Vet Clin North Am Food
Anim Pract 1990; 6:1.

4. Brobst D. J Am Vet Med Assoc 1983; 183:773.

5. Naylor JM. Can Vet J 1989; 30:577.

6. Geiser DR et al. Am J Vet Res 1996; 57:1483.

7. Kasari TR, Naylor JM. Can J Vet Res 1986; 50:502.

8. Ohtsuka H et al. J Vet Med Sci 1997; 59:471.

NATURALLY OCCURRING
COMBINED ABNORMALITIES OF
FREE WATER, ELECTROLYTE AND
ACID-BASE BALANCE

These abnormalities are seldom primary
and usually secondary to a serious disease
state such as abomasal volvulus, rumen
overload or acute intestinal obstruction -
diseases that are in themselves life-
threatening. Fluid and electrolyte abnor-
malities are also life-threatening and

Disturbances of free water, electrolytes and acid-base balance

87

simple correction of the primary abnor-
mality, for example removal of a large
section of a horse's small intestine, is
valueless unless the dehydration, hypo-
natremia and acidosis are also corrected.
The variation that can occur in these
naturally occurring errors of fluid, electro-
lyte and acid-base balance is what makes
their diagnosis and treatment so difficult.
If it were possible to have instant
clinicopathological advice on what the
abnormalities were, and how they were
progressing as determined by constant
laboratory monitoring, there would be
little challenge in it. However, under
normal clinical circumstances these
services are not readily available and it is
necessary to have an understanding of
the basic physiology and pathology of
these diseases to be able to predict by
clinical examination and examination of
the history, the likely deficiencies and
imbalances and their degrees of severity.

In the preceding paragraphs the
individual abnormalities of fluid and
electrolyte homeostasis were described.
In most naturally occurring diseases, the
abnormalities are complex. In example,
the probable events in a case of acute
diarrhea are set out diagrammatically in
Figure 2.8. It is important to remember
that the variation in fluid and electrolyte
imbalance is dynamic as a result of the
compensatory changes occurring in
various organs, especially the respiratory
and circulatory systems and the kidneys.
It is this volatility which makes clinical
pathological monitoring so important.
Some generalizations on the dynamics of
fluid and electrolyte status are as follows:

• The body water and electrolytes are
maintained at a homeostatic level by
the buffering system of the blood, the
lungs and the kidney
° In disturbances of body water and
electrolytes, the changes that occur
are also dynamic, and there is
constant reaction by the homeostatic
mechanism to restore the water and
electrolyte relationship to normal
6 With some exceptions, it is unusual to
find an uncompensated alkalemia or
acidemia. A partial compensation in
the opposite direction of the primary
acid-base imbalance is usually in
progress and it is important to
determine the nature of the primary
disturbance for the selection of
rational therapy

0 Often, the nature of the primary
disturbance can be determined from a
consideration of the history and the
clinical findings
e The dehydration caused by

deprivation of water and electrolytes
(lack of water or inability to drink) is

mild and animals may appear only
mildly dehydrated even after several
days of water deprivation. The feces
are hard and dry, the rumen contents
are firm and dry and urine volume is
considerably decreased
® With the exception of clinical
dehydration, the clinical findings of
electrolyte and acid-base imbalances
are not characteristic
c Without laboratory evaluation, the
nature and degree of electrolyte and
acid-base imbalance must be assumed
and estimated based on the history of
the affected animal and the changes
that are most likely to have occurred.

NATURE OF THE DISEASE AND
HISTORY

The history of the case, the length of
time the animal has been affected and
the tentative diagnosis will provide a
clinical assessment of the possible nature
and degree of electrolyte and acid-base
imbalance. Animals affected with acute
diarrhea due to infectious enteritis are
likely to be in a state of metabolic acidosis
and hyponatremia. In intestinal obstruc-
tion of the horse, there are varying degrees
of dehydration and metabolic acidosis.
Obstruction of the upper intestinal tract,
or abomasal stasis, is characterized by
varying degrees of dehydration, and
metabolic alkalosis with hypochloremia
and hypokalemia. A combination of the
clinical assessment and the available
laboratory evaluation will allow the clini-
cian to make the most rational approach
to treatment.

The information on the duration of
illness must be accurate or it will be mis-
leading. The sequence of clinical findings
in the history may indicate the trend in
severity. Animals that have had a profuse
watery diarrhea for 18-24 hours may be
severely acidemic. Acute intestinal
obstruction in cattle is not as severe as in
the horse. Acute gastric or intestinal
rupture in the horse or in cattle is usually
rapidly fatal. Acidosis in grain overload in
cattle may be fatal in 24-48 hours;
acidosis in the horse with grain overload
may be much more rapidly fatal as
electrolyte disturbances are more severe
in the horse.

CLINICAL FINDINGS

Dehydration is usually obvious clinically
and determination of the PCV and total
serum solids will improve the assessment.

A normal temperature is not a good
prognostic guide but a subnormal tem-
perature suggests a worsening situation.

A gradually progressive tachycardia
indicates that the patient is deteriorating.
In general, in the horse, a heart rate up to
60 beats/min suggests a minor lesion
(but not always), a heart rate between

60-80 beats/min is in the danger area,
80-100 beats/min is serious; more than
100 beats/min is commonly premortal
(except in intestinal tympany that may be
relieved).

A cold clammy skin that remains
tented for more than 30 seconds suggests
severe dehydration. Cyanosis of the oral
mucous membranes and a capillary
refill time of more than 4 s suggests a
poor prognosis, as does rapid respiration
(three to four times normal) with inter-
mittent hyperpnea and apnea.

Muscular tremors and leg buckling
! are grave signs in the horse and are

| commonly followed by collapse and
j death. The inability of any dehydrated
j animal to stand (other reasons being
| eliminated) is ominous. Severe depression
and dullness are commonly observed in
acute conditions, and coma is usually
terminal.

| Metabolic acidosis is characterized
I by varying degrees of mental depression,
i weakness and ataxia. Some of the
| depression and weakness will be due to

j dehydration. In newborn animals with
| metabolic acidosis associated with diarrhea,
i a failure to suck and the lack of a suck
j reflex are common.

CLINICAL PATHOLOGY

Some representative laboratory values in

i examples of body water and electrolyte

| disturbances are given in Table 2.1.

1

j Packed cell volume and total serum
i solids

The PCV ? and the total serum proteins or
j total serum solids will indicate the

f

r

Disturbances of free water, electrolytes and acid-base balance

g|r|g|

SIBi

|| Jjjjl

Acute diarrhea

Acute diarrhea

Metabolic alkalosis due
to abomasal dilatation

Acute intestinal
obstruction

Acute carbohydrate
engorgement in

Clinical pathology

in horse

in calf

impaction/volvulus in cattle

in horse

ruminants

Packed cell volume (%)

60 ± 7

45.3 ± 7.0

42 ± 6

64 ± 5

45 ± 6

Total serum solids (g/dL)

10 ± 2

8.6 ± 1.5

8.2 ± 1.5

11.5 ± 1.5

8.5 ± 1.8

Blood pH (venous)

7.10 ± 0.15

7.08 ± 0.12

7.49 ±0.15

7.15 ± 0.04

7.10 ± 0.05

Plasma bicarbonate (mmol/L)

12 ± 3

13.7 ±4.2

35.4 ± 5.7

18 ± 6

12.5 ± 3.5

Partial pressure of carbon

45 ± 8

46.8 ±6.4

46.4 ± 7.5

48 ± 6

40 ± 6

dioxide (mmHg)

Serum sodium (mmol/L)

126 ± 3

138 ±9.4

138.5 ± 5.4

135 ± 5

132 ± 4

Serum chloride (mmol/L)

99 ± 3

101 .4 ± 7.5

88.6 ± 12.8

98 ±4

93 ± 3

Serum potassium (mmol/L)

3.0 ± 1.2

7.4 ± 1.6

3.4 ±0.6

3.8 ± 0.6

5.0 ± 2.5

Blood urea nitrogen (mg/dL)

60 ± 30

50.1 ± 30.5

40 ± 15

65 ±35

55 ± 25

severity of water loss. Anemic animals
and those affected with diseases causing
hypoproteinemia may provide misleading
values.

The normal range depends on the age
and species of animal, previous excite-
ment and the presence of anemia or
hypoproteinemia. A packed cell volume
of 30-40% is considered normal; between
40% and 50%, fluid therapy may or may
not be necessary; between 50% and 60%,
fluids are necessary for recovery and
above 60% intensive fluid therapy is
necessary and the prognosis is unfavorable .
A total serum solids of 6. 0-7.5 g/dL is
usually considered normal; at 8-10 g/dL
fluids are needed and the prognosis is
favorable and above 12 g/dL the prog-
nosis is unfavorable.

Blood pH and blood gases

Sample collection and analysis
A useful screening test for acid-base status
in animals without evidence of respiratory
disease is the total C0 2 . Total C0 2 is
defined as the amount of total carbon
dioxide in plasma that can be liberated with
a strong acid, and can be calculated from
the results of routine blood gas analysis as:
total C0 2 = [HCCV ] + dissolved C0 2 +
[H 2 C0 3 ] . The [HC0 3 “] is calculated using
the Henderson-Hasselbalch equation, the
dissolved C0 2 is equal to S x Pco^ whereas
[H 2 C0 3 ] is negligible.

Many automatic serum biochemical
analyzers directly measure total C0 2
(instead of calculating its value from the
results of blood gas analysis) but for total
C0 2 measurement it is important that
blood collection tubes are completely
filled before serum is harvested: failure to
completely fill the blood tubes promotes
escape of C0 2 from serum into the partial
vacuum above, thus resulting in measured
total C0 2 values that underestimate true
serum total C0 2 . : Because changes in
total C0 2 reflect changes in actual
[HC0 3 “], total C0 2 can never provide an
independent measure of the nonrespiratory
component of an acid-base disturbance.
Total C0 2 does, however, provide a useful

screening test for the presence of acid-
base disturbances in domestic animals
without clinical evidence of respiratory
disease. In the absence of respiratory
disease, a decrease in total C0 2 indicates
a metabolic acidosis, whereas an increase
in total C0 2 indicates metabolic alkalosis.
Total C0 2 has historically been measured
using the Harleco apparatus, 2 although
this methodology is no longer used due to
the availability of point-of-care analyzers.

If the primary clinical interest is acid-
base assessment, then a jugular venous
blood sample should be anaerobically
obtained in a 3 mL plastic syringe that has
been previously coated internally with
sodium heparin (by drawing sodium
heparin into the syringe barrel and then
expelling all heparin from the syringe into
the barrel before blood collection).
Three mL of air should then be drawn
into the syringe and forcibly expelled; this
process is repeated three times. Evacuating
the syringe in this manner ensures that
minimal heparin is retained to dilute the
blood sample but a sufficient quantity is
still present to prevent coagulation. 3 After
blood collection, the air bubbles should be
removed from the blood in the syringe,
the end should be corked to prevent loss
of C0 2 and addition of 0 2 to the blood
sample and the syringe should be placed
on ice (4°C) until analysis. This will
minimize any time-related changes in
pH, Pco 2 and base excess that occur when
blood is held at room temperature (20°C),
j particularly in blood samples with high
j white blood cell concentrations. The
j change in pH, Pco 2 and base excess per
I hour at 22-24°C are -0.024, +2.5 and -0.5
j respectively. 3 A portable blood gas
i analyzer for equine venous blood is
available and provides reproducible and
i acceptable analysis. 4

If the primary interest is evaluation of
the respiratory system, an arterial blood
; sample should be obtained in the same
j manner but the sample should be kept at
I body temperature (preferable) or room
temperature before blood gas analysis,
which should be performed as soon as

possible. This is because keeping 3mL
plastic syringes on ice (4°C) facilitates
oxygen diffusion through the plastic
syringe barrel, causing an increased Po 2 . 5

Use of point-of-care clinical analyzing
systems has greatly facilitated routine
evaluation of acid-base status in domestic
animals. Thorough assessment of acid-
base status requires blood gas analysis
and serum biochemical analysis, with
blood samples being obtained from a
major vein or any artery. If serum total
protein, albumin and phosphate con-
centrations are approximately normal,
then acid-base status should be evaluated
using blood pH, Pco 2 and extracellular
base excess concentration. This is
the traditional Henderson-Hasselbalch
approach. The presence of unidentified
anions should be investigated by cal-
culating the anion gap. If serum total
protein, albumin, and phosphate concen-
trations are markedly abnormal, then
acid-base status should be evaluated
using blood pH, Pco 2 , measured [SID + ]
and [A TO tL This is the simplified strong
ion approach. The presence of unidentified
strong ions should be investigated by
calculating the SIG.

Blood pH and acid-base interpretation
Normal blood pH varies from 7.35 to
7.45 (venous blood). The degree of
acidemia encountered includes moderate
acidemia (pH 7.30-7.25), severe acidemia
(pH 7.25-7.20), grave (and commonly
fatal except in neonates) acidemia
(pH 7.10-7.00). Horses with volvulus or
strangulation of the intestines gener-
: ally have blood lactate levels over
j 75 mg/dL (8.2 mmol/L) whereas cases of
i impaction have levels of 5-9 mg/dL
! (0.55-1.0 mmol/L). The normal value is
; 6.0 mg/dL (0.78 mmol/L) with a range of
| 4-12 mg/dL (0.44-1.33 mmol/L). The
| survival rate in a series fell from 85% to
] 0% as the lactate concentration increased
| from 75 to 155 mg/dL (8.3 to 17.2 mmol/L).

| ^ Serum electrolytes
' Serum electrolyte concentrations indi-
cate the severity of the electrolyte losses

90

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

and the necessity for replacement with
either balanced electrolyte solution or
specific electrolyte solution. Serum con-
centrations of sodium, chloride and
potassium are usually determined. The
total deficit for each electrolyte can be
estimated using the standard formula
presented under calculation of electrolyte
requirements.

Serum electrolyte concentrations
depend on the initial cause and the
severity of the disease. For example, in
most cases of acute diarrhea there is
hyponatremia and metabolic acidosis,
which are usually marked in the horse
with acute diarrhea. The serum levels of
chloride may be normal or subnormal in
acute diarrhea. The serum levels of
potassium will be below normal initially
but as acidosis develops and becomes
severe, hyperkalemia may occur. In
diseases causing abomasal atony there
will be hypochloremic, hypokalemic
and metabolic alkalosis.

Water and electrolyte abnormalities
are classified into three types based on
the measurement of electrolytes and
osmolality:

• Hypertonic dehydration (true
dehydration/desiccation): osmolality
greater than 300 mosmol/kg
(300 mmol/kg), associated with water
deprivation, some acute
gastrointestinal problems and some
types of diarrhea

® Hypotonic dehydration (acute
desalting water loss): osmolality less
than 260 mosmol/kg (260 mmol/kg),
associated with acute diarrhea,
particularly secretory diarrheas, such
as salmonellosis

° Isotonic dehydration: normal

electrolyte and osmolality levels, as in
horses losing electrolytes and water in
almost equal proportions.

Urea nitrogen and creatinine
Plasma urea nitrogen and plasma
creatinine are metabolic breakdown
constituents that can be used to assess
the degree of dehydration and to dis-
tinguish between prerenal, renal and
postrenal uremia. The plasma urea
nitrogen and creatinine concentration will
be elevated, depending on the severity of
the dehydration and decrease in circu-
lating blood volume. Following treatment
with fluids and electrolytes in prerenal
uremia, the levels of plasma urea and
creatinine will decline.

Total leukocyte and differential
counts

A marked leukopenia and neutropenia
with a degenerative left shift carries an
unfavorable prognosis. A regenerative left
shift with a neutrophilia is a favorable

prognosis. A marked lymphopenia indi-
cates severe stress and the prognosis may
be unfavorable.

Blood glucose

Blood glucose concentration can be
determined using conventional laboratory
techniques, which require the submission
of heparinized blood samples as soon as
possible to avoid erroneous results due to
hemolysis or erythrocyte glycolysis. A
quantitative, rapid method of determining
blood glucose concentrations in mature
cattle and calves is available and the
results correlate with the conventional,
laboratory-based method. 6 The laboratory-
based plasma glucose levels were 10-15%
higher than the blood glucose levels
determined by the rapid field method.
The field method is based on the glucose
oxidase reaction and uses impregnated
test strips and a pocket-sized, digital
readout reflectance meter to measure
colorimetric change.

Anion, strong ion and osmolal gaps

Acid-base balance has traditionally been
evaluated by using the Henderson-
Hasselbalch equation to characterize four
primary acid-base disturbances (i.e.
respiratory acidosis and alkalosis, meta-
bolic acidosis and alkalosis) and by
calculating the anion gap to estimate the
unmeasured anion concentration. Evalu-
ation of the anion gap has become
routine in many medical institutions. The
calculation takes little time, is essentially
without cost and is valuable in assessing a
variety of clinical conditions in which
electrolyte imbalances occur.

The anion gap (AG) represents the
difference between the concentration of
unmeasured anions [UA] and unmeasured
cations [UC] in serum, which can be
expressed in the equation: 7

[Na + ] + [K*] + [UC]= [Ct] +

[HCOf] + [UA],

which can be rearranged to:

[UA] - [UC] = AG = ([Na + ] +

[K + ])-([CC]+[HCOf]).

A change in [UA] or [UC] will cause a
change in the AG. Under normal circum-
stances, approximately two-thirds of the
AG originates from the net negative charge
of serum proteins, and the remainder
represents the serum concentration of
phosphate and strong anions, such as
lactate, sulfate, p-OH butyrate, aceto-
acetate and anions associated with
uremia. 7 The normal range for AG
depends on the age and species. The
normal range for 2-3-week-old foals is
9-22 mEq/L which is higher than that for
2-year-old horses (range 8-13 mEq/L).
The range of AG (mean ± 2 SD) for adult
animals varies for different species:

8-13 mEq/L (horse), 14-20 mEq/L (cow)
and 17-29 mEq/L (sheep). AG values
greater than 30 mEq/L have been seen in
critically ill cattle, with the increase being
attributed to an increase in blood lactate
and ketoacid concentration as well as- to
anions associated with uremia.

A potentially valuable clinical use for
the AG is in estimating the plasma
L-lactate concentration, which provides
information about the adequacy of
oxygen delivery to the tissues, thereby
providing a means for assessing the
severity of cardiovascular or pulmonary
dysfunction, monitoring the response to
treatment and formulating a prognosis for
survival. The normal plasma L-lactate
concentration is generally considered to
be less than 1.5mmol/L. Increases in
plasma L-lactate concentration have been
categorized as mild (2.5-4. 9 mmol/L),
moderate (5. 0-9. 9 mmol/L) and severe
(> 10 mmol/L), with L-lactate concen-
trations greater than 10 mmol/L being
associated with a high mortality in
humans, pigs and horses. 7

Because lactate determinations may
not be available in some laboratories,
calculation of the AG can be considered a
'poor man's plasma lactate'. The cor-
relation between AG and L-lactate
concentrations is excellent in horses with
intestinal disease. The AG of neonatal
calves with experimental diarrhea was
28.6 ± 5.6 mEq/L, and the blood lactate
concentration ranged from 1.1-2.9 mmol/L;
the AG was significantly correlated with
serum phosphate and creatinine concen-
tration. The AG of adult cattle with
abomasal volvulus was 20.5 ± 7.8 mEq/L
and the blood L-lactate concentration
ranged from 0.6-15.0 mmol/L. The AG in
adult cattle is only moderately correlated
with L-lactate concentrations and is
similarly correlated with serum phosphate
and creatinine concentrations in neonatal
calves and adult cattle, as well as with
serum albumin and total protein concen-
trations in adult cattle. Anion gap deter-
mination is of limited usefulness in
predicting blood L-lactate concentration
in sick cattle, whereas the correlation
between AG and serum concentration in
sick cattle suggests that an increased AG
should suggest the potential presence of
uremic anions. 7

In summary, the determinants and
utility of the anion gap in predicting
hyperlactatemia are as follows. 7

° The AG in critically ill cattle is
influenced by at least three factors:
blood L-lactate concentration and the
serum concentrations of phosphate
and creatinine

® There is a substantial quantity of
unmeasured anions in sick cattle

(approximately 7 mEq/L), which
implies that either unidentified
cations or anions other than chloride,
bicarbonate, L-lactate, pyruvate, P-OH
butyrate or phosphate are present in
critically ill cattle or that the formula
used to assign protein charge was
inaccurate

e The correlation coefficient between
AG and blood L-lactate concentration
is similar to that observed in human
patients and less than that seen in
sick horses

° The AG appears to predict blood L-
lactate concentration more accurately
in neonatal calves with experimental
diarrhea than that in adult cattle with
spontaneously occurring abomasal
volvulus.

Strong ion gap

The strong ion gap represents the
concentration of unmeasured strong ions
in plasma and is more specific in detect-
ing the presence of unmeasured strong
ions in plasma than the anion gap. The
SIG concept is a logical extension of
the AG concept and was developed using
the strong ion difference approach in
order to express SIG in terms of other
factors: SIG = A TOT /(l + lO'P Ka -P H >) - AG,
where SIG represents the difference
between unmeasured strong cation
concentration and unmeasured strong
anion concentration in plasma or serum. 8
Calculation of the SIG requires species-
specific values for the total plasma
concentration of nonvolatile weak acids
(A tot ; i.e. the total concentration of plasma
nonvolatile buffers; albumin, globulin and
phosphate) and the negative logarithm
to the base 10 (pICJ of the effective
dissociation constant (iC a ) for plasma
nonvolatile buffers. Values for A TO t and
pK a have been determined for the plasma
of horses (A TOT , 15.0 mmol/L = 0.22 mmol/g
of total protein or 0.47 mmol/g of albumin;
p K a , 6.66) and calves (A TO t/ 23.1 mmol/L
= 0.41 mmol/g of total protein or
0.75 mmol/g of albumin; p.K a , 7.08). 8-10

The normal SIG value is -5 to
+5 mEq/L. An increase in SIG to above
5 mEq/L (a rare occurrence) therefore
reflects an increase in unmeasured strong
cations or a decrease in unmeasured
strong anions. A decrease in SIG to below
-5 mEq/L (a common occurrence) reflects
a decrease in unmeasured strong cations
or, more likely, an increase in unmeasured
strong anions.

The SIG offers a more accurate approach
to identifying unmeasured strong ions in
plasma than does the AG. The critical
difference between the AG and SIG is
that the SIG provides an estimate of the
difference between unmeasured strong
cations and strong anions, whereas AG

Disturbances of free water, electrolytes and acid-base balance

91

provides an estimate of the difference
between unmeasured cations and anions
(including strong ions and nonvolatile
buffer ions such as albumin, globulins,
and phosphate). A change in SIG there-
fore provides a more specific method for
detecting a change in unmeasured strong
ions (such as lactate) than a change in AG.

Osmolal gap

Evaluation of the osmolal gap is a

means of detecting an increased amount
of abnormal osmotically active solute in
the blood. The osmolal gap is the differ-
ence between the measured plasma
osmolality and the osmolality calculated
from the plasma concentration of normally
measured solutes. Sodium and potassium
and their associated anions, along with
glucose and urea, constitute the majority
of normal osmotically active solutes. The
following formula is recommended,
although many clinicians disregard the
contribution of serum urea nitrogen
(SUN) because it is an ineffective osmole
that easily crosses cell membranes:

1.86 x ([Na + ] + [K + ]) + (glucose/18) +

(SUN/2.8) + 8.6.

Examination of the triad of calculated
osmolality, measured osmolality and
the osmolal gap is beneficial in the diag-
nosis and prognosis of a number of
diseases.

The effects of acidemia on the anion
gap and electrolytes can vary depending
on the cause of the acidosis and the
species involved. Experimentally in horses,
the infusion of L-lactic acid and D- and L-
lactic acid results in acidosis with a high
anion gap. 11 An infusion of hydrochloric
acid causes metabolic acidosis with a
decreased anion gap. Saline infusions
cause mild acidosis with no significant
change in anion gap. The plasma potass-
ium was decreased by the infusions of the
organic acids but not by hydrochloric
acid. Hypophosphatemia occurred with
the saline and hydrochloric acid infusions
but not with the organic acids. These
results indicate that large changes in
plasma potassium and serum inorganic
phosphate can occur in acidosis in the
horse and are probably not the direct
result of acidemia. High-intensity exercise
in the horse results in a progressive rise in
plasma potassium and lactate. 12

Arterial blood pressure

Arterial blood pressure and central venous
pressure are not measured routinely but
are occasionally measured in referral
centers where the technical assistance
and instrumentation are readily available.
Mean arterial blood pressure provides a
rough guide for the presence and severity
of terminal shock but not for the severity '
or extent of the initiating lesion.

Jugular or central venous pressure

This is more useful as a monitor during
fluid replacement. Normal pressure is
2-10 cmH 2 0 (0.3-1. 0 kPh), referenced to
the point of the shoulder (scapulohumeral
joint). Below 2 cmH 2 0 (0.3 kPa) requires
fluid therapy; above 15 cmH 2 0 (1.5 kPa)
indicates cardiac failure and volume
overload.

Total body water

Total body water can be measured in
horses before and after exercise using
orally administered deuterium oxide
followed by a series of blood samples
taken for analysis. 13 Mean total body
water content is about 62%. It is not
determined clinically.

PRINCIPLES OF FLUID AND
ELECTROLYTE THERAPY

The most important principle is to
prevent or minimize dehydration and
electrolyte loss whenever possible. This
means the provision of an adequate water
supply, adequate drinking space and
a continuous supply of salt and the
necessary minerals. The next most
important principle is to treat potential
losses of fluid and electrolytes as quickly
as possible to minimize the degree of
dehydration and acid-base imbalance
that may occur in animals with diseases in
which losses are occurring.

The major therapeutic objectives are
to correct the abnormalities that already
exist and to monitor and provide main-
tenance therapy until the animal has
recovered. Collection of the abnormalities
may require 4-6 hours and maintenance
therapy may be necessary for 2-4 days,
depending on the cause of the disease.
There are at least four possible abnor-
malities that could exist at the same time
and must be corrected:

0 Fluid volume deficit
° Plasma osmolar deficits
° Specific electrolyte imbalances
° Acid-base imbalance.

The two major problems are to determine
the nature and degree of the abnor-
malities present and to decide which fluid
and electrolyte replacement solution
should be used.

The ideal situation would be to make
both a clinical and laboratory evaluation
of the animal as described above. The
history and the diagnosis will suggest the
possibility of acidemia or alkalemia and
the electrolyte imbalances that are likely
to be present. The degree of dehydration
can usually be recognized clinically.
Severe dehydration and acidemia should
be treated as quickly as possible. A
summary of the disturbances of fluid and
electrolyte balance that occur in some
common diseases of cattle and horses.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

and the suggested fluid therapy, is
presented in Table 2.2.

Calculation of electrolyte
requirements

The electrolyte deficits can be estimated
using the serum electrolyte values of the
affected animal. The total deficit of the
electrolyte in milliequivalents (mEq) is the
product of the deficit of the electrolyte in
mEq per liter (AmEq/L) and the distri-
bution space for the electrolyte. For
sodium, chloride and bicarbonate, the
distribution space is the extracellular fluid
volume, which approximates 30% of BW in
normally hydrated adults and 50% in
normally hydrated neonates. In other
words, for sodium, chloride and bicar-
bonate, the total milliequivalent deficit =
(AmEq/L) x (estimated euhydrated body
weight in kg) x (0.3 or 0.5).

There is less certainty about the size of
the potassium space because potassium is
mainly an intracellular ion.

Types of intravenous fluid

Fluids are categorized on the basis of their
physical nature (crystalloid or colloid)
and osmolarity (hypotonic, isotonic or
hypertonic). Isotonic or slightly hypotonic
crystalloid solutions are most commonly
administered parenterally, although
under specific circumstances hypertonic
crystalloid solutions or isotonic colloid
solutions are preferred.

Crystalloid solutions

A crystalloid is a substance that forms a true
solution and is capable of being crystallized.
Examples of crystalloid solutions are
Ringer's solution, lactated Ringer's solution,
acetated Ringer's solution, 0.9% NaCl, 7.2%
NaCl (hypertonic saline), 1.3% NaHC0 3 ,
8% NaHCOj, calcium gluconate and 50%
dextrose. Sodium chloride is the classic
crystalloid solution, as table salt (NaCl)
exists as a crystal but dissolves completely
when placed in water. Because crystalloids
dissolve completely in water, crystalloid
solutions containing sodium distribute
throughout the entire extracellular fluid
space and are therefore not confined to the
intravascular space. Sodium-containing
crystalloid solutions are always indicated in
hypovolemia (circuit problem) but are
contraindicated in congestive heart failure
(pump problem) because they provide an
additional sodium load, and animals with
heart failure have already retained too much
sodium. Sodium-containing crystalloid
solutions are also contraindicated in the
presence of severe hypoalbuminemia
because sodium-containing crystalloids will
further decrease plasma albumin concen-
tration and oncotic pressure, resulting in
movement of fluid into the interstitial
spaces and exacerbating tissue edema.

Crystalloid solutions are characterized
in terms of the number of molecules
(numerator) per volume of solution

(denominator). The number of molecules
is expressed in moles (abbreviated as
mol), where 1 mol of compound is
equivalent to the molecular weight of the
compound in grams (formula weights for
NaCl, NaHC0 3 and KC1 are 58.5 g, 85 g
and 74 g respectively). Because body
fluids are dilute, we express moles as
millimoles (mmol = mol/1000) to facilitate
readability.

Crystalloid solutions are commonly
expressed in terms of the number of
charged components (numerator) per
volume of solution (denominator). The
number of charged components is
expressed in equivalents (abbreviated as
Eq), where 1 Eq is the number of each
charged component that combines with
or replaces 1 mol of hydrogen ion (this
means that Eq is always a positive
number). Because body fluids are dilute,
equivalents are expressed as milli-
equivalents (mEq = Eq/1000). To calculate
the number of mEq from mmol, we
simply multiply the number of millimoles
by the valence (charge), whereby: mEq/L
= (mmol/L) x valence. For instance,

1 mmol of NaCl in solution provides

2 mEq: 1 mEq of Na + (1 x 1) and 1 mEq of
Cl” (1 x 1), assuming that NaCl acts as a
strong electrolyte in water (i.e. it com-
pletely dissociates into Na + and Cl" in
water) . In comparison, 1 mmol of CaCl 2 in
solution provides 4 mEq: 2 mEq of Ca 2+

Neonatal calf diarrhea (including piglets
and lambs)

D-lactic acidosis (carbohydrate
engorgement of ruminants)

Acute diffuse peritonitis

Right-side dilatation/abomasal volvulus
of cattle, abomasal impaction
(dietary or vagal nerve injury)

Peracute coliform mastitis

Acute diarrhea in the horses (enteric
salmonellosis

Acute grain engorgement in the horse

Water and electrolyte deprivation.
Esophageal obstruction in horses
Acute intestinal obstruction

Major abnormalities and deficits

Metabolic acidosis, low plasma bicarbonate,
severe dehydration, loss of sodium, hyperkalemia
when acidosis severe

Metabolic acidosis, low plasma bicarbonate,
severe dehydration

Dehydration. Slight metabolic alkalosis due to
paralytic ileus

Metabolic alkalosis, marked hypochloremia,
hypokalemia, severe dehydration

Severe dehydration, mild electrolyte deficits
including mild hypocalcemia. Metabolic
acidosis if diarrhea present
Severe dehydration, marked hyponatremia,
metabolic acidosis. Hypokalemia occurs
following bicarbonate therapy

Metabolic acidosis, dehydration and shock

Moderate dehydration

Metabolic acidosis or alkalosis dependent on
level of obstruction. Severe dehydration in
horse, moderate in cow

' v iL - ■ \ ■■ . .. f- i

Fluid and electrolyte requirements

Equal mixtures of isotonic saline and isotonic
sodium bicarbonate with 5% dextrose.

Balanced electrolytes too, IV and PO. See
Colibacillosis, Ch. 18, for details
Sodium bicarbonate initially followed by balanced
electrolytes, IV. See Acute carbohydrate engorgement
of ruminants, Ch. 6, for details
Balanced electrolyte solutions in large quantities IV
for hydration and maintenance
Balanced electrolyte solutions or high-potassium and
chloride-acidifying solution, IV. May give acidifying
solutions orally. See Right-side displacement of
abomasum Ch. 6, for details: can also use mixture of
2 L of isotonic saline (0.9%), 1 L isotonic potassium
chloride (1 .1 %) and 1 L isotonic dextrose (5%)
Balanced electrolyte solutions IV in large quantities
for hydration and maintenance for 24-48 hours
(100-150 mIVkg B W/24 h)

Hypertonic sodium bicarbonate (5%) 3-5 L 500 kg
BW followed by high-sodium, high-potassium
alkalinizing solution to correct hypokalemia
following bicarbonate therapy. All by the IV route
Hypertonic sodium bicarbonate (5%) 3-5 L/500 kg
BW followed by balanced electrolytes IV
Balanced electrolytes IV. When obstruction relieved,
provide electrolyte solution orally
Isotonic sodium bicarbonate initially, 3-5 L/500 kg
BW followed by balanced electrolytes IV.

Horses may develop hypokalemia following
bicarbonate therapy and must be given potassium
chloride

Disturbances of free water, electrolytes and acid-base balance

93

-Ta b|e<2,’3.Tsh m

administered rrvsta ^§^^H

f

Effective SID
(mEq/L)

!§§ sftfljpl KS ~ r ^

Osmolarity

(mosmol/L)

Hypertonic solutions (>312 mosmol/L)
Alkalinizing

8.4% NaHC0 3

1000

2000

5.0% NaHC0 3

595

1190

10% NaH 2 P0 4

145

1150

Acidifying

50% dextrose

0

2500

7.2% NaCl

0

2460

25% magnesium sulfate

0

2028

23% calcium borogluconate

0

1069

Isotonic solutions (300 to 312 mosmol/L)
Alkalinizing

Tromethamine

210

300

1.3% NaHC0 3

155

310

Carbicarb

75

300

McSherry's solution

54

312

Darrow's solution

53

312

Acidifying

Ringer's solution

0

309

0.9% NaCl

0

308

1.15% KCI

0

308

Hypotonic solutions (<300 mosmol/L)
Alkalinizing

Acetated Ringer's

27

294

Lactated Ringer's

<14

275

Acidifying

5% dextrose

0

250

The effective SID is the difference between the strong cation and strong anion concentration after
metabolizable anions (such as lactate or acetate) have been completely metabolized to produce
bicarbonate. Electrolyte solutions with an effective SID of more than 27 mEq/L are alkalinizing because they
create a strong ion alkalosis. Electrolyte solutions with an effective SID = 0 are acidifying because they
create a strong ion acidosis.

(1 x 2) and 2 mEq of Cl” (2 x 1), and 1 mmol
of dextrose provides 0 mEq, because
dextrose does not dissociate into charged
components in water.

The principal reason we define con-
stituents of plasma in terms of mEq
instead of mmol is because electro-
neutrality must be preserved at all times;
the difference between the charge
assigned to all strong cations (Na + , K + ,
Ca 2+ , Mg 2 *) and strong anions (Cl”,
lactate, sulfate, ketoacids, non-esterified
fatty acids, etc.) in plasma is called the
strong ion difference and this factor
independently and directly alters blood
pH and therefore acid-base status. The
normal SID of plasma is approximately
40 mEq/L, although there are species
differences in the actual value. Electrolyte
solutions with an effective SID of more
than 40 mEq/L are therefore alkalinizing
because they create a strong ion alkalosis.
Electrolyte solutions with an effective SID
= 0 are acidifying because they create a
strong ion acidosis. Electrolyte solutions
of intermediate SID may be alkalinizing
or acidifying depending upon the change
in plasma SID relative to the decrease in
plasma protein concentration (which is
alkalinizing) (Table 2.3).

Isotonic, hypertonic, and hypotonic
crystalloid solutions

The tonicity of the solution is an import-
ant clinical issue. Complete under-
standing of the tonicity concept requires
differentiation of two terms, osmolality
and osmolarity. Osmolality is the number
of dissolved particles per kilogram of
solution and is expressed as mosmol/kg
of solution. The normal plasma osmolality
in large animals is approximately
285 mosmol/kg, and plasma osmolality is
aggressively defended by increasing water
intake (osmolality > 285 mosmol/kg) or
promoting free water excretion (osmolality
<285 mosmol/kg). The correct term in
plasma and extracellular fluid is osmolality,
because this factor is measured in the
laboratory; however, frequently the term
osmolarity is used because 1 kg of plasma
approximates 1 L of plasma and because
osmolarity can be easily calculated from
the concentration of electrolytes in the
fluid solution. Osmolarity is the number
of particles per liter of solution and is
expressed as mosmol/L of solution.

One kg (1 L) of plasma from an adult
large animal has two components, 70 g of
protein and 930 g of plasma water.
Accordingly, the osmolality of normal
plasma (285 mosmol/kg) is equivalent to
a plasma water osmolarity of 306 mosmol/L
((285 mosmol/kg)/(0.93 L/kg)). Ringer's
solution, 0.9% NaCl and 1.3% NaHC0 3
are therefore considered isotonic solu-
tions because they distribute in plasma

water and have calculated osmolarities
of 309 mosmol/L, 308 mosmol/L and
310 mosmol/L respectively.

The normal plasma osmolarity for large
animals is 306 mosmol/L; solutions are
defined as isotonic (300-312 mosmol/L),
hypertonic (> 312 mosmol/L) or hypo-
tonic (<300 mosmol/L). Using this
categorization, it is readily apparent that
some routinely used crystalloid solutions
are hvpotonic; in particular, lactated
Ringer's solution (275 mosmol/L) is mildly
hypotonic and 5% dextrose (250 mosmol/L)
is moderately hypotonic, although, as
glucose is metabolized, 5% dextrose
becomes an increasingly hypotonic solu-
tion. Erythrocytes are resistant to increases
in plasma osmolarity, whereas they are
susceptible to mild decreases in osmolarity;
this is the basis of the red blood cell fragility
test whereby red blood cell suspensions
are placed in solutions of decreasing
osmolarity. Because of hypotonic-induced
hemolysis, parenterally administered fluids
should be isotonic or hypertonic.

Hypotonic crystalloid solutions
Lactated Ringer's solution is a

balanced, polyionic, alkalinizing, hypo-
tonic (275 mosmol/L), crystalloid solution
containing physiological concentrations "
of Na + , K + , Ca 2+ , Cl” and lactate

(CH 3 CH(OH)COO”). Lactated Ringer's
solution alkalinizes because lactate
is predominantly metabolized to the
bicarbonate ion, whereby:

CH 3 CH(OH)COO~ + 30 2 -> 2C0 2 +
2H 2 0 + HC0 3 ~.

The lactate in lactated Ringer's is a
racemic equimolar mixture of L-lactate
andD-lactate; in healthy animals L-lactate
is rapidly metabolized; however, animals
have negligible D-lactate dehydrogenase
activity, leading to slow clearance of
D-lactate, which is primarily through the
urinary system. DL-lactate solutions such
as lactated Ringer's therefore have
approximately half the alkalinizing ability
of L-lactate solutions. The effective SID of
lactated Ringer's solution is less than
14 mEq/L because L-lactate can also be
used in gluconeogenesis instead of
bicarbonate production. Lactated Ringer's
solution is the standard intravenous fluid
for neonates and adult horses because
these animals tend to get acidemic when
inappetent. However, lactated Ringer's
solution is theoretically inferior to acetated
Ringer's solution, because critically ill
animals may have increased blood lactate
concentrations and it is incongruous to
add lactate in this situation.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Acetated Ringer's solution is a

balanced, polyionic, alkalinizing, hypotonic
(294 mosmol/L), crystalloid solution.
Commercially available formulations of
acetated Ringer's solution contain physio-
logical concentrations of Na + , K + , Mg 2+ ,
Cl , acetate (CH 3 COO“) and gluconate
(CH 2 (OH) (CH(OH) } 4 COO“); the gluconate
is problematic because calves (and
presumably all large animals) slowly
metabolize gluconate. 14 Acetated Ringer's
solution alkalinizes because acetate is
metabolized to the bicarbonate ion,
whereby:

CH 3 COCT+ 20 2 -> C0 2 + H 2 0 +

HCOf.

The strong ion approach to acid-base
balance states that acetated Ringer's solu-
tion is alkalinizing because it contains a
metabolizable strong anion (acetate) that,
when metabolized, increases the SID.

Five percent dextrose is 250 mosmol/L
as administered, but plasma osmolarity
decreases as the glucose is metabolized,
leaving free water. Because 5% dextrose
has no sodium to expand the extracellular
volume and has much less energy content
than 50% dextrose on a volume basis, the
only application of 5% dextrose is to
provide free water or as a vehicle for
pharmacological agents.

Isotonic crystalloid solutions
Ringer's solution is a balanced, polyionic,
nonalkalinizing, isotonic, crystalloid solu-
tion that contains physiological concen-
trations of Na + , K + , Ca 2+ , and Cl“. This
solution is mildly acidifying because its
effective SID = 0 mEq/L. Addition of a
fluid with a SID of 0 mEq/L to plasma
(normal SID = 40 mEq/L) will decrease
plasma SID and therefore directly and
independently decrease plasma pH
because a 1 mEq/L decrease in SID
decreases plasma pH by approximately
0.016. Ringer's solution is the standard
intravenous fluid for adult ruminants
because these ruminants tend to get
alkalemic when inappetant. 15

Isotonic saline (0.9% NaCl solution)
is an isotonic crystalloid solution that has
little merit in the routine treatment of sick
ruminants, principally because ruminants
usually develop hypocalcemia and hypo-
kalemia when inappetent. Accordingly,
the use of 0.9% NaCl should be confined
to horses, the irrigation of surgical sites
and wounds, or as a vehicle for adding
other electrolytes and dextrose. Like
Ringer's solution, 0.9% NaCl is mildly
acidifying because effective SID =
0 mEq/L.

Isotonic sodium bicarbonate (1.3%
NaHC0 3 solution) is an alkalinizing
isotonic crystalloid solution that is used to
treat severe acidemia (indicated when-

ever blood pH < 7.20 as a result of
metabolic acidosis). This solution is
alkalinizing because it buffers hydrogen
ion: HC0 3 - + H + C0 2 + H 2 0, and
because it increases SID (effective SID =
155 mEq/L). Sodium bicarbonate is
superior to sodium L-lactate and sodium
acetate for the treatment of metabolic
acidosis because it provides an immediate
source of bicarbonate. On theoretical
grounds, sodium bicarbonate (NaHC0 3 )
should not be used to treat severe
respiratory acidosis because additional
C0 2 generated may worsen the respiratory
acidosis.

Tromethamine (Tham, tris-
hy d r oxy m e t hy 1 aminomethane,

300 mmol/L) is an isotonic solution of an
organic amine that is a safe and effective
buffer. 16 After administration, 70% of the
neutral compound (CH 2 OH) 3 C-NH 2 in
tromethamine is immediately protonated
to the strong cation (CH 2 OH) 3 C-NH 3 + in
plasma, with the net equation being:

(CHfiH) 3 C-NH 2 + H*

(CHfiH) 3 C-NHf.

The remaining 30% of the administered
tromethamine remains unprotonated and
can therefore cross cell membranes and
potentially buffer the intracellular com-
partment. Tromethamine therefore pro-
vides an alternative alkalinizing agent to
sodium bicarbonate; however, trome-
thamine does not currently appear to
offer any important clinical advantages
over sodium bicarbonate in sponta-
neously breathing animals.

Isotonic formulations are available for
intravenous administration with or with-
out electrolytes; administration of trome-
thamine without electrolytes leads to
hyponatremia and it would appear
preferable to administer tromethamine in
conjunction with electrolytes.

Carbicarb is an isotonic buffer
(300 mosmol/L) made from equimolar
disodium carbonate (Na 2 C0 3 ) and
sodium bicarbonate; carbonate avoids
generation of C0 2 when buffering acidemic
blood: 17

C0 3 2 ~ + H + HCOf.

Carbicarb was suspected to decrease
the incidence and magnitude of hyper-
capnia when rapid alkalinization was
needed in animals with mixed metabolic
and respiratory acidosis. Despite numerous
studies comparing Carbicarb to sodium
bicarbonate, the potential clinical advan-
tages of Carbicarb have only been demon-
strated in animals being ventilated or
with extremely limited ventilatory ability.
Carbicarb has been administered intra-
venously to diarrheic calves; however,
these studies have failed to identify a
clinically important advantage over con-

ventional isotonic sodium bicarbonate
administration. 18 Accordingly, there does
not appear to be a compelling reason to
prefer Carbicarb to isotonic sodium
bicarbonate when rapid alkalinization of
conscious animals is required.

Darrow's solution is an isotonic
polyionic solution formulated by Darrow
in 1946 for use in human infants; the
solution has been administered to
calves. 19-20 Compared to other isoosmotic
polyionic solutions, Darrow's solution is
hyponatremic, hyperkalemic and hyper-
lactatemic and does not contain calcium
or magnesium. As such, Darrow's solution
is not recommended for administration to
large animals.

McSherry's balanced electrolyte
solution is an isotonic polyionic solution
formulated by McSherry and Grinyer in
1954 for intravenous and intraperitoneal
administration to dehydrated diarrheic
calves. 21 On theoretical grounds, this is an
excellent parenteral fluid for resuscitating
dehydrated diarrheic calves that deserves
more frequent use. Unfortunately, com-
mercial formulations are currently
unavailable.

Hypertonic crystalloid solutions
Fifty percent dextrose is 2500 mosmol/L
(approximately eight times normal
osmolarity). Fifty percent dextrose sol-
utions are commonly administered to
ruminants with ketosis or hypoglycemia
and produce a transient increase in
cardiac contractility. 22 Some commercially
available formulations in Europe contain
an equimolar mix of dextrose and fructose,
although the addition of fructose does not
appear to produce a more sustained
increase in plasma glucose concentration
than that produced by glucose alone. 23

The necessity for glucose in fluid
therapy has been controversial. Hypo-
glycemia occurs commonly in septicemic
neonates and calves with diarrhea but is
uncommon in most other common
diseases in which there is an acute fluid
and electrolyte disturbance. Dextrose will
promote the movement of extracellular
potassium into the cell, will provide
metabolic water and is a source of
carbohydrate. If glucose is indicated, large
quantities of parenteral glucose are
necessary to meet the maintenance
energy requirements and every effort
must be made to restore the animal's
appetite and to provide the necessary
requirements through dietary intake. The
energy requirements for maintenance are
calculated on the basis of metabolic body
size, kg 073 , which is a measure of the
fasting metabolism in an animal not
eating and not doing any muscular work.
If 1 g oftdextrose given intravenously will
provide 5 kcal (2.1 kj) of energy, the

f

Disturbances of free water, electrolytes and acid-base balance

1 : 1 ?

Body weight
(kg)

Metabolic body
size (kg W 073 )

Metabolizable
energy requirements
(kcal)

Glucose 0%
(L/day)

45

(1 -month-old calf)

16

1760

7

90

27

2970

1.2

180

45

4950

2.0

360

74

8140

3.3

454

67

9510

3.8

544

100

12100

4.8

approximate amounts of dextrose solu-
tion needed to meet the energy needs for
maintenance in cattle are shown in Table
2.4. Table 2.4 comprises a rough estimate
of the requirements and should be used
as a general guideline only. Every effort
should be made to supply the energy
needs through oral intake of energy-
containing foods.

NaCl 7.2% (Hypertonic saline) is

2460 mosmol/L (approximately eight times
normal osmolarity) and is used for the
rapid resuscitation of animals with hypo-
volemia. Hypertonic saline should be
administered at 4-5 mL/kg BW intra-
venously over 4-5 min (1 (ml/kg BW)/min).
Faster rates of administration lead to
hemodynamic collapse due to vasodilation
and decreased cardiac contractility,
whereas slower rates of administration
provide no advantages over isotonic
crystalloid solutions. Like high-volume
0.9% NaCl, small-volume hypertonic
saline consistently induces a mild strong
ion acidosis as its effective SID = 0 mEq/L.
In general, the decrease in pH following
hypertonic saline administration is less
than 0.08 pH units and rapidly dissipates
with time. 23 The effect of hypertonic
saline on acid-base balance is therefore
clinically inconsequential.

The use of small volumes (4-5 mL/kg
BW) of hypertonic saline solution,
ranging in concentration from 7.0% to
7.5%, has been extensively evaluated for
the treatment of various forms of hemor-
rhagic, septic and endotoxic shock. 24
Plasma volume is increased by the
movement of free water from the intra-
cellular space, thereby increasing cardiac
output, mean arterial blood pressure,
systemic oxygen delivery and glomerular
filtration rate. Total peripheral vascular
resistance and pulmonary vascular resist-
ance decrease, and mean circulatory
filling pressure increases. Urine output is
restored and acid-base equilibrium returns
towards normal in conjunction with
improved tissue perfusion.

Hypertonic saline solution is widely
used for the treatment of dairy cattle with
endotoxic shock and endotoxemia associ-
ated with coliform mastitis. Affected cows

are given 2 L of hypertonic saline
(4-5 mL/kg BW) intravenously, followed
by immediate access to drinking water
and other supportive therapy. The small
volume of hypertonic saline followed by
the oral water load increases circulatory
volume rapidly, induces slight metabolic
acidosis, increases renal perfusion and
glomerular filtration rate, and induces
homeostatic changes in serum calcium
and phosphorus. 25 In experimental
endotoxin -induced mastitis of cattle,
small volumes of hypertonic saline given
intravenously (7.5%, 5 mL/kg BW)
resulted in expanded plasma volume and
increased the cows' voluntary water
intake by about 12 times compared to
cows treated with isotonic saline. 26 The
rapid intravenous administration of
hypertonic saline can successfully, but
only transiently, resuscitate calves in
experimental endotoxic shock. 27 Hypertonic
saline (7.2% NaCl, 2400 mosmol/L),

4 mL/kg BW intravenously over 4 min can
be safely administered to endotoxic
calves. 28 On a comparative basis, the
rapid infusion of large-volume isotonic
saline is superior to small-volume
hypertonic saline for initial resuscitation
of experimentally induced acutely
endotoxemic calves. 27

Hypertonic saline has been associated
with greater and more prolonged improve-
ment in cardiopulmonary function and
survival in horses with experimentally
induced hemorrhagic and endotoxemic
shock and in halothane-induced hypo-
tension in horses. 29 When given intra-
venously to normal conscious horses at

5 mL/kg BW, there are increases in
plasma osmolality and serum sodium and
chloride but clinically normal horses
rapidly regulate variable sodium loads. 30

Sodium bicarbonate 8.4% is
2000 mosmol/L (approximately seven
times normal osmolarity). This solution is
used for rapid alkalinization, particularly
in the presence of severe acidemia
(pH < 7.20). The solution osmolarity was
selected because it provides 1 mEq of
HC0 3 ~/mL of solution, which facilitates
calculation of the volume to be admin
istered.The speed of intravenous adminis-

tration of 8.4% sodium bicarbonate should
not exceed 1 (ml/kg BW)/min. There is
one report of the intravenous adminis-
tration of 8.4% sodium bicarbonate to
normovolumic calves with experimentally
induced mixed respiratory and metabolic
acidosis; the study found that rapid
administration of NaHC0 3 (5 mL/kg
intravenously over 5 min) rapidly corrected
the metabolic acidosis, increased blood
pH and improved cardiovascular status
without inducing paradoxical cerebro-
spinal fluid acidosis, 31 suggesting that this
treatment may be of value in treating
dehydrated diarrheic calves. Efficacy
studies in calves with naturally acquired
diarrhea appear indicated. Hypertonic
solutions of sodium bicarbonate are
highly effective for the initial treatment of
acidosis associated with D-lactic acidosis
in calves, acute diarrhea in calves 31 and
strong ion (metabolic) acidosis in new-
born calves. 32

Sodium bicarbonate 5% is

1190 mosmol/L (approximately four times
normal osmolarity). This solution is also
used for rapid alkalinization in the
presence of severe acidemia (pH < 7.20).
The speed of intravenous administration
of 5.0% sodium bicarbonate should not
exceed 2 (ml/kg)/min. Three to five L of
5% sodium bicarbonate may be necessary
as initial therapy to correct the severe
hyponatremia and strong ion (metabolic)
acidosis that occurs in the horse with
acute diarrhea. Following this initial treat-
ment, hypokalemia characterized by
muscular weakness commonly occurs,
which can be treated using a high sodium,
high potassium, alkalinizing solution.

Calcium gluconate 23% or calcium
borogluconate are 1069 mosmol/L
(approximately three and a half times
normal osmolarity). Calcium borogluconate
is the standard treatment for milk fever
(hypocalcemia) in cattle. D-gluconate is
an aldose sugar produced by oxidation of
D-glucose and is the preferred salt for
calcium-containing parenteral solutions
because it does not cause tissue necrosis
as severe as does CaCl 2 . Calcium
gluconate should not be added to sodium
bicarbonate solutions because a white
precipitate (CaC0 3 ) forms immediately
that interferes with normal fluid adminis-
tration. Likewise, calcium gluconate should
not be administered with tetracycline
antibiotics because a yellow precipitate
forms.

Colloid solutions

A colloid is a substance that is too large to
pass through a semipermeable mem-
brane. Examples of colloid solutions
^ administered to ruminants are whole
blood, stroma-free hemoglobin, plasma,
dextrans, hydroxyethyl starches and

6

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

gelatins. As a group, colloid solutions are
excellent for sustained expansion of
plasma volume, which is in marked
contrast to the effect of crystalloid solu-
tions. Colloid solutions are contra-
indicated in congestive heart failure
because these animals have increased
plasma volume. Colloid solutions are also
contraindicated in the presence of oliguric
or anuric renal failure because the
sustained volume overload may lead to
pulmonary edema.

Whole blood is the perfect balanced
colloid/crystalloid solution, with great
0 2 -carrying capacity. It has a short shelf
life (< 24 h at 4°C) and is expensive to
obtain. Whole blood administration runs
the risk of disease transmission and
allergic reactions; the latter are extremely
rare in ruminants with the first blood
transfusion but common enough in
horses for blood typing or cross-matching
to be required. Excellent descriptions for
collecting, storing and administering blood
are available elsewhere (Chapter 9) , 33

Stroma-free hemoglobin is a blood
substitute containing a purified hemo-
globin glutamer-200 solution (13 g
hemoglobin/dL) derived from cattle
blood. A commercially available solution
has a 2-year shelf life at 20°C, an
osmolarity of 300 mosmol/L and an
oncotic pressure of 43 mmHg; the solution
is therefore isotonic but hyperoncotic.
Stroma-free hemoglobin solutions are
excellent at increasing oxygen delivery
and carrying capacity, while providing
similar plasma volume expansion to
dextrans and hydroxyethyl starches. The
major theoretical concerns regarding
administration of stroma-free hemoglobin
solutions are potent vasoconstriction 34 and
hemoglobinuric nephrosis. Some of the
original experimental studies examining the
effects of stroma-free hemoglobin admin-
istration were completed in sheep 33,36 and
there are occasional reports of its successful
administration to critically ill horses in a
clinical situation. It is likely that the high
cost of this product will minimize its
administration to large animals.

Plasma (fresh or frozen) is an
excellent balanced colloid/crystalloid
solution. Compared with blood, plasma
has a much longer shelf life (at least
1 year at -20°C) but is more expensive to
obtain. Details for collection, harvesting,
storing and administering plasma are
available elsewhere, 33 and bovine, equine
and New World camelid plasma is
commercially available. Like blood,
administration of plasma runs the risk of
disease transmission and allergic reactions,
although these risks are less than with
blood transfusion.

Plasma is routinely administered to
foals with inadequate transfer of passive

immunity. Hyperimmune plasma is
occasionally administered to neonatal
foals and adult horses with Gram-
negative septicemia and endotoxemia.
There appears to be only one report
documenting the efficacy of plasma
administered to neonatal calves with
diarrhea, and these calves were probably
colostrum-deprived. The 14-day survival
rate in diarrheic calves that received
600-800 mL of bovine plasma (5 g
protein/dL) and electrolytes intravenously
was 93% (37/40), which was significantly
greater than the survival rate of calves
receiving intravenous electrolytes alone
(54%, 7/13). 37 Another study failed to
identify a beneficial effect of blood trans-
fusion in treating diarrheic calves. 38
Because blood is cheaper to obtain than
plasma, whole blood transfusions are
usually administered when a neonatal
ruminant needs plasma.

Dextran preparations (such as
Dextran-70) are high-molecular-weight
glucose polymers obtained by bacterial
fermentation of sucrose; the fermentation
metabolites then undergo acid hydrolysis
and fractionation. The molecular weight
of dextran can therefore be 'selected', and
two dextran products, Dextran-70 (mean
molecular weight 70 000) and Dextran-40
(mean molecular weight 40 000) are
commercially available. Because the
molecular weight of Dextran-70 is similar
to albumin (molecular weight 65 000),
there is limited diffusion of dextran into
the interstitial space and Dextran-70
therefore acts clinically as a plasma
volume expander; this is in contrast to
isotonic crystalloid solutions, which act as
extracellular fluid volume expanders.
Dextran-70 has been the most widely
used dextran formulation in large animals
and is therefore the recommended pro-
duct for administration. Dextran-70 is
supplied as a 6% concentration in 0.9%
NaCl; this provides a hyperoncotic but
isotonic solution. Reported administration
rates of Dextran -70 are 5-40 (mL/kg)/h,
but it is safer to administer Dextran-70
at less than 20 (mL/kg)/h. One mL of
Dextran-70 expands the plasma volume by
0.8-1. 2 mL, but 50% of the administered
dose is gone by 24 hours. Dextran admin-
istration runs the risk of exacerbating pre-
existing coagulopathies, although the
clinical significance of dextran-induced
prolongation of activated partial thrombo-
plastin time (AFTT) by decreasing factor
VHI:C is probably minimal. The risk of
coagulopathy is dependent upon the
administration rate, total dose administered
(20 mL/kg is maximum 24 h dose in
humans) and the molecular weight of
dextran. The deleterious effects of dextrans
are usually associated with large doses or
prolonged administration.

The use of hypertonic saline-dextran
solution (4 mL/kg, 2400 mosmol/L sodium
chloride in 6% Dextran-70 administered
intravenously once over 4 min) combined
with an isotonic oral alkalinizing solution
containing sodium chloride (3.22 g/L),
potassium chloride (1.12 g/L), sodium
acetate trihydrate (4.76 g/L) and glucose
anhydrous (16.22 g/L), providing
300 mosmol/kg of water and administered
at 55 mL/kg BW, was superior to either
solution alone for the treatment of
experimentally induced hypovolemic
diarrhea in calves. 39 The combined treat-
ment resulted in immediate and sustained
increases in plasma volume, cardiac out-
put and stroke volume, thereby improving
tissue perfusion. Rapid and sustained
rehydration after the combined treatment
was indicated by improvement in
hydration and clinical depression scores
and decreases in hematocrit, blood lactate
concentration and serum creatinine,
albumin and phosphate concentrations.
Resuscitation with oral electrolyte solu-
tion alone was slower but was complete
within 24 hours. Resuscitation with the
hypertonic saline-dextran solution alone
resulted in only transient benefit.

The administration of hypertonic
saline-dextran solution (7.2% NaCl
solution with 6% dextran at the rate of
4 mL/kg BW, intravenously during a
4 min period, combined with oral
administration of isotonic electrolyte
solution at the rate of 50-60 mL/kg BW)
provided a rapid and effective method for
resuscitating severely dehydrated calves
with experimentally induced diarrhea 40 or
with naturally acquired diarrhea. 41

Hydroxyethyl starch preparations
(hetastarch, pentastarch) Two hydro-
xyethyl starch preparations are currently
commercially available; hetastarch and
pentastarch. Hetastarch is a high-
molecular-weight glucose polymer (mean
molecular weight 450 000) that is
chemically synthesized from amylopectin,
producing a highly branched glucose
polymer with a structure similar to that of
glycogen. Because the molecular weight
of hetastarch is much greater than that of
albumin, hetastarch decreases endothelial
permeability by sealing separations of
endothelial cells. Hetastarch is hydrolyzed
in blood by a-amylase, and the addition
of hydroxyethyl groups slows hydrolysis
and therefore prolongs the duration of
plasma volume expansion. Hetastarch is
supplied as a 6% concentration in 0.9%
NaCl; this provides a hyperoncotic but
j approximately isotonic solution. Reported
; administration rates are 5-40 (mL/kg
BW)/h but, like Dextran-70, it is safer to
administer hetastarch at less than
20 (mL/kg BW)/h. Like Dextran-70,
hetastarch administration also runs

Disturbances of free water, electrolytes and acid-base balance

97

the risk of exacerbating pre-existing
coagulopathies. The risk of coagulopathy
is dependent upon the administration
rate and total dose administered
(20 mL/kg B W is the maximum 24 h dose
in humans).

Pentastarch has a mean molecular
weight of 280 000 and is available as a
10% solution. Pentastarch has two
important advantages over hetastarch: it
has less exacerbating effect on pre-
existing coagulopathies and the rate of
elimination is faster. Pentastarch has
rarely been administered to large animals.

Gelatins (modified bovine collagens)
are available for veterinary use. The
formulation uses gelatin with a mean
molecular weight of 30 000 and is a 5.6%
suspension in NaCl. Compared to
dextrans and hydroxyethyl starches,
gelatins have a shorter plasma half-life
but appear to have less effect on
coagulation. In general, gelatins have not
been evaluated as completely as dextrans
and hydroxyethyl starches and, on this
basis, are not currently preferred.

Practical administration of
electrolyte solutions

Under ideal conditions, with laboratory
evaluation of the animal, the deficits can

be accurately assessed and fluids
containing the deficient electrolytes can
be formulated. However, under most
practice conditions this is not possible
and polyionic crystalloid solutions are
in general use. These usually contain
sodium, potassium, chloride and calcium
or magnesium at a concentration similar
to the electrolyte composition of extra-
cellular fluid; the solutions may also
contain lactate or acetate as bicarbonate
precursors. Dextrose may be added to the
solution to make an initial mildly hyper-
tonic solution.

Polyionic crystalloid solutions are safe
and can be used in large quantities
without inducing electrolyte disturbances
provided that circulating blood volume
and renal function have been restored
and are maintained. They can be used for
most situations of dehydration and
moderate acidemia or alkalemia and
moderate electrolyte imbalances.They are
not usually adequate for the treatment
of severe acidemia or alkalemia, or
severe hyponatremia, hypokalemia or
hypochloremia.

For the treatment of severe acidemia or
alkalemia, and severe hyponatremia,
hypokalemia and hypochloremia, specific

electrolyte solutions are necessary.
Generally, they consist of a mixture of the
common simple solutions with supple-
mented electrolytes to correct some major
abnormality. These are considered
necessary to correct abnormalities quickly
that could not be corrected using balanced
electrolyte solutions. These solutions are
summarized in Tables 2.3 and 2.5. Many
intravenous solutions for fluid therapy in
calf diarrhea are available and it is
recommended that they should contain
150 mmol/L of sodium, 5 mmol/L of
potassium and about 50 mmol/L of a
mixture of bicarbonate and precursors 42

When acidemia is not present it is not
necessary to use a fluid containing
bicarbonate. 43

Mature cattle affected with metabolic
alkalosis associated with diseases of the
abomasum are usually hypokalemic,
hypochloremic and dehydrated. For such
cases, a balanced electrolyte solution
containing sodium, chloride and potassium
is satisfactory. A solution containing sodium
(135-155 mEq/L), chloride (150-170 mEq/L)
and potassium (10-20 mEq/L) is effective. 43
In recently calved dairy cattle, calcium
borogluconate is commonly added to the
mixture.

'• t,Vw; Vi ' 7 ■

Lactate or

Solution

Na*

K*

CL

Mg 2 *

Ca 2 * HC0 3 -

acetate Dextrose

Major indications

0.9% sodium chloride

155

155

Expansion of circulating

isotonic saline)

blood volume

1.3% sodium bicarbonate (isotonic)

155

156

Metabolic acidosis

1.3% sodium bicarbonate

155

156

5%

Metabolic acidosis

in 5% dextrose
5% sodium bicarbonate

600

600

Severe metabolic

(hypertonic)

acidosis

Equal mixture of

155

78

78

Metabolic acidosis and

isotonic saline and
isotonic sodium
bicarbonate

dehydration

Balanced electrolyte solution

138

12

100

5

3

50

Metabolic acidosis

(i.e. McSherry's solution)

(acetate)

electrolyte losses and
dehydration

Lactated Ringer's solution

130

4

111

3

28

(lactate)

Metabolic acidosis

High sodium, alkalinizing

190

4

111

60

27

Metabolic acidosis and

solution. Lactated

(lactate)

hyponatremia

Ringer's solution plus
sodium bicarbonate (5 g/L)
High sodium, high potassium,

190

18

125

60

27

Metabolic acidosis,

alkalinizing sodium

(lactate)

hyponatremia,

Lactated Ringer's solution

hypokalemia

plus 1 g/L potassium chloride
and 5 g/L sodium bicarbonate
High-potasium acidifying

154

35

189

Metabolic alkalosis,

solution, isotonic saline

hypochloremia,

plus 2.5-g potassium
chloride/L

hypokalemia

Mixture of

Metabolic alkalosis in

1 L isotonic potassium chloride (1.1 %),

cattle with abomasal

2 L isotonic saline (0.9%) and

$

disease

1 L dextrose 9%

98

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Solutions containing potassium have
been recommended for the treatment of the
potassium depletion that occurs in calves
with acute diarrhea and in inappetent
ruminants and horses. However, in calves
with severe acidemia and hyperkalemia, it is
important to expand circulating blood
volume, restore renal function and correct
the strong ion (metabolic) acidosis before
providing additional potassium, which may
be toxic. Solutions containing potassium
maybe indicated following correction of the
acidosis and dehydration. However, if the
animal's appetite is returned to normal,
the oral potassium intake will usually
correct any existing deficiencies.

For the treatment of hypochloremic,
hypokalemic, metabolic alkalosis, acidify-
ing solutions can be used but preferably
only if constant laboratory evaluation of
the animal is possible. Without laboratory
evaluation, the use of Ringer's solution,
0.9% NaCl or hypertonic saline for
correction of strong ion (metabolic)
alkalosis in adult cattle is recommended,
along with the oral administration of
potassium in animals that are inappetent.
In experimentally induced hypochloremic
hypokalemic metabolic alkalosis in
40-50 kg BW sheep, replacement of the
chloride deficit using 2 L of hypertonic
saline (1.8% sodium chloride) was effec-
tive in returning plasma sodium and
chloride concentrations to normal within
12 hours, and the plasma potassium
concentrations and acid-base balance
returned to normal within 36 hours of
treatment without providing potassium. 44
Small volumes of hypertonic saline are
also effective for the treatment of experi-
mentally induced hypochloremic, hypo-
kalemic metabolic alkalosis in sheep. 45

In summary, four different kinds of
solutions are used in large animal
practice:

o Polyionic crystalloid solutions,

such as lactated Ringer's solution and
acetated Ringer's solution, are
indicated for dehydration and
moderate degrees of acid-base and
electrolyte imbalance
o Hypertonic saline solution and an
oral water load represent a practical
and inexpensive alternative to
parenteral administration of large
fluid volumes

o Hypertonic or isotonic sodium
bicarbonate, such as 8.4%, 5.0%
(hypertonic) or 1.3% (isotonic)
solutions of sodium bicarbonate, are
used for severe strong ion (metabolic)
acidosis and hyponatremia
° Chloride-containing acidifying
solutions, such as Ringer's solution,
are used for treatment of strong ion
(metabolic) alkalosis.

Because cost is a major consideration in
large animal fluid therapy, it may not be
possible to use sterile solutions. Most of
the above solutions can be formulated
using the necessary salts mixed with
distilled water, boiled water or ordinary
tap water and are therefore prepared
inexpensively.

Quantity of fluids required and
routes of administration

The amount of fluid required depends on
the degree of dehydration (an estimate of
the volume losses which have already
occurred), the continuous losses which
are occurring during treatment, and the
maintenance requirements of the animal
during treatment presuming its dietary
intake of water, electrolytes and nutrients
is minimal. The fluids are usually given in
two stages:

o Hydration therapy in the first

4-6 hours at a rate of 100-150 mL/kg
BW intravenously
o Maintenance therapy

(a combination of continuous losses
and maintenance requirements) in
the next 20-24 hours, depending on
the severity and the course of the
disease, at 60-80 mL/kg BW/24 hours
intravenously (approximately
3-4 mL/kg BW/hour). In some cases
of profuse diarrhea, the continuous
losses and maintenance requirements
will be about 150 mL/kg BW over a
24-hour period. The daily
maintenance water requirements of
adult horses range from 54-83 mL/kg
BW, with a mean of 64 mL/kg BW. 46

Some examples of the large quantities of
fluid required for hydration and main-
tenance therapy in cases of acute diarrhea
are outlined in Table 2.6.

Parenteral fluid therapy
The total amount of the estimated
necessary hydration therapy should be
given intravenously using indwelling
intravenous catheters in the first 4-6 hours
in order to expand and maintain circu-
lating blood volume. If acidemia or
alkalemia is present, it also should be

treated immediately. Thus the most
important abnormalities - decreased
circulating blood volume and acid-base
imbalance - are treated first. Restoring
circulating blood volume will restore renal
function, which will assist in correcting
acid-base and electrolyte balance. The
immediate correction of acidemia will
return the tissues to their normal physio-
logical activity. The intravenous route is
preferred for hydration therapy and for
the correction of severe acid-base and
electrolyte imbalances. All other routes
(intraperitoneal, subcutaneous and oral)
are unsatisfactory in the presence of
decreased circulating blood volume.

During the intravenous adminis-
tration, the animal must be monitored
for clinical and laboratory evidence of
improvement or deleterious effects. A
favorable response is indicated by
urination within 30-60 minutes, an
improvement in mental attitude and
some evidence of hydration. Unfavorable
responses include dyspnea because of
pre-existing pneumonia or pulmonary
edema because of too rapid adminis-
tration, failure to urinate because of
renal failure or paralysis of the bladder,
and tetany because of the excessive
administration of alkali. Unusual responses
such as sweating, trembling and
depression within several hours following
the intravenous administration of electro-
lytes or other substances such as
commercial amino-acids may occur if the
infusion is contaminated during adminis-
tration. 47 If a laboratory is available, the
determination of PCV, bicarbonate and
blood pH will provide an excellent
monitoring system during the adminis-
tration of the fluids.

Rate of administration
The rate of administration will depend on
the size of the animal, the severity of the
illness, the type of fluids being administered
and the response of the animal to the
fluids. In calves, isotonic saline (0.9%
NaCl) and sodium bicarbonate solutions
can be given at the rate of 1-3 L/h; in a
mature horse, fluids may be given at the

Degree of
dehydration

Fluid required for:

(% of body

Hydration

Maintenance

Animal

weight)

(L)

(L/24 h)

Mature horse (500 kg)

8

40

25-50

12

60

25-50

Newborn calf (50 kg)

8

4

2.5-5

12

6

2.5-5

Mature cow (700 kg)

8

56 *
84 7

35-70

12

35-70

Disturbances of free water, electrolytes and acid-base balance

99

rate of 10-12 L/h. Hypertonic solutions
such as 5% sodium bicarbonate can be
given to a mature horse at the rate of
3-5 L/h, followed by balanced electrolytes
at 10-12 L/h. Solutions containing added
potassium should be given cautiously, at
the rate of 3-5 L/h. In a cow with severe
dehydration and acidosis due to carbo-
hydrate engorgement, fluids may be given
at the rate of 10-12 L/h.

Adverse reactions in all species
include sudden muscle weakness
(suggests hypokalemia) and sudden
tachycardia and hyperventilation,
which suggest overhydration. When
these occur the fluids should be stopped
and the clinical findings assessed. If
laboratory assistance is available, the
determination of blood pH and bicar-
bonate may provide an explanation for
the reaction.

Intravenous catheters and complications
The administration of large quantities of
fluids intravenously to farm animals is
best done with an indwelling jugular
vein flexible catheter (10-14-gauge) that
is appropriately secured to the animal's
neck to prevent withdrawal from the vein.
Standard aseptic technique must be used.
A plastic, spring-like, coiled tube and
suitable rubber tubing are used to deliver
the fluids from large 20-25 L plastic
containers. The coiled plastic tubing
allows the animal to lie down or stand up
without disrupting the catheter and
tubing. 48 The use of a drip chamber in the
rubber tubing system assists in deter-
mining the flow rate, which can be
adjusted with a clamp. With a 12-gauge
catheter, 25-30 L of fluids can be delivered
as hydration therapy to a mature horse or
cow.

Auricular vein of cattle
The short neck, thick skin and, in some
breeds, pendulous dewlap of cattle make
it difficult to introduce and secure
indwelling jugular catheters for long-term
use. The auricular vein of adult cattle can
be successfully catheterized with an over-
the-needle, 14-gauge catheter, 5 cm long,
permitting 20 L of rehydration solution to
be delivered over 4 hours. 49

Cecal catheters in horses
Percutaneous cecal catheters have been
used to deliver fluid solutions in ponies. 50
The advantages include less cost but
complications include peritonitis, diarrhea,
laminitis and hypocalcemia.

Thrombophlebitis

Long-term jugular vein catheterization
(over a period of a few days) in adult
cattle and particularly horses can result in
thrombophlebitis, suppurative phlebitis,
and catheter sepsis. Inspection of the
affected jugular vein reveals swelling.

firmness and moderate pain. Careful
digital and visual inspection are necessary
to determine the patency of the vein; in
about 50% of cases the vein is completely
thrombosed and occluded and cannot be
used for intravenous administration for
2-3 weeks. The extent and severity of the
thrombophlebitis can be determined by
ultrasonography of the neck and patency
of the vein can be assessed by compress-
ing the vein with the transducer head. 51

The development of thrombophlebitis
is dependent on the method used for skin
preparation and the catheterization
technique. Careful preparation of the skin
and aseptic technique during insertion
and placement of the catheter are crucial
in preventing this complication 52 Heparin
subcutaneously, 150IU/kg BW imme-
diately after insertion of the catheter and
repeated every 12 hours, has been used
prophylactically 52 but this is not deemed
necessary with good technique. Alter-
nating catheters between jugular veins
every 48-72 hours is standard practice in
equine fluid therapy but despite this
precaution complications occur in
20-50% of horses whose jugular veins are
catheterized for 48 hours. 53 By using
catheters made of materials that are less
thrombogenic, inserting them in an
aseptic manner and observing simple
management practices, the duration of
catheter survival increases to about
14 days. The least reactive catheter is
Silastic, followed by polyurethane; poly-
tetrafluoroethylene causes most reaction.
Catheters that are soft are superior to stiff
and rigid ones.

A retrospective study of the risk factors
associated with vein thrombosis in horses
treated with intravenous fluids in a
veterinary teaching hospital found that
the use of carboy fluids, diarrhea and
fever were related; the incidence was
lower in horses that had general anes-
thesia, surgery and received antimicrobial
agents. 54 A variety of aerobic bacteria
were cultured from about 50% of the
intravenous catheters removed from
horses. 55 Bacteria were isolated from 7%
of skin swabs taken from the area around
the catheter after surgical preparation
with iodine soap and before and after
removal of the catheter. However, there
was no correlation between bacterial
culture and the condition.

Oral fluid therapy

Whenever possible, the oral route can be
used to deliver the maintenance require-
ments. Provided there are no abnormalities
of the digestive tract that interfere with
oral administration or the absorption of
the fluids, the oral route is preferred for
maintenance therapy. In ruminants such
as adult cattle, rumen function must be

present for significant absorption of fluids
and electrolytes. The oral administration
of large quantities of fluid to cattle with
rumen atony results in sequestration of
the fluid in the rumen and the develop-
ment of metabolic hypochloremic,
hypokalemic alkalosis.

Oral fluid therapy in calves and adult
cattle

For diarrheic calves, the total 24-hour
maintenance requirement is calculated
and given orally in divided doses every
2-4 hours. Compared to parenteral
therapy, there is less danger from over-
hydration and electrolyte toxicity, and in
acute diarrhea the maintenance of oral
fluid and electrolyte intakes will replace
continuous losses that are occurring
during the diarrhea. Livestock owners
should be informed of the value of
providing newborn animals affected with
diarrhea associated with dehydration,
depression, inactivity or failure to suck
with oral fluids and electrolytes as soon as
possible and of the value of continuing
this treatment until the animal has
returned to normal. Oral electrolyte
solutions and water should be made
available at all times to animals affected
with diarrhea and other diseases in which
there are continuous losses of fluid and
electrolytes. The exception is cattle
affected with carbohydrate engorgement,
in which the water supply should be
restricted to one-half or less until the
animals begin to eat.

Calves with dehydration and diarrhea
absorb electrolyte solutions almost as
effectively as healthy calves. The import-
ant principle underlying the efficacy of
oral fluid therapy is the use of low
concentrations of glucose (about 2%) to
promote sodium absorption from the
intestine. 56 Water follows passively and,
because sodium is the osmotic skeleton of
the extracellular fluid, fluid is held
predominantly where it is needed in the
extracellular space, including plasma.
Amino acids, such as glycine, also act like
glucose to promote sodium absorption. In
enterotoxigenic colibacillosis in calves,
the glucose and amino acid cotransport
mechanisms for sodium transport into
epithelial cells are intact. 57 Thus, water
and salt, together with glucose and glycine,
facilitate the absorption of sodium and
water in calves with diarrhea.

A high-calorie hypertonic oral
rehydration solution containing glutamine
was more effective in correcting plasma,
extracellular fluid and blood volume than
conventional solutions with a lower
calorie content and without glutamine. 58

" Glutamine also promotes enteric sodium
uptake and may be important in sustain-
ing villus form and function. The higher-

100

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

calorie solution (7.5% glucose) also
sustains blood glucose levels at a higher
level than conventional solutions. An
effective oral fluid should also contain or
yield sufficient bicarbonate to correct
metabolic acidosis.

A variety of oral and parenteral
electrolyte replacement solutions are
available commercially. 59 Most prep-
arations are in the form of powders to be
mixed with water. They contain sodium,
chloride, potassium, glucose, glycine and
bicarbonate or its precursors (acetate or
propionate).

The sodium bicarbonate included in
oral fluids for the acidosis in calf diarrhea
is usually effective directly and quickly.
There is speculation that sodium bicar-
bonate may interfere with milk clotting in
the abomasum, which requires an acidic
environment for the action of rennin. 60
There is no direct evidence that oral fluids
containing sodium bicarbonate interfere
significantly with clotting of milk in the
abomasum. Nevertheless, some oral
electrolyte solutions for diarrheic calves
contain acetate, propionate or citrate,
which, when absorbed, act as bicarbonate
precursors; 57 it should be noted that
gluconate is not metabolized in calves
and probably not in other large animals.
Because of their acidic pH, it is claimed
that these fluids do not interfere with
abomasal clotting of milk but, as already
stated, there is no direct evidence to
support the claim and no evidence that
the final outcome in naturally occurring
cases of diarrhea in calves is superior when
oral fluids containing metabolizable bases
(rather than bicarbonate) are used.
Furthermore, the oral fluids containing
the base precursors are most effective in
diarrheic calves with a blood pH over 7.2
(see Colibacillosis of calves, Ch. 18).

The alkalinizing effects of com-
mercial oral electrolyte solutions have
been compared in healthy calves. 61,62 A
sodium bicarbonate-rich solution induced
the best alkalinization effect. The prep-
aration should not be mixed with milk but
given one hour before or after feeding
milk because any fluid substance added
to milk changes the physicochemical
characteristics of milk and may interfere
with optimum clotting of milk by rennin
in the abomasum, although the clinical
significance of this effect remains uncertain.
Bicarbonate-containing oral electrolyte
solutions will restore acid-base imbalance
in calves with viral-induced diarrhea
much more effectively than solutions
without bicarbonate.

The continued feeding of milk to
diarrheic calves while they are receiving
oral fluids and electrolytes is contro-
versial . 61 It has been conventional to
withhold milk from diarrheic calves for

1-2 days and gradually reintroduce milk
over the next few days when there is
evidence of recovery. An extreme practice
was to totally deprive the calf of milk until
the diarrhea ceased. The rationale was
that the ability of the calf's intestine to
digest milk was impaired. It is known that
lactose digestion is impaired in the
rotavirus and coronavirus diarrheas of
young calves. It was also thought that the
presence of milk in the intestine would
provide a substrate for continued growth
of enteric pathogens.

Another different practice was to
continue feeding milk to diarrheic calves
because it resulted in more rapid recovery
from diarrhea, less debilitation, continued
weight gain and improved circulating
plasma volume. This is based on the
premise that continuous feeding provides
the intestinal mucosa with nutrients.

In experimentally induced diarrhea in
calves, the continued feeding of milk
during the course of the diarrhea sus-
tained growth, resulted in greater fat
stores, facilitated regeneration of the
intestinal mucosa and resulted in less
thymic atrophy than calves deprived of
milk. 61 However, the number of calves in
the experiment was small and extra-
polation of the results to the naturally
occurring disease is not yet warranted.
Whole milk and an acidic oral fluid
therapy given to calves with naturally
occurring diarrhea did not adversely
affect the calves or prolong or worsen the
diarrhea, and promoted body weight
gain. 63 However, none of the calves was
severely dehydrated or acidemic and
treatment was begun very early in the
stage of diarrhea (see also E. coli in
Ch. 18).

Oral fluid therapy in horses
Intravenous fluid and electrolyte therapy
has been used extensively for the
treatment of dehydration and electrolyte
disturbances in the horse with diarrhea.
However, oral fluid therapy, as used in
calves, has not been employed to the
same extent. It may be an effective,
practical and economical method of
rehydration of horses with diarrhea that
has not yet been fully explored. 64,65

In the horse with acute diarrhea,
several factors contribute to the nature of
the fluid and electrolyte losses. There are
increases in fecal sodium and water loss
but the fecal potassium excretion may
remain unchanged. 64 Experimentally
induced diarrhea (castor oil) in adult
horses results in dehydration, metabolic
acidosis and large fecal losses of sodium
and urinaiy losses of potassium. 66 Plasma
volume decreased while horses were
clinically dehydrated. The lack of feed
intake, which affects primarily the

potassium intake, can result in losses of
2500-3000 mmol of potassium per day.
Although urinary water and potassium
losses are reduced, potassium depletion
continues; thus potassium losses are very
high and need to be replaced, especially
in the anorexic horse. The large potassium
deficit in diarrheic horses should also
be considered when formulating the
composition of oral fluids. Administration
of 30-40 g potassium chloride or, if
chloride administration is inappropriate,
30-40 g potassium bicarbonate in 2-4 L of
water given by nasogastric tube several
times daily to an inappetent horse with
diarrhea can complement intravenous
fluid therapy and replace the potassium
deficit.

The optimum electrolyte composition
of oral fluids and the amount to be used
have not yet been determined for the
horse. The amount given depends on the
degree of dehydration. Dehydration in
horses becomes clinically apparent when
about 5% of body weight has been lost. In
a 500 kg horse, assuming 90% water loss,
the fluid deficit is about 23 L. 64 Abdominal
discomfort may occur following the
nasogastric tube administration of a series
of 8-10 L doses of oral rehydration fluid. 67
The administration of large amounts may
result in rapid transit through the
stomach and intestines and decreased
absorption. A slower rate of adminis-
tration, such as 8-10 L every few hours,
may be tolerated more effectively and the
transit time in the intestine may be
decreased, enhancing absorption. Volumes
of 6-8 L can be given by nasogastric tube
as often as every 15-20 minutes by
funnel; as much as 20-30 L is possible
j during the first hour and 40 L is possible
; during a 2-hour period. 68 Oral fluids may
! also be administered through a small-
l diameter indwelling nasogastric tube, as
i is used for prolonged enteral nutrition of
horses with dysphagia. 65

Commercially available oral electrolyte
solutions are inadequate for horses
because the concentrations of sodium
■: and potassium are too low to adequately
. replace losses. When treating horses with
acute diarrhea, the ratio of sodium to
chloride ions in the oral solution should
; be approximately 1.4:1, and the need for
■ glucose in an oral rehydration solution for
adult horses has not been clearly
demonstrated. One fonnulation contained
5.27 g of NaCl, 0.37 g of KC1 and 3.78 g
NaHC0 3 per liter of tap water; this
; produced a suitable electrolyte composition
for oral administration (Na 135 mmol/L;
K 5 mmol/L; Cl 95 mmol/L; HC0 3
; 45 mmol/L). 69

Ora) administration of bicarbonate will
result in a pronounced alkalemia within
3-6 hours, with the maximum change in

pH occurring at a sodium bicarbonate
dose of 1 g/kgBW (which represents 40%
of normal extracellular sodium). Doses
above this level do not induce additional
alkalinization, presumably because of
limited absorption of bicarbonate from
the intestinal tract. The oral adminis-
tration of sodium bicarbonate to normal
mature resting horses without ad libitum
access to water induces metabolic alkalosis,
hypernatremia, hypokalemia and hyper-
osmolality for at least 8 hours. 70 The oral
doses were 0.25, 1 and 1.5 g/kg BW in 3 L
water; the intravenous dose was 0.25 g/kg
BW in 3 L water. The effects were dose-
dependent: in the horses given the 1 and
1.5 g/kg BW oral doses, the hypercapnia
persisted for 12 hours, whereas hyper-
capnia lasted 2 hours in horses given the
0.25 g/kg BW dose orally or intravenously.
The effects of these large doses of sodium
bicarbonate on the renal function of
horses indicated increases in urine flow,
fractional clearance of electrolytes and
bicarbonate, electrolyte- free water
reabsorption, urine concentrations of
sodium and bicarbonate, urine excretion,
clearance of sodium and bicarbonate,
urine pH and anion gap. 70

The temperature or glucose concen-
tration of the fluid does not appear to be
important, as the rate of fluid absorption
was similar in dehydrated horses
administered an oral rehydration solution
at 5°C, 21°C or 37°C or containing
glucose at 0%, 2.5% or 3.5%. 71 The
tonicity of the oral rehydration solution is
of minor clinical importance; however,
oral administration of hypertonic solutions
(628 mosmol/kg BW) to dehydrated
horses caused a transient increase in
plasma protein concentration that was
attributed to movement of water into the
bowel lumen. 71 A practical limitation of
oral rehydration solutions in horses is that
they should be ingested voluntarily rather
than by nasogastric intubation. This
limitation has led to recent interest in the
oral administration of pastes.

The oral administration of an electro-
lyte paste has been shown to be effective
in correcting mild to moderate dehydration
in horses, provided animals are monitored
to ensure that they drink water. 72 Oral
electrolyte pastes may be formulated as
follows: 30 g of 1:1 mixture of sodium
chloride and potassium chloride, potassium
chloride and sodium bicarbonate, or
potassium chloride and potassium
carbonate, and administered every
6 hours; 120 g of the latter mixture provides
1400 mmol or more of potassium in a
24-hour period. 65 Administration of
higher doses of oral pastes (0.5 g of
NaCl/kg BW, 0.5 g of KCl/kg BW or a
mixture of 0.25 g of NaCl/kg BW and
0.25 g of KCl/kg BW) to dehydrated

Disturbances of free water.

horses induced a transient period of
hyperhydration and apparent plasma
volume expansion that lasted 12 hours. 72
Although the absorbed electrolytes from
an oral paste are subsequently eliminated
via the urine, this treatment is potentially
of benefit in horses with disease pro-
cesses associated with ongoing fluid
losses, such as diarrhea.

There is no published information on
the use of oral fluid therapy in horses that
are diarrheic as a result of disease of the
small intestine such as enteritis, or
proximal enteritis (duodenitis). It would
seem unlikely that oral fluid therapy
would be indicated or effective for
anterior duodenitis. In horses with colitis,
the small intestinal absorptive capacity is
probably intact and oral fluid therapy
prior to transport of the horse to a clinical
center for intensive fluid therapy may
delay the onset of more serious compli-
cations. Horses with mild dehydration
can be rehydrated effectively with oral
fluid therapy. Horses treated with oral
fluid therapy must be monitored clinically,
and the hematocrit, total plasma protein
concentration and serum electrolytes
should be measured.

Oral fluid therapy in horses with
impaction of the large colon provides an
effective and inexpensive treatment and
should be regarded as the initial treat-
ment of choice. In general, 6-8 L of water
can be administered by nasogastric
I tube and funnel (gravity flow) every
| 15-20 minutes; 68 the administered fluid is
! rapidly transported to the large intestine.
It is generally recommended that the
osmolality of the fluids should be isotonic,
ranging from 280-360 mosmol/L; the
I upper range of tonicity which is safe to
administer is unknown. Oral adminis-
tration of 60 L of lactated Ringer's
solution or an isotonic solution over
| 12 hours was superior in hydrating the
; contents of the right dorsal colon when
I compared to intravenous administration
of an equivalent volume of lactated
Ringer's solution or enteral administration
of 1 g/kg BW of MgS0 4 .7H 2 0 (Epsom's
salts) or anhydrous Na 2 S0 4 as a 1 L
: solution. 69,73 Moreover, enteral adminis-
tration of Epsom's salts has been associ-
| ated with hypermagnesemia, and
! anhydrous Na 2 S0 4 has been associated
| with hypocalcemia. 73

: Fluid and electrolyte therapy in newborn
: piglets and lambs

The most common cause of fluid and
electrolyte imbalance in newborn piglets
and lambs is acute neonatal diarrhea.
There is severe dehydration, acidemia,
hj'ponatremia and, in some cases, hyper-
kalemia due to the acidosis. Balanced
I electrolyte solutions or isotonic saline and

electrolytes and acid-base balance

sodium bicarbonate initially followed by
balanced electrolytes are indicated and
successful. These are given subcutaneously
or intraperitoneally at the rate of 15 mL
per piglet every 2 hours plus the same
amount orally. The safe amount of
sterilized porcine serum or saline and 5%
dextrose that can be given to piglets is
equivalent to about 8% BW intra-
peritoneally, in two divided doses given
8 hours apart. Lambs are also treated
subcutaneously (30-40 mL) and orally
(50-100 mL) every 2 hours.

Parenteral nutrition

Parenteral nutrition is used to provide
adequate nutrition intravenously, as long
as necessary, when feeding by the
gastrointestinal tract is impractical,
inadequate or impossible. The term
parenteral nutrition is preferred to total
parenteral nutrition because the complete
nutritional requirements of large animals
are either not completely known or not
addressed by intravenous fluid adminis-
tration. It should be recognized that
enteral nutrition represents state-of-the-
art medicine because enteral nutrition
supports the repair, maintenance and
growth of the gastrointestinal tract to a
much greater extent than does parenteral
nutrition. It should also be recognized
that parenteral nutrition should only be
i contemplated after at least 5 days of
| inappetence.

The technique is used to supply the
I nutrient requirements, most importantly
; protein, of the animal until it returns to
| normal. In calves affected with persistent
I diarrhea due to chronic disease of the
| alimentary tract, or that cannot or will not
I eat, total intravenous feeding may be
I indicated. 74 High concentrations of
! glucose, protein hydrolysates, lipid emul-
I sions and electrolytes are given by
[ continuous slow intravenous infusion
over a period of several days. Some
encouraging results in calves have been
j published but the cost-effectiveness of
the technique has not been examined. 74

Parenteral nutrition is an acceptable
method of maintaining nutrition in the
! healthy horse over a period of 10 days. 75
i Body weight was maintained at 94% of
; initial values without clinical evidence
I of dehydration. No problems were
[ encountered with the long-term intra-
| venous catheterization. The total daily
’ amounts given are calculated on the basis
i of daily caloric requirement. The intra-
i venous catheter must be inserted down
[ into the cranial vena cava, where a large
volume of blood will dilute the hypertonic
j concentration of the solution. The poten-
% tial problems associated with parenteral
nutrition include difficulty in the main-
i tenance of a steady intravenous drip,

102

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

hypertonicity of the solutions used,
venous thrombosis, excessive diuresis,
catheter sepsis and bacterial contami-
nation of the solutions.

REVIEW LITERATURE

McGinness SG, Mansmann RA, Breuhaus BA.
Nasogastric electrolyte replacement in horses.
Comp Cont Educ PractVet 1996; 18: 942-950.
Ecke P, Hodgson DR, Rose RJ. Review of oral
rehydration solutions for horses with diarrhea.
AustVet J 1997; 75: 417-420.

Schott HC. Oral fluids for equine diarrhea: an
underutilized treatment for a costly disease. Vet J
1998; 155:119-121.

Schott HC, Hinchcliff KW. Treatments affecting fluid
and electrolyte status during exercise. Vet Clin
North Am Equine Pract 1998; 14:175-204.
Berchtold J. Intravenous fluid therapy of calves. Vet
Clin North Am Food Anim Pract 1999;
15:505-532.

Constable PD. Clinical assessment of acid-base
status: Strong ion difference theory. Vet Clin
North Am Food Anim Pract 1999; 15:447-471.
Constable PD. Hypertonic saline. Vet Clin North Am
Food Anim Pract 1999; 15:559-585.

Naylor JM. Oral electrolyte therapy. Vet Clin North
Am Food Anim Pract 1999; 15:487-504.

Roussel AJ. Fluid therapy in mature cattle. Vet Clin
North Am Food Anim Pract 1999; 15:545-558.
Constable PD. Clinical assessment of acid-base
status: Comparison of the Henderson-

Hasselbalch and strong ion approaches. Vet Clin
Path 2000; 29:115-128.

Kudnig ST, Mama K. Perioperative fluid therapy. J Am
Vet Med Assoc 2002; 221:1112-1121.

Constable PD. Fluids and electrolytes. Vet Clin North
Am Food Anim Pract 2003; 19:1-40.

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Pain

THE PROBLEM OF PAIN

Pain is a distressing sensation arising
from stimulation of specific end-organs in
particular parts of the body and perceived
in the thalamus and cerebral cortex. Pain
is basically a protective mechanism to
ensure that the animal moves away from
noxious (damaging) influences, but endo-
genous pain, arising from internal
damaging influences, causes its own
physiological and pathological problems
that require the veterinarian's inter-

vention. In humans, there is an additional
psychological parameter to pain and,
although it is customary to transpose
attitudes from pain in humans to animals,
this is a courtesy rather than an established
scientific principle.

A major difficulty with pain in animals
is the difficulty of pain measurement. Pain
is a subjective sensation known by
experience and which can be described by
illustration, but measurement of pain is
an indirect activity related to its effects
and is an objective phenomenon. A panel
report on recognition and alleviation of
pain in animals proposes a simplified
classification for animal pain and distress
as: pain, anxiety and fear, stress, suffering,
comfort, discomfort and injury. 1 The
recommendations are directed at
academics, teachers and researchers using
laboratory animals, and the pharma-
ceutical industry.

fhin is assessed in animals by three
methods: 1) observation of behavior; 2)
measurement of physiological parameters,
including heart rate, blood pressure,
sweating and polypnea, that indicate
sympathetic activation; and 3) measure-
ment of the plasma concentration of factors
that indicate sympathetic activation,
such as plasma cortisol, epinephrine,
norepinephrine and non-esterified fatty
acid concentrations. Because of the
lability and expense of epinephrine and
norepinephrine analyses, and the poor
specificity of increased plasma non-
esterified fatty acid concentration for
pain, the most commonly utilized labor-
atory measure of pain is plasma cortisol
concentration. Cortisol concentrations
have also been measured in saliva, urine
and feces in order to provide a more
accurate indicator of basal stress, as
plasma cortisol concentrations increase
rapidly in response to handling and
restraint for blood sampling.

Pain in agricultural animals is a matter
of ever-increasing concern. Many agri-
cultural practices that are thought to be
necessary to avoid later painful disease or
injury (e.g. dehorning of cattle, sheep and
goats; tail docking in lambs; the Mules
operation in Merino sheep; tooth clipping
in baby pigs, to improve animal pro-
duction (e.g. castration, spaying) or to
facilitate in animal identification (branding,
eartagging, tattooing or ear notching) are
carried out by producers without
anesthetic. It is not our purpose to engage
in a discussion on the subject of animal
welfare or the prevention of cruelty.

ADVANCES IN ATTITUDE TOWARD
PAIN

There is now a greater awareness of the
existence of pain in animals and the
detrimental effects of pain, 2 which has led

Pain

103

to widespread implementation of post-
operative pain control. 3 Newand improved
analgesics are being developed and
marketed as a result of increased basic
and clinical research in pain. The detri-
mental effects of pain include:

o Suffering and stress resulting in
delayed healing

o Increased catabolism and decreased
feed intake

e Prolonged recovery and longer
recumbency with a greater risk of
postoperative complications
° The potential to cause ineffective
respiratory ventilation with the
development of respiratory acidosis
and acidemia
s Self-mutilation

® The potential of acute pain to lead to
chronic pain.

Pain may be clinically beneficial by acting
as a protective mechanism by moving the
animal away from the noxious stimulus
and providing immobility of the affected
part, thereby promoting healing. Pain is a
valuable diagnostic aid but, once identified,
it is our obligation to treat the pain and
remove or modify its source if possible.

Once it is accepted that pain is
detrimental it then becomes important to
recognize and evaluate the severity of
pain. In the past, veterinary science has
used an anthropomorphological approach
to the assessment of whether or not an
animal is in pain. It is a reasonable
elementary approach to compare the
effects of pain in animals with those in
humans because there are many more
similarities in the neuroanatomical,
physiological and behavioral data
between humans and animals than there
are differences. However, because of the
inherent behavioral and social differences
between humans and animals, this
approach is limited. Current research on
pain in animals includes visual and
subjective assessment of pain supported
by physiological and clinicopathologic
measurements. These studies have
increased the awareness of the problem of
pain in veterinary medicine and resulted
in improved information on the use of
appropriate analgesics.

etiology

Pain sensations are aroused by different
stimuli in different tissues and the agents
that cause pain in one organ do not
necessarily do so in another. In animals
there are three types of pain:

° Cutaneous (or superficial)

G Visceral

° Somatic (or musculoskeletal).

The causes of each type of pain are listed
below.

Cutaneous or superficial pain

Cutaneous or superficial pain is caused by
agents or processes that damage the skin,
such as burning, freezing, cutting and
crushing. Fire burns, frostbite, severe
dennatitis, acute mastitis, laminitis, infected
surgical wounds, footrot, crushing by
trauma, conjunctivitis and foreign body in
the conjunctival sac are all common
causes of pain.

Visceral pain

Examples of visceral pain include:

0 Inflammation of serosal surfaces, as in
peritonitis, pleurisy and pericarditis
« Distension of viscera, including the
stomach, intestines, ureters and
bladder

° Swelling of organs as in

hepatomegaly and splenomegaly
0 Inflammation, as in nephritis,
peripelvic cellulitis and enteritis
o Stretching of the mesentery and
mediastinum.

In the nervous system, swelling of the
brain caused by diffuse edema, or of the
meninges caused by meningitis, are potent
causes of pain. Inflammation of (neuritis)
or compression of (neuralgia) peripheral
nerves or dorsal nerve roots are also
associated with severe pain.

Musculoskeletal (somatic) pain

Muscular pain can be caused by lacer-
ations and hematomas of muscle, myositis
and space-occupying lesions of muscle.
Osteomyelitis, fractures, arthritis, joint
dislocations, sprains of ligaments and
tendons are also obvious causes of severe
pain. Among the most painful of injuries
are swollen, inflamed lesions of the limbs
caused by deep penetrating injury or, in
cattle, by extension from foot rot.
Amputation of a claw, laminitis and septic
arthritis are in the same category. Ischemia
of muscle and generalized muscle tetany,
as occurs in electroimmobilization, 4 also'
appear to cause pain.

The trauma of surgical wounds is a
controversial topic in animal welfare,
especially that associated with minor
surgical procedures such as dehorning,
tail docking and castration in farm
animals. From clinical observation sup-
ported by some laboratory examinations,
e.g. salivary cortisol concentrations after
castration in calves and lambs, it appears
that pain after these procedures is short-
lived, up to about 3 hours. 5

PATHOGENESIS

Pain receptors are distributed as end-
organs in all body systems and organs.
They are connected to the central nervous
system by their own sensory nerve fibers
with their cell bodies in the dorsal root
ganglion of each spinal nerve and via

some of the cranial nerves. Intracord
neurons connect the peripheral neurons
to the thalamus, where pain is perceived,
and to the sensory cerebral cortex, where
the intensity and localization of the pain
are appreciated and the responses to pain
are initiated and coordinated.

The stimuli that cause pain vary between
organs. The important causes include:

° Skin - cutting, crushing, freezing,
burning

® Gastrointestinal tract - distension,
spasm, inflamed mucosa, stretching of
mesentery

*> Skeletal muscle - ischemia,

traumatic swelling, tearing, rupture,
hematoma

° Synovial membranes and cartilage
of joints - inflammation.

Nociception is the normal physiological
process by which pain is perceived. When
a tissue is injured by mechanical, thermal
or chemical means, peripheral nocicep-
tors (specialized free nerve endings of
afferent neurons) are depolarized and the
initial stimulus is felt as pain.

Peripheral nociceptors are located in
skin, fascia, muscles, tendons, blood
vessels, joint capsules, periosteum, sub-
chondral bone, pleura, peritoneum and
viscera. Five classes of peripheral
nociceptor are currently recognized: 1)
thermal nociceptors activated by tem-
peratures above 52°C or below 5°C; 2)
mechanoheat nociceptors activated by
pressure and temperature; 3) polymodal
nociceptors; 4) visceral nociceptors; and
5) silent nociceptors. The first pain or
initial sharp stinging following injury is
due to activation of large-diameter fast-
conduction myelinated nerve fibers called
Type I A8 fibers (thermal nociceptors) or
Type IIA5 fibers (mechanoheat nocicep-
tors). The second pain or slow pain
following injury is due to activation of
small-diameter unmyelinated slow-
conduction fibers called C-fibers; these
fibers transmit a painful stimulus that is
perceived as a sustained burning sensa-
tion that persists past cessation of the
initial sharp painful sensation. Visceral
nociceptors are activated by diffuse
stimulation instead of direct local noxious
stimuli. Silent nociceptors are mechano-
heat nociceptors that are activated when
sensitized by release of proinflammatory
mediators (such as bradykinin, histamine,
leukotrienes, eicosanoids, serotonin, sub-
stance P, adenosine triphosphate (ATP),
low tissue pH and other constituents of
inflammation) into damaged tissues,
thereby establishing peripheral hyper-
algesia. The hyperalgesia during acute
pain is believed to promote healing at the
injured site.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Central hypersensitivity and pre-
emptive analgesia

A state of altered central processing can
also occur in response to chronic acti-
vation of peripheral nociceptors, called
central hypersensitivity or 'wind up'.
This central hypersensitivity results in a
modified response to subsequent afferent
inputs, which last between 10 and 200 times
the duration of the initiating stimulus. The
net result is that stimuli previously
perceived as innocuous, such as touch or
pressure, become perceived as painful
after the system is sensitized. Preinjury
treatment with opioids or local anes-
thetics prevents or decreases the develop-
ment of central hypersensitivity and
behavioral indicators of pain but opioids
and local anesthetics are less effective if
administered after the injury is initiated. It
is the establishment of central hyper-
sensitivity that makes pain much more
difficult to control once it is established
and why analgesics are less effective
at this time. Thus the combination of
peripheral hyperalgesia (particularly
associated with substance P) and central
hypersensitivity results in what is called
clinical pain.

It has been suggested that by pre-
venting the surgical afferent stimuli from
entering the spinal cord, the facilitation of
spinal nociceptive processing could be
prevented and this would decrease the
severity of postoperative pain. This is
known as the concept of pre-emptive
analgesia. Presurgical administration of
an analgesic is more effective than post-
surgical administration of the same dose;
this is relevant to the control of pain
associated with elective surgery. Many
studies (primarily in humans) have
demonstrated that presurgical adminis-
tration of local anesthetic agents and the
administration of NSAIDs or opioids
before the patient is recovered from
anesthesia are appropriate methods for
instituting pre-emptive analgesia.

The physiological responses to pain
are described below. Normal responses
include the release of the morphine-like
endorphin from the brain, 6 providing an
endogenous analgesic system, and also
cortisol release from the adrenal cortex' in
response to any stress. The clinical response
to pain varies not only with the personality
of the patient (some are more stoical than
others) but also with various other
influences. For example, distraction, as in
walking a horse with colic, application of
an alternative pain in the forced elevation
of the tail of a cow (tail jack), and appli-
cation of local anesthetic agents all tend
to relieve pain. In agricultural animals
pain elicits behavioral, physiological and
clinicopathological changes. The behavioral
responses can be interpreted as a form of

distraction, a displacement activity, or as
providing an alternative pain. The physio-
logical and clinicopathological responses
are part of the fight or flight phenomena
and reflect sympathetic activation.

CLINICAL FINDINGS

The general clinical findings of pain are
described here and the indications of pain
associated with individual body systems
or organs are described within each
category.

Physiological responses

Physiological responses to pain are
manifested by the following signs, the
severity of the pain determining the
degree of response:

® Tachycardia
° Polypnea
° Pupillary dilatation
° Hyperthermia
° Sweating.

The cardiovascular responses of tachycardia
and hyperthermia may contribute to a
fatal outcome in animals with reduced
cardiovascular reserve, for example when
dehydration, acid-base imbalance and
endotoxic shock are also present.

Behavioral responses

These include abnormal posture and gait
when the pain is musculoskeletal (e.g.
somatic). The gait abnormalities include
lameness, a shuffling gait and rapid
shifting of weight from one leg to
another. These are subjects of importance
in orthopedic surgery.

The behavioral responses to pain may
also include unrelated activities such as
rolling, pawing, crouching or grinding
of teeth when the pain is visceral.
However, the behavioral activities may
also be related to the site of the pain, e.g.
the horse with colic that looks at its
abdomen, or to a particular function, such
as pain manifest on coughing, walking,
defecating, urinating, etc. The behavioral
aspects of severe pain are very important
in the horse with severe unrelenting
visceral pain due to colic. The rolling,
falling and lunging upwards and back-
wards (often falling against walls) can
result in severe injury and causes panic in
many owners.

Generally, somatic pain is more
localized and easily identified than
visceral pain. Injuries to limbs are usually
identifiable by fractures or localized
tendon strain or muscle injury. With
severe somatic pain, as with a fracture or
septic arthritis, the limb is carried off the
ground and no weight is taken on the
limb. With lesser lesions more weight-
bearing activity is undertaken.

One of the notable factors affecting
pain in animals is the analgesic effect of

the animal lying on its back or of its
adopting a defeated, supine posture. This
may be related to the release of
endorphins. 7

More general behavioral responses to
pain include decreased appetite and
average daily rate of gain, adoption of an
anxious expression (ears retracted),
disinclination to be examined and aversion
to returning to a particular location where
pain has been experienced previously.
Moaning, grunting and grinding of the
teeth (odontoprisis or bruxism) are
generally indicative of pain. If the
vocalization occurs with each respiration,
or each rumination, the pain appears
likely to arise from a lesion in the thoracic
or abdominal cavities. When teeth-
grinding is associated with head-pressing
it is thought to indicate increased intra-
cranial pressure such as occurs with brain
edema or lead poisoning. Grinding of the
teeth as a sole sign of pain is usually
associated with subacute distension of
segments of the alimentary tract. More
extreme kinds of vocalization caused by
pain include moderate bellowing by
cattle, bleating in sheep and goats, and
squealing in pigs.

Elicitation of pain by the
veterinarian

This is an essential part of a clinical
examination. The techniques include the
following:

° Pressure by palpation, including firm
ballottement with the fist and the use
of a pole to depress the back in a
horse or to arch the back upwards
from below in a cow

° Pressure by compression, as with hoof
testers for detecting the presence of
pain in the hoof

° Movement by having the animal walk
actively or by passively flexing or
extending limbs or neck
° Stimulation of pain related to

coughing by eliciting the cough reflex
* Relief of the pain by correction of the
lesion.

Periodicity and duration of pain

Limited duration of pain can be the result
of natural recovery or of surgical or medical
correction of the problem. Constant pain
results from a static state whereas periodic
or intermittent pain is often related to
periodic peristaltic movement. In humans
and in companion animals some import-
ance also attaches to observing the time
of onset of pain, whether it is related
to particular functions or happenings
and whether the patient gains relief by
adopting particular postures or activities.
These factors are unlikely to be of import-
ance as an aid to a diagnosis in agri-
cultural animals.

Pain

103

treatment

Several aspects concerning the relief of
pain in agricultural animals are important.
Cost has always been a deterrent to the
use of local anesthetics and analgesics.
However, with changing attitudes towards
animal pain, this issue is more frequently
examined. Treatment of the causative
lesion is a major priority, but the treated
lesion may remain painful for varying
lengths of time. Relief and the control of
pain should be a major consideration
and the following principles require
consideration:

» Relief of pain is a humane act.
Improved, less painful methods of
castration, dehorning, tail-docking.
Mules operation in sheep, spaying
cattle and treating painful lesions of
the hooves of farm animals must be
explored and implemented. Surgical
operations such as laparotomies must
be performed using appropriate
analgesia

0 Analgesia may obscure clinical
findings that may be necessary to
observe, properly diagnose or
maintain surveillance of a case. This is
of major importance in equine colic
» Control of pain is necessary to
prevent animals from inflicting
serious self-injury associated with
uncontrollable behavior as a result of
severe visceral pain (see Equine colic)
c Analgesics for visceral pain are readily
available and relatively effective
c A major problem in the clinical
management of pain is for cases of
severe, slowly healing, infected
traumatic wounds of the
musculoskeletal system. Pain is likely
to be very severe, continuous and to
last for periods of up to several weeks.
Affected animals cannot bear weight
with the affected limb, have great
difficulty in moving, lose much weight
and prefer prolonged recumbency. At
the present time, there are no
effective analgesics available that can
be administered easily and daily for a
few weeks without undesirable side-
effects. The development of such
products is urgently required.

Analgesia

The analgesic agents and techniques
available include the following:

° Surgical procedures, e.g. neurectomy
by section of peripheral nerves, as
practiced in horses

0 Local destruction of peripheral nerves
by chemical means, e.g. the epidural
injection of agents such as ethyl
alcohol may prevent straining
0 Local destruction of peripheral nerves
by thermal means, e.g. cautery of the

wound edge after gouge dehorning in
calves 8

“ Analgesia using nonopiate drugs
when sedation is not required or is
contraindicated

0 Opiate analgesics (narcotic analgesics).
Analgesic agents

There are five main types of analgesic
agent administered parenterally or topically
to large animals: 1) local anesthetic
agents such as lidocaine, mepivacaine
and bupivacaine; 2) nonsteroidal anti-
inflammatory drugs (NSAIDs) such as
flunixin meglumine, ketoprofen, phenyl-
butazone and meloxicam; 3) a 2 -agonists
such as xylazine and detomidine;

4) opioids such as morphine, fentanyl,
butorphanol and buprenorphine; and

5) vanilloids such as capsaicin. In general,
local anesthetic agents, a 2 -agonists and
opioids are used to provide short-term
analgesia (hours), and parenteral NSAIDs
and topical vanilloids are used to provide
long-term analgesia (days to months).
Standard anesthesiology texts should be
consulted regarding techniques for local
analgesia using regional or peripheral
nerve blocks and local anesthetic agents,
or for general analgesia using a 2 -agonists
and opioids.

Local anesthetic agents
Lidocaine, mepivacaine and bupivacaine
exert their analgesic effect by addressing
both the first pain and second pain after
injury by blocking the voltage-gated
sodium channels in peripheral nerves,
thereby preventing propagation of
depolarization. Type IAS, type HAS and C-
fibers are blocked before other sensory
and motor fibers, meaning that it is
possible (but sometimes a clinical
challenge) to selectively block pain while
leaving the animal able to maintain
normal motor function. The main advan-
tages of local anesthetic agents are their
cost and predictable and local effect, the
main disadvantage is short duration of
action. Topical formulations of lidocaine
(2.5%) and prilocaine (2.5%) are available
that appear to be useful for transdermal
administration of a local anesthetic in
large animals prior to intravenous catheter
placement, venipuncture, arthrocentesis
or collection of cerebrospinal fluid. 9

Nonsteroidal anti-inflammatory drugs
These drugs appear to exert most of their
analgesic effect by addressing the second
pain (slow pain) due to sensitization of
C-fibers by eicosanoids; NSAIDs are not
currently believed to exert a central
analgesic effect. Animals receiving NSAIDs
should be normally hydrated in order to
minimize potential renal effects such as
tubular nephrosis and papillary necrosis
(see diseases of the kidney) .

Flunixin meglumine

This NSAID has excellent anti-
inflammatory, antipyretic and analgesic
properties, and is the preferred NSAID for
acute soft tissue or visceral pain, although
it is also efficacious against musculo-
skeletal pain. Flunbin meglumine provides
excellent analgesia in equine colic and
postsurgical pain, hr a comparison of three
NSAIDs used to minimize postsurgical
pain in horses, flunixin meglumine
(1 mg/kg BW), phenylbutazone (4 mg/kg
BW) or carprofen (0.7 mg/kg BW) were
administered once intravenously. 10 All
three NSAIDs were effective in control-
ling postsurgical pain but the duration of
clinical effect was longer for flunixin
meglumine (12.8 h) than carprofen (11.7 h)
or phenylbutazone (8.4 h).

The usual loading dose is 1. 1-2.2 mg/kg
BW (ruminants) or 1.1 mg/kg BW (horses)
followed by a maintenance dose of
1.1 mg/kg BW every 24 hours, 11 although
some studies have administered repeated
injections at 8-12 hours. Flunixin
meglumine is usually administered once
or twice a day for its analgesic effect and
is usually administered parenterally
(preferably intravenously because of the
rare instances of myonecrosis following
intramuscular injections, particularly in
horses), although oral formulations exist.
Intramuscular doses are rapidly absorbed,
with the maximal concentration occurring
within 1 hour. Large doses given to
individual ponies may, however, be
toxic. 12 Toxic effects are similar to those
with phenylbutazone and include ulcer-
ation of the colon, stomach and mouth;
the latter two are most evident when
administered orally.

Ketoprofen

This NSAID has anti-inflammatory, anti-
pyretic and analgesic properties, and is
labeled in Europe for the treatment of
pain in cattle associated with mastitis,
lameness and trauma (3.3 mg/kg BW,
intravenously or intramuscularly, every
24 h for 3d). Oral formulations are also
available in Europe for the treatment of
suckling calves. On theoretical grounds,
ketoprofen may have superior analgesic
properties to currently available NSAIDs
because it blocks both the cyclooxygenase
and 5-lipoxygenase branches of the
arachidonic acid cascade as well as
potentially having antibradykinin activity.
However, the latter two effects have not
been demonstrated in large animals at
recommended dose rates. 13 Ketoprofen
has been shown to provide analgesia for
several hours after gouge dehorning of
calves 14 and surgical castration of calves. 15

Phenylbutazone

This NSAID is used extensively as an
analgesic for horses, especially for

106

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

musculoskeletal pain. It is most effective
for the relief of mild to moderate musculo-
skeletal pain. The half-life of the drug in
plasma is about 3.5 hours so that repeated
treatment is recommended. A plasma
concentration of 20 pg/mL appears to be
clinically effective in horses, whereas a
plasma concentration of 60-90 pg/mL
appears to be clinically effective in cattle. 16

After oral use in horses the peak levels
in plasma are reached at 2 hours, but after
intramuscular injection this does not
occur until after 6 hours, so that the oral
or intravenous routes are the usual routes
of administration. Unless care is taken to
inject the drug slowly when using the
intravenous route, severe phlebitis, some-
times causing complete obstruction of the
jugular vein, may result. For horses the
recommended dose rate is 4.4 mg/kg BW
daily for 5 days orally or intravenously.
Treatment on day 1 may be at 4.4 mg/kg
BW twice, constituting a loading dose. 17
Treatment beyond 5 days may be
continued at minimal effective dose rates.
However, prolonged use, especially in
ponies, at a dose of 10-12 mg/kg BW daily
for 8-10 days, may be followed by
ulceration of alimentary tract mucosa,
including the oral mucosa, and fatal fluid
retention due to hypoproteinemia! 8 The
pathogenesis of these lesions is thought
to be due to a widespread phlebopathy. 19
Phenylbutazone should not be used if
there is pre-existing gastrointestinal
ulceration, clotting deficits or cardiac or
renal dysfunction. Its use should be under
close veterinary supervision so that the
dose rate may be kept to a minimal
effective level and so that it is used only
when there is a clear clinical indication to
do so. It should be withdrawn if there is
no indication of a therapeutic response or
if signs of toxicity appear. If there is doubt
about toxicity or a prolonged course is
advised, periodic hematological examin-
ations are recommended.

For cattle, the recommended oral dose
is 10-20 mg/kg BW initially followed by
daily doses of 4-6 mg/kg BW or eveiy
other dose of 10-14 mg/kg BW. 16,20
Clearance is slowed in neonates, so the
dosage protocol would need to be adjusted
in suckling calves. 21 Phenylbutazone is
moderately effective in cattle with painful
conditions of the limbs. In most countries
phenylbutazone is not approved for use
in food-producing animals because of the
risk of drug residues in the food chain and
the known toxicity of phenylbutazone in
humans.

Salicylates

Aspirin or acetylsalicylic acid is the most
commonly administered analgesic in
cattle but is not very effective and there is
limited clinical evidence of its efficacy. The

recommended dose rate is 100 mg/kg BW
orally every 12 hours, 22 and oral adminis-
tration is most common. Because there
may be limited absorption from the small
intestine, the salicylates may be given
intravenously (35 mg/kg BW every 6 h in
cattle; 25 mg/kg BW every 4 h in horses),
but this is no longer practiced with
the widespread availability of flunixin
meglumine and phenylbutazone.

Carprofen

This is the safest NSAID, because
of its weak inhibition of peripheral
prostaglandins.

Diclofenac

This NSAID, when given to lambs before
castration with bloodless castrators,
significantly reduced the time spent
trembling or in abnormal postures fol-
lowing the castration procedure. 23

Xylazine

Xylazine was shown to be the most
effective analgesic for the relief of
experimentally induced superficial, deep
and visceral pain in ponies when it
was compared to fentanyl, meperidine
(pethidine), methadone, oxymorphone
and pentazocine. 24 However, its short
duration of action and the accompanying
sedation and decreased gastrointestinal
motility and increased urine formation
limit its use to short-term analgesia.

Narcotic analgesics

Meperidine (Demerol, pethidine) is
extensively used as an analgesic for
visceral pain in the horse. Methadone
hydrochloride and pentazocine are also
used, to a limited extent, and their use is
detailed in the treatment of colic in the
horse. Butorphanol, a synthetic narcotic
used alone 23 or in combination with
xylazine, 26 provides highly effective
analgesia in horses. In general, narcotic
analgesics are not as effective in ruminants
because they have a different distribution
of mu and kappa receptors to monogastric
animals.

Narcotic agents are used in somatic
pain in humans and may have wider
applicability in animals. A recent clinical
application has been transdermal delivery
of fentanyl, which is a potent mu and
kappa agonist opioid analgesic drug that
is highly lipid-soluble. Fentanyl patches
have been applied to the skin of horses,
pigs, sheep, goats and llamas. The rate
and magnitude of uptake is dependent on
core temperature and environmental
temperature (and therefore blood flow to
the skin at the site of the patch), thickness
of the skin at the site of the patch and
adherence of the patch to the skin. 27 A
significant limitation to the use of opioids
is their addictive nature in humans,
necessitating storage under strict control

with written records of their usage required
in most countries.

Vanilloids

Capsaicin is derived from hot chili
peppers ( Capsicum annum) and is the
main vanilloid used in horses; these
agents are characterized by their ability to
activate a subpopulation of nociceptor
primary afferent neurons. Capsaicin
induces a transient primary hyperalgesia
that is followed by a sustained period of
desensitization that is species-, age-, dose-
and route-of-administration-dependent.
The sustained densensitization is respon-
sible for capsaicin's efficacy as an
analgesic agent. Capsaicin therefore has
dual effects: initial transient primary
hyperalgesia (manifest as a burning
sensation) and long-term desensitization.
Topical application of capsaicin ointment
over the site of the palmar digital nerves
has been used in horses as an adjunctive
method of analgesia in equine laminitis,
with demonstrated efficacy. 28 The major
clinical disadvantage of using capsaicin is
the initial transient primary hyperalgesia.

Balanced analgesia

Because multiple mechanisms for pain
modulation all act together, the concept
of balanced analgesia has been pro-
posed, similar to the way in which the use
of different combinations of sedative and
anesthetic agents results in the best
aspects of each agent producing balanced
anesthesia. 2 Among horses receiving
NSAIDs at the end of an anesthetic, those
that received butorphanol during surgery
required less additional analgesia com-
pared to those that did not receive any
opioid. Thus, combinations of drugs can
be used to produce sequential blocks in
nociceptive pathways.

Administration routes
The main routes used for administration
of analgesics have been local infiltration,
subcutaneous, intramuscular and intra-
venous. Other routes, including the oral,
epidural, intra-articular and topical, are
now being explored. 2

Xylazine and lidocaine given as
epidural analgesia abolished pain and
tenesmus in cows with acute tail-head
trauma which was characterized by acute,
intense pain and discomfort, severe
tenesmus and a limp tail. 29 Extended pain
relief was required for up to 3 weeks.
Xylazine in the epidural space has also
been used to provide analgesia for the
castration of bulls. 30 In the horse epidural
analgesia using a combination of
butorphanol and local anesthetics has
been used to provide perineal analgesia. 2

Supportive therapy

The application of moist heat to a local
lesion causing pain is effective and makes

Stress

107

medical sense. Its value depends on how
frequently and for how long it can be
applied.

Providing adequate bedding is import-
ant for an animal that is recumbent for
long periods or that is likely to injure itself
while rolling. A thick straw pack is most
useful if it can be kept clean and densely
packed. Sawdust is most practical but has
the problem that it gets into everything,
especially dressings and wounds. Rubber
floors and walls, as in recovery wards, are
effective but are usually available only for
short periods.

The provision of adequate amounts
and quality of feed and water is essential,
especially if the animal is immobilized
and because appetite is often poor.

Distracting a horse with colic by walk-
ing it continuously is a common practice
to prevent the animal from behavioral
activities such as rolling, which may cause
self-inflicted injuries. It is valuable, but
has obvious limitations.

REVIEW LITERATURE

Cunningham FM, Lewes P. Advances in anti-
inflammatory therapy. BrVet J 1994; 150:115-134.
Lascelles BDX. Advances in the control of pain in
animals. Vet Annu 1996; 36:1-15.

Lamont LA, Tranquilli WJ, Grimm KA. Physiology of
pain. Vet Clin North Am Small Anim Pract 2000;
30:703-728.

Muir WW, Woolf CJ. Mechanisms of pain and their
therapeutic implications. J Am Vet Med Assoc
2001; 219:1346-1356.

Underwood WJ. Pain and distress in agricultural
animals. J Am Vet Med Assoc 2002; 221:208-211.

REFERENCES

1. Kitchen H et al. J Am Vet Med Assoc 1987;
191:1186.

2. Lascelles BDX. V?t Annu 1996; 36:1.

3. Johnson CB et al. V?t Rec 1993; 133:336.

4. Rushen J, Congdon P. Aust Vet J 1986; 63:373.

5. Fell RL et al. Aust Vet J 1986; 63:16.

6. \&n Ree JM.Tijdschr Diergeneeskd 1985; 110:3.

7. Schoental R. Vet Rec 1986; 119:223.

8. Sylvester SP et al. AustVet J 1998; 76:118.

9. Erkert RS, MacAllister CG. J Am Med Assoc
2005; 226:1990.

10. Johnson CB et al.Vet Rec 1993; 133:336.

11. Hardee GE et al. Res Vet Sci 1985; 39:110.

12. Trillo MA et al. Equine Pract 1984; 6(3):21.

13. Landoni MF et al.Vet Rec 1995; 137:428.

14. McMeekan CM et al. Res Vet Sci 1998; 64:147.

15. Earley B, Crowe MA. J Anim Sci 2002; 80:1044.

16. Williams RJ et al. Am J Vet Res 1990; 51:371.

17. Taylor JB et al.Vet Rec 1983; 113:183.

18. Snow DH et al. Am J Vet Res 1981; 42:1754.

19. Meschter CL et al. Cornell Vet 1984; 74:282.

20. De Backer P et al. JVet PharmTher 1980; 3:29.

21. Semrad SD et al. Am JVet Res 1993; 54:1906.

22. Davis LF.. J Am Vet Med Assoc 1980; 176:65.

23. MolonyV et al.Vet J 1997; 153:205.

24. Pippi NL, LumbWV. Am JVet Res 1979; 40:1082.

25. Kalprvidh M et al. Am J Vet Res 1984; 45:211.

26. Robertson JT, Muir WW. Am J Vet Res 1983;
44:1667.

27. GrubbTL et al. Am JVet Res 2005; 66:907.

28. Seino KK et al. JVet Intern Med 2003; 17:563.

29. Shaw JM. Vet Rec 1997; 140:23.

30. Caulkett NA et al. Comp Cont Educ Pract Vet
1993; 15:1155.

Stress

Stress is a systemic state that develops as
a result of the long-term application of
stressors. It includes pain, which is dis-
cussed above. Stressors are environmental
factors that stimulate homeostatic,
physiological and behavioral responses in
excess of normal. The most objective
measure of the presence and magnitude
of stress is the plasma cortisol con-
centration. The importance of stress is
that it may:

0 Lead to the development of
psychosomatic disease
0 Increase susceptibility to infection
° Represent an unacceptable level of
consideration for the welfare of animals
° Reduce the efficiency of production.

The general adaptation syndrome,

described in humans, has no counterpart
in our animals and it is lacking in accurate
definitions, precise pathogenesis and
general credibility.

CAUSES OF STRESS

For animals, a satisfactory environment is
one that provides thermal comfort,
physical comfort, control of disease and
behavioral satisfaction. An environment
that is inadequate for these factors will
lead to stress. The environmental influences
that elicit physiological responses from
animals are outlined below and some can
be classified as stressors. The effects of
most of these influences on production or
performance indices have been measured
quantitatively and many of them have
been equated with blood levels of adrenal
corticosteroids, which quantify them as
stressors in the different species:

° Road transportation for prolonged
periods, especially during inclement
weather and when overcrowded, is
considered to be a major stress
associated with an increased
incidence of infectious disease in all
farm animal species. The effects of
prolonged road transportation have
been measured in young calves , 1
cattle , 2 sheep 3-4 and horses 3
° Climate, especially temperature,
either as excessive heat or cold, is a
stressor. In particular, a change of
climate places great pressure on heat
production and conservation
mechanisms in, for example,
conditions of sudden wind and rain,
which affect the comfort of animals
° Excessive physical effort, as in
endurance rides for horses, struggling
in restrained animals, fear, and the
excitement and fear in capture
myopathy syndrome in wildlife, are all
potential stressors

° Pain, especially analgesia-masked
pain in severe colic in horses, is a
stressor. The pain of dehorning and
castration of farm animals is also a
transient stressor, depending upon
the species and method used
° Crowding - temperature, humidity,
the physical exhaustion associated
with standing up for long periods,
being walked on, difficulty in getting
to food and water, etc. are relevant.
Two other factors could be important.
One is the effect of crowding on
behavior. For example, pigs in
overcrowded pens appear to bite one
another more than when they are
housed at lower densities, and are
more restless than normal when
temperatures in the pens are high.

The biting is much more severe
between males than between females.
Also, it is known that pigs bite each
other when establishing precedence
in a group, e.g. after mixing of
batches, and that this is more severe
when feed is short. The other possible
factor that might affect the animal's
response to crowding is a
psychological appreciation of the
unattractiveness of crowding
(or of isolation). This, however, is
an unknown phenomenon in
animals

° Presence or absence of bedding.

This is a comfort factor separate from
temperature and wetness. Whether
comfort affects physiological
mechanisms is not currently known
0 Housing generally includes the
matter of comfort as well as that of
maintaining moderate temperatures,
but whether there is a factor other
than the physical is not known
° Nutritional deficiencies including
lack of energy, bulk and fluid
° Quietness versus excitement.
Harassment by humans or other
animals sufficient to cause fear does
elicit stress response in animals and
this is thought to be one of the
significant causes of stress-related
diseases in animals. Thus,
transportation, entry to saleyards,
feedlots, fairs and shows, and simply
the mixing of several groups so that
competition for superiority in the
social order of the group is
stimulated, are causes of stress. Entry
to an abattoir, which has the
additional fear-inspiring factors of
noise and smell, is likely to be very
stressful for those reasons, but it is
unlikely that a fear of impending
death is relevant. Such situations are
I stressful to the point of causing
marked elevation of plasma
epinephrine concentrations

108

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Herding and flocking instincts.

Animal species that are accustomed

to be kept as herds or flocks may be

distressed for a period if they are

separated from the group.

PATHOGENESIS

Stress is thought to develop when the
animal's mechanisms concerned with
adapting its body to the environment are
extended beyond their normal capacities.
The daily (circadian) rhythm of homeo-
static and physiological changes in response
to normal daily changes in environment
requires the least form of adaptation.
Marked changes in environment, such as
a dramatic change in weather, on the
other hand, place a great strain on adap-
tation and are classified as stressors.

The body systems that are principally
involved in the process of adaptation to
the environment are the endocrine system
for the long-term responses and the
nervous system for the sensory inputs
and short-term responses. The endocrine
responses are principally the adrenal
medullary response, related to the 'flight
or fight'situation, which requires immediate
response, and the adrenal cortical response,
which becomes operative if the stressful
situation persists.

In humans, a large part of the 'stress'
state is the result of stimuli arising in the
cerebral cortex and is dependent on the
capacity to develop fear and anxiety about
the effect of existing or anticipated stress-
ful situations. Whether or not these
psychological inputs play any part in
animal disease is important, but undecided.
The evidence seems to suggest that
psychic factors do play such a part but
that it is relatively minor.

The critical decision in relating 'stress'
to disease is to decide when an environ-
mental pressure exceeds that which the
animal's adaptive mechanisms can
reasonably accommodate - in other
words, to define when each of the
pressures outlined above does, in fact,
become a stressor. There is a great dearth
of definition on the subject. Probably the
most serviceable guideline is /Stress is any
stimulus, internal or external, chemical
or physical or emotional, that excites
neurons of the hypothalamus to release
corticotrophin-releasing hormone at rates
greater than would occur at that time of
the day in the absence of the stimulus'.
This definition uses 'stress' where
'stressor' would have been more common
usage. Other than that, it is acceptable.
The critical threshold of stress occurs in
the adrenal cortex, and its physical
determination is subject to a chemical
assay of adrenocorticotropic hormone
(ACTH). This was the basis of the original
'Stress and the general adaptation

syndrome' as set down by Selye. The
original concept is still attractive because
of its simplicity and logic. However,
evidence supporting the hypothesis
remains limited. The importance of the
concept for our animals is unproven. The
deficiency in evidence is that of obtaining
a standard response to a standard appli-
cation of a stimulus. There is a great deal
of variation between animals, and stimuli
that should be significant stressors appear
to exert no effect at all on adrenocortical
activity.

Stress and road transportation

The response of different farm animal
species to the effects of road transportation
has been examined. In unaccustomed
cattle that are forced to run and are then
herded together, there are increases in the
hematocrit and blood concentrations of
catecholamines, cortisol, total lipid, glucose
and lactose. 6 Transportation of calves,
4-6 months of age, for only 4 hours results
in a leukocytosis with neutrophilia, a
decrease in T- lymphocyte population, a
suppression of lymphocyte blastogenesis
and enhancement of neutrophil activity. 7
The effects of road transportation on
cattle varies according to age: the trans-
portation of 1-3-week-old calves for up
to 18 hours was not as stressful as in older
calves. 1,2 The lack of response of the
younger calves to transport may be due to
their lack of physiological adaptation to
coping with the transportation. 1 During
transportation, plasma cortisol concen-
trations and serum creatine kinase
activities increase. There is clinical evi-
dence of dehydration and increases in
serum non-esterified fatty acid, |3-
hydroxybutyrate and urea concentrations,
which reflect changes in normal feeding
patterns. 2 Based on the physiological
measurements and subjective measure-
ments of behavior, a 15 -hour transportation
period under good conditions is not
unacceptable with regard to animal
welfare. 2 Transportation is exhausting and
causes dehydration but lairage facilitates
recovery from both. 8 When sheep are
subjected to a journey of up to 24 hours it
is best to be done as an uninterrupted
trip, because it is the initial stages of
loading and transport that are most
stressful. 3,4 In a 15-hour road journey in
sheep, the major change in hormone
release occurs during the first 3 -hour
period and is much less in the remaining
12 hours. 9

The effects of road transport on indices
of stress in horses have been examined. 5
A road journey lasting up to 24 hours is
not particularly stressful for horses, if they
are healthy, accustomed to the trailer and
their travel companions, permitted to stop
at least as frequently as every 3.75 hours

and traveling in a well -ventilated trailer. 5
There was no indication that road
transport was a risk factor for pulmonary
disease; however, confinement of horses
with their heads elevated for up to
24 hours (similar to during transportation)
results in bacterial colonization and
multiplication within the lower respir-
atory tract. 10 Horses are also less physically
stressed when facing backwards in a
trailer. 11

Based on plasma cortisol concen-
trations, confinement of young bulls on a
truck and motion are considered stressful
factors in road transport. 12 Transport
stress increases fecal, urine and tissue
losses, with most of the increased loss
taking place during the first 5-11 hours of
transport. 13 During transportation of
feeder calves (195 kg) the major portion
of transport stress occurs during the early
phases of transport; longer periods may
not add significantly to the overall stress
imposed on the calf. It is possible that the
major stress may be related to the
handling of the animals during loading
and unloading. 2

Other possible sources of stress

Dehorning dairy calves at 8 weeks of age
resulted in an increase in plasma cortisol
concentration within 1 hour after the
procedure but there was no evidence of
prolonged stress. 14

The effects of maternal dietary restriction
of protein and/or metabolizable energy
on the humoral antibody response in
cows and the absorption of immuno-
globulins by their cold-stressed calves
indicates that there were no major or
sustained differences compared to
controls.

Different types of stress also result in
distinctive changes in the plasma concen-
trations of metabolites and hormones. 10
An environmental stress, such as noise,
will stimulate a hypothalamic-adrenal-
cortex response; while a sympathetic-
adrenal-medulla response occurs with a
stressor such as transportation. 15

CLINICAL PATHOLOGY

The direct criterion of stress is the assay of
plasma ACTH; stress may be indirectly
assayed using plasma cortisol concen-
tration, which is a less expensive and
more widely available assay. Salivary
cortisol concentration is a good indicator
of stress in sheep. Saliva samples are easy
to collect and the laboratory assay is
simple to perform. It needs to be remem-
bered that elevation of plasma and saliva
cortisol concentrations are a normal
physiological response and do not necess-
arily imply the existence of a damaging
state in the environment.

During prolonged periods of road
transportation of cattle and sheep, there

Stress

109

are significant changes in serum concen-
trations of total proteins, non-esterified
fatty acids (NEFAs), glucose, creatine
kinase, P-hydroxybutyrate and urea.
These changes can be used to assess the
degree of stress and the deprivation from
feed and water during transportation . 16
Prolonged feed deprivation reduces liver
glycogen stores and increases concen-
trations of NEFAs and ketones in the
plasma. Dehydration will elevate the con-
centrations of plasma proteins and the
osmolality of the blood. Physical stress
such as fatigue or exercise will result in
increases in creatine kinase. Psychological
stressors such as fear result in elevations
of cortisol and corticosterone.

STRESS SYNDROMES
Stress-related psychosomatic disease

In humans there is a significant neuronal
input from the cerebral cortex to the
hypothalamus in response to the psycho-
logical pressure generated by stress.
Inability to monitor anxiety and feelings
of harassment in our animals makes it
impossible to determine the presence or
otherwise of psychological stress in them.
However, psychosomatic diseases as they
occur in humans are almost unknown
in farm animals. The pathogenesis of
psychosomatic disease appears to be
based on the ability of the cerebral cortex
to effectively override the normal feed-
back mechanisms by which the pituitary
gland regulates the secretion of corti-
costeroids from the adrenal cortex. In
other words, the normal adaptive mechan-
isms do not operate and hyperadreno-
corticism and adrenal exhaustion develop.

Stress and susceptibility to infection

Field observations support the view that
stress reduces resistance to infection. This
seems to be logical in the presence of
higher than normal adrenocortical
activity. The most intensively explored
relationship of this kind has been that of
exposure of calves to weaning and
transportation and their subsequent
susceptibility to shipping fever. The
prevalence appears to be increased and is
still further enhanced by the introduction
of other stress factors.

Stress and animal welfare

The harassment of domesticated animals
by humans has become a matter of great
concern for the community at large.
Intensive animal housing has become an
accepted part of present-day agribusiness
but the consuming public is inclined to
the view that these practices are cruel. The
literature that has built up around the
argument sets out to demonstrate that
environmental stress in the shape of
intensive housing, debeaking, tail docking
and so on is sufficient to cause a stress

reaction as measured by increased
corticosteroid secretion. Such has not
turned out to be the case and this is
understandable in the light of the known
variation among animals in their
response to environmental circumstances
requiring their physiological adaptation. If
it could be shown that this relationship
did exist and that the increased
adrenocortical activity caused reduction
in resistance to infection, the task of the
responsible animal welfare person would
be much easier. The absence of this
experimental data makes the continuing
argument less resolvable, but it is now
generally accepted that producers have a
responsibility to their animals and to
society generally to maintain an accept-
able standard of humane care of animals.
These arguments are usually expressed as
codes of animal welfare, to which most
concerned people conform. However,
they are not statutory directives and are
not capable of active enforcement. Some
courts of law accept them as guidelines
on what the human-animal relationship
in agriculture should be. Many aspects
of the codes are arbitrary and are
understandably heavily sprinkled with
anthropomorphic sentiments. The study
of ethology, which has expanded greatly
during the recent past, may eventually
provide some answers to this active, often
bitterly fought-over field.

The status of animals used in experi-
ments has always been a bone of
contention between the experimenters
and some sections of the general public.

In general, these arguments revolve
around anthropomorphic propositions
that animals are subject to fear of pain,
illness and death in the same way as
human beings. There is no consistent
evidence in physiological terms that
supports these views. However, the public
conscience has again achieved a good
deal of acceptance to its view that animal
experimentation should be controlled and
restricted, and carefully policed to avoid
unnecessary experiments and hardship in
animals under our control.

Stress and metabolic disease

There is an inclination to label any disease j
caused by a strong pressure from an j
environmental factor as a 'stress' disease, j
for instance hypocalcemia of sheep and I
hypomagnesemia of cattle in cold weather, j
acetonemia and pregnancy toxemia of I
cattle and sheep on deficient diets, white j
muscle disease of calves and lambs after j
vigorous exercise. These diseases do have j
environmental origins, but their causes j
are much simpler than a complex j
interaction of the cerebral-cortical- ,
hypothalamic-adrenocortical axis. They f
can be prevented and cured without any j

intervention in the 'stress' disease
pathogenesis. This is not to say that there
is no adrenocortical basis for the patho-
genesis of the above-listed diseases, but
attempts to establish the relationship
have so far been unsuccessful.

Stress and its effect on economic
performance

The constant struggle for domination of
other animals in an animal population is
most marked in chickens and pigs and
the relationship between status in the
hierarchy and productivity in these species
has been established, with the low-status
animals producing less well. It is also
known that birds that are highly sensitive
and easily startled are poor producers; they
are easily identified and culled.

The relationship between stress and
production appears to be a real one. For
example, heat stress in the form of high
environmental temperatures reduces
roughage intake and hence milk pro-
duction in lactating dairy cows and the
relationships between stress and infertility
and stress and mastitis in cattle are
also well documented. The sensitivity of
animals to environmental stress is greatest
at times when they are already affected by
metabolic stresses, e.g. during late preg-
nancy and early lactation. The adoption
of a policy of culling erratic, excitable
animals appears to have an economic
basis.

MANAGEMENT OF STRESS

The widespread public debate about the
welfare of food-producing domestic
animals dictates that veterinarians, animal
scientists and the livestock industry must
develop systems of handling and housing
that will minimize stressors and provide
an environment that makes the animals
most contented and at the same time
most productive. In civilized human
society it should be realistic to expect that
the animals that we use for food pro-
duction or as companions should live
their lives free from abuse or adverse
exploitation. It will be necessary to deter-
mine how best to monitor the wellbeing
of animals and determine whether or not
they are under stress. Guidelines dealing
with codes of practice for livestock pro-
duction are available in many countries.
In addition to housing, handling and
experimental intervention, it will also be
important to give due care to the appro-
priate selection and use of anesthetics
and analgesics when pain is being inflicted,
as in dehorning and castration. The effects
of sedatives such as acepromazine and
xylazine on the stress response in cattle
has been examined but the results are
inconclusive . 17

The welfare of animals during trans-
portation is a major issue that has

110

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

resulted in legislation governing the
transport of animals and to define accept-
able and unacceptable procedures . 16 Many
countries now have codes of practice
for the handling and transportation of
animals. Welfare is determined by the
length of the trip and the conditions
under which animals are transported,
including stocking density, ventilation,
temperature and humidity, noise and
vibration. Prolonged deprivation of feed
and water during long transportation
results in hunger and thirst, and methods
to minimize these consequences must be
examined . 16

REVIEW LITERATURE

Howard JL, ed. Stress and disease in cattle. Vet Clin
North Am Food Anim Pract 1988; 4:441-618.
Griffin JFT. Stress and immunity: a unifying concept.

Vet Immunol Immunopathol 1989; 20:263-312.
Wariss PD. The welfare of animals during transport.
Vet Annu 1996;36: 73-85.

REFERENCES

1. KnowlesTG et al.Vet Rec 1997; 140:116.

2. Wariss PD et al.Vet Rec 1995; 136:319.

3. KnowlesTG et al.Vet Rec 1996; 139:335.

4. Knowles TG et al.Vet Rec 1995; 136:431.

5. Smith BL et al. EquineVet J 1996; 28:446.

6. Hattingh J et al. J South Afr Vet Assoc 1989;
60:219.

7. Murata H et al. BrVet J 1987; 143:166.

8. Atkinson PJ.Vet Rec 1992; 130:413.

9. Broom DM et al. BrVet J 1996; 152:593.

10. Raidal SL et al. AustVetJ 1995; 72:45.

11. Waran NK et al.Vet Rec 1996; 139:7.

12. Kenny FJ, Tarrant PV. Appl Anim Behav Sci 1987;
17:209.

13. Cole NA et al. Am JVet Res 1988; 49:178.

14. Laden S A et al. J Dairy Sci 1985; 68:3062.

15. Mitchell G et al.Vet Rec 1988; 123:201.

16. Wariss PD. Vet Annu 1996; 36:73.

17. Brearley JC et al. J Vet Pharmacol Ther 1990;
13:367.

Localized infections

Localized infections are common in farm
animals and many are bacterial infections
secondary to traumatic injuries. Because
most of them have a surgical outcome, by
incision and drainage or by excision or
amputation, they are not usually included
in medical textbooks. They are presented
briefly here because of their importance
in the differential diagnosis of causes of
toxemia and also because of their space-
occupying characteristics, causing com-
pression of other structures. Also, the initial
treatment is often medical, especially if
the location of the lesion cannot be
identified.

ETIOLOGY

Abscesses and similar aggregations of
pyogenic material in certain anatomical
locations are described elsewhere in
this book. The common ones include:
pharyngeal, retroperitoneal, hepatic,
splenic, pulmonary, cerebral, pituitary,

spinal cord and subcutaneous abscesses.
Other similar lesions include embolic
nephritis, guttural pouch empyema,
lymphadenitis, pharyngeal phlegmon,
osteomyelitis tooth root abscesses and
infections of the umbilicus and associated
vessels.

More widespread accumulations of
necrotic/toxic pyogenic debris occur and
are described under the headings of:
pericarditis, pleurisy, peritonitis, metritis,
mastitis, meningitis and pyelonephritis.

Other pyogenic lesions worthy of note
include the following:

° Inguinal abscess in horses. Some of
these probably originate as
postcastration infections, but some
obviously have other origins, possibly
as a lymphadenitis arising from
drainage of a leg with a chronic skin
infection

° Traumatic cellulitis and phlegmon
in soft tissue, especially skeletal
muscle. The neck is a common site of
infection in the horse, with lesions
resulting from infected injection sites
or the injection of escharotic
materials, e.g. iron preparations
intended only for intravenous
administration. Penetrating traumatic
wounds, often severely infected, are
among the serious occurrences to the
legs and hooves of horses and cattle.
These commonly penetrate joint
capsules, bursae and tendon sheaths,
and under-run periosteum. In cattle,
the common causes are agricultural
implements, in horses they are more
commonly caused by running into
protruding objects, including stakes
and fencing material
0 Abscessation and cellulitis of the
tip or the proximal part of the tail.
Occurs in steers in feedlots and rarely
extends to the hindquarters and the
scrotum ; 1 the cause is presumed to
originate from the presence of an
aggregate of feces on the tip of the
tail (manure ball) which gets caught
in fencing material. Bacterial isolated
from the lesion indicates a mixed
infection

® Perirectal abscess occurs in horses,
caused usually by minor penetrations
of the mucosa during rectal
examination. Some of these rupture
into the peritoneal cavity, causing
acute, fatal peritonitis. Others cause
obstruction of the rectum and colic
because of the pain and compression
that result . 2 They are readily palpable
on rectal examination
° Perivaginal abscess occurs in heifers
and cows, caused by vaginal tears
during parturition, particularly after
dystocia. Occasionally these rupture

into the peritoneal cavity, causing
acute, fatal peritonitis. More
commonly, the abscess causes
obstruction of the rectum and urethra,
with the animal exhibiting signs of
abdominal pain and stranguria
because of the pain and compression
that results. Perivaginal abscesses are
readily palpable on rectal and vaginal
examination

0 Urachal abscess - see omphalitis
0 Pituitary abscess occurs in cattle as a
single entity or in combination with
other lesions . 3 Pituitary abscesses
cause a wide range of signs with
emphasis on dysphagia due to
jawdrop, blindness and absence of a
pupillary light reflex, ataxia and
terminal recumbency with nystagmus
and opisthotonos . 4 A high-quality
Arcanobacterium (Actinomyces or
Corynebacterium) pyogenes vaccine
against the disease is reported to have
performed well 5 but theoretically
should provide minimal to no efficacy
against pituitary abscesses.

® Facial abscess in cattle and goats.
Facial abscesses secondary to injury of
the cheek mucosa caused by plant
awns are common in beef cattle being
fed hay containing a variety of awns
that may penetrate the oral mucosa.

A. pyogenes is the commonly isolated
bacterium. Localized abscesses of the
face and neck are common in some
flocks of goats . 6 A. pyogenes is most
commonly isolated, followed by
Corynebacterium pseudotuberculosis and
Staphylococcus spp. The abscesses are
most common on the jaw and sternal,
facial and cervical regions
» Tooth root abscesses in llamas,
alpacas, goats and sheep. Tooth root
abscesses are a common dental
disease of llamas and alpacas. Tooth
root abscesses can arise without a
known cause or may result from
trauma, foreign body migration (such
as grass seeds), malocclusion and
abnormal tooth wear, and periodontal
disease . 7 Fusobacterium necrophorum
and A. pyogenes are most commonly
isolated from tooth root abscesses in
New World camelids. Tooth root
abscesses are most frequently found
in mandibular molar teeth in New
World camelids, the mandibular
incisors in pigs and the first maxillary
molar in horses . 7

Bacterial causes of localized infection

These include those bacteria that are
common skin contaminants in animals,
including A. pyogenes, F. necrophorum,
streptococci and staphylococci. Clostridial
infections are common but occur
sporadically. They are described under

Localized infections

111

Malignant edema. C. pseudotuberculosis is
common as a cause of local suppuration
in horses and is the specific cause
of caseous lymphadenitis of sheep.
Rhodococcus equi also causes pulmonary
and subcutaneous abscesses in horses
and cervical lymphadenitis in pigs.
Strangles, R. equi infection in foals,
melioidosis and glanders are all charac-
terized by extensive systemic abscess
formation. Histophilus somni causes systemic
abscess formation in sheep. Mycobacterium
phlei and other atypical mycobacteria
are rare causes of local cellulitis and
lymphadenitis/lymphangitis manifesting
as'skin tuberculosis' in cattle. Streptococcal
cervical abscess in pigs is another specific
abscess-forming disease.

PORTAL OF ENTRY

Most localized infections begin as
penetrating wounds of the skin, caused
accidentally or neglectfully because of
failure to disinfect the skin adequately
before an injection or incision, as in
castration, tail docking, etc.

Metastatic implantation from another
infectious process, especially endocarditis,
carried by blood or lymph, is the next most
common cause. In this way a chain of
lymph nodes can become infected. Cranial
and caudal vena caval syndromes produce
similar embolic showers in the lungs.

PATHOGENESIS

The local infection may take the form of a
circumscribed aggregation of bacterial
debris and necrotic tissue, known as an
abscess. This may be firmly walled off by
a dense fibrotic capsule or be contiguous
with normal tissue. When such an abscess
occurs in a lymph node, it is a bubo.
When the infective material is purulent
but diffusely spread through tissues,
especially along fascial planes, it is known
as a phlegmon, and when it is inflam-
matory but not purulent the same lesion
is a cellulitis.

The species of bacteria in the abscess
determines the type of pus present and its
odor. Staphylococci produce large quan-
tities of thick yellow pus, streptococci
produce less pus and more serous-like
exudates. Pus associated with A. pyogenes
is deep- colored, yellow or green in color
and very thick and tenacious. The pus of
F. necrophorum is very foul-smelling and
usually accompanied by the presence
of gas.

Deposition of bacteria in tissues is
sufficient to establish infection there in
most instances. Conditions that favor
abscess development include ischemia,
trauma and the presence of a cavity or a
hematoma. A continuing process of pus
formation results in enlargement to the
stage of pointing and rupturing of an
abscess, or spread along the path of least

resistance into a nearby cavity or vessel,
or discharge to the exterior through a
sinus. Continuing discharge through a
sinus indicates the persistence of a septic
focus, usually a foreign body, such as a
grass seed, a sequestrum of necrotic bone
or an osteomyelitis lesion.

CLINICAL FINDINGS

The clinical signs of abscesses and other
local aggregations of pyogenic lesions are
described under each of the headings
listed under etiology. General clinical
findings which suggest the presence of a
localized infection, which is not readily
obvious clinically, include the following:

0 Fever, depression, lack of appetite -
the signs of toxemia

° Pain resulting in abnormal posture, e.g.
arching of the back, or gait
abnormality, including severe lameness
° Weight loss, which can be dramatic in
degree and rapidity

° Obstruction of lymphatic and venous
drainage, which can cause local
swelling and edema. Sequels to these
developments include extensive
cellulitis if there is a retrograde spread
of infection along lymph drainage
channels, and phlebitis and
thrombophlebitis when there is stasis
in the veins

° Careful palpation under anesthesia or
heavy sedation may be necessary to
overcome the muscle spasm caused
by pain. Calves with extensive
abscessation emanating from the
navel, and horses with inguinal
abscesses, can only be satisfactorily
examined by deep abdominal and
rectal palpation

° Radiological examination may elicit
evidence of osteomyelitis, and
examination of a fistulous tract may
be facilitated in this way, especially if
a radiopaque material is infused into
the track.

CLINICAL PATHOLOGY
Hemogram

A complete blood count is helpful in
supporting a diagnosis of local abscess.
Unless the infection is completely isolated
by a fibrous tissue capsule or is small in
size relative to the size of the animal
(tooth root abscess or osteomyelitis),
there will be a leukocytosis with a left shift
and an elevation of polymorphonuclear
leukocytes in acute lesions or of
lymphocytes and monocytes in more
chronic ones. A moderate normochromic
anemia is usual in chronic lesions, and
mild proteinuria is common.

Sample of lesion for culture and
staining

Attempts to identify the presence of an ’
infectious agent and to establish its

identity are usually undertaken but care is
necessary to avoid spreading infection from
a site in which it is presently contained.
Techniques used include paracentesis,
careful needle aspiration from an abscess,
blood culture (with the chances of isolation
of bacteria being very small unless there is
phlebitis or endocarditis) and aspiration
of cerebrospinal fluid.

The isolation of bacteria from a well-
contained abscess may be difficult
because of the paucity of organisms.
Special techniques may be necessary
and examination of a smear stained
with Gram stain, and perhaps also with
Ziehl-Neelsen stain if the circumstances
suggest it, is an essential part of the exam-
ination. Determination of sensitivity of
the bacteria to antibiotics is usually
undertaken.

Necropsy findings

The presence and location of the local
infection can be demonstrated at
necropsy.

TREATMENT
Drainage of abscesses

Surgical drainage of readily accessible
intact abscesses is the treatment of choice
and in most cases the only effective
method of therapy. A needle aspirate may
be indicated when the nature of the lesion
is uncertain. The site is prepared surgically
and the abscess is drained, flushed and
topically medicated. If the abscess has
not yet pointed with a soft spot, hot
fomentations and hydrotherapy may aid
in the maturation of a superficial abscess.
An analgesic may be required during this
stage of therapy. Tooth root abscesses
require extraction of the affected tooth to
effect a cure . 7

Antimicrobial agents

Antimicrobial agents given parenterally
can be used for the treatment of deep
abscesses not readily accessible to
surgical drainage. Ideally, a sample of the
contents of the abscess should be
cultured and antimicrobial susceptibility
determined. The agent must achieve high
plasma concentrations to facilitate pene-
tration into an abscess and daily treat-
ment for several days is usually necessary.
However, antimicrobial agents alone may
be ineffective, even if the organism
appears sensitive to the drug in vitro in
cases where the abscess is surrounded by
a dense capsule - presumably the capsule
prevents diffusion of the drug into the
abscess cavity. Lipophilic antibiotics, such
as rifampin, florfenicol or macrolides, are
theoretically advantageous in penetrating
into abscesses. Rifampin should be
administered with another antimicrobial
agent in order to delay the development
of antibiotic resistance.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

REFERENCES

1. Buczek] et al. Med Wet 1984; 40:643, 707.

2. Sanders-Sharis M. J Am Vet Med Assoc 1985;
187:499.

3. Taylor PA, Meads EB. Can Vet J 1963; 4:208.

4. Fbrdrizet JA. Comp Cont Educ Pract Vet 1986;
8:S311.

5. Cameron CM et al. Onderstepoort JVet Res 1976;
43:97.

6. Gezon HM et al. J Am Vet Med Assoc 1991;
198:257.

7. Cebra ML et al. J Am Vet Med Assoc 1996;
209:819.

Disturbances of appetite,
food intake and nutritional
status

Hunger is a purely local subjective
sensation arising from gastric hypermotility
caused in most cases by lack of distension
by food.

Appetite is a conditioned reflex
depending on past associations and
experience of palatable foods, and is not
dependent on hunger contractions of the
stomach. The term appetite is used loosely
with regard to animals and really expresses
the degree of hunger as indicated by the
food intake. When we speak of variations
from normal appetite we mean variations
from normal food intake, with the rare
exception of the animal that demonstrates a
desire to eat but fails to do so because of
a painful condition of the mouth or other
disability. Variation in appetite includes
increased, decreased or abnormal appetite.

Hyperorexia, or increased appetite,
due to increased hunger contractions, is
manifested by polyphagia or increased
food intake. Partial absence of appetite
(inappetence) and complete absence of
appetite (anorexia) are manifested by
varying degrees of decreased food intake
(anophagia).

Abnormal appetites include cravings
for substances, often normally offensive,
other than usual foods. The abnormal
appetite may be perverted, a temporary
state, or depraved, the permanent or habit
stage. Both are manifested by different
forms of pica or allotriophagia.

POLYPHAGIA

Starvation, functional diarrhea, chronic
gastritis and abnormalities of digestion,
particularly pancreatic deficiency, may
result in polyphagia. Metabolic diseases,
including diabetes mellitus and hyper-
thyroidism, are rare in large animals but
are causes of polyphagia in other species.
Internal parasitism is often associated
with poor growth response to more than
adequate food intakes.

Although appetite is difficult to assess
in animals it seems to be the only

explanation for the behavior of those that
grossly overeat on concentrates or other
palatable feed. The syndromes associated
with overeating are dealt with under the
diseases of the alimentary tract (Chs 5
and 6).

ANOPHAGIA OR A PHAGIA

Decreased food intake may be due to
physical factors, such as painful con-
ditions of the mouth and pharynx, or to
lack of desire to eat. Hyperthermia, toxemia
and fever all decrease hunger contractions
of the stomach. In species with a simple
alimentary tract a deficiency of thiamin in
the diet will cause atony of the gut and
reduction in food intake. In ruminants a
deficiency of cobalt and a heavy infes-
tation with Trichostrongylidae helminths
are common causes of anophagia, and
low plasma levels of zinc have also been
suggested as a cause. In fact alimentary
tract stasis due to any cause results in
anophagia. Some sensations, including
severe pain, excitement and fear, may
override hunger sensations and animals
used to open range conditions may
temporarily refuse to eat when confined
in feeding lots or experimental units.
Some sheep that have been at pasture
become completely anophagic if housed.
The cause is unknown and treatment,
other than turning out to pasture, is
ineffective.

A similar clinical sign is feed aversion,
seen most commonly in pigs, which is
rejection of particular batches of feed that
are contaminated by fungal toxins, e.g.
Fusarium spp., or by the plant Delphinium
barbeyi.

One of the important aims in
veterinary medicine is to encourage an
adequate food intake by sick and
convalescing animals. Alimentary tract
stimulants applied either locally or
systemically are of no value unless the
primary disease is corrected first. To
administer parasympathomimetic drugs
parenterally when there is digestive tract
atony due to peritonitis is unlikely to
increase food intake. In cattle, the intra-
ruminal administration of 10-20 L of
rumen juice from a normal cow will often
produce excellent results in adult cattle
that have been anorexic for several days,
provided the primary cause of the
anorexia is corrected. The provision of the
most palatable feed available is also of
value.

Parenteral or oral fluid and electrolyte
therapy is indicated in animals that do not
eat or drink after a few days. For animals
that cannot or will not eat, or in those
with intractable intestinal disease, the use
of total intravenous feeding (parenteral
nutrition) maybe indicated. The subject of

therapeutic nutrition for farm animals
that cannot or will not eat appears to have
been ignored. However, in most cases
farm animals will begin to eat their nor-
mally preferred diets when the original
cause of the anophagia or aphagia is
removed or corrected. Intensive fluid
therapy may be necessary during the
convalescence stage of any disease that
has affected feed intake and that may
result in a mild depression of serum
electrolytes.

A reduced feed intake in high-
producing dairy cattle during the first few
days or weeks of lactation and in fat beef
cattle in late pregnancy may result in fatty
infiltration and degeneration of the liver
and high mortality. Treatment with
glucose parenterally and propylene glycol
orally to minimize the mobilization of
excessive amounts of body fat is indicated.

In nervous anophagia the injection
of insulin in amounts sufficient to cause
hypoglycemia without causing con-
vulsions is used in human practice, and in
animals the use of tranquilizing drugs
may achieve the same result.

In ruminants the effects of blood
glucose levels on food intake are contro-
versial, but it seems probable that neither
blood glucose nor blood acetate levels
are important factors in regulating the
appetite. The anorexia that is characteristic
of acetonemia and pregnancy toxemia of
ruminants appears to be the result of the
metabolic toxemia in these diseases.
Electrolytic lesions in the hypothalamic
region can stimulate or depress food intake
depending on the area affected. This
indicates the probable importance of the
hypothalamus in the overall control of
appetite.

REVIEW LITERATURE

Langhans W, Scharrer E. Pathophysiology of

inappetence. JVet Med Assoc 1986; 33:401-413,

414-421.

P ICA OR ALLOTRIOPHAGIA

Pica is the ingestion of materials other
than normal food and varies from licking
to actual eating or drinking. It is associ-
ated in most cases with dietary deficiency,
either of bulk or, in some cases, more
specifically fiber, or of individual nutrients,
particularly salt, cobalt or phosphorus. It
is considered as normal behavior in
rabbits and foals, where it is thought to be
a method of dietary supplementation or
refection of the intestinal bacterial flora.
Boredom, in the case of animals closely
confined, often results in the develop-
ment of pica. Chronic abdominal pain
due to peritonitis or gastritis and central
nervous system disturbances, including
rabies and nervous acetonemia, are also
causes of pica.

Disturbances of appetite, food intake and nutritional status

The type of pica may be defined as
follows: osteophagia is the chewing of
bones; infantophagia is the eating
of young; coprophagia is the eating of
feces. Other types include wood-eating in
sheep, bark-eating, the eating of carrion
and cannibalism. Salt hunger can result in
coat-licking, leather-chewing, earth-
eating and the drinking of urine. Urine
drinking may also occur if the urine is
mixed with palatable material such as
silage effluent. Bark-eating is a common
vice in horses, especially when their diet
is lacking in fiber, e.g. when they are
grazing irrigated pasture.

Cannibalism

Cannibalism may become an important
problem in housed animals, particularly
swine, which bite one another's tails,
often resulting in severe local infections.
Although some cases may be due to
protein, iron or bulk deficiency in the diet,
many seem to be the result of boredom in
animals given insufficient space for
exercise. A high ambient temperature and
generally limited availability of food also
appear to contribute. Male castrates are
much more often affected than females
and the bites are also much more severe
in males. Provision of larger pens or a
hanging object to play with, removal of
incisor teeth and the avoidance of mixing
animals of different sizes in the same pen
are common control measures in pigs. In
many instances only one pig in the pen
has the habit and his removal may
prevent further cases. One common
measure that is guaranteed to be success-
ful in terms of tail-biting is surgical
removal of all tails with scissors during
the first few days of life, when the needle
teeth are removed. Unfortunately the
cannibalistic tendency may then be
transferred to ears. As in all types of pica,
the habit may survive the correction of the
causative factor.

Infantophagia

Infantophagia can be important in pigs
in two circumstances. In intensively
housed sows, especially young gilts,
hysterical savaging of each pig as it is
born can cause heavy losses. When sows
are grazed and housed at high density on
pasture it is not uncommon to find
'cannibal' sows who protect their own
litters but attack the young pigs of other
sows. This diagnosis should be considered
when there are unexplained disappear-
ances of young pigs.

Significance of pica

Pica may have serious consequences:
cannibalism may be the cause of many
deaths; poisonings, particularly lead
poisoning and botulism, are common
sequelae; foreign bodies lodging in the

alimentary tract or accumulations of wool,
fiber or sand may cause obstruction;
perforation of the esophagus or stomach
may result from the ingestion of sharp
foreign bodies; grazing time is often
reduced and livestock may wander away
from normal grazing. In many cases the
actual cause of the pica cannot be
determined and corrective measures may
have to be prescribed on a basis of trial
and error.

STARVATION

Complete deprivation of food causes
rapid depletion of glycogen stores and a
changeover in metabolism to fat and
protein. In the early stages there is
hunger, increase in muscle power and
endurance, and a loss of body weight. In
sheep there is often a depression of serum
calcium levels sufficient to cause clinical
hypocalcemia. The development of
ketosis and acidosis follows the increased
fat utilization. A marked reduction in feed
intake in pony mares in late pregnancy is
often a precursor of hyperlipemia, a
highly fatal disease discussed in Chapter
28 on metabolic diseases. The most
pronounced biochemical change in ponies
occurring as a result of experimental food
deprivation is a lipemia, which reaches a
peak by the eighth day of fasting but
quickly returns to normal when feeding is
resumed. This degree of change in blood
lipids appears to be a characteristic of
ponies and horses; it is much higher than
occurs in pigs.

In lactating cows, a short period of
starvation results in depression of plasma
glucose and an increase in plasma lipid
concentrations. Milk yield falls by 70%.
On refeeding most levels return to normal
in 5 days but blood lipid and milk yield
may take as long as 49 days to recover to
normal levels. In horses, fecal output falls
to zero at day 4 and water intake is
virtually nil from that time on, but urine
volume is maintained. In spite of the
apparent water imbalance there is no
appreciable dehydration, plasma protein
levels and PCV staying at normal levels. A
significant loss of skin turgor (increase in
skin tenting) due to the disappearance of
subcutaneous fat as cachexia develops
may occur. Muscular power and activity
decrease and the loss of body weight may
reach as high as 50-60%. The metabolic
rate falls and is accompanied by a slowing
of the heart and a reduction in stroke
volume, amplitude of the pulse and blood
pressure. The circulation is normal as
indicated by mucosal color and capillary
refill.

In the final stages, when fat stores are
depleted, massive protein mobilization
occurs and a premortal rise in total

urinary nitrogen is observed, whereas
blood and urine ketones are likely to
diminish from their previous high level.
Great weakness of skeletal and cardiac
musculature is also present in the
terminal stages and death is due to
circulatory failure. During the period' of
fat utilization there is a considerable
reduction in the ability of tissues to utilize
glucose and its administration in large
amounts is followed by glycosuria. In
such circumstances readily assimilated
carbohydrates and proteins should be
given in small quantities at frequent
intervals but fatty foods may exacerbate
the existing ketosis. Diets for animals that
have been through a period of great
nutritional stress because of deprivation
of food or because of illness are described
below under inanition.

Starvation of farm livestock is an
animal welfare issue with economic and
ethical considerations. When starving
animals are identified by a neighboring
farmer or veterinarian they are commonly
reported to the appropriate authorities,
which may be provincial or state appointed
inspectors (animal care officers) who have
the authority to take appropriate action.
The animals are examined and corrective
action is taken, including possession of
the animals and relocating them to a
commercial feeding facility. 1 Predicting
survival of starved animals is a major
challenge. Economics becomes an import-
ant aspect because the financial costs of
stabilizing a group of starved horses may
exceed their free market price. Responsible
management of chronically starved
commercial animals should include
options for immediate euthanasia. Ethical
considerations include deciding if certain
severely starved animals should be
euthanized. In some cases, enforcement
officers may be reluctant to recommend
mass euthanasia of otherwise healthy
horses based on personal aversion. 1

Chronically starved horses lose body
weight, become weak and their body
condition score may decline to below 2 on
the basis of 1-9, and death is common,
especially during cold weather. 1 Chronically
starved horses frequently respond poorly
to refeeding. About 20% of severely
malnourished horses can be expected to
die in spite of attempts at refeeding. 2
Recovery of severely malnourished horses
to an average body condition score may
require 6-10 months. 3

INANITION (MALNUTRITION)

Incomplete starvation - inanition or
malnutrition - is a more common field
. condition than complete starvation. The
diet is insufficient in quantity; all essential
nutrients are present but in suboptimal

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

amounts. The condition is compatible
with life, and in general the same pattern
of metabolic change occurs as in complete
starvation but to a lesser degree. Thus
ketosis, loss of body weight and muscular
power and a fall in metabolic rate occur.
As a result of the reduction in metabolic
activity there is a fall in body temperature
and respiratory and heart rates. In
addition there is mental depression,
anestrus in cows but not ewes, and
increased susceptibility to infection. This
increased susceptibility to infection that
occurs in some cases of malnutrition
cannot be accepted as a general rule. In
the present state of knowledge it can only
be said that 'some nutritional influences
affect resistance to some forms of
infection'.

A significantly reduced food intake
also increases susceptibility to some
poisons, and this has been related to the
effects of starvation on hepatic function.
In ruminants, the effects of starvation on
the activity of liver enzymes is delayed
compared to the effects in monogastric
animals, due apparently to the ability of
the ruminal store of feed to cushion the
effect of starvation for some days. The
most striking effect of short-term mal-
nutrition in sheep and cattle compared to
rats was the very rapid and large
accumulation of neutral fat in hepatocytes.
If there is a relative lack of dietary protein
over a long period of time, anasarca
occurs, particularly in the intermandibular
space.

Malnutrition makes a significant
contribution to a number of quasi-specific
diseases, 'weaner ill-thrift' and 'thin sow
syndrome' among them, and these are
dealt with elsewhere.

Controlled malnutrition in the form of
providing submaintenance diets to animals
during periods of severe feed shortage is
now a nutritional exercise with an exten-
sive supporting literature. For pastured
animals it is a fact of economic life that
significant loss of body weight is planned
and tolerated for some parts of each year
because the well-known phenomenon of
compensatory growth enables the animal
to make up the lost weight, with no
disadvantage, during the times of plenty.
Animals fed on submaintenance diets
undergo metabolic changes reflected in
blood and tissue values as well as the
more significant changes in weight.
Experimental restriction of feed intake to
65% of normal levels in nonlactating,
nonpregnant heifers does not cause
significant falls in serum calcium and
phosphorus levels, nor in plasma glutamic
oxaloacetic transaminase (GOT), aspartate
transferase (AST), lactate dehydrogenase
(LDH) or creatine phosphokinase (CPK)
activities. Serum alkaline phosphatase (AP)

activity was also maintained. In sheep
that are losing weight because of under-
nutrition there is a significant decrease in
plasma creatinine concentration.

Experimental feed restriction, followed
by fasting, followed by ad libitum access
to feed, such as might occur in nature,
had no serious ill-effects on goats. The
goats lost weight significantly but did not
overeat on being allowed access to feed.

A deficiency of one or more specific
dietary essentials also causes a form of
partial starvation and is dealt with in
Chapter 30.

Outbreaks of incomplete starvation
may occur in cattle, sheep and horses

that are kept outdoors during the cold
winter months in regions of the northern
hemisphere. The feed usually consists of
poor-quality grass hay or cereal grain
straw and no grain supplementation.
During prolonged exposure to the cold
environment the animals will increase
their daily intake in an attempt to satisfy
maintenance requirements and, in cattle,
abomasal impaction with a high case
mortality may occur. Animals affected
with severe inanition are usually weak
and recumbent and may or may not eat
when offered a palatable feed.

Malnutrition and starvation may
occur in calves under 1 month that are
fed poor-quality milk replacers containing
excessive quantities of nonmilk carbo-
hydrates and proteins. The diet is not well
digested by young calves and chronic
diarrhea and gradual malnutrition occur.
Affected calves recover quickly when fed
cows' whole milk for several days. At
necropsy there is a marked reduction in
muscle mass, lack of depot fat and serious
atrophy of fat. Starvation may also occur
in beef calves sucking poorly nourished
heifer dams with an insufficient supply of
milk. The mortality will be high during
cold weather when the maintenance
requirements are increased. Affected
calves will initially suck vigorously and
persistently, they will attempt to eat dry
feed, drink surface water and urine and
bawl for several hours. Eventually they lie
in sternal recumbency with their head
and neck turned into their flanks and die
quietly. The response to therapy is usually
unsatisfactory and the case fatality rate
is high. The convalescence period in
survivors is prolonged and treatment is
usually uneconomic. Affected animals
must be brought indoors and kept warm
and well bedded during treatment and
realimentation. Initially, fluid therapy
using balanced electrolyte solutions
containing glucose and amino acids may
be necessary to restore the animal's
strength and appetite. This is followed by
the provision of controlled amounts of a
highly palatable digestible diet. High-

quality legume hay is excellent, small
amounts of ground grain are of value and
the daily administration of a multiple B
vitamin and mineral mixture will reple-
nish those lost during inanition. Skim-
milk powder is an excellent source of
carbohydrate and protein for young
animals that have been partially starved.
Adult animals cannot digest large
quantities of milk powder because of the
relative lack of the appropriate digestive
enzymes.

Horses that have been ill with a poor
appetite should be tempted with green
grass first, and failing that tried with good-
quality hay - preferably alfalfa. It is best to
dilute it with good grass hay to begin
with, and increase the mix to 100% legume
hay over a week. An average horse will
require 1.5-2 kg BW/day. Grain can be
added, mixed with molasses or as a mash.
Low-fiber diets are recommended to
ensure maximum digestibility. A supple-
ment of B vitamins may be advantageous
until full appetite and intake are regained.
Horses with broken jaws or that are
unable to eat at all for some reason can be
allowed to go without food for 3 days, but
beyond that time they should be fed by
stomach tube. A suitable ration is:

o Electrolyte mixture (NaCl, 10 g;

NaHCO s , 15 g; KC1, 75 g;

K 2 HP0 4 , 60 g; CaCl 2 , 45 g;

MgO, 24 g) 210 g

° Water 21 L

° Dextrose, increased from

300 g/d in 7 days to 900 g

o Dehydrated cottage cheese,

increased from 300 g/day in
7 days to 900 g

The ration is divided into two or three
equal amounts and fed during one day.
Adult horses that are weak and recumbent
may be supported in a sling to avoid
decubitus ulceration and other secondary
complications associated with prolonged
recumbency.

THIRST

Thirst is an increased desire for water
manifested by excessive water intake
(polydipsia). There are two important
causes of thirst: dryness of the pharyngeal
and oral mucosae increases the desire for
water, irrespective of the water status of
body tissues; in addition, cellular dehy-
dration due to a rise in blood osmotic
pressure causes increased thirst. Specific
observations in ponies have shown that
water intake is increased in response to
either an increase in the osmotic pressure
of tissue fluid or a decrease in the volume
of their body fluids.

Cellular dehydration occurs commonly
in many cases of dehydration due to

Weight loss or failure to gain weight (ill-thrift)

115

vomiting, diarrhea, polyuria and excessive
sweating. Increased thirst in early fever is
due to changes in cell colloids leading to
increased water retention. A marked
polydipsia and polyuria occur in salt
deficiency in lactating dairy cattle, in
addition to weight loss, a fall in milk
production and salt hunger. Salivary
sodium levels are best used for diagnosis.
A similar syndrome occurs in the 'thin
sow syndrome'.

In humans, several other factors appear
to exert some effect on water intake: a
deficiency of potassium and an excess of
calcium in tissue fluid both increase thirst;
an increased thirst also occurs in uremia
irrespective of the body's state of
hydration. It has been suggested that
these chemical factors may cause direct
stimulation of the thirst center in the
hypothalamus. Clinically, diabetes insipidus
produces by far the most exaggerated
polydipsia.

The clinical syndrome produced by
water deprivation is not well defined.
Animals supplied with saline water will
drink it with reluctance and, if the salinity
is sufficiently great, die of salt poisoning.
Cattle at pasture that are totally deprived
of water usually become quite excited and
are likely to knock down fences and
destroy watering points in their frenzy.
On examination they exhibit a hollow
abdomen, sunken eyes and the other
signs of dehydration. There is excitability
with trembling and slight frothing at the
mouth. The gait is stiff and uncoordinated
and recumbency follows. Abortion of
decomposed calves, with dystocia due to
failure of the cervix to dilate, may occur
for some time after thirst has been
relieved and cause death in survivors. At
necropsy there is extensive liquefaction of
fat deposits, dehydration and early fetal
death in pregnant cows.

Experimental water deprivation has
been recorded in camels and lactating
and nonlactating dairy cows. In camels
death occurred on the seventh to ninth
day of total deprivation; body weight loss
was about 25%. Lactating cows allowed
access to only 50% of their regular water
supply become very aggressive about the
water trough, spend more time near it
and lie down less. After 4 days milk yield
is depressed to 74% and body weight to
86% of original figures. There is a
significant increase in serum osmolality
with increased concentrations of urea,
sodium, total protein and copper. The
PCV is increased, as are activities of
creatinine kinase and serum AST. With
complete deprivation for 72 hours, the
changes are similar but there are
surprisingly few clinical signs at that time.
The composition of the milk does not
change markedly and blood levels return

to normal in 48 hours. After deprivation
of half of their water intake, cattle reduced
their water loss by all routes, but plasma
and total blood volumes were unchanged.

Sheep, even pregnant ewes, are capable
of surviving even though access to water
is limited to only once each 72 hours, but
there is a significant loss (26%) of body
weight. Deprivation of water that allows
access to water only once every 96 hours
is not compatible with maintaining the
pregnancy.

REFERENCES

1. WhitingTL et al. Can Vet J 2005; 46:320.

2. Kronfeld DS. J Equine Vet Sci 1993; 13:298.

3. Poupard DP. J EquineVet Sci 1993; 13:304.

Weight loss or failure to
gain weight (ill-thrift)

This section is concerned with the
syndrome of weight loss in the presence
of an adequate food supply and a normal
appetite. In the absence of any primary
disease, an animal or group of animals
that presents with this as the problem is a
major diagnostic dilemma. Several poorly
identified diseases in this category are
'weaner ill-thrift', 'thin sow syndrome',
'thin ewe syndrome', 'weak calf syndrome'
(see Ch. 36).

Errors by the owner in the estimation
of body weight can lead to inadequate
feeding if the ration is based on the
requirements needed for growth and
maintenance per unit of body weight.
Scales are rarely available and estimations
by weight-bands are generally inaccurate
and subject to too much variability. A
reasonably satisfactory alternative used
in cattle, sheep and horses is a body
condition score estimated on the basis of
the amount of body covering of muscle,
fat and connective tissue.

Detailed below is a checklist of causes
that should be considered when an
animal has a weight loss problem in the
absence of signs indicative of a primary
wasting disease.

NUTRITIONAL CAUSES

'Hobby farm malnutrition' is a sur-
prisingly common cause, especially in
companion horses. Inexperienced owners
keep their animals where they are not
able to graze pasture and are entirely
dependent on stored feed, but underfeed
for economy's sake. A knowledge of the
animals' needs and of the apprcoimate
energy and protein values of feeds are
necessary to prepare an appropriate
ration. In a hospital situation any horse
presented with a weight loss problem and
without a potential diagnosis on first
examination should be weighed, fed an
energy-rich diet ad libitum for 4 days.

then re-weighed. A horse that has
previously been underfed will gain 3-5 kg
in weight per day.

The feed must be inspected. Mature
meadow hay may be efficient only
as a filler, and poorly filled oat grain
may be very poorly nutritive on a weight
basis. Gentle animals that are fed in a
group with others may be physically
prevented from getting a fair share of
available feed, especially if trough space
is inadequate.

This problem is also common when
urban people try to raise a few veal calves
or sheep to help defray the costs of their
rural acreage. It is common in these
circumstances to equate rough meadow
grass with proper nutrition for young or
pregnant ruminants.

Other considerations are as follows:

° Diets that are inadequate in total
energy because they cannot replace
the energy loss caused by the animal's
level of production can be important
causes of weight loss in heavy-
producing animals. This subject is
discussed under the heading of
production disease. An example is
acetonemia of high-producing cows
in which body stores of fat and
protein are raided to repair the energy
deficiency of the diet
° Malnutrition as a result of a ration
that is deficient in an essential trace
element is unusual in the
management situation being
discussed. A nutritional deficiency of
cobalt does cause weight loss in
ruminants but is likely to have an area
effect rather than cause weight loss in
single animals. Copper, salt, zinc,
potassium, selenium, phosphorus,
calcium and vitamin D deficiencies
are also in this category. Experimental
nutritional deficiencies of riboflavin,
nicotinic acid, pyridoxine and
pantothenic acid in calves and
pigs can also be characterized by
ill-thrift

° Inadequate intake of an adequate
supply of feed is dealt with under
diseases of the mouth and pharynx
and is not repeated here, but it is
emphasized that the first place for a
clinician to look in a thin animal is its
mouth. The owner may have forgotten
just how old the animal is and one
often finds a cow without any incisor
teeth attempting to survive on pasture
° Other factors that reduce an animal's
food intake when it is available in
adequate amounts include anxiety,
the excitement of estrus, new
surroundings, loss of newborn, bad
' weather, tick or other insect worry
and abomasal displacement.

116

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

EXCESSIVE LOSS OF PROTEIN AND
CARBOHYDRATES

* Glucose loss in the urine in diabetes
mellitus or chronic renal disease, the
former indicated by hyperglycemia
and both by glycosuria, are obvious
examples of weight loss as a result
of excessive metabolic loss of
energy

1 Protein loss in the feces. Cases of
protein-losing gastroenteropathy are
unusual and are difficult to identify
without access to a radioactive isotope
laboratory. The loss may occur
through an ulcerative lesion, via a
generalized vascular discontinuity or
by exudation through intact mucosa
as a result of hydrostatic pressure in
blood vessels, e.g. in verminous
aneurysm, or lymphatics in cases of
lymphangiectasia of the intestine. The
identification of a neoplasm
(lymphosarcoma or intestinal or i

gastric adenocarcinoma are the usual
ones) or of granulomatous enteritis is
not possible without laparotomy and
biopsy of the alimentary segment.

One is usually led to the possibility of
this as a diagnosis by either a low
serum total protein or low albumin
level in a normal total protein level, ;
and in the absence of other protein
loss as set out below
Proteinuria for a lengthy period can i
cause depletion of body protein j

stores, resulting in weight loss. :

Chronic glomerulonephritis is the !

usual cause. Examination of the urine
should be part of every clinical
examination of a patient, but is not
commonly so in horses because of
the difficulty of obtaining a j

specimen without recourse to i

catheterization. Moving the horse into
a box stall with fresh straw, or the
intravenous injection of furosemide,
are possible methods when
straightforward collection is not
possible. The latter provides an
abnormally dilute sample
Internal and external parasitoses in
which blood sucking is a significant
pathogenetic mechanism can result in
severe protein loss, as well as anemia
per se. j

FAULTY DIGESTION, ABSORPTION OR
METABOLISM

Faulty digestion and absorption are (
commonly manifested by diarrhea, and
diseases that have this effect are dealt
with under the heading of malabsorption
syndromes (see Enteriti). In grazing .
ruminants, the principal causes are the
nematode worms Ostertagia, Nematodirus, '
Trichostrongylus, Chabertia, Cooperia and
Oesophagostomum and the flukes Fasciola j

and Paramphistomum. In cattle there are,
in addition, tuberculosis, coccidiosis,
sarcosporidiosis and enzootic calcinosis.
In sheep and goats there are Johne's
disease, viral pneumonia without clinical
pulmonary involvement, and hemon-
chosis. In horses there are strongylosis,
habronemiasis and heavy infestations
with botfly larvae. In pigs there are
stephanuriasis, hyostrongylosis (includ-
ing the 'thin sow syndrome'), infestation
with Macracanthorhynchus hirudinaceus,
and ascariasis. Gastrointestinal neoplasia
must also be considered as a possible
cause

Chronic villous atrophy occurs most
severely with intestinal parasitism or
as a result of a viral infection
Other lesions caused by parasitic
invasion that affect digestion and
absorption are gastric granuloma
associated with Habronema spp. in
horses and verminous arteritis, also in
horses

Abnormal physical function of the
alimentary tract, as in vagus
indigestion of cattle and grass
sickness in horses, can be a potent
cause of failure to absorb nutrients,
but the syndrome is usually
manifested by poor food intake and
grossly abnormal feces
Inadequate utilization of absorbed
nutrients is a characteristic of chronic
liver disease. It is usually
distinguishable by a low serum
albumin level, by liver function tests
and by serum enzyme estimations. A
clinical syndrome including edema,
jaundice, photosensitization and
weight loss is a common
accompaniment
Neoplasia in any organ. The
metabolism of the body as a whole is
often unbalanced by the presence of a
neoplasm so that the animal wastes
even though its food intake seems
adequate

Chronic infection, including specific
diseases such as tuberculosis,
sarcocystosis. East Coast fever,
trypanosomiasis (nagana), maedi-
visna, caprine arthritis-encephalitis,
enzootic pneumonia of swine and
nonspecific infections such as atrophic
rhinitis of pigs, abscess, empyema and
chronic peritonitis have the effect of
reducing metabolic activity generally
as well as reducing appetite. Both
effects are the result of the toxemia
caused by tissue breakdown and of
toxins produced by the organisms
present. Less well understood are the
means by which systemic infections,
e.g. equine infectious anemia, scrapie
in sheep and other slow viruses.

produce a state of weight loss
progressing to emaciation
° Food refusal is a well- recognized
syndrome in pigs, due in some
cases to mycotoxins in the feed, and
'off feed effects' are similarly
encountered in feedlot cattle on
rations containing a large proportion
of wheat grain

0 Many diseases of other systems,
e.g. congestive heart failure, are
manifested by weight loss because
of inadequate oxygenation of
tissues.

Determination of the specific cause of
weight loss in an individual animal
depends first on differentiation into one

of the three major groups:

° Nutritional causes, diagnosed by
assessment of the animal's total food
intake

Protein or carbohydrate loss in the
animal's excretions, diagnosed by
clinicopathological laboratory tests
rt Faulty absorption of the food
ingested, diagnosed by tests of
digestion as set out in Chapter 5.

! Shortfalls in performance

\ The present-day emphasis on the need
j for economically efficient performance by
j farm animals introduces another set of
j criteria, besides freedom from disease,
j to be taken into consideration when
\ deciding an animal's future. The same
| comment applies, and much more
j importantly, when a herd's productivity is
j being assessed. This is usually done by
j comparing the subject herd's perform-
j ances to that of peer herds, or animals in
j similar environmental and management
j conditions.

; It is usual to use the production
i indexes that are the essential outputs of
! the particular enterprise as the criteria of
productivity. Thus, in dairy herds the
i criteria could be:

j

j Milk or butterfat production per cow
j per lactation (liters per cow or liters

\ per hectare)

j Reproductive efficiency as mean

j intercalving interval

j ' Percentage calf survival to 1 year of
age

j Longevity as percentage mortality per

j year or average age of cows in herd
plus culling rate per year
I The culling rate needs to differentiate
between sale because of disease or
poor production and sale as a
productive animal
Acceptability of product at sale - as
: indicated by bulk tank milk somatic

Physical exercise and associated disorders

117

cell count, rejection of milk because of
poor-quality, low- fat content, low
solids -not -fat content.

If it is decided that performance falls too
far short of the target, an investigation is
warranted. Some targets for productivity
in each of the animal industries are
available, but they vary a great deal
between countries depending on the
levels of agriculture practiced and the
standards of performance expected. For
this reason, they are not set down here;
nor is the degree of shortfall from the
target that is acceptable - this depends
heavily on the risk aversion or accept-
ability m the industry in that country. For
example, if the enterprise is heavily
capitalized by high -cost housing and
land, the standard of performance would
be expected to be higher than in a more
exploitative situation where cattle are
pastured all year. In the latter, a reason-
able flexibility could be included in the
assessment of productivity by permitting
it to fall within the scope of 2 SD of the
mean productivity established by peer
herds.

If it is decided that performance is
below permissible standards an investi-
gation should be conducted and should
include the following groups of possible
causes:

° Nutrition - its adequacy in terms of
energy, protein, minerals, vitamins
and water

° Inheritance - the genetic background
of the herd and the quality of its
heritable performance
n Accommodation - to include

protection from environmental stress
by buildings for housed animals and
terrain and tree cover for pastured
animals; also consideration of
population density as affecting access !
to feed, water and bedding areas !

General managerial expertise - the
degree of its application to the
individual flock »r herd. This is
difficult to assess and then only i

indirectly, e.g. the efficiency of heat
detection, achievement of planned
calving pattern

Disease wastage - as clinical disease
or, more particularly, subclinical
disease. The latter may include such
things as quarter infection rate as an
index of mastitis, fecal egg counts I
relative to parasite burden, metabolic j
profile relative to metabolic disease
prevalence rate, etc.

These investigations tend to require
special techniques in addition to the ;
clinical examination of individual animals. :
They are mostly self-evident, but atten- j
tion is drawn to the section on exam- 1

ination of a herd or flock in Chapter 1.
It will be apparent that there is a great
deal of merit in having herds and flocks
under constant surveillance for pro-
ductivity and freedom from disease, as is
practiced in modern herd health pro-
grams. Monitoring performance and
comparing it with targets is the basis of
that system.

The specific syndromes that fall within
this category of disease, and which are
dealt with elsewhere in this book are
ill- thrift of weaner sheep, 'thin sow
syndrome', 'weak calf syndrome', 'poor
performance syndrome' of horses. Tow
butterfat syndromes' and 'summer slump'
of milk cows. Two performance shortfalls
encountered commonly by field veteri-
narians are ill-thrift in all species and
poor performance syndrome in horses,
presented in the two sections following.
More specialized problems are dealt with
in Herd health (details below).

REVIEW LITERATURE

Radostits OM. Herd health. Food animal production

medicine, 3rd ed. Philadelphia, PA: WB Saunders,

2000 .

Physical exercise and
associated disorders

EXERCISE PHYSIOLOGY

The act of performing physical work
requires expenditure of energy at rates
above the resting metabolic rate. Increases
in metabolic rate can be supported by
anaerobic metabolism through the use of
intramuscular adenosine triphosphate
stores and conversion of glycogen or
glucose to lactate for short periods of
time. Ultimately, however, all energy is
derived by aerobic metabolism and is
limited by the rate of delivery of oxygen to
tissue and its utilization in mitochondria.
To support the increased energy expen-
diture required to perform work such as
racing, carrying a rider or pulling a cart,
the metabolic rate is increased. Increases
in metabolic rate are supported by
increases in oxygen delivery to tissue and
carbon dioxide removal. Increased oxygen
consumption is dependent upon an
increase in oxygen delivery to tissues
which is possible by increases in cardiac
output, muscle blood flow and, in horses,
an increase in hemoglobin concentration
with a concomitant increase in the
oxygen-carrying capacity of blood. The
increased transport of oxygen from the air
to the blood is accomplished principally
by increases in respiratory rate and tidal
volume. Factors that affect oxygen
transport from the air to the mitochondria
have the potential to impair performance.
For instance, laryngeal hemiplegia reduces

minute ventilation and exacerbates the
normal exercise-associated hypoxemia in
horses, atrial fibrillation decreases cardiac
output and hence oxygen delivery to
tissues and anemia reduces the oxygen-
carrying capacity of the blood.

The increase in cardiac output with
exercise of maximal intensity in horses is
very large - horses have a cardiac output
of about 75 (mL/min)/kg at rest and
750 (mL/min)/kg (300L/min for a 400 kg
horse) during maximal exercise. Associated
with the increase in cardiac output are
increases in right atrial, pulmonary
arterial and aortic blood pressures.
Systemic arterial blood pressure during
exercise increases as the intensity of
exercise increases with values for systolic,
mean and diastolic pressures increasing
from 115, 100 and 80 mmHg (15.3, 13.3
and 10.6 kPa) at rest to 205, 160 and
120 mmHg (27.3, 21.3 and 16kPa),
respectively, during intense exercise.

Pulmonary artery pressure increases
from a mean of approximately 25 mmHg
(3.3 kPa) to almost 100 mmHg (13.3 kPa)
during intense exercise. The increase in
pulmonary artery pressure with exercise
may contribute to exercise-induced
pulmonary hemorrhage.

The increase in metabolic rate during
exercise causes a marked increase in
metabolic heat generation with a sub-
sequent increase in body temperature.
The increase in body temperature is
dependent on the intensity and duration
of exercise and the ability of the horse to
dissipate heat from the body. Intense
exercise of short duration is associated
with marked increases in body tempera-
ture but such increases rarely cause
disease. However, prolonged exercise of
moderate intensity, especially if perfonned
in hot and humid conditions, may be
associated with rectal temperatures in
j excess of 42.5°C (108. 5°F). Heat is
j dissipated primarily by evaporation of
j sweat from the skin surface. Sweating
results in a loss of body water and
i electrolytes, including sodium, potassium,
calcium and chloride. The size of these
losses can be sufficient to cause dehy-
! dration and abnormalities of serum
electrolyte concentrations and also
! impaired cardiovascular and thermo-
j regulatory function.

j Recovery from exercise is influenced by
j the fitness of the individual, with fitter
\ horses recovering more rapidly, the
1 intensity and duration of the exercise
l bout, and activity during recovery. Horses
! allowed to walk after a bout of intense
• exercise recuperate more quickly than do
horses that are not allowed to walk,
jj Recovery is delayed if the horse cannot
drink to replenish body water or in hot
and humid conditions.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

REVIEW LITERATURE

Hinchcliff KW, Kaneps AJ, Geor RJ. Equine sports
medicine and surgery: basic and clinical sciences of
the equine athlete. Edinburgh, UK: Saunders, 2004.

POOR RACING PERFORMANCE
AND EXERCISE INTOLERANCE IN
HORSES

The definition of poor racing performance
is difficult. Horses that have a proven
record of performing well and that then
fail to perform at their previous level are
readily apparent and a physical cause of
the reduction in performance can often be
identified. More difficult are the horses .
that do not have a history of satisfactory
performance and are best labeled as
'failure to perform to expectation'. Horses
in this group may indeed have a clinical
abnormality but commonly the reason is
lack of innate ability or inadequate
training - both causes that must be raised
with the owner and trainer carefully and
tactfully, and only after a thorough
examination of the horse.

Exercise intolerance in race horses is
best defined as the inability to race at
speeds previously attained by that horse
or attained by peers. In its most extreme
form exercise intolerance is evident as
failure to complete the race, whereas its
mildest form is evident as a slight decre-
ment in performance, such as losing a race
by several lengths or one or two seconds, or
failure to perform to expectation.

APPROACH TO THE HORSE WITH
EXERCISE INTOLERANCE

Horses with a history of a recent decre-
ment in performance or those that are not
performing to expectation should be
examined in a systematic fashion.

History

A detailed history should be collected that
focuses on documenting the reduction in
performance, its time course and the
presence and evolution of any clinical
signs. This can be accomplished by asking
the following questions of the owner or
trainer:

o What evidence is there of poor
performance? This query should
focus on providing objective evidence
of a reduction in performance through
examination of race times or results.
This also allows the severity of the
reduction in performance to be
documented

° What is the horse's training
schedule? The training regimen
should be appropriate for the horse's
level of competition
o Describe the horse's exercise
intolerance. Does it start the race
strongly and 'fade' in the last part of
the race, or is it unable to maintain a

suitable speed for the complete race?

Is the horse slow to recover its normal
respiratory rate after exercise? Can it
sweat? Does it consistently veer or
'pull' towards one side?
o Is there any history of illness in
this horse or other horses in the
same stable or at the race track?

Has the horse had a fever or been
inappetent? Is the horse on any
medication? Specific attention should
be paid to any history of respiratory
disease

• Does the horse make an unusual
noise associated with respiration
when running? Horses with upper
airway obstructions almost always
make an abnormal noise during
exercise

« Does the horse cough either at rest,
during or after exercise? Coughing
may be an indication of lower
respiratory tract disease
o Has the horse ever had blood at the
nostrils after exercise or has it been
diagnosed as having exercise-
induced pulmonary hemorrhage?

° Is the horse lame? Does it ever show
signs of muscle stiffness or abnormal
gait?

° What is the history of anthelmintic
administration?

Clinical examination

A thorough clinical examination should
be performed. The physical examination
should include a detailed examination of
the musculoskeletal, cardiovascular and
respiratory systems and may include the
collection of samples of body fluids for
laboratory analysis. Ancillary testing,
such as radiography, endoscopy, nuclear
scintigraphy and stress testing, may be
available at larger centers.

The horse should be examined at rest
for evidence of musculoskeletal disease
and then should be observed at the walk
and trot for signs of lameness. Subtle
lameness that is sufficient to impair
performance may be difficult to detect in
a horse slowly trotting, and other
examinations, such as observation during
and after high-speed running at a track,
radiography and nuclear scintigraphy,
may be necessary. The major muscle
groups, including the quadriceps, should
be palpated for firmness or pain suggestive
of rhabdomyolysis.

The heart should be auscultated care-
fully for evidence of valvular incompetence
or arrhythmias. Mild (grade II— III/VI)
systolic ejection murmurs heard loudest
on the left thorax are common in fit race
horses and should not be mistaken for
evidence of valvular disease. Electro-
cardiography to diagnose abnormalities
of rhythm or echocardiography to demon-

strate the extent of valvular lesions are
indicated if abnormalities are detected on
cardiac auscultation.

The respiratory system should be
carefully examined by auscultation of
the thorax in a quiet area. The thorax
should be auscultated initially with the
horse at rest; if no abnormalities are
detected the horse's tidal volume should
be increased by rebreathing air from a
large bag held over its nose, or by
exercise. Radiography of the thorax may
demonstrate changes consistent with
exercise-induced pulmonary hemor-
rhage, recurrent airway obstruction or
pneumonia. Aspirates of tracheal fluid or
bronchoalveolar lavage fluid should be
examined for evidence of inflammation or
hemorrhage. The upper respiratory tract,
including pharynx, larynx, trachea and
carina, should be examined with a flexible
endoscope.

Laboratory testing

Collection of blood and urine samples for
laboratory analysis are indicated if specific
abnormalities are detected on physical
examination. For instance, exercise-
associated rhabdomyolysis can be con-
firmed by measurement of serum creatine
kinase and aspartate aminotransferase
activity. However, blood samples are
often submitted for analysis as a matter of
routine. Specific attention should be paid
to the hemogram, in particular the white
blood cell count, for evidence of inflam-
mation and the hematocrit for evidence of
anemia. Care should be taken to not
assign minor abnormalities an undue
significance until corroborating evidence
is obtained. Tracheal or bronchoalveolar
lavage fluid may provide evidence of
lower respiratory tract disease. Examin-
ation of feces for helminth ova may
demonstrate parasitism.

Exercise stress testing

Examination of horses during and
after high-speed exercise on a treadmill
is now routine in many referral centers.
Values of a number of performance-
related variables have been determined
for Standardbred and Thoroughbred
race horses, with better athletes having
greater aerobic capacity. However, at this
time the main use of high-speed exercise
testing is detection of exercise-induced
arrhythmia, such as paroxysmal ventri-
cular tachycardia or atrial fibrillation,
rhabdomyolysis and upper airway
obstruction. Upper airway obstruction is a
common cause of poor performance that
can often be diagnosed by rhinolaryngo-
scopic examination of horses at rest
or after brief nasal occlusion. However,
some causes of obstruction are best diag-
nosed using rhinolaryngoscopy during
exercise.

Physical exercise and associated disorders

CAUSES OF EXERCISE INTOLERANCE
OR POOR PERFORMANCE

Any disease that adversely affects the
normal function of a horse has the poten-
tial to impair performance. Listed below
are some common causes of exercise
intolerance in race horses.

Musculoskeletal system

s Lameness is a common cause of
poor performance. Subtle lameness
may be difficult to detect but may be
sufficient to cause a decrement in
performance. Causes and diagnosis of
lameness are discussed in textbooks on
that topic and are not further covered
here

o Rhabdomyolysis.

Cardiovascular system

Fbor performance attributable to cardio-
vascular disease may be caused by:

o Atrial fibrillation, usually readily
diagnosed by electrocardiographic
examination. Fhroxysmal atrial
fibrillation induced by exercise that
resolves soon after exercise ceases
causes poor performance and is
difficult to diagnose
o Ventricular arrhythmias
o Valvular incompetence, such as mitral
or tricuspid regurgitation secondary to
acquired or congenital disease.
Endocarditis is rare in horses
o Congenital anomalies including
ventricular septal defect
o Myocarditis or myocardial disease
(rare)

o Aorto- iliac thrombosis.

Respiratory system

Upper airways (see Obstructive diseases
of the equine larynx)

0 Laryngeal hemiplegia
® Intermittent dorsal displacement of
the soft palate
o Epiglottic entrapment
° Epiglottic hypoplasia
n Arytenoid chondritis
n Pharyngeal cysts
0 Upper air obstruction associated
with hyperkalemic periodic
paralysis

° Guttural pouch empyema
° Retropharyngeal abscesses
0 Redundant or flaccid alar folds.

Lower airways

0 Pneumonia secondary to influenza
virus or equine herpesvirus-1 or
-4 infection

0 Parasitic pneumonia due to
Dictyocaulus amfieldi
o Severe exercise-induced pulmonary
hemorrhage

• Lower airway inflammatory disease
and recurrent airway obstruction
0 Granulomatous pneumonia.

Hematologic and biochemical
abnormalities

Anemia

o Parasitism, especially caused by
Strongylus sp. and cyathostomes

• Chronic disease, such as the presence
of an abscess

• Equine infectious anemia
8 Piroplasmosis

0 Gastric ulceration (anemia is an
unusual manifestation of this disease)

0 Iron deficiency

a Administration of inhibitors of folic
acid synthesis or prolonged oral
administration of inactive folic acid
» Phenylbutazone toxicity
» Excessive phlebotomy
® Gastric squamous cell carcinoma
o Administration of recombinant
human erythropoietin.

Hypoproteinemia

® Parasitism, especially caused by
Strongylus sp. and cyathostomes
0 Malnutrition, especially inadequate
protein intake

0 Protein losing enteropathy such as
lymphosarcoma or granulomatous
enteritis

Electrolyte abnormalities
° Hypokalemia and hyponatremia
secondary to excessive loses in sweat
and inadequate intake.

Nervous system disease

® Spinal ataxia caused by cervical
compressive myelopathy (static or
dynamic, equine protozoal
myeloencephalitis, and equine
degenerative myelopathy
0 Sweeney
8 Stringhalt.

Miscellaneous

o Hypothyroidism (very rare)
o Pituitary tumor (equine Cushing's
disease

8 Iatrogenic hypoadrenocorticism
o Hepatic disease of any cause, but
beware of iron overload
o Renal disease
o Secondary nutritional
hyperparathyroidism
8 Malnutrition
o Performance-altering drug

administration such as |3-adrenergic
antagonists or sedatives.

TREATMENT

Treatment should be directed towards
correcting the underlying disease.
Routine administration of hematinics to
horses with a normal hemogram is
unnecessary. If after careful and compre-
hensive examination an organic cause for
the poor performance is not found,
attention should be given to the horse's
training program. Training programs for

horses are described elsewhere (see
below).

REVIEW LITERATURE

Hinchcliff KW, Kaneps AJ, Geor RJ. Equine sports
medicine and surgery: basic and clinical sciences
of the equine athlete. Edinburgh, UK: Elsevier
Health Sciences 2004.

EXERCISE-ASSOCIATED DISEASES

Many exercise-induced diseases are
associated with specific activities. For
instance, heat stroke and exhaustion are
very rare in Standardbred and Thorough-
bred horses raced over distances of up
to 3 miles (5 km) but common in
horses participating in endurance races
(50-100 km) or the second day of three-
day event competitions. Conversely,
exercise -induced pulmonary hemorrhage
occurs only in horses that race at high
speed. The exercise-associated diseases
exertional rhabdomyolysis, synchronous
diaphragmatic flutter, hyperthermia and
exercise- induced pulmonary hemorrhage
are dealt with in other sections of this
book.

EXHAUSTION

All physical work, if of sufficient intensity
and duration, causes fatigue. The mech-
anisms underlying fatigue vary with the
type of work or exercise performed. Thus
fatigue in a race horse running 3 km at
high speed has a different genesis from
fatigue in an endurance horse that has
run 100 km at low speed. Typically,
Standardbred and Thoroughbred race-
horses recovery quickly and exhaustion
rarely occurs. However, horses perform-
ing endurance exercise require longer to
recover, and the processes associated with
fatigue may progress to the extent that
recovery is delayed or impossible without
treatment. The failure to recover and the
clinical and clinicopathologic signs
associated with this have been labeled
'exhausted horse syndrome'.

The exhausted horse syndrome is
associated with endurance races, three-
day eventing, trail riding and fox and bird
hunting - all activities in which there is
prolonged submaximal exercise. The
likelihood of the disorder is increased in
unfit horses or when horses are exercised
in hot and humid conditions, especially
if they are not accustomed to such
conditions. 1

Pathogenesis

The pathogenesis of exhaustion is com-
plicated but probably involves depletion of
body glycogen and electrolytes, especially
sodium, chloride and potassium, hypo-
volemia due to large losses of water in
. sweat, hyperthermia and acid-base
disturbances. Endurance exercise is
associated with the production of large

RART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

amounts of heat, which are dissipated
primarily by evaporation of sweat. 2
Approximately 11 L of sweat are lost each
hour during submaximal exercise, and
this loss causes a significant decline in
total body water, sodium, potassium and
chloride content and serum concen-
trations of these ions. 3 Loss of chloride
causes a metabolic alkalosis. Hypovolemia
impairs thermoregulation by reducing
blood flow to the skin and probably
results in a reduction in gastrointestinal
blood flow contributing to intestinal
ischemia and development of ileus. 4
Body temperature increases to danger-
ous levels (43°C, 109°F) and the horse
cannot continue to exercise. If the
exercise-induced abnormalities are suf-
ficiently severe then the combination of
hyperthermia and dehydration may
initiate a cascade of events terminating
in shock, multiple organ failure and
death. 1

Clinical signs

The clinical signs of the exhausted horse
syndrome include failure to continue to
exercise, depression, weakness, failure to
eat and drink, delayed return of heart rate
and rectal temperature to normal values,
poor skin turgor and capillary refill time,
a stiff stilted gait consistent with
rhabdomyolysis, and decrease or absent
borborygmi. 1 Urine is concentrated and
the horse ceases to urinate.

Clinicopathologic examination reveals
hemoconcentration, hypochloremia,
hypokalemia and variable changes in
serum sodium concentration. There is
usually a metabolic alkalosis (increased
blood bicarbonate concentration),
although some severely affected horses
will also have a metabolic acidosis
associated with increased blood lactate
concentration. Serum creatinine and urea
nitrogen concentrations are increased
because of dehydration and/or renal
disease. Serum creatine kinase activity
may be markedly increased in horses with
rhabdomyolysis.

Treatment

Treatment consists of rapid restoration of
hydration status, correction of electrolyte
and acid-base abnormalities and reduc-
tion in body temperature. Fluid therapy is
addressed in detail elsewhere. Suitable
fluids for administration to exhausted
horses are Ringer's solution, isotonic
sodium chloride with added potassium
chloride (10 mEq/L) and calcium
gluconate (10-20 mL of 24% solution per
liter), or lactated Ringer's solution.
Theoretically, lactated Ringer's solution
should not be given to horses with
metabolic alkalosis, but clinical experi-
ence indicates its safety and efficacy. 1

Horses should be aggressively cooled
by application of cold water or water and
ice. In spite of folk lore to the contrary,
application of ice cold water to hyper-
thermic horses is not dangerous or associ-
ated with rhabdomyolysis. 5 NSAIDs, for
pain relief and prophylaxis of the effects
of endotoxemia, can be given when the
horse is no longer hypovolemic.

Prevention

Prevention rests in ensuring that partici-
pating horses are adequately trained for
the event and acclimated to the environ-
mental conditions. Horses should be
healthy, preferably as determined by a
veterinary examination before the race,
and should be monitored during the event
for signs of excessive fatigue, dehydration
or hyperthermia.

REFERENCES

1. Foreman JH. Vet Clin North Am Equine Pract
1998; 14:205.

2. Hodgson DR et al. J Appl Physiol 1991; 74:1161.

3. Schott HC et ai. Am J Vet Res 1997; 58:303.

4. Schott HC et al. Compend Cont Educ Pract Vet
1996; 18:559.

5. Williamson L et al. Equine Vet J Suppl 1995;
18:337.

Diagnosis and care of
recumbent adult horses

Diagnosis and management of adult
horses that are recumbent can be
challenging. The large size of adult horses,
the variety of conditions that can cause
recumbency, the difficulty in performing a
thorough clinical examination and the
need for prolonged and intensive care all
present formidable obstacles to manage-
ment of recumbent horses. Causes of
prolonged (> 8 h) recumbency in horses are
; listed in Table 2.7. Other causes of acute
recumbency of shorter duration are usually !
| obvious on initial examination and include
septic or hemorrhagic shock, such as occurs
i in horses with colic or internal or external ;
; hemorrhage.

EXAMINATION OF THE RECUMBENT !
HORSE I

History

Careful questioning of the horse's -
i attendants can reveal valuable infor-
j mation regarding the cause of recumbency.
Causes such as observed trauma, foaling j
and excessive unaccustomed exercise are ;

!

readily determined from the history. In j
j addition to inquiries about the cause of j
the recumbency, estimates of the duration i
: of recumbency should be obtained from i
the attendants. This can often be best ;
elicited by asking when the horse was last ;
i observed to be standing. A history of ;
; recent illness, abnormal behavior or ;
unusual use immediately before the horse

became recumbent is useful. The horse's
age, sex, breed and use should be deter-
mined. Information regarding manage-
ment, vaccination and deworming status,
feeding and health of other horses can be
revealing. Outbreaks of recumbency
suggest either an infectious (equine
herpesvirus -1) or toxic (botulism,
ionophore) cause. Questions should be
directed toward discerning the cause of
the horse's recumbency rather than
collecting information.

Physical examination

Physical examination of recumbent horses
is challenging but should be as complete
as practical and safe. The examination
should begin with a general assessment
of the horse and its surroundings and can
be directed at answering a series of
questions:

° Are the surrounding conditions safe
for the horse and people? Is the
footing sound?

° Is there evidence of the horse
struggling or thrashing?

° Has the horse defecated and urinated
recently?

° Is there evidence of exposure to toxins
or physical evidence of the reason for
recumbency?

Examination of the horse should begin
with measurement of heart rate, respir-
atory rate and temperature (rectal tem-
perature might not be accurate if there is
dilation of the anus), examination of
mucous membranes and an assessment
of its hydration, body condition and level
of consciousness. The horse should be
thoroughly examined for evidence of
trauma. Although the examination should
be complete, initial examination of cases
for which the cause of recumbency is
not immediately obvious should focus
on the nervous and musculoskeletal
systems.

Is the horse alert and able to sit in
sternal recumbency or is it
unconscious and in lateral
recumbency? Can the horse rise
with assistance?

Is the horse's mentation normal?

Are there any spontaneous
voluntary or involuntary
movements 7

Can the horse eat and drink?

Are the cranial nerves normal?

Is there evidence of trauma to the
head or neck?

Is there evidence of paresis or
paralysis? Are only the hind limbs
involved or are both the hind limbs
and forelimbs involved?

Are the peripheral reflexes normal
(withdrawal, patellar, cervicofacial,
cutaneous, anal, penile)?

Diagnosis and care of recumbent adult horses

Cause

Clinical signs and diagnosis

Treatment

Prognosis and comments

Neurologic disease

Botulism

Horse alert. Flaccid paralysis, dysphagia,
weak corneal or palpebral reflex.

Often multiple animals affected.

Toxin isolation in mice

Administration of specific antitoxin
or multivalent antitoxin.

Supportive care

Can require prolonged treatment.
Prognosis poor for recumbent horses ,

Tetanus

Horse alert. Rigid paralysis. Signs
worsened by stimuli. Often history
of recent wound and lack of vaccination

Tetanus antitoxin (IV or intrathecally).
Penicillin. Wound debridement,
edation (acepromazine, chloral
hydrate). Minimize stimulation
(dark, quiet stall)

Guarded prognosis

Trauma - vertebral

Alert horse. Signs depend on site of
lesion. Can be difficult to detect
vertebral fractures in adult horses.
Radiography

None specific

Poor prognosis

Trauma - cranial

Unconscious or severely altered
mentation. Seizures. Head wounds.
Blood from ears and nostril.
Imaging (radiography, CT, MRI)

Anti-inflammatory drugs including
flunixin meglumine, phenylbutazone,
corticosteroids. Drugs to reduce
swelling (mannitol and hypertonic
saline). Control of seizures (diazepam,
midazolam, barbiturates). Heroic
craniotomy

Very poor prognosis

Cervical vertebral
instability

Alert horse. Acute-onset ataxia and
recumbency. Young horse (< 4 years old).
Radiography and myelography

Anti-inflammatory drugs.

Rest. Surgical vertebral stabilization

Poor prognosis

Vestibular disease

Normal to depressed, depending
on cause. Signs of vestibular disease
include circling and falling to one side,
head tilt and nystagmus. Diagnosis by
endoscopic examination of guttural
pouches, radiography of skull and
examination of CSF

Antibiotics, anti-inflammatory
disease. Surgical or medical
treatment of guttural pouch disease

Poor to guarded prognosis

Equine herpesvirus-1
myoencephalopathy

Usually alert horse. Recumbency follows
period of posterior ataxia with fecal
and urinary incontinence. Fever in early
stages of disease. CSF xanthochromic.

Viral isolation or detection of virus by PCR.
Serology. Often multiple horses affected

Supportive care

Guarded prognosis. Affected
horses can be infectious

Arboviral encephalitis

Alert horse or altered mentation.

Supportive care. Dexamethasone

Epidemiology is characteristic. Prognosis

(Eastern, Western,
West Nile, Japanese B

depending on the disease. CSF consistent
with inflammation. Viral isolation or
detection by PCR. Serology

for West Nile encephalitis

is poor for recumbent horses.
Vaccines available

Migrating parasite larvae
(Table 35.2)

Mentation depends on anatomic
site of parasite. Eosinophils in CSF

Ivermectin 400 pm/kg orally.
Corticosteroids

Sporadic disease

Neoplasia (melanoma,
lymphosarcoma,
cholesterol granuloma,
Table 35.2)

Alert horse. Signs of spinal cord
compression. Diagnosis by
imaging (radiography, myelography, CT).
CSF usually normal

No specific treatment

Hopeless prognosis

Equine motor neurone
disease

Alert horse. Good appetite. Profound
muscle weakness and atrophy. Prolonged
periods of recumbency but usually able
to stand when stimulated

Supportive care. Vitamin E

Guarded to poor prognosis.
Lifelong disease

Equine protozoal
myeloencephalitis

Variable mentation and signs of
neurologic disease. Diagnosis based on
neurologic examination and results of
Western blot of CSF or serum

Antiprotozoal medications

Guarded to fair prognosis

Rabies

Variable mentation. Protean signs of
neurologic disease. Important zoonosis.
Diagnosis by immunofluorescent
antibody testing of brain

No treatment. If suspected then
appropriate barrier isolation measures
must be instituted until the
horse dies or recovers, or another
diagnosis is confirmed

Rare cause of recumbency in horses

Postanesthetic myelopathy

Acute-onset posterior paresis evident
on recovery from general anesthesia

Supportive care

Poor to hopeless prognosis

Diagnosis and care of recumbent adult horses

123

o Is cutaneous sensation present in all
regions? If not, what are the anatomic
boundaries of desensitized areas?

» Is the position of the limbs normal? Is
there evidence of crepitus, swelling or
unusual shape of the limbs or axial
skeleton?

» Are the horse's feet normal? Does it
have laminitis? What is the response
to application of hoof testers?
o Are abnormalities detected on rectal
examination (fractured pelvis,
distended bladder, fecal retention,
pregnancy), provided that it is safe to
perform one?

Other body systems should be evaluated as
indicated or necessary. The heart and lungs
should be auscultated, although detecting
abnormal lung sounds in a recumbent
horse is difficult. The horse should be rolled
so that a complete examination can be
performed. Assisting the horse to stand
using a rope tied to the tail and thrown
over a rafter, or preferably using a sling, can
be useful in assessing the severity of the
horse's illness (can it stand at all?) and in
facilitating a complete physical examin-
ation. If there is a suspicion that the horse
has colic a nasogastric tube should be
placed to check for accumulation of liquid
gastric contents, a rectal examination
performed and peritoneal fluid collected.

Ancillary diagnostic testing includes
radiography of limbs and/or axial spine as
indicated by the history or physical
examination; myelography if a compressive
lesion of the cervical spinal cord is
suspected; endoscopic examination of the
pharynx and guttural pouches (especially
in horses with a history of falling, see
Rupture of the longus capitus muscle,
ultrasonography of the chest and abdo-
men; collection of cerebrospinal fluid; and
electromyography.

Hematologic abnormalities are some-
times reflective of the causative disease.
Serum biochemical abnormalities are
reflective of -the causative disease and in
addition are influenced by muscle damage
caused by the horse being recumbent
(increased creatine kinase and aspartate
aminotransferase activity), inappetent
(increased total and indirect bilirubin, and
triglyceride concentrations), and unable
to drink or gain access to water (increased
serum urea nitrogen, creatinine, sodium,
chloride, total protein and albumin
concentrations). Cerebrospinal fluid is
reflective of any inciting disease but is
usually normal.

MANAGEMENT AND CARE

The principles of care are treatment of the
primary disease, prevention of further
illness or injury, assisting the horse to
stand, and provision of optimal nutrition
and hydration.

Treatment of the primary disease is
covered in other sections of this book.
Similarly, maintenance of hydration and
electrolyte status is covered elsewhere.
Maintenance of normal hydration is
sometimes problematic in recumbent
horses because of limited access to water
and unwillingness to drink. Provision of
fresh, palatable water is essential. Intra-
venous or enteral (nasogastric intubation)
administration of fluids and electrolyte
solutions might be necessary in some
recumbent horses, especially early in their
illness.

Horses with diseases that cause
recumbency often have problems with
fecal and urinary incontinence or reten-
tion. Catheterization of the urinary
bladder might be necessary to relieve
distension in horses with neurogenic
upper motor bladder or lower motor
bladder dysfunction, or in male horses
that are reluctant to urinate when
recumbent. Catheterization of the bladder
is often repeated. To minimize the risk of
iatrogenic cystitis, the procedure should
be performed aseptically. Administration
of bethanechol might increase detrusor
muscle tone and aid urination, and
phenoxybenzamine (0.5 mg/kg intra-
venously over 15 min) might decrease
sphincter tone in horses with upper
motor neurone bladder.

Horses that can eat should be fed a
balanced, palatable and nutritious diet.
Tempting horses with reduced appetite
with treats such as apples, carrots and
horse treats might stimulate appetite for
hay and grain. Horses that are unable to
eat should be fed through a nasogastric
tube. Slurries of alfalfa pellets or com-
mercial diets can be administered through
nasogastric tubes. The maintenance
needs of a sedentary 425 kg horse are
approximately 15-18 Mcal/d. The main-
tenance needs of a recumbent horse are
unknown, but are probably less than that
of normal sedentary horses.

COMPLICATIONS - PREVENTION

A major challenge in managing recumbent
horses is preventing further injury.
Recumbent horses often make repeated
efforts to stand, which, while encouraging
to all involved, can result in further injury.
Horses attempting to stand can injure
their head, especially the periorbital
regions, and skin over bony prominences
such as over the wing of the ilium.
Minimizing further injury is achieved by
use of a sling or tail rope to assist horses
to stand, housing in a padded stall with
deep, soft bedding (although this can
interfere with the horse's ability to stand),
and protection of the head and distal
limbs with a helmet and bandages,
respectively. Recumbent horses kept in

well-grassed pasture often do well and
have minimal self-inflicted trauma.

Decubital ulcers occur over pressure
points such as the wing of the ilium, point
of the shoulder and zygomatic arch, and
can become severe. Recumbent horses
that paddle can abrade the skin over limb
joints with subsequent increased risk
of septic arthritis. Bandages, helmets,
ointments such as silver sulfadiazine
paste, and soft bedding minimize but do
not eliminate these abrasions. Recumbent
horses that cannot or do not voluntarily
move from side to side should be rolled
every 2-4 hours.

Peripheral pressure neuropathy can
occur in recumbent horses. The radial
nerve and facial nerve are most often
affected. Prevention is achieved by use of
padded bedding, slings, frequent rolling
and a helmet.

Recumbent horses can sustain muscle
damage from pressure on large muscle
groups. For large or well-muscled horses
this can result in large increases in serum
creatine kinase activity and myoglobinuria.
Myoglobinuria can cause acute renal
failure, although this degree of myo-
globinuria in recumbent horses is
unusual.

Pneumonia can occur as a result of
recumbency. Horses that are dysphagic
are at increased risk of aspiration of feed
material and saliva, and hence develop-
ment of aspiration pneumonia. Horses
receiving corticosteroids are at increased
risk of bacterial and fungal ( Aspergillus
spp.,) pneumonia. While not every
recumbent horse should be administered
antimicrobials, this is indicated in horses
at increased risk of developing pneumonia.
Antimicrobials should have a broad
spectrum, including activity against
Streptococcus spp., such as a combination
of penicillin and an aminoglycoside.

Slinging horses is labor-intensive and
requires the use of a sling that is designed
for use with horses. Horses should not be
lifted using hip slings intended for use
with cattle. Use of these slings to lift
horses by grasping over the wing of each
ilium is inhumane and unsuccessful.
Horses in slings should be closely
monitored and not allowed to hang in the
sling. The horses should be assisted to
stand in the sling every 6 or 8 hours. The
sling should be used to help the horse to
get up and provide some support while it
is standing, but the horse should not have
all its weight borne by the sling for more
than a few minutes. Horses that have an
excessive amount of weight borne by the
sling for a prolonged period of time have
trouble breathing and are likely to
develop colic, rupture of the urinary
bladder, diaphragmatic hernia or rectal
prolapse.

PART 1 GENERAL MEDICINE ■ Chapter 2: General systemic states

Potentially catastrophic complications
include septic arthritis, radial nerve injury,
bladder rupture, diaphragmatic hernia,
rectal prolapse, colon torsion and long
bone fracture. The risk of these compli-
cations can be minimized by the practices
detailed above, but cannot be eliminated.

REVIEW LITERATURE

Chandler K. Clinical approach to the recumbent adult
horse. In Practice 2000; June:308
Davis EG et al. Treatment and supportive care of
recumbent horses. Compend Contin Educ Pract
Vet 2004; 26:216.

Rush BR et al. Compend Contin Educ Pract Vet 2004;
26:256.

Nout YS, Reed SM. Management and treatment of the
recumbent horse. Equine Vet Educ 2005; 17:324

REFERENCE

1. Stephen JO et al. J Am Vet Med Assoc 2000;
216:725.

Sudden or unexpected
death

When an animal is found dead without
having been previously observed to be ill,
a diagnosis, even after necropsy exam-
ination, is often difficult because of the
absence of a detailed history and clinical
findings. A checklist of diseases for con-
sideration when sudden or unexpected
death occurs in a single animal or group
of animals is provided below. Details of
each of the diseases listed are available in
other sections of this book. The list
applies particularly to cattle, but some
occurrences in other species are noted. It
is necessary to point out the difference
between 'found dead'and'sudden death'.

When animals are observed in-
frequently, for example at weekly intervals,
it is possible for them to be ill with
obvious clinical signs for some days
without being observed. In these circum-
stances the list of possible diagnoses is
very large. It is also correspondingly large
when animals are kept together in large
groups and are not observed as indivi-
duals. This is likely to happen in beef
cattle, especially in feedlots or as calves
with dams at pasture, when the animals
are unaccustomed to human presence
and move away when approached. The
list below refers to animals that are
closely observed as individuals at least
once daily.

SUDDEN OR UNEXPECTED DEATH
IN SINGLE ANIMALS

SPONTANEOUS INTERNAL
HEMORRHAGE

This condition could be due to cardiac
tamponade in cows, ruptured aorta or
atrium, inherited aortic aneurysm or
verminous mesenteric arterial aneurysm

in horses and esophagogastric ulcer or
intestinal hemorrhagic syndrome in pigs.

RUPTURE OF INTERNAL CAROTID
ARTERY ANEURYSM

This condition may occur secondary to
mycosis of guttural pouch of the horse. In
one survey of sudden deaths in horses
while racing, most (68%) were un-
diagnosed, although it was assumed that
they died of exercise- associated ventri-
cular arrhythmias. Of those that were
diagnosed, most were due to spontaneous
hemorrhage. 1 Similar conclusions have
resulted from other surveys. 2 Most
reported cases of sudden death in the
horse are the result of cardiovascular
accidents. 3,4

Fracture of the pelvis can result in fatal
hemorrhage within the gluteal muscles of
the horse 5 and rupture of the middle
uterine artery at parturition in cattle may
occur with uterine prolapse.

PERACUTE ENDOGENOUS TOXEMIA

This condition can arise from rupture of
the stomach of horses, abomasum of
cows and colon in mares at foaling. Large
amounts of gastrointestinal contents are
deposited rapidly into the peritoneal
cavity. In newborn animals, especially
foals, fulminating infections are the
commonest cause.

Peracute exogenous toxemia in a

single animal could be as a result of
snakebite, but the snake would have to be
very poisonous and the animal of small
body weight to cause death without any
observable illness.

TRAUMA

Trauma may cause death by either
internal hemorrhage or damage to the
central nervous system, especially the
brain or atlanto -occipital joint sufficient
to damage the medulla oblongata. In
most cases the trauma is evident: there
has been fighting, or a fall has occurred,
or the animal has attempted to jump an
obstacle. In horses a free gallop downhill
may result in a serious fall or collision
with, for example, a wall, especially if the
ground is slippery.

Inapparent trauma usually occurs
when animals are tied up by halter and
rush backwards when frightened or are
startled by an electric fence and the halter
shank is long. Sometimes the animal will
plunge forward and hit its forehead
between the eyes on a protruding small
object such as a bolt used in a fence.
Sadism, especially by the insertion of
whip handles or pitchfork handles into
the anus or vulva, may also be inapparent.

GASTROINTESTINAL CONDITIONS

Gastric rupture in the horse may occur
following overeating highly fermentable
feed, administration of excessive quan-

tities of fluids by nasogastric tube, gastric
impaction or when gastric motility is
markedly reduced in acute grass sickness
or gastric distension with fluid. Peracute
enteritis in the horse can cause rapid
unexpected death.

Volvulus or gastrointestinal accidents
account for almost 50% of sudden deaths
in sows, followed next by gastric ulcer-
ation, retained fetuses and toxemia. 6

Recumbent cattle that become lodged
in a small hollow in the ground may die of
bloat 7 because the cardia becomes covered
with ruminal fluid and eructation is not
possible.

IATROGENIC DEATHS

These may be due to overdose with
intravenous solutions of calcium salts in
an excited cow, too-rapid fluid infusion in
an animal with pulmonary edema, intra-
venous injection of procaine penicillin
suspension, and intravenous injections of
ivermectin in horses. These are not hard
to diagnose and the producer or veteri-
narian is usually obviously embarrassed.

One of the most sudden death occur-
rences is the anaphylactoid reaction in a
horse to an intravenous injection of an
allergen such as crystalline penicillin.
Death occurs in about 60 seconds. Intra-
arterial injections of penicillin or pheno-
thiazine tranquilizers have also been
reported to cause sudden death. 3

SUDDEN DEATH IN HORSES

An analysis was made of the causes of
death in horses and ponies over 1 year of
age that died suddenly and unexpectedly. 8
No cause of death was found in 31% of
cases and 16% died from the following
causes: hemorrhage in the respiratory
tract, central nervous system and adverse
drug reactions. Cardiovascular lesions
were the cause in 14% and the remaining
3% had lesions of the gastrointestinal
tract.

Sudden death in racehorses is com-
monly due to massive hemorrhage into
the lungs, abdomen or brain. 5 In horses
that were found dead but appeared
normal when last seen, the cause of death
was not determined in 33%. Lesions of
the gastrointestinal tract were the cause
of death in 39% and respiratory tract
lesions in 9%. Lesions of both the central
nervous system and cardiovascular
system were the cause of death in 5%.
The remaining 10% had miscellaneous
causes.

SUDDEN OR UNEXPECTED DEATH
IN A GROUP OF ANIMALS

The diseases listed below could obviously
affect single animals if the animals were
housed or run singly.

Sudden or unexpected death

LIGHTNING STRIKE OR
ELECTROCUTION

This usually affects a number of animals
that are found together in a pile or group.
Rarely, electrical current only electrifies a
contact object intermittently and deaths
will be intermittent. In most cases
the history and an examination of the
environment reveals the cause.

NUTRITIONAL DEFICIENCY AND
POISONING

At pasture, sudden death may come from
the sudden exposure of the cattle to
plants that cause bloat, hypomagnesemia,
cyanide or nitrite poisoning, fluoroacetate
poisoning, fast death factor (produced by
algae in a lake or pond) or acute inter-
stitial pneumonia. Acute myocardiopathy
in young animals on diets deficient in
vitamin E or selenium is in this group, as
is inherited myocardiopathy in Herefords.
Gross nutritional deficiency of copper in
cattle causes 'falling disease', a mani-
festation of acute myocardiopathy.

Acute myocardiopathy and heart failure
is associated with poisons in Phalaris spp.
pasture, grass nematodes on Lolium
rigidum, the hemlocks Cicuta and Oenanthe
spp. and the weeds Fadogia, Pachystigma,
Pavette, Ascelapius and Aeriocarpa,
Crystostegia and Albizia, Cassia spp. The
trees oleander and yew ( Taxus spp.) may
also be causes, and those species contain-
ing fluoroacetate, such as the gidgee tree
and the weeds Gastrolobium, Oxylobium,
Dichapetalum and Ixioloena spp. may be
implicated. There are a number of plants
that cause cardiac irregularity and some
sudden deaths, e.g. Urginea, Kalanchoea
spp., but more commonly congestive
heart failure is caused. Monensin, lasolocid
and salinomycin toxicities are increasingly
common causes in horses and, to a less
extent, cows.

ACCESS TO POTENT POISONS

Access to potent poisons may occur in
housed animals or in those fed prepared
feeds.

There are few poisons that cause
sudden death without premonitory signs.

Cyanide is one, but is an unlikely poison
in these circumstances. Monensin, mixed
in a feed for cattle that is then fed to
horses, or fed in excess to cattle, does
cause death by heart failure. Organo-
phosphates are more likely, but clinical
signs are usually apparent. Lead is in a
similar category; however, very soluble
lead salts can cause death quickly in
young animals.

DISEASES ASSOCIATED WITH
INFECTIOUS AGENTS

These cause septicemia or toxemia, and
include anthrax, blackleg, hemorrhagic
septicemia and (especially in sheep,
but occasionally in cattle) peracute
pasteurellosis. In pigs, mulberry heart
disease and perhaps gut edema should be
considered. In horses, colitis is probably
the only disease that will cause sudden
death. In sheep and young cattle,
enterotoxemia associated with C. perfringens
should be included and this may be
involved in rumen overload in feedlot
cattle on heavy grain feed. Circumstances,
feeding practices, climate and season of
the year usually give some clue as to the
cause.

NEONATAL AND YOUNG ANIMALS

In very young, including neonatal,
animals, congenital defects that are
incompatible with life - prematurity,
septicemia because of poor immune
status or toxemia associated with parti-
cular pathogens, especially E. coli, and
hypothyroidism - are important causes of
sudden death.

ANAPHYLAXIS

Anaphylaxis after injection of biological
materials, including vaccines and sera, is
usually an obvious diagnosis, but its
occurrence in animals at pasture can
cause obscure deaths. In these circum-
stances it usually affects one animal and
clinical illness is often observed. A similar
occurrence is sudden death in a high
proportion of piglets injected with an iron
preparation when their selenium-vitamin
E status is low.

125

PROCEDURE FOR INVESTIGATION
OF SUDDEN DEATH

This is as follows:

0 Keep excellent records because of the
probability of insurance enquiry or
litigation

° Take a careful history, which may
indicate changes of feed composition
or source, exposure to poisons or
administration of potentially toxic
preparations

° Make a careful examination of the
environment to look for potential
sources of pathogens. Be especially
careful of your personal welfare if
electrocution is possible - wet
concrete floors can be lethal when
combined with electrical current
unless you are wearing rubber boots

° Carefully examine dead animals for
signs of struggling, frothy nasal
discharge, unclotted blood from
natural orifices, bloat, pallor or
otherwise of mucosae, burn marks on
body, especially on the feet, or signs
of trauma or of having been
restrained. Pay particular attention to
the forehead by palpating the frontal
bones - these may have been
fractured with a heavy blunt object
without much damage to the skin or
hair

° Ensure that typical cadavers are
examined at necropsy, preferably by
specialist pathologists at independent
laboratories, where opinions are more
likely to be considered authoritative
and unbiased

° Collect samples of suspect materials
for analysis. Preferably, collect two
samples, one to be analyzed and one
to be made available to a feed
company, if indicated.

REFERENCES

1. Gelberg HB et al. J Am Vet Med Assoc 1985;
187:1354.

2. Platt H. BrVet J 1982; 138:417.

3. Luckc VM. EquineVet J 1987; 19:85.

4. Allen JR et al. Equine \fet J 1987; 19:145.

5. Brown CM, Mullaney TP. In Pract 1991; 13:121.

6. Sanford SE et al. Can Vet J 1994; 35:388.

7. Rafferty GC. Vet Rec 1996; 138:72.

8. Brown CM et al. EquineVet J 1988; 20:99.

"PART 1 GENERAL MEDICINE

Diseases of the newborn

perinatal and postnatal

DISEASES 127

General classification 127
General epidemiology 128
Special investigation of neonatal
deaths 131

CONGENITAL DEFECTS 132

Intrauterine growth retardation 137
Neonatal neoplasia 137

PHYSICAL AND ENVIRONMENTAL
CAUSES OF PERINATAL
DISEASE 138

This chapter considers the principles of
the diseases that occur during the first
month of life in animals born alive at
term. Diseases causing abortion and
stillbirth are not included. The specific
diseases referred to are presented separately
under their own headings.

The inclusion of a chapter on diseases
of the newborn, and at this point in the
book, needs explanation. The need for the
chapter arises out of the special sensitivities
which the newborn have:

° Their immunological incompetence
° Their dependence on adequate
colostrum containing adequate
antibodies at the right time
° Their dependence on frequent intake
of readily available carbohydrate to
maintain energy
5 Their relative inefficiency in
maintaining normal body
temperature, upwards or downwards.

All these points need emphasizing before
proceeding to the study of each of the
body systems.

There are no particular aspects of a
clinical examination that pertain only to
or mostly to neonates. It is the same
clinical examination as is applied to
adults, with additional, careful examin-
ation for congenital defects and diseases,
which may involve the umbilicus, the
liver, the heart valves, the joints and
tendon sheaths, eyes and meninges.
Although one should avoid any suggestion
that an examination of an adult could be
cursory, it is necessary to ensure that an
examination of a newborn animal is as
complete as practically possible. This is
partly for an emotional reason: the neonate
always evokes a sentimental reaction. It is
also important for the economic reason
that in most species the offspring, when
already on the ground, represents a very
considerable part of the year's investment

Perinatology 138
Prematurity and dysmaturity of
foals 139

Parturient injury and intrapartum
death 139
Fetal hypoxia 140
Hypothermia 141
Maternal nutrition and the
newborn 143

Poor mother-young relationship 143
Induction of premature parturition 144

DISEASES OF CLONED
OFFSPRING 145

and productivity. There is also the much
greater susceptibility to infectious disease,
dehydration and death, and diagnosis and
treatment must be reasonably accurate and
rapid. Supportive therapy in the form of
fluids, electrolytes and energy and nursing
care are especially important in the new-
born in order to maintain homeostasis.

Perinatal and postnatal
diseases

One of the difficulties in the study of
these diseases is the variation in the type
of age classification that occurs between
publications, which makes it difficult to
compare results and assessments. The
term perinatal is usually used to describe
morbidity or mortality that occurs at birth
and in the first 24 hours of life. The term
neonatal is usually used to describe
morbidity or mortality between birth and
14 days. However, there is variation in the
use of these terms. To ensure that our
meanings are clear, we set out below
what we think is the most satisfactory
classification of all the diseases of the
fetus and the newborn, which is adapted
from a scheme proposed for lambs. The
importance of this type of classification is
with the assessment of risk for a given
type of disease and in the prediction of
likely causes that should be investigated
by further examinations. This approach is
not of major importance in the assess-
ment of disease in an individual animal,
although it is of importance in helping
establish the priority in diagnostic rule-
outs. The classification is, however, of
considerable value in the approach to
perinatal morbidity and mortality in large
flocks or herds where an assessment of
the age occurrence of morbidity and
mortality can guide subsequent examin-

3

NEONATAL INFECTION 146

Failure of transfer of colostral
immunoglobulins 149

Principles of control and prevention of
infectious diseases of newborn farm
animals 157

Omphalitis, omphalophlebitis and
urachitis in newborn farm animals
(navel-ill) 159

CLINICAL ASSESSMENT AND
CARE OF CRITICALLY ILL
NEWBORNS 160

ations to the probable group of cases,
with optimal expenditure of investigative
capital.

GENERAL CLASSIFICATION

FETAL DISEASES

These are diseases of the fetus during
intrauterine life, e.g. prolonged gestation,
intrauterine infections, abortion, fetal
death with resorption or mummification,
goiter.

PARTURIENT DISEASES

These are diseases associated with
dystocia, causing cerebral anoxia or fetal
hypoxemia, and their consequences and
predispositions to other diseases; injury
to the skeleton or soft tissues and
maladjustment syndrome of foals are also
included here.

POSTNATAL DISEASES

These are divided into early, delayed and
late types:

° Early postnatal disease (within
48 hours of birth). Deaths that occur
during this period are unlikely to be
caused by an infectious disease unless
it has been acquired congenitally.

Most diseases occurring in this period
are noninfectious and 'metabolic', e.g.
hypoglycemia and hypothermia due
to poor mothering, hypothermia due
to exposure to cold, low vigor in
neonates due to malnutrition.
Congenital disease will commonly
manifest during this period but may
sometimes manifest later. Infectious
diseases are often initiated during this
period but most manifest clinically at
a later age because of their incubation
period; some, e.g. navel infection,
septicemic disease and
enterotoxigenic colibacillosis, have a
short enough incubation to occur
during this period

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

° Delayed postnatal disease (2-7 days
of age). Desertion by mother,
mammary incompetence resulting in
starvation and diseases associated
with increased susceptibility to
infection due to failure of transfer of
colostral immunoglobulins (the
predisposing causes to these occur in
the first 12-24 hours of life). Examples
include colibacillosis, joint ill, lamb
dysentery, septicemic disease, most of
the viral enteric infections in young
animals, e.g. rotavirus and coronavirus
° Late postnatal disease (1-4 weeks of
age) . There is still some influence of
hypogammaglobulinemia, with late-
onset enteric diseases and the
development and severity of
respiratory disease in this period, but
other diseases not directly associated
with failure of transfer of
immunoglobulins such as
cryptosporidiosis, white muscle
disease and enterotoxemia start to
become important.

GENE RA L EPIDEMIOLO GY

Diseases of the newborn and neonatal
mortality are a major cause of economic
loss in livestock production. In cattle,
sheep and pigs the national average
perinatal mortalities exceed by far the
perinatal mortality experienced in herds
and flocks with good management. In
these species the identification of the
management deficiencies that are the
cause of a higher than acceptable mortality
in a herd or a flock is a most important
long-term responsibility of the practicing
veterinarian and, in most instances, is
more important than the identification of
the causal agent or the short-term treat-
ment of individual animals with neonatal
disease. In contrast, in horses the indivi-
dual is of extreme importance and the
primary thrust is in the treatment of
neonatal disease.

All animals must be born close to term
if they are to survive in a normal farm
environment. Minimal gestational ages
for viability (in days) for each of the
species are:

Calf -240
Foal -300
Lamb - 138
Piglet - 108.

LAMBS

Mortality rates

Neonatal lamb mortality is one of the
major factors in impairment of pro-
ductivity in sheep -raising enterprises
around the world. 1 " 3 Mortality can
obviously vary with the management
system (intensive versus extensive lambing,
highly supervised versus minimally

supervised, variations in the provision of
shelter, etc.), and according to whether
there is a particular disease problem in
a given flock. Nonselective mortality
surveys have shown population mortality
rates in lambs, from birth to weaning, that
vary from 9-35% and there are flocks that
may exceed this upper figure in the face of
a major problem. In well- managed flocks
neonatal mortality is less than 10% and in
some is below 5%. The majority of
neonatal mortality is due to noninfectious
disease.

Major causes

Surveys from various sheep-raising areas
in the world consistently show that the
majority of lamb mortalities can be
attributed to three main causes: 1-4

° The complex of hypothermia/
exposure/hypoglycemia/starvation
0 Stillbirth and dystocia/stillbirth
° Abortion.

These syndromes have a multifactorial
etiology but can account for over 65% of
the mortality that occurs in the first few
days of life. 4,5

Fetal disease

Infectious abortion can cause consider-
able fetal, parturient and postnatal
mortality in infected flocks but it is a
relatively minor cause of perinatal mortality
overall. In contrast to other large animal
species, abortion storms in sheep are
often accompanied by significant mortality
in liveborn animals. Many agents associ-
ated with abortion in ewes produce
placentitis and cause abortion in late
pregnancy. This frequently results in the
birth of liveborn, growth-retarded and
weak lambs that die during the first few
days of life. Any investigation of perinatal
mortality in sheep should also consider
the presence of agents causing abortion,
although abortion and the birth of dead
lambs is always prominent in abortion
outbreaks.

Parturient disease

i Stillbirth occurs largely as a result of
, prolonged birth and fetal hypoxemia,
j Prolonged birth and dystocia is a parti-
cular problem in large single lambs. 6
; Higher rates of stillbirth can also occur in
j flocks that are in poor condition. Pro-
i longed birth is a major risk factor for
1 subsequent postnatal disease. 4

Postnatal disease

The hypothermia/exposure/ hypo-
glycemia/starvation complex is the

> most important cause of postnatal
! disease. The determinants for the occur-
I rence of this complex are the birth size of
j the lamb, the energy reserves of the lamb,
j and environmental factors at birth and
; during the following 48 hours which

influence heat loss. These include
environmental temperature, wind velocity
and evaporative cooling determined by
the wet coat of the lamb at birth or the
occurrence of rain.

Birth size

Birth size is determined by the nutrition
and genetics of the ewe, and by litter size
which is also determined by the parity
and genetics of the ewe. Reflecting these
influences, most surveys of neonatal
mortality in lambs show:

° A significant association between the
body condition score or nutrition of
the late pregnant ewe and perinatal
mortality

° A relation between birth weight and
mortality (depending upon the breed,
a birth weight of less than 2.5-3.0 kg
has increased risk for death)

° A higher mortality in lambs from
multiparous ewes
6 A pronounced effect of litter size,
with mortality in lambs born as
triplets being higher than in those
born as twins, which in turn is higher
than that in lambs born as singles.

These relationships can be confounded by
an increase in mortality in large-birth-
weight lambs bom as singles because of
dystocia and by the greater mortality in
lambs born to maiden ewes associated
with poor mothering and desertion.

Environmental factors

Environmental factors of temperature,
wetness and wind also confound the
above relationships; their influence varies
according to the management system.

The identification of the above deter-
minants of mortality is of more than
academic value as almost all can be
changed by the identification of at-risk
groups and the institution of special
management procedures, or by the
identification and mitigation of adverse
environmental factors.

Infectious disease

Infectious disease can be important in
some flocks and occurs after 2 days of age.
The major infectious diseases of lambs
that cause mortality are enteritis and
pneumonia. 7 Their prevalence varies with
the management system - enteric disease
and liver abscess are more common in
shed lambing systems than with lambing
at pasture. 8 Risk for pneumonia is greatest
in very light or heavy lambs and in lambs
from maiden ewes and ewes with poor
milk production. 9

Other factors

Other factors can be important in indivi-
dual flocks or regions. Lambs found dead
or missing may account for significant
losses under some conditions, such as

mountain or hill pastures. 2 Predation, or
predation injury, is an important cause of
loss in some areas of the world and,
depending upon the region, can occur
from domestic dogs, coyotes, birds or feral
pigs. Poor mothering and an inability of
the ewe to gather and bond to both lambs
of twins can be a problem in Merinos and
can cause permanent separation of lambs
from the ewe and subsequent death from
starvation.

Management at lambing can also
influence the patterns of mortality. Inten-
sive stocking at the time of lambing to
allow increased supervision can allow a
reduction in mortality associated with
dystocia and the hypothermia/exposure/
hypoglycemia/starvation complex. It can
ensure the early feeding of colostrum to
weak lambs but it can also result in a
greater occurrence of mismothering associ-
ated with the activities of 'robber' ewes
and it also increases the infection pressure
of infectious agents, resulting in an
increased incidence of enteric and other
disease. 7

Mortality rate can differ between
breeds and lambs from crossbred dams
may have higher survival rates.

Recording systems

Simple systems for recording, determining
and evaluating the major causes of lamb
mortality in a flock, for determining the
time of death in relation to birth and
relating the deaths to the weather and
management system are available. 4,10
These systems of examination are effec-
tive in revealing the extent of lamb losses
and the areas of management that require
improvement and are much more cost-
effective than extensive laboratory exam-
inations, which may give little information
on the basic cause of the mortality. More
intensive examination systems that com-
bine these simple examinations with
selected biochemical indicators of deter-
minant factors are also described. 5

DAIRY CALVES
Mortality rates

A 1992 review of publications on calf
mortality reported mortality rates in dairy
calves that varied from a low of approxi-
mately 2% to a high of 20% with mortality
on individual farms varying from 0-60%. 11
A survey of calf mortality in 829 dairy
operations in the USA showed consider-
able variation with region and with
management system. 12 The best estimate
for the average on-farm calf mortality rate
is 6% 11 This mortality is in addition to
that associated with stillborn or weak-
born calves which is reported to occur in
11% of primiparous and 5.7% of multi-
parous Holstein cows in the USA. 13

The exact cause of death in these
stillborn or weakbom calves is not known.

Perinatal and postnatal diseases

129

In addition to the influence of parity,
dystocia has a major influence on rates
and rates are also higher where gestation
length was shorter than 280 days.
Calving-associated anoxia may be an
important contributing factor in these
deaths. 14

Mortality in twin-born calves is
approximately three times that of single-
born calves. Disease morbidity rates also
vary with the farm and, as might be
expected, with the disease under consider-
ation and the age of the calf. 12,15,16

Major causes

Fetal disease and the postnatal septicemic,
enteric and respiratory diseases are the
most common causes of loss.

Fetal disease

Definition of fetal loss and abortion varies
between studies but the median fre-
quencies of observed abortions is
approximately 2% and of fetal loss in
dairy cattle diagnosed pregnant 6. 5%. 17
The majority of these have no diagnosed
cause.

Parturient disease

Calving in dairy cattle is usually super-
vised, but prolonged calving with con-
sequent hypoxemia (and occurring with
or without dystocia) and twin birth is
associated with significantly higher risk
for mortality in the first 21 days of
life. 12,18,19

Postnatal disease

Calves are at highest risk for death in the
first 2 weeks of life and especially in the
first week. Septicemic and enteric disease
are most common during this period,
with respiratory disease being more
common after 2 weeks of age. 14,20,21 Failure
of transfer of colostral immunoglobulins
is a major determinant of this mortality. 12
The economic significance of neonatal
disease can be considerable and the
occurrence of disease as a calf can also
subsequently affect days to first calving
intervals and long-time survival in the
herd. 14,22 Death also causes a loss of
genetic potential both from the loss of the
calf and the reluctance of the farmer to
invest in higher-price semen in the face of
a calf mortality problem.

Meteorological or seasonal influences
may have an effect on dairy calf mortality
rate and this can vary with the region. In
cold climates during the winter months, an
increase in mortality may be associated with
the effects of cold, wet and windy weather,
whereas in hot climates there may be an
increase in mortality during the summer
months in association with heat stress.

Management

Management is a major influence and in
well managed dairy herds calf mortality

usually does not exceed 5% from birth to
30 days of age. Risk factors for disease
morbidity and mortality in dairy calves
relate to the infection pressure to the
calf and factors that affect its nonspecific
and specific resistance to disease. It is
generally recognized that mortality is
associated with the type of housing for
calves, calving facilities, the person caring
for the calves and attendance at calving.
Thus calves that are born in separate
calving pens have a lower risk of disease
than those born in loose housing or
stanchion areas 23 and the value of good
colostrum feeding practices is apparent. 11,12
Studies on the role of calf housing and the
value of segregated rearing of calves in
reducing infection pressure generally
show beneficial health results 7,21,24,25 but
the value of this system of rearing is prob-
ably best measured by its adoption in
many dairies where climatic conditions
allow this to be an option for housing
young calves. The quality of management
will be reflected in rates of failure of
transfer of passive immunity and will also
affect the infection pressure on the calf
during the neonatal period. Quality of
management is very hard to measure
but is easily recognized by veterinary
practitioners.

The epidemiological observations that
calf mortality is lower when females or
family members of the ownership of the
farm manage the calves, rather than when
males or employees perform these duties,
is probably a reflection of this variation in
quality of management and suggests that
owner-managers and family members
may be sufficiently motivated to provide
the care necessary to ensure a high
survival rate in calves. Even so, calf health
can be excellent with some hired calf-
rearers and very poor with some owner
calf-rearers. Besides visual assessments of
hygiene an effective measure of the
quality of calf management can be
provided by a measure of rates of failure
of transfer of passive immunity.

BEEF CALVES
Mortality rates

Mortality in beef herds is usually recorded
as birth to weaning mortality and has
ranged from 3-7% in surveys, with higher
rates in calves born to heifers; signifi-
j cantly higher mortality can occur in herds
I with disease problems. 26-31 The majority
i of this mortality occurs within the first
j week of life and most of it occurs in the
j parturient or immediate postnatal period
j as a result of prolonged birth or its
| consequences.

I

j Major causes

j Dystocia resulting in death is common
[ ; and dystocial calves, twin-born calves and
; calves born to heifers are at greater risk

130

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

for postnatal disease. 31-34 Enteric and
respiratory disease occurs in outbreaks in
some years and very cold weather can
result in high loss from hypothermia. In a
survey of 73 herds in the USA the overall
mortality rate was 4.5% and causes were
dystocia (17.5%), stillbirths (12.4%),
hypothermia (12.2%), enteric disease
(11.5%) and respiratory infections
(7.6%). 31

Fetal disease

Abortion rates appear to be lower than in
dairy cattle, usually less than 1%. 30 The
majority of these are not diagnosed as to
cause but of those that are, infectious
abortion is the most common diagnosis. 35

Parturient disease

Accurate prospective and retrospective
studies have shown that 50-60% of the
parturient deaths in beef calves are
associated with slow or difficult birth and
that the mortality rate is much higher in
calves born to heifers than from mature
cows. 26,30,32 Dystocial birth can lead to
injury of the fetus and to hypoxemia and
may not necessarily be associated with
fetal malposition. Birth size is highly
heritable within all breed types of cattle 36
and perinatal mortality will vary between
herds depending upon their use of bulls
with high ease of calving ratings in the
breeding of the heifer herd. Milk fever
and over- fatness at calving are other
preventable causes. Selective intensive
supervision of calving of the heifer herd
can also result in a reduction of perinatal
mortality.

Postnatal disease

Scours and pneumonia are the next most
important causes of mortality in beef
calves, followed by exposure to extremely
cold weather or being dropped at birth
into deep snow or a gully. The incidence
of diarrhea is greatest in the first 2 weeks
of life and there is considerable variation
in incidence between herds. 37 However,
explosive outbreaks of diarrhea or exposure
chilling can be significant causes of
mortality in certain years. 29 The purchase
of a calf for grafting, often from a market,
is a significant risk for introduction of
disease to a herd.

Body condition score of the dam can
influence calf mortality, with high con-
dition scores having a higher risk for
dystocial mortality and low scores for
infectious disease. Mortality from diarrhea
is often higher in calves born to heifers,
possibly because heifers are more closely
congregated for calving supervision or
because of a higher risk for failure of
transfer of passive immunity in this age
group. Congenital abnormalities can be
an occasional cause of mortality in some
herds. 27

PIGLETS
Mortality rates

Preweaning mortality ranges from 5-48%,
with averages ranging from 12-19%, of all
pigs bom alive 38,39 More than 50% of the
preweaning losses occur before the end of
the second day of life. Mortality increases
as the mean litter size increases and as the
mean birth weight of the pig decreases. In
most herd environments the minimal
viable weight is approximately 1 kg. The
mean number of piglets weaned is related
to the size of the litter up to an original size
of 14 and increases with parity of sows up
to their fifth farrowing. Preweaning
mortality is negatively correlated with herd
size and farrowing crate utilization, and
positively correlated with the number of
farrowing crates per room. 39

Major causes

Surveys of neonatal mortality in piglets
have repeatedly indicated that the most
important causes of death in piglets from
birth to weaning are noninfectious in
origin 38 ' 40 The major causes are starvation
and crushing (75-80%) (although these
may be secondary to, and the result of,
hypothermia), congenital abnormalities
(5%) and infectious disease (6%). The
major congenital abnormalities are con-
genital splayleg, atresia ani and cardiac
abnormalities. Infectious diseases may
be important on certain individual farms
but do not account for a major cause of
mortality.

Fetal disease

Fetal disease rates in most herds are low
unless there is an abortion storm or poor
control of endemic infections such as
parvovirus. In contrast to other species,
the majority of abortions are diagnosed
and are infectious.

Parturient disease

Stillbirths account for 4-8% of all deaths
of pigs born and 70-90% are type II or
intraparturient deaths, in which the piglet
was alive at the beginning of parturition.
The viability of newborn piglets can be
accurately evaluated immediately after
birth by scoring skin color, respiration,
heart rate, muscle tone and ability to
stand. Stillbirths are more commonly
born in the later birth orders of large
litters and it is a relatively common
practice for sows to be routinely given
oxytocin at the time of the birth of the first
piglet in order to shorten parturition.
Controlled trials have shown that, while
oxytocin administration at this time will
result in a significant decrease in farrow-
ing time and expulsion intervals there is a
significant increase in fetal distress, fetal
anoxia and intrapartum death and an
increase in piglets bom alive with ruptured
umbilical cords and meconium staining. 41

Postnatal disease

The large percentage of mortality caused
by crushing and trampling probably
includes piglets that were starved and
weak and thus highly susceptible to being
crushed. The estimated contribution of
crushing and starvation to neonatal
mortality varies from 50-80%. The body
condition score of the sow at the time of
farrowing, the nursing behavior of the
sow, her ability to expose the teats to all
piglets and the sucking behavior of the
piglets have a marked effect on survival. 42

Cold stress is also an important cause
of loss and the provision of a warm and
comfortable environment for the new-
born piglet in the first few days of life is
critical. The lower critical temperature of
the single newborn piglet is 34°C (93°F).
When the ambient temperature falls
below 34°C (93°F) the piglet is subjected
to cold stress and must mobilize glycogen
reserves from liver and muscle to main-
tain deep body temperature. The provision
of heat lamps over the creep area and
freedom from draughts are two major
requirements.

Management

Minimizing the mortality rate of newborn
piglets will depend on management tech-
niques, which include:

0 Proper selection of the breeding stock
for teat numbers, milk production and
mothering ability

® The use of farrowing crates and creep
escape areas to minimize crushing
injuries

9 Surveillance at farrowing time to
minimize the number of piglets
suffering from hypoxia and dying at
birth or a few days later
° Batch farrowing, which allows for
economical surveillance
® Fostering to equalize litter size
9 Cross-fostering to equalize non-
uniformity in birth weight within
litters

9 Artificial rearing with milk substitutes
containing purified porcine
gammaglobulin to prevent enteric
infection. 41

FOALS

Mortality rates

Foals are usually well supervised and
cared for as individual animals. Neonatal
death is less frequent than in other
species but equivalent rates of morbidity
and mortality occur on some farms. 43
Infectious disease is important, along
with structural and functional abnor-
malities that are undoubtedly better
recognized and treated than in any of the
other large animal species. In a large
survey of thoroughbred mares in the UK,
only 2% cf newborn foals died; 44 only

Perinatal and postnatal diseases

131

41% of twins survived and 98% of singles
survived. In contrast, a mortality rate of
22% between birth and 10 days is
recorded in an extensively managed
system. 45 Between 25-40% of mares that
are bred fail to produce a live foal 46 and an
extensive study of breeding records
indicated that 10% of mares that are
covered either aborted or had a non-
surviving foal. 47

Fetal disease

This is a major cause of loss and in one
study infections accounted for approxi-
mately 30% of abortions. 46 In a retro-
spective study of 1252 fetuses and neonatal
foals submitted for postmortem examin-
ation over a 10-year period in the UK,
equine herpes virus and placentitis
accounted for 6.5% and 9.8% of the
diagnoses respectively. 48 The placentitis
occurred in late gestation and was concen-
trated around the cervical pole and lower
half of the allantochorion associated with
ascending chronic infections of bacteria or
fungi resident in the lower genital tract.

Parturient disease

Neonatal asphyxia, dystocia, placental
edema and premature separation of the
placenta, umbilical cord abnormality
and placental villous atrophy are other
important causes of mortality in this
period. In the UK study 48 umbilical cord
disorders accounted for 38.8% of the final
diagnoses. Umbilical cord torsion usually
resulted in death of the fetus in utero but
the long cord/cervical pole ischemia dis-
order resulted in intrapartum death and a
fresh fetus with lesions consistent with
acute hypoxia.

Twins are at higher risk for sponta-
neous abortion.

Postnatal disease

Fbstnatal disease causing mortality from
birth to 2 months of age includes: lack of
maturity 36%, structural defect 23%, birth
injury 5%, convulsive syndrome 5%,
alimentary disorder 12%, generalized
infection 11% and other (miscellaneous)
9%. Of the infectious diseases, gastro-
intestinal and septicemic disease have
greatest importance. 49,31 ’ Whereas in the
past many of these conditions would have
been fatal, there have been significant
advances in the science of equine
perinatology in the 1980s and 1990s and
protocols for the treatment of neonatal
disease have been developed that have
been based on equivalents in human
medicine. These have proved of value in
the management and treatment of pre-
maturity, immaturity, dysmaturity and
neonatal maladjustment syndromes in
newborn foals, as well as in enteric and
septicemic disease. Different levels of
intensive care have been defined that

start from those that can be applied at the
level of the farm and increase in sophisti-
cation, required facilities and instrumen-
tation to those that are the province of a
specialized referral hospital. Early followup
studies indicate that this approach is of
considerable value in foals with neonatal
disease and that most surviving foals
become useful athletic adults. 51

SPECIAL INVESTIGATION OF
NEONATAL DEATHS

The following protocol is a generic guide
to the investigation of deaths of newborn
animals. It will require modification accord-
ing to the species involved.

1. Determine the duration of pregnancy
to ensure that the animals were born
at term

2. Collect epidemiological information
on the problem. Where possible, the
information should include the
following:

* What is the abnormality?

8 What is the apparent age at onset
and the age at death?

8 What clinical signs are consistently
associated with the problem?

0 What is the prevalence and
proportional risk in particular
groups (maternal, paternal,
nutritional, vaccinated, etc.)?

8 What is the parity of the dam that
gave birth to the animal and what
proportional risk does this reflect
within the group?

° What is the birth history of
affected animals? Are births
supervised, what is the frequency
of observation and what are the
criteria for intervention? What is
the proportional risk associated
with prolonged birth?

0 Is there an effect of litter size and
what is the health of the other
litter mates?

° Has there been any difference in
management of the dams of the
affected animals to the group as a
whole 7

51 What is the farm policy for feeding
colostrum?

° What have been the environmental
conditions during the past
48 hours? In housed animals the
quality of the environment should
be measured objectively

3. Conduct a postmortem examination
of all available dead neonates. The
determination of body weight is
essential and measures of
crown-rump length can also give an
indication of gestational age. In order
of precedence the purpose of the
postmortem examination is to
determine:

° The time of death in relation to
parturition (e.g. fetal disease,
parturient disease, early or delayed
postnatal death). This can be
determined from the state of the
lungs, the nature of the severed
end of the umbilical artery and the
presence of a clot, the state of the
brown fat deposits, whether the
animal has walked and if it has
sucked prior to death
° The possibility that animals born
alive have died because of cold
stress, hypoglycemia and
starvation. An indication can be
obtained from an examination of
the brown fat reserves, the
presence or absence of milk
in the gastrointestinal tract and
fat in the intestinal lymphatics.

The presence of subcutaneous
edema in the hind limbs is also
relevant

0 The possible presence of birth
injury or trauma. In addition to
examination of the ribs and liver
for trauma and the presenting
areas for subcutaneous edema, the
brain should be examined for
evidence of hemorrhage
0 The presence of infectious disease.
If necessary samples can be
submitted for examination
° The presence of congenital disease

4. If abortion is suspected, specimens of
fetal tissues and placenta are sent for
laboratory examination. Examinations
requested are pathological and
microbiological for known pathogens
for the species of animal under
consideration

5. A serum sample should be collected
from the dam for serological evidence
of teratogenic pathogens followed by
another sample 2 weeks later.

Samples from unaffected dams should
also be submitted. A precolostral
serum sample from affected animals
may assist in the diagnosis of
intrauterine fetal infections

6. Investigate management practices
operating at the time, with special
attention to clemency of weather, feed
supply, maternalism of dam and
surveillance by the owner - all factors
that could influence the survival
rate. 51 - 52 Where possible, this should
be performed using objective
measurements. For example, in
calf-rearing establishments the
efficacy of transfer of colostral
immunoglobulins should be
established by the bleeding of a
proportion of calves and actual

j measurement; food intake should
be established by actual
measurement, etc.

132

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

REVIEW LITERATURE

Edwards BL. Causes of death in new-born pigs. Vet
Bull 1972; 42:249.

Randall GCB. Perinatal mortality. Some problems of
adaptation at birth. AdvVet Sci 1978; 22:53.
English PR, Morrison V. Causes and prevention of
piglet mortality. Pig News Info 1984; 4:369-376.
Rossdale PD, Silver M, Rose RJ. Equine perinatal
physiology and medicine. Equine Vet J 1984;
4:225-398.

Rook JS, Scholman G, Wing-Procter S, Shea M.
Diagnosis and control of neonatal losses in sheep.
Vet Clin North Am Food Anim Pract 1990;
6:531-562.

Haughey KC. Perinatal lamb mortality: its

investigation, causes and control. J South Af r Vet
Assoc 1991; 62:78-91.

Rossdale PD, McGladdery AJ. Recent advances in
equine neonatology. Vet Annu 1992; 32:201-208.
KasariTR, Wikse SE. Perinatal mortality in beef herds.
Vet Clin North Am Food Anim Pract 1994;
10:1-185.

Edwards SA. Perinatal mortality in the pig:
environmental or physiological solutions. Livestock
Prod Sci 2002; 78:3-13.

Herpin P, Damon M, Le Dividitch J. Development of
thermoregulation and neonatal survival in pigs.
Livestock Prod Sci 2002; 78:25-45.

Mellor DJ, Stafford KJ. Animal welfare implications of
neonatal mortality and morbidity in farm animals.
Vet J 2004; 168:118-133.

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Congenital defects

Synopsis ' . . ' . - .

Etiology Genetic, infectious, toxic and
physical causes are recognized for some
defects but the etiology of most is not
known

Epidemiology Low but significant
incidence in all animals. Epidemiology
depends on cause

Clinical findings Congenital defects can
be structural or functional. Clinical signs
depend on organ system(s) affected

Clinical pathology Specific serological
and chemical tests can be used in the
diagnosis and control of some congenital
disease and, if available, are detailed under
specific disease headings
Necropsy findings Specific to the
particular problem

Diagnostic confirmation Abnormalities of
structure or function that are present at
birth are obviously congenital defects. They
may or may not be inherited, and inherited
defects may or may not be manifest at
birth

Control Avoidance of exposure to
teratogenic agents. Vaccination for some
teratogenic infections, identification of
carriers for genetic defects

ETIOLOGY

Congenital disease can result from
defective genetics 1,2 or from an insult or
agent associated with the fetal environ-
ment. A neonate with a congenital defect
is an adapted survivor from a disruptive
event of a genetic or environmental
nature or of a genetic-environmental
interaction at one or more of the stages in
the sequences of embryonic and fetal
development. 3

Genetic abnormalities, detailed in
Chapter 35, may result in a wide spectrum
of disorder that can vary from severe
malformations with deformation to the

presence of inborn errors of metabolism
in animals that may be born apparently
normal and develop storage disease later
in life 3

Susceptibility to injurious environ-
mental agents depends upon the nature
and the severity (dose size and duration
of application) of the insult, and decreases
with fetal age. Prior to attachment, the
zygote is resistant to teratogens but
susceptible to chromosomal aberrations
and genetic mutations. Agents that disrupt
blastula and gastrula stages and that
interfere with normal apposition of the
uterine mucosa are usually embiyotoxic
and induce early embryonic death.

The period during which an organ
system is being established is a parti-
cularly critical period for that system and
different teratogens, if applied at that
time, can produce similar defects. One
example would be the complex of
arthrogryposis and cleft, which can occur
in the calves of cattle grazing certain
species of lupine, 4 in calves infected in
utero with Akabane virus 5 and as an
inherited disease in Charolais calves. 6

Many noninherited congenital defects
in animals occur in 'outbreaks', which is
a reflection of the exposure of the preg-
nant herd to a viral, plant or other
teratogen during a period of fetal suscep-
tibility. Because this occurs in early preg-
nancy it is often very difficult to determine
the nature of this exposure at the time the
animals are born.

Some teratogens are quite specific in
the defect that they produce and their
action may be limited to a single species;
a tentative diagnosis as to cause can be
based on this association. Others produce
a wide variety of abnormality that may
also occur with other teratogens and cause
is less obvious.

The exact etiology of most congenital
defects is unknown. Influences that are
known to produce congenital defects are
presented here.

Chromosomal abnormality and
inheritance

Most chromosomal abnormalities are
associated with poor fertility and early
embryonic death. 7 A few are structural or
numerical aberrations of chromosomes.
The importance of chromosomal abnor-
mality to congenital defects in farm
animals has not been studied extensively
but a study of 55 aborted and stillborn
calves found six with an abnormal
chromosome component. 8 Chromosomal
abnormality is usually associated
with multiple deformations. 8-11 Most
chromosomal abnormalities are mutant
genes and the majority are inherited as
recessive traits. There are many examples
among domestic animals (see Ch. 35).

Congenital defects

133

Virus and other infections

Members of the Bumjavirus (Akabane
virus. Cache valley virus and Rift Valley
fever virus), Orbivirus (bluetongue virus,
epizootic hemorrhagic disease virus and
Chuzan virus), Pestivirus (bovine virus
diarrhea virus, border disease virus, hog
cholera virus) families, Japanese B
encephalitis virus and Wesselsbron virus
are recognized teratogens. 12 Other viruses
also can result in fetal death without
malformation. Examples are as follows:

o Akabane virus - this infection of
pregnant cattle, sheep and goats
causes arthrogryposis, microencephaly
and hydrocephalus. 12 Infection of, and
disease of, the fetus depends on the
stage of pregnancy and the fetus's
immunological status. In cattle
infected between 76-104 days of
pregnancy hydranencephaly
predominates; arthrogryposis
predominates with infections between
104-173 days gestation and
poliomyelitis after 173 days. In sheep
the window of susceptibility for
congenital defects is between 30 and
50 days

« Cache valley virus - congenital
infection of lambs with Cache valley
virus 13 produces disease very similar
to that produced by Akabane virus in
cattle. The period of susceptibility for
congenital defects is 36-45 days of
pregnancy

° Rift valley fever virus infection of
pregnant sheep results in placentitis
and abortion but attenuated vaccine
strains produce arthrogryposis and
brain defects

e Bluetongue virus - vaccination of
ewes with attenuated vaccine virus
between days 35 and 45 of pregnancy
causes a high prevalence of
porencephaly in lambs. Natural
infections of sheep (50-80 days of
gestation) and cattle (60-120 days of
gestation) can result in fetal death
and resorption, or the birth of
stillborn and weakborn animals and
animals with hydrocephalus and
hydranencephaly and occasionally
arthrogryposis. Similar defects are
produced by Chuzan, Aino and Kasba
virus infections

• Bovine virus diarrhea - infection with
cytopathogenic strains before
100 days can result in abortion and
mummification, cerebellar hypoplasia
and optic defects, including cataracts,
retinal degeneration and hypoplasia
and neuritis of the optic nerves. Other
defects are brachygnathia, curly coats,
abortion, stillbirth and
mummification. Infection of the
bovine fetus between 45 and 125 days

of gestation with a noncytopathic
biotype of the virus can result in the
development of a persistently viremic
and immunotolerant calf that is
carried to term, born alive, remains
persistently viremic and may later
develop mucosal disease
° Border disease virus - the window of
susceptibility is from 16-90 days
gestation, and, depending upon the
fetal age at infection and the presence
of a fetal immune response, fetal
infection may result in fetal death,
growth retardation, the birth of
persistently infected lambs or lambs
born with hypomyelinogenesis,
hydranencephaly and cerebellar
dysplasia. Coat defects may also be
seen

° Hog cholera virus - vaccination of
sows with modified vaccine virus
between days 15 and 25 of pregnancy
produces piglets with edema,
deformed noses and abnormal
kidneys. Natural infection with field
virus can cause reproductive
inefficiency and cerebellar hypoplasia
in piglets

° An unidentified virus is associated
with the All type of congenital tremor
in pigs

° Congenital infection with

Wesselsbron virus and with Rift Valley
fever is recorded as producing central
nervous system disease in cattle and
sheep 14

0 Japanese B encephalitis virus in pigs
can result in abortion or in the birth
of weak, mummified or stillborn
piglets and live piglets with
neurological abnormalities. The
window of susceptibility is from
40-60 days gestation
° Pseudorabies virus infection of the
pregnant sow can result in myoclonia
congenita in piglets
° Viral, bacterial and protozoal agents
that produce abortion in animals can
also produce intrauterine growth
retardation and the birth of weakborn
neonates that are highly susceptible
to mortality in early life.

Nutritional deficiency

There are many congenital defects in
animals that are known to be caused by
deficiencies of specific nutrients in the
diet of the dam. Examples are as follows:

° Iodine - goiter and increased neonatal
mortality is caused in all species;
prolonged gestation occurs in horses
and sheep. Congenital
musculoskeletal lesions are seen in
foals (congenital hypothyroid
dysmaturity syndrome). Deficiency
may be due to a primary deficiency, or
induced by nitrate or Brassica spp.

Syndromes are also produced by-
iodine excess, often associated with
feeding excess seaweed or seaweed
products

° Copper - enzootic ataxia in lambs is
due either to a primary copper
deficiency or to a secondary deficiency
where the availability of copper is
interfered with by other minerals, e.g.
molybdenum and iron
° Manganese - chondrodystrophy and
limb deformities in calves 13
° Vitamin D - neonatal rickets
° Vitamin A - eye defects, harelip and
other defects in piglets
° Vitamin E and/or selenium -
congenital cardiomyopathy and
muscular dystrophy
° Congenital cobalt deficiency is

reported to reduce lamb vigor at birth
and to increase perinatal mortality
because of impaired immune function
in the lamb. 16 A similar effect on
immune function in neonatal lambs
and calves has been proposed with
copper deficiency 17

° Malnutrition of the dam can result in
increased neonatal mortality and is
suspected in the genesis of limb
deformities 17 and in congenital joint
laxity and dwarfism in calves 18-19
° Vitamin A deficiency induced by
feeding potato tops or water with
high nitrate content has been
associated with congenital blindness
in calves.

Poisonous plants

Their teratogenic effects have been
reviewed in detail 20 Some examples are
given below.

° Veratrum californium fed to ewes at
about the 14th day of pregnancy can
cause congenital cyclopia and other
defects of the cranium and brain in
lambs, as well as prolonged
gestation. 6 When fed at 27-32 days of
pregnancy it can produce limb
abnormalities. Tracheal stenosis has
been produced by feeding at
31-33 days of gestation. The alkaloid
cyclopamine is the teratogenic
substance 20

° 'Crooked calf disease' is associated
with the ingestion of Lupinus sp.
during pregnancy. This is a major
problem on some range lands in
western North America. There are
approximately 100 species of Lupinus
in Canada and the USA but the
disease has been mainly associated
with L. sericeus, L. leucophyllus,

L. caudatus and L. laxiflorus 21 These
are believed to be toxic because of
their content of anagyrine, but some
piperidine alkaloids may also produce
the disease. 22 The disease has been

134

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

reproduced by feeding anagyrine-
containing lupines to pregnant cattle
between 40 and 90 days of gestation
but can occur with later feeding in
natural grazing. The syndrome is one
of arthrogryposis, torticollis, scoliosis
and cleft palate 4

• Astragalus and Oxytropis spp.

locoweeds cause limb contracture in
calves and lambs, also fetal death and
abortion

° Tobacco plants - ingestion of
Nicotiana tabacum (burley tobacco)
and N. glauca (tree tobacco) by sows
between 18 and 68 days, with peak
susceptibility between 43 and 55 days
of gestation, can cause limb
deformities in their piglets. The
teratogen is the piperidine alkaloid
anabasine. Cleft palate and
arthrogryposis has also been
produced experimentally in the
fetuses of cattle and sheep fed
N. glauca during pregnancy but the
plant is not palatable and this is an
unlikely cause of natural disease 20

» Conium maculatum, poison hemlock,
fed to cows during days 55-75 of
pregnancy, to sheep in the period
30-60 days of pregnancy and to sows
in the period 30-62 days of pregnancy
will cause arthrogryposis, scoliosis,
torticollis and cleft palate in the
fetuses. 20 Cattle are most susceptible.
Piperidine alkaloids coniine and -
coniceine are responsible 22,23

° Leucaena leucocephala (or mimosine, its
toxic ingredient) causes forelimb
polypodia (supernumerary feet) in
piglets when fed experimentally to
sows

° Fungal toxicosis from the feeding of
moldy cereal straw has been
epidemiologically linked to outbreaks
of congenital spinal stenosis and bone
deformities associated with premature
closure of growth plates in calves. 24

Farm chemicals

° Some benzimidazoles (parbendazole,
cambendazole, oxfendazole,
netobimin) are important teratogens
for sheep, producing skeletal, renal
and vascular abnormality when
administered between 14 and 24 days
of pregnancy 23

o Methallibure, a drug used to control
estrus in sows, causes deformities in
the limbs and cranium of pigs when
fed to sows in early pregnancy

° Apholate, an insect chemosterilant, is
suspected of causing congenital
defects in sheep

® The administration of trichlorfon to
pregnant sows can result in the birth
of piglets with cerebellar hypoplasia
and congenital trembles 26

0 Organophosphates have been
extensively tested and found to be
usually nonteratogenic. 27 A supposed
teratogenic effect is probably more a
reflection of the very common usage
of these substances in agriculture
(see under poisoning by
organophosphates)

° Griseofulvin given to a mare in the
second month of pregnancy is
suspected of causing microphthalmia
and facial bone deformity in a foal. 28

Physical insults

° Severe exposure to beta or gamma
irradiation, e.g. after an atomic
explosion, can cause a high incidence
of gross malformations in developing
fetuses

® Rectal palpation of pregnancy using
the amniotic slip method between 35
and 41 days of pregnancy in Holstein
Friesian cattle is associated with
atresia coli in the calf at birth, 29 but
there is also a genetic influence. 30 It is
probable that the cause is palpation-
induced damage to the developing
colonic vasculature
° Hyperthermia applied to the dam
experimentally causes congenital
deformities, but this appears to have
no naturally occurring equivalent. The
most severe abnormalities occur after
exposure during early pregnancy
(18-25 days in ewes). Disturbances of
central nervous system development
are commonest. Defects of the spinal
cord manifest themselves as
arthrogryposis and exposure of ewes
to high temperatures (42°C, 107. 5°F)
causes stunting of limbs; the lambs
are not true miniatures as they have
selective deformities with the
metacarpals selectively shortened. The
defect occurs whether nutrition is
normal or not 31 Hyperthermia
between 30 and 80 days of pregnancy
in ewes produces growth retardation
in the fetus. Developmental
abnormalities have been reproduced
experimentally in explanted porcine
embryos exposed to environmental
temperatures similar to those that
may be associated with reproductive
failure due to high ambient
temperatures in swine herds. 32

Environmental influences

Currently, there is considerable interest in
the possible teratogenic effects of man-
made changes in the environment. The
concern is understandable because the
fetus is a sensitive biological indicator of
the presence of some noxious influences in
the environment. For example, during an
accidental release of polybrominated
biphenyls much of the angry commentary
related to the probable occurrence of

congenital defects. The noxious influences
can be physical or chemical. In one exam-
ination of the epidemiology of congenital
defects in pigs, it was apparent that any
environmental causes were from the
natural environment; manmade environ-
mental changes, especially husbandry
practices, had little effect. 33 A current
concern in some regions is an apparent
increase in congenital defects believed to
be associated with exposure to radio-
frequency electromagnetic fields associated
with mobile telephone networks, 34 ' 35 but
there is little hard data.

EPIDEMIOLOGY

Individual abnormalities differ widely in
their spontaneous occurrence. The deter-
mination of the cause of congenital defects
in a particular case very often defies all
methods of examination. Epidemiological
considerations offer some of the best
clues but are obviously of little advantage
when the number of cases is limited. The
possibility of inheritance playing a part is
fairly easily examined if good breeding
records are available. The chances of coming
to a finite conclusion are much less prob-
able. Some of the statistical techniques
used are discussed in Chapter 34 on
inherited diseases. The determination of
the currently known teratogens has
mainly been arrived at following epi-
demiological studies suggesting possible
causality followed by experimental
challenge and reproduction of the defect
with the suspected teratogen.

An expression of the prevalence of
congenital defects is of very little value
unless it is related to the size of the
population at risk, and almost no records
include this vital data. Furthermore, most
of the records available are retrospective
and based on the number of cases
presented at a laboratory or hospital.

Reported prevalence rates of 0.5-3.0%
for calves and 2% for lambs are comparable
with the human rate of 1-3%. 36 A much
higher rate for animals of 5-6% is also
quoted. 21 A study of over 3500 cases of
abortion, stillbirth and perinatal death in
horses found congenital malformations in
almost 10%. 37 A very extensive literature
on congenital defects in animals exists
and a bibliography is available. 38 40

Some breeds and families have extra-
ordinarily high prevalence rates because
of intensive inbreeding. The extensive
use, by artificial insemination, of certain
genetics can result in a significant increase
in the occurrence and nature of congenital
defects when the bulls are carriers of
genetic disease. The use of bulls that were
carriers for the syndrome 'complex
vertebral malformation' resulted in an
approximately threefold increase in the
presence of arthrogryposis, ventricular

Congenital defects

135

septal defect and vertebral malformations
in Holstein-Friesian calves submitted to
diagnostic laboratories in the Netherlands
between 1994 and 2000. 41

In the USA an extensive registry has
been established at the veterinary school
at Kansas State University.

Checklists of recorded defects are
included in the review literature.

R^THOGENESIS

Ihe pathogenesis of many of the con-
genital defects of large animals is poorly
understood but it is apparent that disease
produced by each teratogen is likely to
have its own unique pathogenesis.
Congenital defects in large animals have
examples of defects induced from struc-
tural malformations, from deformations,
from the destruction of tissue by
extraneous agents and from enzyme
deficiencies - or from a combination of
these.

Structural malformations and
deformations

Structural malformations result from a
localized error in morphogenesis. The
insult leading to the morphogenic error
takes place during organogenesis and
thus is an influence imposed in early
gestation. Deformations occur where
there is an alteration in the shape of a
structure of the body that has previously
undergone normal differentiation. De-
forming influences apply later in the early
gestational period, after organogenesis.

Deformation is the cause of arthro-
gryposis and cleft palate produced by
the piperidine alkaloids from Conium
maculatum and Nicotiana spp. and by
anagyrine from Lupinus spp., which
produce a chemically induced reduction
in fetal movements. Ultrasound examin-
ation of the normal fetus shows that it has
several periods of stretching and vigorous
galloping during a 30 minute examination
period. In contrast, the fetus that is under
the influence of anagyrine has restricted
movement and lies quietly, often in a
twisted position. Restricted fetal limb
movement results in arthrogrypotic
fixation of the limbs, and pressure of the
tongue on the hard palate when the neck
is in a constant flexed position inhibits
closure of the palate. In experimental
studies there is a strong relation between
the degree and duration of reduced fetal
movement, as observed by ultrasound,
and the subsequent severity of lesions at
birth. 21

Restriction in the movement of the
fetus, and deformation, can also result
from teratogens that produce damage
and malfunction in organ systems, such
as the primary neuropathy that occurs in
the autosomal recessive syndrome in
Charolais cattle and the acquired neuro-

pathy in Akabane infection, both of which
result in arthrogryposis through absence
of neurogenic influence on muscle
activity.

It has been suggested, with some good
evidence, that the etiology and patho-
genesis of congenital torticollis and head
scoliosis in the equine fetus are related to
an increased incidence of transverse
presentation of the fetus. 42,43 Flexural
deformities of the limbs are also believed
to be due to errors in fetal positioning and
limited uterine accommodation, which
may be further complicated by maternal
obesity. Abnormal placental shape may
also be important in the genesis of
skeletal deformations. 44

Viral teratogenesis

Viral teratogenesis is related to the
susceptibility of undifferentiated and
differentiated cells to attachment, pen-
etration and virus replication, the patho-
genicity of the virus (cytopathogenic
versus noncytopathogenic strains of
bovine virus diarrhea), the effects that the
virus has on the cell and the stage of
maturation of immunological function of
the fetus at the time of infection. Viral
infections can result in prenatal death, the
birth of nonviable neonates with severe
destructive lesions, or the birth of viable
neonates with growth retardation or
abnormal function (tremors, blindness).
The gestational age at infection is a major
influence. In sheep infected with border
disease virus between 16 and 90 days of
gestation, the occurrence of the syndromes
of early embryonic death, abortion and
stillbirth or the birth of defective and
small weak lambs is related to the fetal
age at infection. Certain viruses cause
selective destruction of tissue and of
organ function late in the gestational
period and the abiotrophies are examples
of selective enzyme deficiencies. The
pathogenesis of the viral diseases is given
under their specific headings in later
chapters.

Inherited congenital defects
A number of inherited congenital defects,

some of which are not clinically manifest
until later in life, are associated with
specific enzyme deficiencies. Examples
are maple syrup urine disease (MSUD),
citrullinemia, factor XI deficiency in cattle
and the lysosomal storage diseases.
Inherited lysosomal storage diseases
occur when there is excessive accumu-
lation of undigested substrate in cells. In
mannosidosis, it is due to an accumu-
lation of saccharides due to a deficiency
of either lysosomal a-mannosidase or
P-mannosidase. In GM} gangliosidosis,
disease is due to a deficiency of P-
galactosidase and in GM 2 gangliosidosis a
deficiency of hexosaminidase. 45

The age at development of clinical
signs and their severity is dependent
on the importance of the enzyme that
is deficient, the biochemical function
and cell type impacted and, in storage
disease, the rate of substrate accumu-
lation. Factor XI deficiency is manifest
with bleeding tendencies but is not
necessarily lethal. In contrast, calves
with citrullinemia and MSUD develop
neurologic signs and die shortly after
birth, whereas the onset of clinical disease
can be delayed for several months with a-
mannosidosis.

CLINICAL AND NECROPSY FINDINGS

It is not intended to give details of the
clinical signs of all the congenital defects
here but some general comments are
necessary. Approximately 50% of animals
with congenital defects are stillborn.
The defects are usually readily obvious
clinically. Diseases of the nervous system
and musculoskeletal system rate high in
most published records and this may be
related to the ease with which abnor-
malities of these systems can be observed.
For example, in one survey of congenital
defects in pigs, the percentage occurrence
rates in the different body systems were
as follows:

0 Bones and joints 23%

° Central nervous system 17%

° Special sense organs 12%

° Combined alimentary and respiratory
tracts (mostly cleft palate and atresia
ani) 27%

° Miscellaneous (mostly monsters) 9%

° Genitourinary and abdominal wall
(hernias) each 5%

0 Cardiovascular system 3%.

In a survey of congenital defects in calves
the percentage occurrence rates were:

° Musculoskeletal system 24%

° Respiratory and alimentary tracts 13%
° Central nervous system 22%

0 Abdominal wall 9%

° Urogenital 4%

° Cardiovascular 3%

° Skin 2%

° Others 4%

0 (Anomalous-joined twins and
hydrops amnii accounted for 20%).

In a survey of foals the approximate per-
centage occurrence rates were:

° Musculoskeletal system 50%

° Respiratory and alimentary tracts 20%
° Urogenital 9%

° Abdominal wall 6%

° Cardiovascular 5%

° Eye 5%

° Central nervous system 5%.

Contracted foal syndrome and cranio-
facial abnormalities were the most com-

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

136

mon congenital defects in a study of
stillbirth and perinatal death in horses . 37,46

Many animals with congenital defects
have more than one anomaly: in pigs, the
average is two and considerable care must
be taken to avoid missing a second and
third defect in the excitement of finding
the first. In some instances, the combi-
nations of defects are repeated often
enough to become specific entities.
Examples are microphthalmia and cleft
palate, which often occur together in
piglets, and microphthalmia and patent
interventricular septum in calves.

There are a number of defects that
cannot be readily distinguished at birth
and others that disappear subsequently. It
is probably wise not to be too dogmatic in
predicting the outcome in a patient with
only a suspicion of a congenital defect or
one in which the defect appears to be
causing no apparent harm. A specific
instance is the newborn foal with a cardiac
murmur.

Sporadic cases of congenital defects are
usually impossible to define etiologically i
but when the number of affected animals j
increases it becomes necessary and I
possible to attempt to determine the j
cause. ‘

|

CLINICAL PATHOLOGY

The use of clinical pathology as an aid \
to diagnosis depends upon the disease
that is suspected and its differential i
diagnosis. The approach varies markedly
with different causes of congenital j
defects: specific tests and procedures are |
available for some of the viral teratogens, i
for congenital defects associated with j
nutritional deficiencies and for some |
enzyme deficiencies and storage diseases, j
and the specific approach for known I
teratogens is covered in the individual J
diseases section. ;

When an unknown viral teratogen is ;
suspected, precolostral blood samples i
should be collected from the affected ;
neonates and also from normal contem-
poraries that are subsequently born in the ;
group. Precolostral serum can be used for :
investigating the possible fetal exposure
of the group to an agent and the buffy
coat or blood can be used for attempted
virus isolation. IgG and IgM concentrations |
in precolostral serum may give an
indication of fetal response to an infecting ;
agent even if the agent is not known and
there is no serological titer to known
teratogenic agents.

Enzyme-based tests have been used to j
virtually eradicate carriers of a manno-
sidosis in cattle breeds in Australia and ■
New Zealand 47 and DNA-based tests are j
used to detect and eliminate the carriers j
of diseases such as generalized glyco- :
genosis in cattle . 48

DIFFERENTIAL DIAGNOSIS

• The diagnostic challenge with
congenital defects is to recognize and
identify the defect and to determine the
cause

• Syndromes of epidemic disease resulting
from environmental teratogens are
usually sufficiently distinct that they can
be diagnosed on the basis of their
epidemiology combined with their
specific clinical, pathological and
laboratory findings and on the
availability of exposure

• Congenital defects occurring
sporadically in individual animals pose a
greater problem. There is usually little
difficulty in defining the condition
clinically, but it may be impossible to
determine what was the cause. With
conditions where there is not an
obvious clinical diagnosis, an accurate
clinical definition may allow placement
of the syndrome within a grouping of
previously described defects and
suggest possible further laboratory
testing for further differentiation.

The examination for cause of an unknown
congenital defect is usually not undertaken
unless more than a few newborn animals
in a herd or area are affected in a short
period of time with similar abnormalities. A
detailed epidemiological investigation will
be necessary which will include the
following:

• Pedigree analysis. Does the frequency of
occurrence of the defect suggest an
inherited disease or is it characteristically
nonhereditary?

• Nutritional history of dams of affected
neonates and alterations in usual
sources of feed

• Disease history of dams of affected
neonates

• History of drugs used on dams

• Movement of dams during pregnancy to
localities where contact with teratogens
may have occurred

• Season of the year when insults may
have occurred

• Introduction of animals to the herd.

The major difficulty in determining the
cause of nonhereditary congenital defects
is the long interval of time between when
the causative agent was operative and
when the animals are presented, often 6-8
months. Detailed clinical and pathological
examination of affected animals offers the
best opportunity in the initial approach to
determine the etiology based on the
presence of lesions that are known to be
caused by certain teratogens.

REVIEW LITERATURE

Dennis SM, Leipold HW. Ovine congenital defects.
Vet Bull 1979; 49:233.

Parsonson IM, Della-Porta AJ, Snowdon WA.
Development disorders of the fetus in some
arthropod-bovine virus infection. Am JTrop Med
Hyg 1981; 30:600-673.

Leipold HW, Huston K, Dennis SM. Bovine
congenital defects. AdvVet Sci Comp Med 1983;
27:197-271.

Leipold HW. Cause, nature, effect and diagnosis of
bovine congenital defects. In: Proceedings of the
14th Warld Congress on Diseases of Cattle 1986;
1:63-72.

Rousseaux CG. Developmental anomalies in farm
animals. I. Theoretical considerations. Can \bt J
1988; 29:23-29.

Rousseaux CG, Ribble CS. Developmental anomalies
in farm animals. II. Defining etiology. Can Vet J
1988; 29:30-40.

De Lahunta A. Abiotrophy in domestic animals: a
review. Can JVet Res 1990; 54:65-76.

Angus K. Congenital malformations in sheep. In Pract
1992; 14:33-38.

Ihntcr KE, Keeler RC, James LF, Bunch TD. Impact of
plant toxins on fetal and neonatal development.
A review. J Range Manag 1992; 45:52-57.

Dennis SM. Congenital abnormalities. Vet Clin North
Am Food Anim Pract 1993; 9:1-222.

Rousseaux CG. Congenital defects as a cause of
perinatal mortality of beef calves. Vet Clin North
Am Food Anim Pract 1994; 10:35-45.

Mee JF. The role of micronutrients in bovine
periparturient problems. Cattle Pract 2004;
12:95-108.

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INTRAUTERINE GROWTH
RETARDA TION

This is a special form of congenital defect.
It is a failure to grow properly, as apposed
to a failure to gain body weight, and
occurs when the developmental age is
less than the chronological (gestational)
age. Runt is a common colloquial agri-
cultural term. Normal fetal growth rate is
determined by genetic and epigenetic
factors and cross-breeding experiments
suggest that fetal size is regulated by the
embryonic/fetal genotype and also an
effect of maternal genotype. 1 Litter size
has an effect on birth weight in all
species. A genetic association with intra-
uterine growth retardation has been
shown in Japanese Black calves. 2

There is a strong positive association
between placental mass and fetal size at
birth in all species and the majority of
cases of growth retardation result from
inadequate placentation, disturbance in
utero-placental blood flow or placental
pathology.

ETIOLOGY

There are a number of different etiologies.

Heat stress to ewes in the final third of
pregnancy will result in intrauterine
growth retardation but it is not as severe
as when ewes are exposed in the second
third of pregnancy - the period of
placental growth. 3-4 Hyperthermia results
in a redistribution of blood away from the
placental vascular bed and a decrease in
cotyledon mass with consequent reduc-
tion in birth weight. The degree of growth
restriction is directly related to the degree
of hyperthermia to which the ewe is
exposed and her heat tolerance. The
growth retardation affects fetal weight
more than fetal length and, while there is
some reduction in the growth of the
brain, it is relatively less than that of the
internal organs, resulting in an increased
braindiver weight ratio at birth. 5

Viral infections, such as border
disease and bovine virus diarrhea in
ruminants and parvovirus in pigs, pro-
duce growth-retarded neonates, 6-7 as do
bacterial and other infections that result
in placentitis.

Inadequate placentation is the cause
of runt piglets. Runts are smaller, thinner
and have disproportionately larger, domed
heads than normal pigs. A deficiency in
specific trace elements is suspect in some
field cases of growth retardation in
ruminants but there is no evidence for
deficient trace element nutrition in runt
pigs. 8

Inadequate nutrition can result in in-
utero growth retardation. Growth retar-
dation can be produced in fetal pigs,
lambs and calves by maternal caloric
undernutrition. Nutritional restriction in
ewes reduces the number of placental
lactogen receptors that mediate amino
acid transport in fetal liver and glycogen
synthesis in fetal tissue, leading to
depletion of fetal liver glycogen stores.
This has been postulated as a possible
cause of the fetal growth retardation that
accompanies maternal caloric under-
nutrition; 9 runt pigs have a reduced
metabolic rate and lower skeletal muscle
respiratory enzyme activity. 10 This
deficiency persists after birth - runt pigs
have a lower core temperature and a
lessened ability to increase their metabolic
rate and heat production in response to
cold. 11

Paradoxically, overnourishing the
adolescent ewe will also result in placental
growth restriction and in in-utero growth
retardation. 4-12 This effect is most evident
in the second third of pregnancy. This
syndrome is accompanied by the birth of
lambs with a shorter gestational age,
commonly reduced by 3 days. It is thought
that the fetal hypoxia and hypoglycemia
that accompanies placental insufficiency
might stimulate the maturation of the
fetal hypothalamic-pituitary-adrenal axis,
initiating early parturition. The growth of
those lambs that survive initially lags
behind that of normal lambs but there is
compensatory growth and no difference
in weight at 6 months-of age. 13

Measurements that can be used to
determine the presence of growth retar-
dation in a dead fetus include crown-
rump (anal) length, brain weight, body
weight, brain to body weight ratios, long
bone weight and appendicular ossifi-
cation centers. Formulas are available
to determine the degree of growth
retardation. 14

In the live animal the presence of
radiodense lines in long bones and the
examination of closure of ossification
centers can provide evidence for prior
stressors in pregnancy that induce fetal
growth retardation, such as malnutrition
or infection of the dam, that may not be
found by other examinations. 7-15-16

Intrauterine growth retardation is
accompanied by an impaired cellular
development of tissues such as the small

intestine and skeletal muscle and dis-
proportionately large reductions in the
growth of some organs such as the
thymus, spleen, liver, kidney, ovary and
thyroid. There is an associated impair-
ment of thermogenesis, immune and
organ function at birth. 17 ' 19 In lambs there
is impaired development of secondary
wool follicles.

The survival of fetuses with growth
retardation requires special nutritional
care and the provision of adequate heat,
and is discussed in the section on Critical
care for the newborn. In large piggeries
that practice batch farrowing, the survival
of runts can be significantly improved by
the simple practice of fostering them
together in one litter on one sow so that
they do not have to compete with larger-
birth-size and more vigorous pigs, by
ensuring adequate colostrum intake and
adequate environmental warmth and by
feeding using a stomach tube in the first
few hours of life if indicated.

REVIEW LITERATURE

Fowden AL, Rossdale PD. Foetal maturation; com-
parative aspects of normal and disturbed
development. Equine Vet J Suppl 1993; 14:1-49.
Redmer DA, Wallace JM, Reynolds LP. Effect of
nutrient intake during pregnancy on fetal growth
and vascular development. Domestic Anim
Endocrinol 2004; 27(3):199-217.

REFERENCES

1. OusyJCet al. Equine Vet J 2004; 36:616.

2. OgataY et al. J Jpn Vet Med Assoc 1997; 50:271.

3. McCrabb GJ et al. J Agric Sci 1993; 120:265.

4. Wallace JM et al. J Physiol 2005; 565:19.

5. Wallace JM et al. Placenta 2000; 21:100.

6. DoneJT et al. Vet Rec 1980; 106:473.

7. Caffrey JF et al. Res \bt Sci 1997; 62:245.

8. Gurtler H et al. In: Proceedings of the 6th
International Trace Element Symposium 1989;
2:534.

9. Freemark M et al. Endocrinology 1989; 125:1504.

10. Dauncey MJ, Geers R. Bio! Neonate 1990; 58:291.

11. Hayashi M et al. Biol Neonate 1987; 51:205.

12. Wallace JM et al. Biol Reprod 2004; 71:1055.

; 13. Da Silva P et al. Reproduction (Cambridge) 2001;

\ 122:375.

| 14. Richardson C et al. Vet Rec 1990; 126:279.

; 15. O'Connor BT, Doige CE. Can J Vet Res 1993;

! 57:25.

i 16. Smyth JA, Ellis WA Vet Rec 1996; 139:599.

17. Greenwood PL, Bell AW. In: Proceedings of the
6th International Symposium on Reproduction in

; Domestic Animals 2003; 6:195.

18. Holdstock NB et al. Pferdheilkunde 2001; 17:659.

19. Da Silva P et al. Reproduction (Cambridge) 2003;

: 126:249.

: NEONATAL NEOPLASIA

Congenital neoplasia is rare, occurring at
a substantially lower rate than in adults,
and accounts for a minor percentage of
findings in surveys of neonatal mortality. 1-2
; It is probable that genetic rather
j than environmental factors influence its
r development.

Clinical signs depend upon the type of
neoplasm and its site and they can result

138

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

in dystocia or abortion. A variety of
tumors have been recorded in all large
animal species and are predominantly of
mesenchymal origin. 2,3

In calves, malignant lymphoma is most
commonly reported. It is usually multi-
centric and also affects the skin. Sporadic
bovine leukosis of young calves may also
be present at birth Other tumors reported
predominant in calves include diffuse
peritoneal mesothelioma, mixed meso-
dermal tumor, mast cell tumor,
hemangiomas and cutaneous melanoma. 2-4

Melanomas (both benign and malig-
nant) also occur in foals and piglets.
Duroc Jersey, Vietnamese pot-bellied pigs
and Sinclair miniature pigs have a
high incidence of congenital malignant
melanoma, which is fatal in approxi-
mately 15% of affected pigs but regresses
spontaneously, and without recurrence, in
the remainder. 5-6

A breed predisposition to cardiac
rhabdomyoma is recorded in Red Wattle
pigs. 7

Papillomatosis is rare but lingual
papillomatosis is reported as a cause of
enzootic disease of piglets in China. 5

REFERENCES

1. Giles RCetal.J Am Vet Med Assoc 1993; 203:1170.

2. Midsop W. J Comp Pathol 2002; 127:96.

3. Midsop W.Vet Q 2002; 24:1.

4. Yeruham I et al.Vet Dermatol 1999; 10:149.

5. Midsop W.Vet Q 2003; 25:17.

6. Morgan CD. Vet Immunol Immunopathol 1996;
55:189.

7. McEwen BjE.CanVet J 1994; 35:48.

Physical and environmental
causes of perinatal disease

Disease in the neonate can result directly
from noxious influences in the postnatal
period but it can also be predisposed or
produced by noxious influences in the
period before and during birth.

PERINATOLOGY

The clinical care of the newborn animal in
large animal veterinary medicine has
traditionally started at the time of birth
but there is a growing recognition of the
importance of antenatal and parturient
events to the subsequent viability of the
neonate. This has been particularly recog-
nized by equine clinicians and has led to
the clinical concept of perinatology. 1 One
purpose of perinatology is to expand the
care of the neonate into the antenatal and
parturient period by measurements that
reflect fetal health or that can predict risk
to fetal viability. Measures that can be
used are still being developed and evaluated
but the following include those that have
apparent value. 2-3

Heart rate

In the horse, fetal heart rate recorded by
electrocardiography (ECG) or by ultra-
sound can be used as a measure of fetal
viability, for the detection of twins and as
a monitor for fetal distress during
parturition. Fetal heart rate decreases
logarithmically from approximately
110 beats/min at 150 days before term to
60-80 beats/min near to term. 4 It has
been suggested that a base heart rate of
80-92 beats/min with baseline variations
of 7-15 beats/min and occasional acceler-
ations above this is normal for the fetal
heart rate of equines, and that bradycardia
is evidence of abnormality. 2 Continued
monitoring traces may be needed to
assess fetal distress. Cardiac arrhythmia is
common at the time of birth and for the
first few minutes following and is believed
to result from the transient physiological
hypoxemia that occurs during the birth
process. 5

Ultrasound examination

The foal can be examined by ultrasound
to establish the presentation, the presence
of twins, the heart rate, the presence and
quality of fetal movement, the presence
of placentitis, placental thickness, the
presence of echogenic particles in the
amniotic fluid and an estimate of body
size from the measurement of the aortic
and orbit diameters. Measurements of
fetal heart rate, fetal aortic diameter,
uteroplacental contact, maximal fetal fluid
depths, uteroplacental thickness and fetal
activity have allowed the development of
an objective measurement profile to
assess fetal wellbeing. 2-6

The examination of the amniotic
fluid for the determination of pulmonary
maturity and other measures of foal
health may be limited as there is a
cosiderable risk for abortion and
placentitis, even with ultrasound-guided
amniocentesis, and the technique is not
recommended for routine clinical use. 7-8

Prematurity

Foals born at less than 320 days of
gestational age are considered premature
and those less than 310 days are at
significant risk for increased mortality.
Traditionally, external signs have been
used to predict a premature foaling and
the common signs used are the enlarge-
ment of the udder, milk flow and the
occurrence of vaginal discharge. Causes
of early foaling include bacterial or fungal
placentitis and twin pregnancy. 9 Several
assays are used as alternate methods of
determining if foaling is imminent and if
problems are present.

Plasma progestogen concentrations
decline in pregnancy to reach a low around

150 days of gestation. In Thoroughbreds,
they remain below 10 ng/mL until
approximately 20 days prior to foaling
when they start to increase but in ponies
there is a greater variation. 10-11 Concen-
trations decline 24 hours before parturition.
Plasma progestogen cannot be used to
accurately predict the time of foaling and
a single sample is not diagnostic. 8 There is
a strong correlation between the presence
of plasma progestogen concentrations
above 10 ng/mL before a gestational age
of 310 days and the presence of placental
pathology 2 and a rapid drop in concen-
tration to below 2 ng/mL that persists for
more than 3 days indicates impending
abortion. Current research is examining
the profiles of individual progestogens
during pregnancy to determine if the
profile of any one can be used as a
predictor of fetal distress. 12

During the last week of gestation the
concentration of calcium and potassium
in milk increases and that of sodium
decreases. The rise in calcium concen-
trations are the most reliable predictor of
fetal maturity 3 and milk calcium concen-
trations above 10 mmol/L, in combination
with a concentration of potassium that is
greater than sodium, are indicative of fetal
maturity. Milk calcium concentrations
above 10 mmol/L in the earlier stages
of pregnancy are suggestive of fetal
compromise. 2 Commercial milk test strips
are available for estimating mammary
secretion electrolyte concentrations; how-
ever, it is recommended that testing be
done in an accredited laboratory. 13

REVIEW LITERATURE

Rossdale PD, Silver M, Rose RJ. Perinatology. Equine
Vet J Suppl 1988; 5:1-61.

Ellis DR. Care of neonatal foals, normal and
abnormal. In Pract 1990; 12:193-197.

Rossdale PD, McGladdery AJ. Recent advances in
equine neonatology. Vet Annu 1992; 32:201-208.
Rossdale PD. Advances in equine perinatology
1956-1996: a tribute. Equine Vet Educ 1997;
9:273-277.

Davies Morel MCG, Newcombe JR, Holland SJ.
Factors affecting gestation length in the
Thoroughbred mare. Anim Reprod Sci 2002;
74:175-185.

REFERENCES

1. Rossdale PD. Equine Vet Educ 1997; 9:273.

2. Rossdale PD, McGladdery AJ. Equine Vet Educ
1991; 3:208.

3. Vaala WE, Sertich PL. Vet Clin North Am Equine
Pract 1994; 10:237.

4. Matsui K et al. Jpn J Vet Sci 1985; 47:597.

5. Yamamoto K et al. Equine Vet J 1992; 23:169.

6. ReefVB et al. Equine Vet J 1996; 28:200.

7. Schmidt AR et al. Equine Vet J 1991; 23:261.

8. LeBlanc MM. Equine Vet J 1997; 24:100.

9. Ellis DR. In Pract 1990; 12:192.

10. Rossdale PD et al. J Reprod Fertil Suppl 1991;
44:579.

11. Ousey JC et al. Pferdheilkunde 2001; 17:574.

12. Ousey JC et al. Theriogenology 2005; 63:1844.

13. Ousey J. EquineVet Educ 2003; 15:164.

prematurity and

D YS MATURITY OF FOALS

Foals that are bom before 300 days are
unlikely to survive and foals bom between
300 and 320 days of gestation are con-
sidered premature but may survive with
adequate care. 1,2 Premature foals are
characterized clinically by low birth weight,
generalized muscle weakness, poor ability
to stand, lax flexor tendons, weak or
no suck reflex, lack of righting ability,
respiratory distress, short silky haircoat,
pliant ears, soft lips, increased passive
range of limb motion, and sloping pastern
axis. Radiographs may show incomplete
ossification of the carpal and tarsal bones
and immaturity of the lung and there may
be clinical evidence of respiratory distress.
Full term foals born after 320 days of
gestation but exhibiting signs of pre-
maturity are described as dysmature.

Premature foals have hypoadrenal
corticalism. They are neutropenic and
lymphopenic at birth and have a narrow
neutrophil to lymphocyte ratio. 3,4 In
premature foals older than 35 hours the
neutrophil count can be used to predict
survival and foals that remain neutropenic
after this time have a poor prognosis. 4,3
Premature foals also have low plasma
glucose, low plasma cortisol and a blood
pH of less than 7.25. An extensive
collaborative investigation of equine
prematurity has been conducted and
information on foal metabolism 6 ^ 9 and
guidelines for laboratory and clinical
assessment of maturity are available. 5,10

The placenta is critical to the fetus in
the antenatal period and pregnancies
involving placental pathology commonly
result in foals that suffer premature-like
signs at whatever stage they are delivered. 11
Placental edema, placental villous atrophy
and premature separation of the placenta
are significant causes. 12,13

Precocious lactation of the mare can
be associated with placentitis. The exam-
ination of the placenta for evidence of
placentitis and for the presence of larger
than normal avillous areas should be part
of normal foaling management. A study
of the equine placenta showed a high
correlation between both allantochorionic
weight and area and foal weight in
normal placentas. Normal placentas had
a low association with subsequent
perinatal disease in the foals. In contrast,
abnormal placental histology was associ-
ated with poor foal outcome (three normal
foals from 32 abnormal placentas). Cords
longer than 70 cm were often associated
with fetal death or malformation. Edema,
sacculation and strangulation are other
abnormalities and can be associated with
microscopic deposits of mineral within
the lumen of placental blood vessels. 12

Physical and environmental causes of perinatal disease

Pi?

REFERENCES

1. Mee JF.Vet Rec 1991; 128:521.

2. Koterba AM. Equine Vet Educ 1993; 5:271.

3. Rossdale PD, McGladdery AJ. Equine Vet Educ

1991; 3:208.

4. Chavatte P et al. J Reprod Fertil Suppl 1991;

44:603.

5. Vaala WE. Compend Contin Educ PractVet 1986;

8:S211.

6. WilsmoreT. In Pract 1989; 11:239.

7. Silver M et al. Equine Vet J 1984; 16:278.

8. Fowden AL et al. Equine Vet J 1984; 16:286.

9. Pipkin FB et al. Equine Vet J 1984; 16:292.

10. Rossdale PD. Equine Vet J 1984; 16:275, 300.

11. Rossdale PD et al. J Reprod Fertil Suppl 1991;

44:579.

12. Giles RC et al. J Am Vet Med Assoc 1993;

203:1170.

13. Galvin N, Collins D. IrVet J 2004; 57:707.

PARTURIENT INJURY AND
INTRAPARTUM DEATH

During parturition extreme mechanical
forces are brought to bear upon the fetus
and these can result in direct traumatic
damage or can impair fetal circulation of
blood by entrapment of the umbilical cord
between the fetus and the maternal
pelvis, which may lead to hypoxemia or
anoxia and death of the fetus during the
birth process. Neonates that suffer birth
trauma and anoxia but survive are at risk
for development of the neonatal mal-
adjustment syndrome, 1 have reduced
vigor, are slower to suck and are at
increased risk for postnatal mortality.

In all species, but in ruminants in
particular, the condition of the dam can
have a marked influence on the prevalence
of birth injury and its consequences. The
effect is well illustrated in sheep, where
the two extremes of condition can cause
problems. Ewes on a high plane of
nutrition produce a large fetus and also
deposit fat in the pelvic girdle, which
constricts the birth canal, predisposing to
dystocia. Conversely, thin ewes may be
too weak to give birth rapidly. 2 Pelvic
size can influence the risk of birth injury
and ewe lambs and heifers mated before
they reach 65% of mature weight are at
risk. Pelvimetry is used to select heifers
with adequate pelvic size for breeding but
the accuracy and validity is seriously
questioned. 3,4 Breed is also a determinant
of length and ease of labor and the
subsequent quickness to time to first
suckle. 5

TRAUMA AT PARTURITION

Traumatic injuries can occur in
apparently normal births, with prolonged
birth and as a result of dystocia, which
may or may not be assisted by the owner.
Incompatibility in the sizes of the fetus
and the dam's pelvis is the single most
important cause of dystocia, and birth
weight is the most important contributing
factor. In cattle, expected progeny differ-

ence (EPD) estimates for calf birth, weight
are good predictors of calving ease. 3 In
foals, calves and lambs the chest is most
vulnerable to traumatic injury but there is
the chance of vertebral fracture and
physical trauma to limbs with excessive
external traction.

Fractured ribs are common in foals
and can lead to laceration of the lungs
and heart and internal hemorrhage. 6
Rupture of the liver is common in some
breeds of sheep 7,8 and can also occur in
calves and foals. A retrospective study of
rib and vertebral fractures in calves
suggests that most result from excessive
traction and that as a result smaller
dystocial calves are more at risk. 9
Vertebral fractures occur as the result
of traction in calves with posterior
presentations and in calves with hip lock.
Trauma is a major cause of neonatal
mortality in piglets but it occurs in the
postparturient phase and is associated
with being overlain or stepped on by the
sow. It is possible that the underlying
cause of crushing mortality in piglets is
hypothermia. 10

Intracranial hemorrhage can result in
damage to the brain. A high proportion
(70%) of nonsurviving neonatal lambs at,
or within 7 days of birth have been shown
to have single or multiple intracranial
hemorrhages, the highest incidence being
in lambs of high birth weight. Similar
lesions have been identified in foals
and calves. Experimentally controlled
parturition in ewes showed that duration
and vigor of the birth process affected the
severity of intracranial hemorrhages and
further studies indicated that these birth-
injured lambs had depressed feeding
activity and that they were particularly
susceptible to death from hypothermia
and starvation. 11,12

Birth anoxia associated with severe
dystocia in cattle can result in calves with
lower rectal temperatures in the perinatal
period than normal calves and a decreased
ability to withstand cold stress. 13

Intracranial hemorrhage, especially
subarachnoid hemorrhage, occurs in
normal full-term deliveries as the result of
physical or asphyxial trauma during or
immediately following delivery. 14 The
forceful uterine contractions associated
with parturition can result in surges of
cerebral vascular pressure resulting in
subarachnoid hemorrhage. It is also of
common occurrence in foals born before
full term. 15 In one study, the highest
incidence occurred in pony foals in which
parturition was induced prior to 301 days
of gestation. Similar hemorrhage
occurred in pony foals born by cesarean
section at 270 and 280 days of gestation
Ind appeared associated with anoxic
damage.

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

In a prolonged Birth, edema of parts of
the body, such as the head and parti-
cularly the tongue, may also occur. This
occurs particularly in the calf and the
lamb, possibly because of less close super-
vision at parturition and also because the
young of these species can sustain a
prolonged birthing process for longer
periods than the foal without their own
death or death of the dam. The edema can
interfere with subsequent sucking but the
principal problem relative to neonatal
disease is the effect of the often prolonged
hypoxia to which the fetus is subjected.
There is interference with the placental
circulation and failure of the fetus to reach
the external environment. The hypoxia may
be sufficient to produce a stillborn neonate,
or the neonate may be alive at birth but not
survive because of irreparable brain
damage. Intrapartum deaths due to pro-
longed parturition occur in piglets.

REVIEW LITERATURE

Kasari TR, Wikse SE. Perinatal mortality in beef herds.
Vet Clin North Am Food Anim Pract 1994;
10(1):1-185.

Sanderson MW, Chenoweth PJ. Compend Contin
Educ PractVet 2001; 23(9 Suppl):S95.

Szenci O. Role of acid-base disturbances in perinatal
mortality of calves: a review. Vet Bull 2003;
73(7):7R-14R

Redmer DA, Wallace JM, Reynolds LP. Endocrine
regulation of tissue differentiation and develop-
ment with focus on the importance of nutrition
and IGFs. Domestic Anim Endocrinol 2004;
27:199-217.

REFERENCES

1. Hess-Dudan F, Rossdale PD. Equine Vet Educ
1996; 8:24, 79.

2. Wilsmorc T. In Pract 1989; 11:239.

3. Rice LE. Vet Clin North Am Food Anim Pract
1994; 10:53.

4. Vestweber JG. Vet Clin North Am Food Anim
Pract 1997; 13:411.

5. Dwyer CM et a I. Reprod Fertil Develop 1996;
8:1123.

6. Giles RC et al. J Am Vet Med Assoc 1993;
203:1170.

7. Johnston WS, Maclachlan GK. Vet Rec 1986;
118:610.

8. Greene LE, Morgan KL. Prevent Vet Med 1993;
17:251.

9. Schuijt G. J Am Vet Med Assoc 1990; 197:1196.

10. Edwards SA. Livestock Prod Sci 2002; 78:3.

11. Haughey KG. AustVet J 1980; 56:49.

12. Haughey KC. WdoI Technol Sheep Breed 1984;
31:139.

13. Bellows RA, Lammoglia MA. Theriogenology
2000; 53:803.

14. Hess-Dudan F, Rossdale PD. Equine Vet Educ
1996; 8:24, 79.

15. Palmer AC et al. Equine Vet J 1984; 16:383.

FETAL HYPOXIA

Hypoxemia and hypoxia can occur as a
result of influences during the birth pro-
cess or because of pulmonary immaturity
in premature births. 1,2

Transient tachypnea occurs following
birth and is believed to be due to transient

hypoxemia associated with the birth
process and the absorption of pulmonary
fluid.

Prolonged tachypnea, with flaring of
the nostrils, open-mouth breathing,
exaggerated rib retraction and paradoxical
breathing patterns, is highly suggestive of
primary pulmonary abnormality. Failure
of respiration can occur at this stage and
creates an urgent need for resuscitation
measures. In the foal, body position can
have a major effect on arterial oxygen
tension. 3 A foal that is unable to stand or
to right itself from lateral recumbency is at
risk from atelectasis 4 and should be
moved frequently. Hypoxia and hyper-
capnia resulting from mismatching of
ventilation and perfusion are accentuated
by prolonged recumbency.

Placental dysfunction or occlusion of
the umbilicus in the second stage of labor
can result in a much more serious
situation so that the neonate is born in a
state of terminal, as distinct from primary,
apnea. It will be stillborn unless urgent
and vigorous resuscitation is initiated .
immediately. Resuscitation includes:

• Establishing a patent airway by
extending the head and clearing the
nostrils of mucus and, if necessary, by
postural drainage to clear excess fluids
from the airways

° Artificial ventilation. This is easier if
the foal is intubated but can also be
achieved by sealing one nostril by
hand and breathing forcibly into the
other (or inflating with a rubber tube j
from an oxygen cylinder, delivering at j
a rate of 5 L/min). The chest wall j

should be moved only slightly with
each positive breath. Continue at 25 j
ventilations/min until respiration is
spontaneous i

Administering 200 mL 5% sodium j

bicarbonate solution intravenously to j

j counter acidosis. However, respiratory ;
j acidosis with hypoxemia and
hypercapnia should be primarily
j treated by assisted ventilation.

■ In general, the response of the neonate ;
j to hypoxemia is an increase in blood j
i pressure and a redistribution of cardiac I
• output with increased blood flow to the
1 brain, heart and adrenal gland and a :
i reduction in flow to the lungs, kidney,

I gastrointestinal tract and carcass. 5,6 These
i regulatory changes fail with developing
hypoxia and metabolic acidosis and '
i failure leads eventually to cerebral anoxia.

; The avoidance of acidemia and the main-
tenance of an adequate oxygen supply are
i essential in the care of hypoxemic and
j premature foals.

j A special cause of hypoxia, due usually
; to hypovolemia in addition to inadequate
: oxygenation of blood, occurs in the foal as

a result of an inadequate placental blood
transfusion, when the umbilical cord is
severed too early after birth. This is one
cause of the neonatal maladjustment
syndrome, which is detailed in another
section of this text.

Intrapartum hypoxemia due to pro-
longed parturition is common, 7 parti-
cularly in calves born to first-calf beef
heifers, and is considered to be one cause
of the 'weak calf syndrome' described in
Chapter 36.

A similar syndrome has been pro-
duced experimentally by clamping the
umbilical cord of the bovine fetus in utero
for 6-8 minutes, followed by a cesarean
section 30-40 minutes later. Calves born
following this procedure may die in 10-15
minutes after birth or survive for only up
to 2 days. 8 During the experimental
clamping of the umbilical cord, there is a
decline in the blood pH, Po 2 and standard
bicarbonate levels and an increase in Pco 2
and lactate levels. 8 There is also increased
fetal movement during clamping and a
release of meconium, which stains the
calf and the amniotic fluid. Those that
survive for a few hours or days are dull,
depressed, cannot stand, have poor
sucking and swallowing reflexes and their
temperature is usually subnormal. They
respond poorly to supportive therapy. A
slight body tremor may be present and
occasionally tetany and opisthotonus
occur before death. Calves that are barely
able to stand cannot find the teats of the
dam because of uncontrolled head move-
ments. At necropsy of these experimental
cases, there are petechial and ecchymotic
hemorrhages on the myocardium and
endocardium, an excess of pericardial
fluid, and the lungs are inflated. When
the experimental clamping lasts only
4 minutes, the calves usually survive.

Meconium staining (brown dis-
coloration) of the coat of the newborn at
birth is an important indicator that it has
suffered hypoxia during or preceding the
birth process; such neonates require close
supervision in the early postnatal period.
In lambs, severe hypoxia during birth
results in death shortly following birth
and there is an increased risk in those
that survive for metabolic acidosis and
depressed heat production capacity, which
causes hypothermia. 9

Fetal anoxia associated with premature
expulsion of the placenta occurs in all
species but may be of greatest importance
in cattle. 10 It occurs in all parities of cow
and with little relation to calving diffi-
culty, although malpresentation is a pre-
disposing factor. Prepartum diagnosis in
cattle is hindered by the low prevalence of
prepartum vaginal hemorrhage, and the
majority of fetuses die during the birth
process. The placenta is expelled with the

fetus. Premature separation of the

placenta ('red bag') occurs in foals when
foals experience difficulty in breaking
through the cervical star region of an
edematous thickened placenta. This is an
emergency and requires immediate
attention.

In all species the prevention of intra-
partum hypoxia depends on the provision
of surveillance. Universal surveillance is
usually not practical for species other
than the horse, and in cattle, for example,
it tends to concentrate on the group at
most risk so that surveillance, and assist-
ance if necessary, is provided for first-calf
heifers at the time of calving. Heifers that
do not continue to show progress during
the second stage of parturition should be
examined for evidence of dystocia, and
obstetrical assistance should be provided if
necessary.

The treatment and care of foals with
this syndrome is described under Critical
care of the newborn later in the chapter.
The monitoring, treatment and care of
agricultural animals with this syndrome
should follow the same principles but is
usually limited by the value of the animal
and the immediate access to a laboratory.
Measures such as the time from birth to
sternal recumbency, time from birth to
standing and time from birth to first
suckle have been used to grade calves and
identify those that might require inter-
vention and treatment, but the best
method of evaluation is an assessment
of muscle tone. 11 There is no effective
practical treatment for calves affected
with intrapartum hypoxia other than the
provision of ventilation as for the foal and
the correction of the acidosis. The airway
should be cleared and, if physical stimu-
lation of ventilation gives no response,
then mechanical ventilation should be
attempted. The practice of direct mouth-
to-mouth ventilation assistance should be
strongly discouraged, especially in lambs,
because of the risk from zoonotic disease
agents. Doxapram hydrochloride has been
used in calves to stimulate respiration. 11

The provision of wannth, force-feeding
of colostrum and fluid therapy are logical
support approaches.

REVIEW LITERATURE

Szenci O. Role of acid-base disturbances in perinatal
mortality of calves; a review. Vet Bull 2003;
73(7):7R-14R.

references

1- Hess-Dudan F, Rossdale PD. Equine Vet Educ
1996; 8:24, 79.

2. Rose R. Equine Vet J Suppl 1987; 5:11.

3. Chavatte P et al. J Reprod Fertil Suppl 1991; 44:603.

4. Rossdale PD, McGladdery AJ. Vet Annu 1992;
32:201.

5. Ruark DW et al. Am J Physiol 1990; 258:R1108,
R1116.

6. Rossdale PD. Vet Clin North Am Large Anim
Pract 1979; 1:205.

Physical and environmental causes of perinatal disease

141

7. Vestweber JG. Vet Clin North Am Food Anim

Pract 1997; 13:411.

8. Dufty J, SlossV. AustVet J 1977; 53:262.

9. Eales FA, Small J. ResVet Sci 1985, 39:219.

10. Mee JF. Vet Rec 1991; 128:521.

11. Szenci O. Vet Bull 2003; 73:7R.

HYPOTHERMIA

The environment of the neonate can have
a profound effect on its survival. This is
especially true for lambs and piglets, in
which hypothermia and hypoglycemia
are common causes of death. Hypothermia
can also predispose to infectious disease
and can adversely affect the response of
neonates in coping with an exogenous
endotoxin challenge. Endotoxin exposure
of hypothermic pigs results in an even
greater reduction in body temperature. 1

LAMBS

Lambs are very susceptible to cold and
hypothermia is an important cause of
mortality in the early postnatal period.
Cold stress to neonatal lambs exists in
three forms, ambient temperature, wind
and evaporative cooling. The healthy
newborn lamb has a good ability to
increase its metabolic rate in response to
a cold stress by shivering and non-
shivering thermogenesis (brown adipose
tissue) . The energy sources in the neonatal
lamb are liver and muscle glycogen,
brown adipose tissue and, if it sucks, the j
energy obtained from colostrum and |
milk. The ingestion of colostrum can I
be essential for early thermogenesis in 1
lambs, especially twin lambs. 2 I

The critical temperature (the ambient i
temperature below which a lamb must I
increase metabolic heat production to j
maintain body temperature) for light
birth-weight lambs is 31-37°C in the first j
days of life.

The risk for mortality from hypo-
thermia is highest in lambs of small birth I
size. Heat production is a function of i
body mass while heat loss is a function of
body surface area. Large-birth-size lambs i
have a greater body mass in relation to
their surface areas and are thus more ;
resistant to environmental cold stress. In •
contrast, small-birth-size lambs, with a I
smaller body mass relative to surface area,
are more susceptible. The dramatic nature !
of this relationship was shown in early j
studies on cold stress and survival in
lambs many years ago. Birth weight is
lower in twins and triplets and in the
progeny of maiden ewes. Susceptibility is
also influenced by maternal nutrition in
pregnancy (see next section), as this
can both influence placental mass, birth
weight and the energy reserves of the
neonate, and also affect the activity of the
ewe at parturition, and the resultant poor
mothering behavior and mismothering
can result in starvation in the lamb.

Lambs are particularly susceptible to
cold stress during the first 5 days of life.
During this period hypothermia can
result from heat loss in excess of summit
metabolism or from depressed heat pro-
duction caused by intrapartum hypoxia,
immaturity and starvation. 3

Heat loss in excess of summit
metabolism

Low-birth-weight lambs born into a cool
environment where there is wind are
especially susceptible because of the evap-
orative cooling of fetal fluids on the
fleece. 4 To a small newborn lamb the
evaporative cooling effect of a breeze of
19 km/h (12mph) at an ambient tem-
perature of 13°C (55°F), common in
lambing seasons in many countries, can
be the equivalent of a cold stress
equivalent to 25°C. The heat loss in these
circumstances can exceed their ability to
produce heat (summit metabolism) and
progressive hypothermia and death
results. Hypothermia due to heat loss in
excess of summit metabolism can also
occur when there is rain or just with cold
and wind. This mortality occurs primarily
in the first 12 hours of life.

Hypothermia from depleted energy
reserves

Hypothermia occurring in lambs after
12 hours of age is usually due to depletion
of energy reserves in periods of cold
stress. There are three major causes. Milk
is the sustaining energy source.

One of the early manifestations of
developing hypothermia is the loss of
sucking drive; severe cold stress and
developing hypothermia can result in low
milk intake and depletion of energy
reserves.

The second important cause is mis-
mothering; the third is related to birth
injury. Dystocia-related hypoxia results
in acidemia, a reduction in summit meta-
bolism and disturbance in thermo-
regulation and can result in hypothennia. 5
Birth -injured lambs, usually large single-
born lambs, have depressed sucking and
feeding activity. 6 ' 7 Systems are available
for the categorization of deaths based on
postmortem examination. 7 - 9

In lambs that have hypothermia associ-
ated with heat loss in excess of summit
metabolism, heat is required for therapy,
but in lambs with starvation hypothermia
the administration of glucose is also
necessary. Glucose is administered intra-
peritoneally at a dose of 2g/kg body
weight using a 20% solution. Following
the administration of the glucose, the
: lambs should be dried with a towel if wet
j and rewarmed in air at 40°C (104°F). This
j can be done in a warming box using a
: - radiant heater as the heat supply. Care
■ should be taken to avoid the occurrence

2

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

of hyperthermia. Careful attention must
be given to the nutrition of the lambs
after rewarming otherwise relapse will
occur. A feeding of 100-200 mL of col-
ostrum will also be beneficial but lambs
should not be fed before they are
normothermic, as aspiration pneumonia
is a risk. Experimental hypothermia in
lambs has shown little direct long-term
pathological effect. 10

In most countries the selection of time
of lambing is dictated by nutritional
considerations and the seasonality of the
ewes' sexual behavior and lambing occurs
at a time of year when cold stress is likely.
The control of loss from hypothermia in
newborn lambs requires supervision at
lambing and protection from cold. Shed
lambing will reduce cold stress loss. The
provision of shelter in lambing paddocks
may be effective but site is important as
birth sites in lambing paddocks are not
randomly distributed and there is vari-
ation in the preferred sites between
breeds. 5 Some ewes will seek shelter at
lambing but many ewes in wool will not.
In some flocks, sheep are shorn before
lambing in an attempt to force this
shelter-seeking trait.

Experimentally, there is a strong
relationship between breed and the
degree of hypothermia produced. 10 There
is also convincing evidence that rearing
ability is heritable in sheep, that some of
this relates to traits within the newborn
lamb, and that a significant reduction
in neonatal mortality associated with
susceptibility to hyperthermia could be
achieved with a genetic approach. 6-7,10 ' 12

Lambs are also susceptible to hyper-
thermia and thermoregulation is not
efficient at high environmental tempera-
tures. Heat prostration and some deaths
can occur in range lambs when the
environmental temperature is high,
especially if lambs have to perform pro-
longed physical exercise and if there is an
absence of shade.

CALVES

Hypothermia as a result of environmental
influence is less common in full-term
healthy calves than in lambs but mortality
rates have been shown to increase with
decreasing ambient temperature and
increasing precipitation on the day of
birth. 13 The critical temperature for
neonatal calves is much lower than for
lambs, approximately 13°C, and Bos
taurus calves are more resistant to cold
stress than Bos indicus , 14

Experimentally produced hypothermia
in calves has also been shown to cause
little overt injury except for peripheral
damage to exterior tissues. 15,16 During
cooling, there can be significant peripheral
hypothermia prior to any marked reduc-

tion in core body temperature. Calves
have a remarkable ability to resist and
overcome the effects of severe cold
temperatures. 14,16 However, there is a
relationship between the occurrence of
cold weather and calf deaths, including
those due to the 'weak calf syndrome',
and deficiencies in thermoregulation
occur in animals born prematurely and in
dystocial calves. As in lambs, dystocia will
reduce teat-seeking activity and sucking
drive and dystocial calves have lower
intakes of colostrum 17 and lower body
temperatures and decreased ability to
withstand cold stress. 18

Rewarming of hypothermic calves can
be by radiant heat but immersion in warm
water produces a more rapid response
and with minimal metabolic effort. The
prevention of hypothermia requires the
provision of shelter from wet and wind
for the first few days of life. Cows can be
calved in a shed, or alternately sheds for
calves can be provided in the fields. Beef
calves will use shelters in inclement
weather; these may not improve their
health status, although they are in com-
mon use. 19

PIGLETS

Hypothermia from heat loss and
hypothermia/hypoglycemia from starvation
are major causes of loss in neonatal pigs. 20
Newborn piglets have a reasonably good
ability to increase their metabolic rate in
response to cold stress but they have
limited energy reserves, especially limited
brown adipose tissue, and they con-
sequently rely on a continual intake of milk
for their major energy source, sucking
approximately every hour. Young pigs
have a good ability for peripheral vaso-
constriction at birth but surface insulation
is deficient because at this age there is no
subcutaneous layer of fat. The critical
temperature for young pigs is 34°C.

Thermoregulation is inefficient during
the first 9 days of life and is not fully
functional until the 20th day. Newborn
piglets must be provided with an external
heat source in the first few weeks of life.
The body temperature of the sow cannot
be relied upon for this and the preferred
air temperature for neonatal pigs is 32°C
(89.5°F) during the first day and 30°C
(86°F) for the first week. In contrast, the
preferred temperature for the sow is
about 18°C. A separate environment
(creep area) must be provided for the
piglets. Providing there is an adequate
ambient temperature to meet the require-
ments of the piglets, and good floor
insulation, hypothermia will not occur in
healthy piglets of viable size unless there
is a failure of milk intake.

Birth anoxia, with resultant reduced
vigor, reduced teat-seeking activity and

risk for hypothermia, occurs particularly
in later-birth -order pigs in large litters
from older sows. Failure of milk intake
can also occur with small-birth- size
piglets and is influenced by litter size, low
number of functional teats relative to
litter size and teat sucking order.

FOALS

There have been few studies on thermo-
regulation in foals but the large body
mass in relation to surface area renders
healthy newborn foals, like healthy
calves, relatively resistant to cold. Also,
foals are less likely to be born in a hostile
environment than other farm animals.
Significant foal mortality from hypo-
thermia as a result of starvation and expo-
sure can occur in extensively managed
herds and dystocia, low birth weight and
poor mothering are contributing factors. 21

Sick and premature foals may have
difficulty in maintaining body tempera-
ture in normal environments and the
metabolic rates of sick foals and pre-
mature foals are approximately 25%
lower than healthy foals. 22,23

The relatively larger surface area to
mass ratio, lower energy reserves and
lower insulation of the coat of premature
foals, coupled with the lower metabolic
rate, places them at particular risk for
hypothermia. Dystocial foals also have
lower metabolic rates but dysmature foals
appear to thermoregulate normally. 22,24
Methods of investigation that allow post-
mortem differentiation of placental
insufficiency, acute intrapartum hypoxemia,
inadequate thermogenesis and starvation
as causes of mortality in foals are
described. 8

Hypothermia should be suspected in
premature foals when the rectal tempera-
ture falls below 37.2°C (99°F) and should
be corrected with external warmth,
rugging or moving to a heated environ-
ment. If fluids are being administered
they should be heated to normal body
temperature.

REVIEW LITERATURE

Alexander G., Barker JD, Slee J. Factors affecting the
survival of newborn lambs. A seminar in the CEC
programme of coordination of agricultural
research held in Brussels, January 22-23, 1985.
Brussels: Commission of the European

Communities, 1986.

Rook JS, Scholman G, Wing-Proctor S, Shea M.
Diagnosis and control of neonatal loss in sheep.
Vet Clin North Am Food Anim Pract 1990;
6(3):531-562.

Haughey KC. Perinatal lamb mortality: its

investigation, causes and control. J South AfrVet
Assoc 1991; 62:78-91.

Carstens GE. Cold thermoregulation in the newborn
calf. Vet Clin North Am Food Anim Pract 1994;
10(1):69-106.

Mellor DJ, Stafford KJ. Animal welfare implications of
ne6natal mortality and morbidity in farm
animals. Vet J 2004; 168:118-133.

REFERENCES

1 . Carroll JA et al. Am J Vet Res 2001; 62:561.

2. Hamadeh SK et al. Sheep Goat Res J 2000;
16(2):46.

3. EalesFA etal.Vet Rec 1984; 114:469.

4 . McCutcheon SN et al. NZ J Agric Res 1983;
26:169, 175.

5 . EalesFA, Small J. Res Vet Sci 1985; 39:219.

6. Haughey KC. Wool Technol Sheep Breed 1984;
31:139.

7 . Haughey KC. J South Afr Vet Assoc 1991; 62:78.

8. Rook JS et al. Vet Clin North Am Food Anim Pract
1990; 6:531.

9. Eales FA et al. Vet Rec 1986; 118:227.

10. Slee J et al. Aust J Exp Agric 1991; 31:175.

11. Alexander G et al. Aust J Exp Agric 1990; 30:759.

12. Nash ML et al. Vet Rec 1996; 139:64.

13. Azzam SM et al. J Anim Sci 1993; 71:282.

14. Carstens GE.Vet Clin North Am Food Anim Pract
1994; 10:69.

15. Olson DP et al. Am J Vet Res 1981; 42:758, 876.

16. Olson DP et al. Am J Vet Res 1983; 44:564, 572,
577, 969.

17. \feimorel M et al. Can J Anim Sci 1989; 69:103,
113.

18. Bellows RA, Lammoglia MA. Theriogenology
2000; 53:803.

19. Olson DP et al. Bovine Pract 1989; 24:4.

20. English PR. Vet Annu 1993; 33:107.

21. HaasAD. Can Vet J 1996; 37:91.

22. OuseyJC et al.Vet J 1997; 153:185.

23. Rossdale PD. Equine Vet J Suppl 1988; 5:19.

24. Ousey JC et al. EquineVet J 2004; 36:616.

MATERNAL NUTRITION AND THE
NEWBO RN

Effects on both the dam and the fetus can
occur from overfeeding or underfeeding
of the dam, and there can be effects from
the influences of trace element deficiencies
or toxic substances. Severe undemutrition
of the dam can affect fetal size, and its
thermogenic rate, with consequences
mentioned earlier. Prepartum protein
restriction has most effect. 1 Severe under-
nutrition of the dam can also lead to weak
labor, increased rates of dystocia and can
limit the development of the udder.
Colostrogenesis may be impaired, with a
greater risk of infectious disease in the
neonate, and milk production may be
significantly reduced or delayed, with a
risk of starvation.

Most information is available for the
effects of nutrition of the pregnant ewe on
fetal growth rate, udder development, the
availability of energy in the body reserves
of fetuses at term, and the amount and
energy content of colostrum. 2 " 1 In sheep,
maternal nutrition can have a significant
influence on fetal growth rate and on
placental size. The underfeeding of hill
sheep in late pregnancy markedly reduces
the term weight of the udder and the
prenatal accumulation and subsequent
rates of secretion of colostrum. 4 A low
plane of nutrition in late pregnancy
results in a marked decrease in fetal body
lipid and brown fat reserves, and marked
reductions in the total production of
colostrum and in the concentration in

Physical and environmental causes of perinatal disease

143

colostrum during the first 18 hours after
parturition. 4 However, exposure of late
pregnant ewes to cold by shearing
increases lamb birth weight and lamb
brown fat reserves. 5 ' 6

Inadequate nutrition can also result
in in-utero growth retardation. Growth
retardation can be produced in fetal pigs,
lambs and calves by maternal caloric
undemutrition. Nutritional restriction in
ewes reduces the number of placental
lactogen receptors that mediate amino
acid transport in fetal liver and glycogen
synthesis in fetal tissue, leading to
depletion of fetal liver glycogen stores.
This has been postulated as a possible cause
of the fetal growth retardation that
accompanies maternal caloric under-
nutrition. Runt pigs have a reduced
metabolic rate and lower skeletal muscle
respiratory enzyme activity. This deficiency
persists after birth - runt pigs have a lower
core temperature and a lessened ability to
increase their metabolic rate and heat
production in response to cold. Paradoxi-
cally, ovemourishing the adolescent ewe
will also result placental growth restriction
and in in-utero growth retardation. 7,8 This
effect is most evident in the second third of
pregnancy. This syndrome is accompanied
by the birth of lambs with a shorter
gestational age, commonly reduced by
3 days. It is thought that the fetal hypoxia
and hypoglycemia that accompanies
placental insufficiency might stimulate the
maturation of the fetal hypothalamic-
pituitary-adrenal axis initiating early
parturition.

Maximum lamb survival is achieved at
intermediate lamb birth weights and the
nutritional management of the preg-
nant ewe in fecund flocks is very
important. 9 Ewes with multiple lambs can
be selected using ultrasound and fed
separately from those with singles. Preg-
nant maiden ewes should also be fed
to their separate requirements. The
recommendation is for a body condition
score of 3.0-3 .5 at mating, with a fall of
0.5 in score during the second and third
months of pregnancy and a subsequent
rise in score to 3.55 to the point of
lambing, and with a distinct weight gain
in late pregnancy. Equivalent condition
scores are also appropriate for other
species.

Toxic substances and trace element
deficiencies can result in increased risk for
fetal and neonatal mortality and are
discussed under those headings. One of
particular significance is agalactia, pro-
longed gestation and fetal distress at birth
seen in mares fed grain contaminated
with ergot ( Claviceps purpurea ) and in
mares grazing tall fescue ( Festuca
arundinacea ) containing the endophyte
fungus Acremonium coenophialum.

REFERENCES

1 . Carstens GE. Vet Clin North A m Food Anim Pract
1994; 10:69.

2. Mellar DJ. Br Vet J 1983; 139:307.

3. Mellor DJ, Murray L. ResVet Sci 1982; 32:177, 377.

4. Mellor DJ, Murray L. ResVet Sci 1985;39:230, 235.

5. Symonds ME, Lomax MA. Proc Nutr Soc 1992;
51:165.

6. Symonds ME et al. J Physiol 1992; 455:487.

7. Wallace JM et al. J Physiol 2005; 565:19.

8. Wallace JM et al. Biol Reprod 2004; 71:1055.

9. Fogarty NM et al. Aust J Exp Agric 1992; 32:1.

POOR MOTHER-YOUNG
RELATIONSHIP

Any examination of neonatal mortality
suspected of being caused by hypo-
thermia, starvation or infection due to
failure of transfer of passive immunity,
and even trauma by crushing in piglets,
must take into account the possibility that
poor mothering and a poor mother-
young bond may be the primary cause.
Inadequate maternal care leads to rapid
death of the newborn under extensive
conditions where there is no human
intervention to correct the problem. The
defect is most likely to be on the side of
the dam but may originate with the
offspring. A poor relationship may be
genetic or nutritional and, on the part of
the offspring, may be the result of birth
trauma.

For both the dam and the young there
is a much greater chance of establishing a
good bond if the animal has been reared
in a group rather than as an individual.
Because sight, smell, taste and hearing are
all important in the establishment of a
seeking and posturing to suckle activity
by the dam and a seeking, nuzzling and
sucking activity by the offspring, any
husbandry factor that interferes with the
use of these senses predisposes to
mortality. Weakness of the offspring due
to poor nutrition of the dam, harassment
at parturition by overzealous attendants
and high growth of pasture are obvious
examples. This can be a problem in cattle,
pigs and sheep, and occasionally in
horses, especially with extensive foaling
practices. 1 In pigs it may be developed to
an intense degree in the form of farrow-
ing hysteria, and is dealt with under that
heading. In sheep it can be a significant
contributor to neonatal death from
starvation, especially in highly strung
breeds like the Merino. 2

Bonding occurs rapidly after birth,
although there is some minor variation
between species with bonding starting
within a few minutes of birth in sheep but
taking up to 2-3 hours in some horses. 3
The strength of bonding also appears to
vary between species. 4 The bonding of the
dam to the neonate is usually quite
•' specific, although this can be modulated
by management systems, and the neonate

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

may be less selective and will often
attempt to suck other dams. With sheep
lambed under intensive lambing practices,
this can lead to high rates of mismothering
and subsequent abandonment, when
preparturient 'robber' ewes adopt lambs
from multiple births. A high degree of
shepherding is required to minimize loss
in these management systems, whereas
in extensive systems a strong bonding is
established providing the ewe and lamb
are allowed to remain relatively undisturbed
on the lambing site for 6 hours. 2

Vaginal cervical stimulation and the
central release of oxytocin are believed
to be important in initiating maternal
behavior 5,6 though caudal epidural anes-
thesia for delivery does not effect mother-
ing or bonding. 7 Sucking is also a major
determinant. Recognition is olfactory and
auditory and mediated by the release of
neurotransmitters. 8

Bonding is often slower with primi-
parous dams and is also delayed where
there is postpartum pain. A failure of
bonding leads to rejection and abandon-
ment of the neonate.

Maternal care is also important to
neonatal survival and there is significant
difference in litter mortality from crushing
and injury between sows related to sow
behavior and their response to piglet
distress calls. 9 A description of normal
and abnormal behavioral patterns of the
mare and foal is available 10 and tech-
niques for fostering are described. 3,11

REFERENCES

1. Haas SD et al. Can\fet J 1996; 37:91.

2. Nowak R. Appl Anim Behav Sci 1996; 49:61.

3. Chavatte P. Equine Vet Educ 1991; 3:215.

4. Hopster H et al. Appl Anim Behav Sci 1994; 44:1.

5. Kendrick KM et al. Brain Res Bull 1991; 26:803.

6. Romeyer A et al. Physiol Behav 1994; 55:395.

7. Scott PR, Gessert ME. Vet Rec 1996; 138:19.

8. Ohkura S, Kendrick KM. J Reprod Dev 1995;
41:143.

9. Wechsler B, Hegglin D. Appl Anim Behav Sci
1997; 51:39.

10. Houpt KA. CompendContin Educ PractVet 1984;
6:S114.

11. Alexander G et al. Aust J Exp Agric 1987; 27:771.

INDUCTION OF PREMATURE
PARTURmON

CALVES

The medical induction of parturition by
the parenteral injection of corticosteroid
into pregnant cows during the last 6 weeks
of pregnancy has raised the question of
animal welfare and of the possible effects
of prematurity on the disease resistance
of the newborn calf. The induction of
premature parturition in cattle has found
application in five main areas:

° With pastoral-based dairy production,
synchronization of the calving period
has allowed maximal utilization of

seasonally available pastures by the
synchronization of peak demand for
dry matter intake with spring flush in
pasture growth. In pastoral-based
herds with breeding for seasonal
calving, late-calving cows will be
induced and these average
approximately 8% of the herd 1
8 Ensuring that calving coincides with
the availability of labor to facilitate
observations and management of
calving and to overcome the
inconvenience caused by late-calving
cows

° Minimizing dystocia in small heifers
° The therapeutic termination of

pregnancy for various clinical reasons,
including potential problems such are
associated with pregnancy in feedlot
heifers

° As an aid in the control of milk fever
using vitamin D analogs 2

A variety of short-acting and long-acting
corticosteroids have been used. A single
injection of a short-acting formulation is
used when it is desirable to induce calving
in the last 2-3 weeks of gestation. Earlier
in pregnancy the long-acting formulations
are more reliable. Sometimes this is
followed in 5-8 days by treatment with a
short-acting glucocorticoid. Parturition
occurs 30-60 hours (mean 48 h) after
injection.

Some reports have indicated that the
mortality rate of induced calves was
higher than expected, and that the level of
serum immunoglobulins was lower
because of interference with absorption
by the corticosteroid. Mortality in calves
born as a result of induced parturition is
primarily as a result of prematurity and
calf mortality is generally low when
calving is induced within 12 days of
parturition, although there are welfare
concerns. 3 The calves are usually lighter in
weight. The health of calves that survi ve is
generally good, provided they receive
adequate quantities of colostrum. When
short-acting corticosteroids are used to
induce calving close to term, the ability of
the calves to absorb immunoglobulins
from colostrum is not impaired. However,
calves born earlier in pregnancy after
using long-acting corticosteroid are
lethargic, slow to stand and to suck
properly and their ability to absorb
immunoglobulins is impaired. 2 Up to
60% of calves born following induction
with long-acting corticosteroids are at
risk for failure of transfer of immuno-
globulins. The colostrum available to such
calves also has a reduced content of
immunoglobulins, and there may also be
a reduction in the total volume of
colostrum available from the induced-
calving cows.

Artificial induction of parturition is an
important risk factor for retention of the
placenta and the incidence is reported to
vary from 20% to 100% 1,4,5 Subsequent
reproductive performance of induced
cows can be impaired. 1 A risk for acute
Gram-negative bacterial infections is
reported in a low (0.3%) proportion
of cows following induction with
dexamethasone. 6

When parturition is induced in large
herds of beef cattle, particularly with a high
percentage of heifers, increased surveillance
will be necessary after the calves are bom to
avoid mismothering. Every attempt must be
made to establish the cow-calf pair
(neonatal bond) and move them out of the
main calving area. Heifers that disown their
calves must be confined in a small pen and
be encouraged to accept the calf and let it
suck - sometimes a very unrewarding chore
for the cowman. Calf mortality can be very
high where calving is induced earlier than
35 weeks of pregnancy. 3

FOALS

The induction of parturition in mares for
reasons of economy, management con-
venience, concern at prolonged gestation
or clinical conditions such as prepubic
tendon rupture, or research and teaching
is now being practiced. 7,8

Foaling is induced with oxytocin and
occurs within 15-90 minutes of its
administration. 9 High doses of oxytocin
are potentially dangerous to the foal and
low doses (10-20 IU) are preferred.
Glucocorticoids, antiprogestagens and
prostaglandins that are effective in
inducing pregnancy in other species are
either ineffective in the mare or capricious
in their efficacy, and can also be associ-
ated with adverse effects on the foal 8
Induction of parturition in the mare it
is not without risk and has been associ-
ated with the birth of foals that are weak,
injured or susceptible to perinatal infec-
tions. The period of fetal maturation is
relatively short in the horse and is con-
sidered to be the last 2-3 days of
gestation. Because spontaneous parturition
in healthy mares can occur between 320
and 360 days there is the risk of delivering
a foal that is premature and nonviable.
Fetal maturity is the major prerequisite for
successful induced parturition and the
three essential criteria are: 8

0 A gestational length of more than
330 days

° Substantial mammary development
and the presence of colostrum in the
mammary gland with a calcium
concentration greater than 10 mmol/L
° Softening of the cervix.

The risfe in calcium concentration is the
most reliable predictor of fetal maturity

Diseases of cloned offspring

145

and milk calcium concentrations above
10 mmol/L, in combination with a con-
centration of potassium that is greater
than sodium, are indicative of fetal
maturity. Commercial milk test strips are
available for estimating mammary secre-
tion electrolyte concentrations, however,
it is recommended that testing be done in
an accredited laboratory. 8,10-12

In mature foals, head lifting, sternal
recumbency and evidence of suck reflex
occurs within 5 minutes of spontaneous
full-term deliveries. The foal can stand
within 1 hour and suck the mare within
2 hours. The behavior and viability of the
premature foal after induced parturition
have been described. 13 The overall survival
rate of foals delivered from induced
parturition before 320 days of gestation
was 5%. 13 Four patterns of neonatal
adaptation were observed on the basis of
righting, sucking and standing ability. If
the suck reflex was weak or absent and
the foals were unable to establish righting
reflexes, the prognosis of survival was
poor. Foals born before 300 days of gesta-
tion did not survive for more than
90 minutes; foals born closer to 320 days
of gestation had a better chance of
survival and exhibited behavioral patterns
of adaptation.

In addition to the potential delivery of
a premature or weak foal, other adverse
effects of induction can be dystocia, pre-
mature placental separation and retained
placenta.

PIGLETS

The induction of parturition of gilts and
sows on days 112, 113 or 114 of gestation
is highly reliable and can be achieved by a
single intramuscular injection of 175 mg
of cloprostenol or 5-10 mg of prostaglandin
F 2a . 14 The sows farrow approximately
20-24 hours later. The interval to onset
can be decreased by the use of oxytocin. 15

Induction of parturition has been used
on large-scale farms to allow a concen-
tration of labor and improve supervision
and care at the time of farrowing, and to
reduce the incidence of the mastitis/
metritis/agalactia syndrome 16 and reduce
the percentage of stillborn piglets. The
end-day of a batch farrowing system can
be fixed and weekend farrowing avoided.
The subsequent fertility of the sows is not
impaired. Induction on day 110 may
be associated with a slight increase in
perinatal mortality.

lambs

The induction of parturition in sheep is
not commonly practiced but it can be
used to synchronize lambing in flocks
where there are accurate dates of mating
for individual ewes. Unless accurate dates
are available there is risk of prematurity.
Also, ewes that are more than 10 days

from their normal parturition date are
unlikely to respond. 17

Induction of parturition is also used as
a therapeutic ploy to terminate pregnancies
in sheep with pregnancy toxemia.

Induction is usually with
dexamethasone, betamethasone or
flumethazone. 18,19 Lambing occurs
36-48 hours later and there may be breed
differences in response. Variability in
lambing time can be reduced by the use of
clenbuterol and oxytocin. 20

REVIEW LITERATURE

MacDiarmid SC. Induction of parturition in cattle
using corticosteroid: a review. Part 1. Reasons for
induction, mechanisms of induction and
preparations used. Anim Breed Abstr 1983;
51:403-19.

MacDiarmid SC. Induction of parturition in cattle
using corticosteroid: a review. Part 2. Effects of
induced calving on the calf and cow. Anim Breed
Abstr 1983; 51:499-508.

Pressing AL. Pharmacologic control of swine
reproduction. Vet Clin North Am Food Anim
Pract 1992; 8:707-23.

Hemsworth PH, Barnett JL, Beveridge L Mathews LR.
The welfare of extensively managed dairy cattle: a
review. Appl Anim Behav Sci 1995; 42:161-82.
Ingoldby L, Jackson P. Induction of parturition in
sheep. In Pract 2001; 23:228-31.

Macmillan KL. Advances in bovine theriogenology in
New Zealand. 1. Pregnancy, parturition and the
postpartum period. NZ Vet J 2002; 50(3
Suppl):67-73.

REFERENCES

1. Macmillan KL. NZVet J 2002; 50(3 Suppl):67.

2. MacDiarmid SC. Anim Breed Abstr 1983;
51:403-99.

3. Morton JM, Butler KL. Vet Rec 1995; 72:5.

4. Verkerk GA et al. Proc NZ Soc Anim Prod 1997;
57:231.

5. Guerin P et al.Vet Rec 2004; 154:326

6. Browning JW et al. AustVet J 1990; 67:28.

7. Camillo F et al. EquineVet J 2000; 32:307.

8. Ousey J. EquineVet Educ 2003; 15:164.

9. Macpherson ML et al. J Am Vet Med Assoc 1997;
210:199.

10. Ousey JC et al. EquineVet J 1984; 16:259.

11. Leadon DP et al. EquineVet J 1984; 16:256.

12. LeBlanc MM. Equine \fet J 1997; 24:100.

13. Leadon DP et al. Am J Vet Res 1986; 47:1870.

14. Podany J et al. Pig News Info 1987; 8:24.

15. Pressing AL. Vet Clin North Am Food Anim Pract
1992; 8:707.

16. Scott E. Pig J 1994; 32:38.

17. Ingoldby L, Jackson P. In Pract 2001; 23:228.

18. Niemann H. Reprod Domest Anim 1991; 26:22.

19. Kastelic JP et al. Can Vet J 1996; 37:101.

20. Kiesling DO, Meredith S. Theriogenology 1991;
36:999.

Diseases of cloned
offspring

The successful cloning of domestic
animals using somatic-cell nuclear trans-
fer has resulted in birth of offspring with
a high frequency of clinical abnormalities.
Cloning of livestock and horses is
achieved by transfer of nuclear material
from the cell of an adult animal to the

enucleated egg of an animal of the same
species (somatic-cell nuclear transfer)
with subsequent implantation of the
resulting embryo in a surrogate dam and
birth of a live, viable offspring. 1 However,
the use of nuclear material from somatic
cells of adult animals, and from fetal cells,
does not result in normal development of
the embryo and placenta. The abnormal
development is a consequence of altered
methylation of the genome in transferred
nuclear material. 2 In normal reproduction,
the paternal genome is demethylated
during passage through the oocyte and
fusion with the maternal genome. Con-
sequently, the methylation marks of the
two genomes (paternal and maternal) are
different at the end of the cleavage
process. Transfer of somatic nuclear
material into an enucleated oocyte results
in exposure of both genomes to the active
demethylating process in the cytoplasm
of the oocyte and uniform demethylation
of both genomes. 2,3 The loss of these
parent-specific epigenetic markers results
in widespread dysregulation of imprinted
genes and subsequent abnormalities in
the placenta, fetus and newborn.

A small proportion of transferred
blastocysts develop in viable animals. For
cattle, of 134 recipients that received
blastocysts, 50 were pregnant 40 days
after blastocyst transfer and 23 had full-
term pregnancies. 4 For all species studied,
fewer than 3% of cloned embryos result
in birth of viable animals. 1 Abnormalities
in placenta and newborn cloned animals
are reported for cattle and sheep but not
for pigs and equids (horses and mules). 1,5
Factors influencing the risks of abnor-
malities in newborns have not been well
defined, but include the source of the
nuclear material, with frequency of birth
of live animals born after somatic cell
nuclear transfer from well-differentiated
tissue (e.g. fibroblasts) or fetal somatic
cells being lower than after nuclear
transfer from embryonic cells (7%, 15%
and 34%, respectively). 6

The cause of placental, fetal and
neonatal abnormalities is abnormal
expression of imprinted genes as a con-
sequence of transfer of nuclear material
from differentiated somatic cells, conditions
and media used for maintenance and
culture of cytoplasts and blastocysts, and
techniques used for handling cells. 1,7
Candidate genes for large offspring
syndrome include IGF-2 and IGFBP-2,
insulin-like growth factor (IGF) concen-
trations in plasma of cloned calves being
higher than that of normal calves 7,8
although others, such as genes related to
endothelin-1 production, might well be
involved. 9

1 Clinical findings in cloned calves
and lambs include abortion, placental

6

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

abnormalities, large birth size, poor
extrauterine viability, respiratory disease,
cardiovascular abnormalities and neuro-
logic disease compatible with neonatal
encephalopathy. Abortion occurs after day
90 of gestation in 30-50% of pregnancies
in cattle resulting from transfer blasto-
cysts containing transferred nuclear
material. 6 Abnormalities, including hydro-
allantois, are present in approximately
25 % of advanced pregnancies. 6 Placental
abnormalities include hydroallantois, a
reduction in the number of placentomes
(from a normal of approximately 100 to as
few as 26-70 in cloned calves), 7,10 abnor-
mally large placentomes (140 g in cloned
calves vs 33 g in conventional calves) and
edema of the placenta. 6,7,11 Maternal
retention of the placenta is common and
occurs in most cows. 11 Duration of
gestation is probably longer in cloned
calves, although the frequent delivery of
cloned calves by cesarian section makes
assessment of gestational duration diffi-
cult. Cloned calves are heavier than con-
ventional calves, often by as much as
25%, a well-recognized part of the 'large
offspring syndrome' that affects calves
born as a result of reproductive mani-
pulation, including in-vitro fertilization. 6,12
Viability of cloned calves that are born
alive (commonly by cesarian section) is
less than that of conventional calves -
only approximately two -thirds of cloned
calves born alive survive more than
1 month, 10 although others report better
survival. 11 Similar results are reported for
horses. 13

A high proportion of cloned calves
have clinically detectable abnormalities

at or soon after birth, including sepsis,
neonatal encephalopathy, respiratory
failure, umbilical abnormalities, anemia,
flexure contracture, abdominal distension
and renal dysfunction. Respiratory failure
is a common finding and might reflect
persistent fetal circulation or inadequate
surfactant production, as evidenced by
the high pulmonary artery pressures and
signs consistent with patent ductus
arteriosus. Left heart failure, which can
also cause pulmonary hypertension, is
reported in cloned calves. 11 Umbilical
abnormalities are evident as abnormal
umbilical cord structure (multiple arteries
and veins) and large size, with a high risk
of hemorrhage from the umbilical cord
after birth. Cloned calves have higher
body temperatures than do conventional
calves. 7

Hematological abnormalities include
anemia and decreased mean corpuscular
volume. Biochemical abnormalities include
hypoxemia, azotemia and hypoglycemia.
Plasma leptin and IGF-2 concentrations
are higher, and thyroxine lower, in cloned
calves. 7 Serum cortisol and ACTH stimu-

j lation tests do not differ between cloned
I and conventional calves. 7

Necropsy examination reveals
placentomegaly, presence of excess pleural
and peritoneal fluid, hepatomegaly,
interstitial pneumonia or pulmonary con-
solidation and alveolar proteinosis, right
j ventricular dilation and hepatocellular
vacuolation. 11

Treatment is supportive and directed
toward correcting hypoxemia and providing
nutritional, fluid and environmental
support (see above).

There are currently no recognized
methods for preventing these abnor-
I malities, but presumably improvements
| in methodology and culture techniques
| will result in fewer cloned offspring with

i these abnormalities.

I

j REFERENCES

f 1. Vanderwall DK et al. J Am Vet Med Assoc 2004;
j 225:1694.

j 2. Jaenisch R. New Engl J Med 2004; 351:2787.

3. KangYK et al. Nat Genet 2001; 28:173.

4. KatoY et al. J Reprod Fertil 2000; 120:231.

5. TsunodaY, KatoY. Differentiation 2002; 69:158.

6. HeymanY et al. Biol Reprod 2002; 66:6.

7. Chavette-Palmer P et al. Biol Reprod 2002;
66:1596.

8. Young LE et al. Theriogenology 1999; 51:196.

9. Wilkins PA et al. JVet Intern Med 2005; 19:594.

10. Hill JR et al. Cloning 2001; 3:83.

11. Hill JR et al. Theriogenology 1999; 51:1451.

12. Young LE et al. Rev Reprod 1998; 3:155.

13. GalliC et al. Nature 2004; 424:635.

Neonatal infection

Synopsis

Etiology Common infections for each
animal species are listed under etiology
below. Most are bacterial.

Epidemiology Commonly predisposed
by management and environmental factors
that increase the exposure risk and load
| and decrease the resistance of the
j neonate.

i Clinical findings Septicemia or
I bacteremia with localization is most
common but signs can be specific for the
infecting agent.

Clinical pathology White blood cell
and differential counts, toxic change,
serum immunoglobulin concentrations,
arterial oxygen concentrations, metabolic
acidosis, fibrinogen levels, blood culture.
Necropsy findings Specific to disease.
Diagnostic confirmation Specific to
disease.

Treatment General therapy may include
antibacterial therapy, blood or plasma
transfusion, correction of acid-base
disturbance, fluid and electrolyte therapy,
and supportive treatment.

Infection is a common cause of morbidity
and mortality in neonates. There are a
number of specific infectious pathogens

that can cause disease. Other infectious
agents, normally considered to have low
virulence, can also cause disease if the
immunological status of the neonate
is not at an optimum level. Maternal
immunoglobulins are not transferred
transplacentally in ungulates and the new-
borns are at particular risk for infectious
disease during the neonatal period
because they rely on the acquisition of
immunoglobulins from colostrum for
passive antibody protection.

ETIOLOGY

In domestic farm animals the common
infections that can produce disease
during the neonatal period are as follows.
(Relative importance and prevalence
statistics are not given, as these vary from
area to area and with differing manage-
ment systems.)

Calves

Bacteremia and septicemia associated
with Escherichia coli, Listeria
monocytogenes, Pasteurella spp.,
streptococci or Salmonella spp.

‘ Enteritis associated with

enterotoxigenic E. coli, Salmonella spp.,
rotavirus and coronavirus,
Cryptosporidium parvum and
Clostridium perfringens types A, B and
C; and occasionally by the vims of
infectious bovine rhinotracheitis and
bovine virus diarrhea.

Pigs

Septicemia with or without
localization in joints, endocardium
and meninges associated with
Streptococcus suis, Streptococcus
equisimilis, Streptococcus zooepidemicus
and L. monocytogenes
° Bacteremia, septicemia and enteritis
associated with E. coli
« Transmissible gastroenteritis,
Aujeszky's disease, swine pox,
enterovirus infections, and vomiting
and wasting disease are associated
with viruses

3 Enteritis associated with

C. perfringens, Campylobacter spp.,
rotavirus and Coccidia spp.
o Arthritis and septicemia associated
with Erysipelothrix rhusiopathiae.

Foals

o Septicemia with localization

associated with E. coli, Actinobacillus
equuli, Klebsiella pneumoniae,
a-hemolytic streptococci,

S. zooepidemicus, L. monocytogenes,
Rhodococcus equi and Salmonella
typhimurium

° Enteritis associated with C. perfringens
types A, B, and C., Clostridium difficile,
R. eqiii, Salmonella spp., Strongyloides
westeri, C. parvum and rotavirus.

Neonatal infection

147

Lambs

o Septicemia or bacteremia with
localization in joints and/or synovia
and/or leptomeninges associated with
E. coli, L. monocytogenes, streptococci,
micrococci, E. rhusiopathiae and
Chlamyodophila spp.
o Enteritis associated with

enterotoxigenic E. coli, Salmonella spp.,
rotavirus and coronavirus and
C. parvum

° Lamb dysentery associated with
C. perfringens type B and C
o Gas gangrene of the navel associated
with Clostridium septicum, Clostridium
novyi and Clostridium chauvoei
® Pyemia associated with Staphylococcus
aureus, Fusobacteriwn necrophorum and
Arcanobacterium pyogenes
o Pneumonia, polyserositis and

peritonitis associated with Pasteurella
multocida and Mannheimia
haemolytica.

The following agents are recorded as
causing neonatal infections but are less
common than those listed above and not
of as great importance.

Calves

Pseudomonas aeruginosa, Streptococcus
pyogenes, Streptococcus faecalis, S.
zooepidemicus, Pneumococcus spp.; enteritis
due to Providencia stuartii, Chlamydophila
spp., A. ecjuuli.

Lambs

S. aureus (tick pyemia); enteritis due to
E. coli, rotavirus; pneumonia due to
Salmonella abortus-ovis.

Foals

Enterobacter cloacae, S. aureus, Pasteurella
multocida, P. aeruginosa, A. pyogems, Serratia
marcescens.

All species

Nonspecific infections are associated with
pyogenic organisms, including Arcano-
bacterium pyogenes and Fusobacteriwn
necrophorus; S. faecalis, S. zooepidemicus,
Micrococcus spp. and Pasteurella spp. occur
in all species.

EPIDEMIOLOGY

The occurrence of neonatal disease is
broadly influenced by two main factors:
the exposure or infection pressure of the
infectious agent to the neonate and
the ability of the neonate to modulate the
infection so that disease does not occur.
With some agents the organism is suffi-
ciently virulent in its own right that an
exposure can lead to disease. With others,
the majority, the defenses of the host
must be compromised or the infection
challenge must be very high before
clinical disease occurs. Management of
the neonate has a great influence on both
these factors and the recognition and

correction of these risks is the key to the
prevention of neonatal disease in both
the individual and the group.

Sources of infection

Postnatal infection

The vast majority of infections are
acquired by the neonate after birth from
the enteric or respiratory tract flora of the
dam, from the environment or from close
contact with other infected neonates.
Depending upon the specific agent, the
reservoir of infection may be in a carrier
animal or in the environment. Details for
the common neonatal diseases are given
under the individual disease headings in
the chapters on special medicine.

Prenatal infection

Some bacterial infections that manifest
with neonatal disease are acquired in
utero. The majority of these are agents
that cause abortion, and neonatal septi-
cemia is only part of the spectrum of
abortion and perinatal death associated
with these agents. Examples would be
many of the agents producing abortion in
sheep.

Some septicemic infections in foals,
particularly those associated with A.
ecjuuli, S. zooepidemicus, Salmonella
abortivoequina and possibly some E. coli
septicemic infections, are acquired by
prenatal infection. If the disease is intra-
uterine in origin it must gain entrance via
the placenta, and probably by means of a
placentitis due to a blood-borne infection
or an existing endometritis. In the latter
case, disinfecting the uterus before
mating becomes an important hygienic
precaution; disinfecting the environment
may have little effect on the incidence of
the disease.

Viral infections that are acquired in
utero are listed in the section on con-
genital disease.

Routes of transmission
The portal of infection is commonly by
ingestion but may occur via aerosol
infection of the respiratory tract. Organisms
capable of invading to produce a bacteremia
and septicemia invade through the
nasopharynx or through the intestinal
epithelium. An alternate route of infection
and invasion is via the umbilicus. Routes
of excretion are via the feces in enteric
disease and the nasal secretions, urine
and sometimes the feces in septicemic
disease to result in contamination of the
neonatal environment.

Where neonates are in groups or in
close contact, direct transmission by fecal,
respiratory secretion and urine aerosols
can also occur. Neonatal bull calves that
are group-housed and that suck each
other's navels can transmit infection by
this activity.

Risk factors and modulation erf
infection

Immunity

All newborn farm animals are more
susceptible to infection than their adult
counterparts. The calf, lamb, piglet and
foal are born without significant levels of
immunoglobulins and possess almost no
resistance to certain diseases until after
they have ingested colostrum and absorbed
sufficient quantities of immunoglobulins
from the colostrum. Failure of transfer
of colostral immunoglobulins is a major
determinant and is discussed under that
heading later in this chapter.

Immune responsiveness
All components of the immune system
are present in foals and calves at birth but
the immune system of the newborn
animal is less mature than its adult
counterpart, at least for the first 30 days of
life, and does not respond as effectively to
many antigens.

Immune responsiveness is age-
dependent but also varies with the
antigen. 1 In colostrum-fed animals part of
the inefficiency of the newborn to pro-
duce humoral antibody following infec-
tion of antigen is the interference from
circulating colostral antibody and the
downregulation by colostrum of endo-
genous immunoglobulin production. 2 ^

Colostrum -deprived calves respond
actively to injected antigens and are
believed to be immunologically competent
at birth with respect to most antigens.
Immune competence begins during fetal
life and the age of gestation at which this
occurs varies according to the nature of
the antigen. The bovine fetus will produce
antibody to some viruses, beginning at
90-120 days, and by the third trimester of
gestation it will respond to a variety of
viruses and bacteria. 5 The lamb will
respond to some antigens beginning as
early as 41 days and not until 120 days for
others. The piglet at 55 days and the fetal
foal also respond to injected antigens.

The presence of high levels of antibody
in the precolostral serum of newborn
animals suggests that an in-utero infec-
tion was present, which is useful for
diagnostic purposes. The detection of
immunoglobulins and specific antibodies
in aborted fetuses is a useful aid in the
diagnosis of abortion in cattle.

Exposure pressure

The exposure pressure is a factor of the
cleanliness of the environment of the
neonate. The phenomenon of a 'buildup
of infection'' in continual-throughput
housing for neonatal animals has been
recognized for decades and has been
translated to many observations of risk for
¥ neonatal disease associated with sub-
optimal hygiene and stocking density in

18

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

both pen and paddock birthing areas.
Details for the individual species are
provided in the section on perinatal disease.

Age at exposure

With several agents that produce
neonatal disease, the age of the neonate
at infection and the infecting dose have a
significant influence on the outcome.
Examples are the importance of age with
respect to susceptibility to disease associ-
ated with some enteric infections. Disease
associated with enteropathogenic E. coli
and with C. perfringens type B and C
occurs only in young animals and if infec-
tion can be avoided by hygiene in this
critical period disease will not occur
regardless of subsequent exposure.
Colostrum-deprived calves show signifi-
cant resistance to challenge at 7 days of
age with strains of E. coli that invariably
produce septicemic disease if challenged
at the time of birth and isolation of an
immunocompromised neonate is an
important factor in its survival. Thus the
management of the neonate and its
environment is a critical determinant of
its health. Age at exposure also varies
with the epidemiology of the pathogen
and segregated early weaning is used to
reduce transmission of and infection with
certain pathogens in pigs.

Animal risk factors

Animal risk factors that predispose
infection include those that interfere with
sucking drive and colostral intake, such as
cold stress and dystocia. These are detailed
in the preceding section on perinatal
disease.

PATHOGENESIS

The pathogenesis varies with the neonatal
infectious disease under consideration
and is given for each of these in the
special medicine section.

Following invasion via the nasopharynx
and the gastrointestinal tract, the usual
pattern of development is a bacteremia
followed by septicemia with severe
systemic signs; or a bacteremia with few
or no systemic signs, followed by
localization in various organs. If the
portal of entry is the navel, local inflam-
mation occurs -'navel ill' - which can be
easily overlooked if clinical examination is
not thorough. From the local infection at
the navel, extension may occur to the liver
or via the urachus to the bladder and
result in chronic ill-health. Extension
systemically may produce septicemia. 6

Localization is most common in the
joints, producing a suppurative or non-
suppurative arthritis. Less commonly
there is localization in the eye to produce
a panophthalmitis, in the heart valves
to cause valvular endocarditis, or in the
meninges to produce a meningitis.

In some cases these secondary lesions
take time to develop and signs usually
appear at 1-2 weeks of age. This is
especially true with some of the strepto-
coccal infections, where bacteremia may
be present for several days before
localization in the joints and meninges
produces clinical signs. Bacterial meningitis
in newborn ungulates is preceded by a
bacteremia followed by a fibrinopurulent
inflammation of the leptomeninges,
choroid plexuses and ventricle walls but
does not affect the neuraxial parenchyma.
It is proposed that the bacteria are
transported in monocytes, which do not
normally invade the neuraxial parenchyma.

Dehydration, acid-base and electrolyte
imbalance can occur very quickly in
newborn animals, whether diarrhea and
vomiting (pigs) are present or not, but
obviously are more severe where there is
fluid loss into the gastrointestinal tract. In
Gram-negative sepsis the prominent
signs are those of endotoxemia.

CLINICAL FINDINGS

The clinical findings depend on the
rapidity of growth of the organism, its
propensity to localize and its potential to
produce toxemia. With organisms that
have a low propensity for toxemia there
is fever, depression, anorexia and signs
referable to localization. These include
endocarditis with a heart murmur;
panophthalmitis with pus in the anterior
chamber of the eye; meningitis with
rigidity, pain and convulsions; and
polyarthritis with lameness and swollen
joints. With more virulent organisms
there are clinical signs of toxemia as well
as bacteremia, including fever, severe
depression, prostration, coma, petechiation
j of mucosae, dehydration, acidosis and
i rapid death. 7 ' 8

| The clinical and clinicopathological
j characteristics of the septicemic foal have
j been detailed in an outbreak of septicemia
S in colostrum- deprived foals 9 and on the
j clinical records of 38 septicemic foals
i admitted to a referral clinic, 10 where the
j survival rate of septicemic foals, 26%, was
j markedly less than the rate for all other
: foal admissions. The major clinical
j findings included lethargy, unwillingness
j to suck, inability to stand without assist-
j ance but remaining conscious, unawareness
j of environment and thrashing or con-
j vulsing, diarrhea, respiratory distress,
! joint distension, central nervous system
| abnormalities, uveitis and colic. Fever was
i not a consistent finding.

! A sepsis score has been developed for
\ foals based on 14 measures related to
! historical, clinical and laboratory data
i (Table 3.6). The score derived from the
j collective differential scoring of these data
S has been found to be more sensitive and

i

specific for infection than any parameter
taken individually. 7 However, a subsequent
study of 168 foals presented to a
university hospital found that the sepsis
score correctly predicted sepsis in 58 out
of 86 foals and nonsepsis in 24 out of 45
foals resulting in a sensitivity of 67%, a
specificity of 75%, a positive predictive
value of 84% and a negative predictive
value of 55%, and it was suggested that
the score system should be used with care
as the low negative predictive value
limited its clinical utility. 11

A sepsis score, based on fecal con-
sistency, hydration, behavior, ability to
stand, state of the umbilicus and degree
of injection of scleral vessels, is described
for calves and has reasonable predictive
value. 12

The clinical findings specific to indivi-
dual etiological agents are given under
their specific headings in the special
medicine section of this book.

CLINICAL PATHOLOGY

Clinical pathology is used as an integral
part of the evaluation of a sick neonate
and to help formulate a treatment plan. A
major evaluation is to attempt to confirm
the presence or absence of sepsis and this
type of evaluation has been developed
most successfully in the foal. Blood
culture is part of this examination but the
time for a positive result limits its value in
the acutely ill neonate. Laboratory
findings in foals with neonatal sepsis are
variable and depend upon the severity,
stage and site of infection. 8 Serial exam-
inations are commonly used. In examin-
ations relating to the possible presence of
septicemia, particular emphasis is placed
on the results of the white blood cell and
differential counts, the presence of toxic
change, serum immunoglobulin concen-
trations, arterial oxygen concentrations,
presence of metabolic acidosis and
fibrinogen levels. 7 ' 8 ' 12

• The principles of diagnosis of infectious
disease in newborn animals are the
same as for older animals. However, in
outbreaks of suspected infectious
disease in young animals there is usually
a need for more diagnostic microbiology
and pathology

• With outbreaks, owners should be
encouraged to submit all dead neonates
as soon as possible for a meaningful
necropsy examination

• In addition to postmortem examination
it is necessary to identify the factors that
may have contributed to an outbreak of
disease in newborn calves, piglets or
lambs and only detailed epidemiological
investigation will reveal these

treatment

The first principle is to obtain an
etiological diagnosis if possible. Ideally a
drug sensitivity of the causative bacteria
should be obtained before treatment is
given, but this is not always possible. It
may be necessary to choose an anti-
bacterial based on the tentative diagnosis
and previous experience with treatment
of similar cases.

Outbreaks of infectious disease are
common in litters of piglets and groups of
calves and lambs, and individual treat-
ment is often necessary to maximize
survival rate. There is usually no simple
method of mass-medicating the feed and
water supply of sucking animals and each
animal should be dosed individually as
necessary. Supportive fluid and electrolyte
therapy and correction of acid-base
disturbances are described in detail in
Chapter 2.

The provision of antibodies to sick
and weak newborn animals through the
use of blood transfusions or serum is
often practiced, especially in newborn
calves in which the immunoglobulin
status is unknown. Whole blood given at
the rate of 10-20 mL/kg body weight,
preferably by the intravenous route, will
often save a calf that appears to be in
shock associated with neonatal diarrhea.
The blood is usually followed by fluid
therapy. Serum or plasma can also be
given at half the dose rate. The blood
should not be taken from a cow near
parturition as the circulating immuno-
globulins will be low from the transfer
into the mammary gland.

Plasma is often incorporated into the
therapeutic regimen in foals, both for its
immunoglobulin content and for its effect
on blood volume and osmotic pressure.
Stored plasma can be used. A dose of
20 mL plasma/kg body weight given
slowly intravenously is often used, but
significantly higher doses are required to
elevate circulating immunoglobulins by
an appreciable amount. 8 Blood may be
collected, the red blood cells allowed to
settle and the plasma removed and stored
frozen. The donor plasma should be
prescreened for compatibility. Lyophilized
hyperimmune equine serum as a source
of antibodies may also be fed to foals
within 4 hours after birth. Good nursing
care is also essential.

Further information on treatment is
given in the section on critical care for the
newborn later in this chapter.

CONTROL

Methods for avoidance of failure of
transfer of passive immunity and the
principles for prevention of infectious
disease in newborn farm animals follow
in this chapter. The control of individual

Neonatal infection

149

diseases is given under specific disease
headings elsewhere in this book.

REFERENCES

1. Watson DL et al. Res Vet Sci 1994; 57:152.

2. Kitching RP, Salt JS. BrVet J 1995; 151:379.

3. Ellis JA et al. J Am Vet Med Assoc 1996; 208:393.

4. Aldridge BM et al. Vet Immunol Immunopathol
1998; 62:51.

5. Tierney TJ et al. Vet Immunol Immunopathol
1997; 57:229.

6. Staller GS et al. J Am Vet Med Assoc 1995; 206:77.

7. Brewer BD, Koterba AM. EquineVet J 1988; 20:18.

8. Carter GK. Compend Contin EducPractVet 1986;
8:S256.

9. Robinson JA et al. EquineVet J 1993; 25:214.

10. Koterba AM et al. Equine Vet J 1984; 16:376.

11. Corley KTT, Furr MO. JVet EmergCritCare 2003;
13:149.

12. FecteauG et al. Can Vet J 1997; 38:101.

FAILURE OF TRANSFER OF
COLOSTRAL IMMUNOGLOBULINS

The acquisition and absorption of adequate
amounts of colostral immunoglobulins is
essential to the health of the neonate as it
is born virtually devoid of circulating
immunoglobulin and relies on antibody
acquired from colostrum for protection
against common environmental patho-
gens. Adequate antibody transfer is the
cornerstone of all neonatal preventive
health programs. This has been recognized
for many years and it is discouraging that a
study conducted in 2002 in the USA by the
National Animal Health Monitoring
System found that over 40% of dairy heifer
calves sampled by the National Dairy
Heifer Evaluation Project had failure of
transfer of colostral immunoglobulins. 1

Much of the description that follows
refers to the calf because more studies on
transfer of passive immunity have been
conducted in calves. However, most of the
information is applicable to the other
species; where there are differences these
are mentioned.

NORMAL TRANSFER OF
IMMUNOGLOBULINS

The major immunoglobulin in colostrum

is IgG, but there are also significant
amounts of IgM and IgA. IgG, is present
in highest concentration and is con-
centrated in colostrum by an active,
selective, receptor-mediated transfer of
IgG, from the blood of the dam across the
mammary secretory epithelium. This
transfer to colostrum begins approxi-
mately 4-6 weeks before parturition and
results in colostral IgG, concentrations in
first milking colostrum that are several -
fold higher than maternal serum con-
centrations. The transfer of the other
immunoglobulin classes is believed to be
nonselective and lesser concentrations in
colostrum are achieved.

Following ingestion by the newborn,
a significant proportion of these immuno-

globulins in ingested colostrum is trans-
ferred across the epithelial cells of the
small intestine during the first few hours
of life and transported via the lymphatic
system to the blood. Immunoglobulins in
the blood are further varyingly distributed
to extravascular fluids and to body
secretions depending upon the immuno-
globulin class.

These absorbed immunoglobulins
protect against systemic invasion by
microorganisms and septicemic disease
during the neonatal period. Unabsorbed
immunoglobulins and immunoglobulins
resecreted back into the gut play an
important role in protection against
intestinal disease for several weeks fol-
lowing birth. In calves, passive immunity
also influences the occurrence of respir-
atory disease during the first months of
life and may be a determinant of lifetime
productivity. In foals, failure of transfer of
passive immunity presents a significant
risk for the development of an illness
during the first 3 months of life.

Lactogenic immunity

The IgG concentration in milk falls
rapidly following parturition in all species
and immunoglobulin concentrations in
milk are low. In the sow, the concen-
tration of IgA falls only slightly during the
same period and it becomes a major
immunoglobulin of sows' milk. IgA is
synthesized by the mammary gland of the
sow throughout lactation and serves as an
important defense mechanism against
enteric disease in the nursing piglet. In
the piglet, IgA in milk is an important
mucosal defense mechanism whereas in
the calf there is little IgA in milk but some
enteric protection is provided by colostral
and milk IgG, and IgG derived from
serum that is resecreted into the
intestine. 2,3

FAILURE OF TRANSFER OF PASSIVE
IMMUNITY

Failure of transfer of colostral immuno-
globulins is the major determinant of
septicemic disease in all species. 4,5 It also
modulates the occurrence of mortality
and severity of enteric and respiratory
disease in early life 6 and, in some studies,
performance at later ages. 7-9 While an
important determinant for neonatal
disease and subsequent performance, it is
not the sole determinant and it is not
surprising that some studies have found
only a minor relationship.

In terms of the modulation of disease,
there can be no set cut-point for
circulating immunoglobulins as the cut-
point will vary according to the farm, its
environment, infection pressure and also
the type of disease. Figures are given
5 as a guide. With dairy calves serum
IgG, concentrations of 500 mg/dL are

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

associated with protection against
septicemic disease and concentrations of
1000 mg/dL or more are sufficient to
reduce the risk of infectious disease in most
environments. With foals, the equivalent
IgG, concentrations for protection are
given as 400 mg/dL and 800 mg/dL. 10 - 11

Rates of failure of transfer of passive
immunity are high in both sucking and
artificially fed dairy calves but are less in
beef calves. 12,13 Failure rates in foals are
lower and approximate 13-16% , 11,14 Rates
in lambs are also comparatively low.

In animals that are fed colostrum
artificially, risk for failure of transfer of
passive immunity is primarily dependent
upon the amount or mass of immuno-
globulin present in a feeding of colostrum,
the time after birth that this is fed, and the
efficiency of its absorption by the calf. The
mass of immunoglobulin fed is deter-
mined by the concentration of immuno-
globulin in the colostrum and the volume
that is fed. Feeding trials with calves
suggest that a mass of at least 100 g of
IgG, is required in colostrum fed to a
45 kg calf to obtain adequate (> 1000 mg/dL
IgG)) passive blood immunoglobulin
concentrations. 15

In animals that suck colostrum
naturally such as foals, risk for failure of
transfer of passive immunity is primarily
dependent upon the concentration of
immunoglobulin in the colostrum, the
amount that is ingested and the time
of first suckling. Inadequate colostral
immunoglobulin concentration and delay
in ingestion of colostrum are the two
important factors in failure of transfer of
passive immunity in foals. 16

1. Amount of immunoglobulin in

colostrum fed:

a. Volume of colostrum fed

b. Concentration of immunoglobulins in

colostrum

2. The amount of colostrum actually

suckled or fed

3. Efficiency of absorption of

immunoglobulins by neonate

4. Time after birth of suckling or feeding

Determinants of immunoglobulin
concentration in colostrum

Nominal concentrations of immuno-
globulin in the first milking colostrum of
cows are shown in Table 3.1. There can be
substantial variation in the concen-
tration of immunoglobulin in colostrum
in all species and the ingestion of a
'normal' amount of colostrum that
has low immunoglobulin concentration
may provide an insufficient amount of
immunoglobulin for protection. In a study
of over 900 first- milkings colostrum from
American Holstein cows, only 29% of the
colostrum samples contained a sufficiently
high concentration of immunoglobulin to
provide 100 g IgG in a 2 L volume. 17 The
equivalent percentages for 3 and 4 L
volume feedings were 71% and 87%.

A similar situation exists with horses.
The mean concentrations of IgG in
colostrum of mares 3-28 days before
foaling is greater than 1000 mg IgG/dL,
while at parturition the mean concen-
trations may vary from 4000-9000 mg/dL.
The concentrations decrease markedly
to 1000 mg/dL in 8-19 hours after
parturition. 18

It is apparent that variation in colostral
immunoglobulin concentration can be a
cause of failure of transfer of passive
immunity.

Some causes of this variation are:

° The concentrations of

immunoglobulin in colostrum fall
dramatically following parturition.
Only the first milking of colostrum
after calving should be considered for
feeding to calves for immunoglobulin
transfer. The concentrations in
second- milking colostrum are
approximately half those in the first
milking and by the fifth postcalving
milking, concentrations approach
those found during the remainder of
lactation

The immunoglobulin concentration of
colostrum decreases after calving even
when the cow is not milked. In order
to facilitate early feeding of colostrum
to a calf, herd policy may be to feed
stored colostrum taken from a

!

previously calved cow rather than the
newborn calf's dam. It is important
that this colostrum be milked as soon
as possible after parturition.

Colostrum that is collected 6 hours or
later after calving has a significantly
lower concentration than that
collected 2 hours after calving 17,19
Colostrum from cows or mares that
have been premilked to reduce
udder edema or from dams that leak
colostrum prior to parturition will
have low immunoglobulin
concentrations and alternate
colostrum should be fed for
immunoglobulin transfer as there is a
higher rate of failure in their foals and
calves

In cattle, dry periods of less than
30 days may result in colostrum of
lower immunoglobulin concentration
Premature foaling or the induction
of parturition can result in colostrum
with low immunoglobulin
concentration and/or low volume
In cattle, average colostral
immunoglobulin concentrations are
higher in cows in third or higher
lactation groups compared to
younger cows. However, colostrum
from all lactation numbers can
produce adequate immunoglobulin
mass. There is no scientific basis for
not feeding first-milking colostrum
from first-lactation cows
Larger-volume first-milking colostrum
tends to have lower immunoglobulin
concentrations than smaller-volume
colostrum, and colostrum weight can
be used to select colostrum of higher
immunoglobulin concentration for
calf feeding (Table 3.2)

A recent study has shown that
immunoglobulin concentrations are
higher in the early temporal fractions
of a single milking of first-milking
colostrum. 20 This might suggest that
segregation of the first portion of the
first-milking colostrum could provide
colo strums with higher
immunoglobulin concentration for
feeding

Tm'xoJ if^jl

-l.= e ln,.’i rS ll5f?

rf!,

Animal

Immunoglobulin

Concentration (mg/mL)
Serum Colostrum

Milk

Total immunoglobulin (%)
Serum Colostrum

Milk

Cow

IgG,

11.0

47.6

0.59

50

81

73

lgG 2

7.9

2.9

0.02

36

5

2.5

IgM

2.6

4.2

0.05

12

7

6.5

IgA

0.5

3.9

0.14

2

7

18

Sow

IgG

21.5

58.7

3.0

89

80

29

IgM

1.1

3.2

0.3

4

1

IgA

1.8

10.7

7.7

7

*14

70

Neonatal infection

Vi ^.VriTi

tnVr^ii ©i.i

r ■

IgG,

concentration (mg/mL)

Weight (lb)

% of colostrums

Mean Range

< 10

20

67

24-136

11-20

38

58

17-136

21-30

26

46

15-93

> 30

16

39

19-76

o There are breed differences in the
concentration of immunoglobulins in
first milking colostrum. In cattle, beef
breeds have higher concentrations.
Many dairy breeds, including
American Holsteins, produce
colostrum of relatively low
immunoglobulin concentration, and a
significant proportion of calves that
suckle cows of these breeds ingest an
inadequate mass of immunoglobulin.
Channel Island breeds have a greater
concentration of immunoglobulin in
colostrum that Holsteins. Breed
differences are also seen in horses,
with Arabian mares having higher
colostral immunoglobulin
concentrations than Standardbreds,
which in turn are higher than those of
Thoroughbreds. Breed differences also
occur in sheep, with higher
concentrations in meat and wool
breeds than dairy breeds 21
° Heat stress to cattle in the latter part
of pregnancy results in lower colostral
immunoglobulin concentrations 22
° One study found that calves from
cows with mastitis have lower serum
immunoglobulins. 23 Colostral volume
but not colostral immunoglobulin
concentration is reduced in mastitic
quarters and it is unlikely that mastitis
is a major determinant of the high
rate of failure of transfer of passive
immunity in dairy calves 24
0 There is a significant positive but
weak correlation between total
lactational milk and immunoglobulin
concentration in that cow's
colostrum. 17 Selection for production
does not appear to be a negative
influence on colostral
immunoglobulin concentration,
although dilution by high volume
production in first-milking colostrum
is a factor in low colostral
immunoglobulin concentration 25
0 The pooling of colostrum in theory
could avoid the variation in
immunoglobulin concentration of
individually fed colostrum and could
provide a colostrum that reflects the
antigenic experience of several cattle.
In practice, colostrum pools from
Holsteins invariably have low
immunoglobulin concentrations

because high-volume, low-
concentration colostrum dilutes the
concentration of the other samples in
the pool. If pools are used, the
diluting influence of low-
immunoglobulin-concentration, high-
volume colostrum should be limited
by restricting any individual cow's
contribution to the pool to 9 kg
(20 lb) or less. However, pooling
increases the risk of disease
transmission, as multiple cows are
represented in a pool and the pool is
fed to multiple calves. This can be
important in the control of Johne's
disease, bovine leukosis and
Mycoplasma bovis
1 Bacterial contamination of

colostrum can have a negative effect
on transfer of passive immunity and
one study 26 found high bacterial
counts in 85% of colostrums sampled
from 40 farms in the USA. Colostrum
that is to be fed or stored should be
collected with appropriate preparation
and sanitation of the cow and of the
milking equipment used on fresh
cows

0 Pasteurization of colostrum (both
pasteurization at 63°C for 30 min and
HTST 72°C for 15 s) reduces
colostrum IgG concentration. A recent
study 27 of batch pasteurization at
63°C for 30 minutes showed that the
percentage reduction in colostral IgG
concentration varied with the batch
size, with a 24% reduction in
57 L batch size and a 58% reduction
in a larger batch size. Calves fed 2 L
of pasteurized colostrum had twofold
lower serum concentrations of IgG
than controls

" Old mares (older than 15 years) may
have poor colostral immunoglobulin
concentration.

Volume of colostrum ingested

Holstein cows

The volume of colostrum that is fed has a
direct influence on the mass of immuno-
globulin ingested at first feeding. The
average volume of colostrum ingested by
nursing Holstein calves in the first 24
hours of life is reported as 2.4 L but there
is wide variation around this mean 28 and
a significant proportion of dairy calves fail

to ingest an adequate mass of immuno-
globulin in management systems that
provide colostrum solely by allowing the
calf to suck the dam. 6,29

In natural suckling situations, calves
may fail to ingest adequate colostrum
volumes before onset of the closure
process, and therefore absorb insufficient
colostral immunoglobulin. Early assisted
suckling may help avoid this. In dairy
calves the volume of colostrum that is
ingested can be controlled in artificial
feeding systems using nipple bottle
feeders or esophageal tube feeders.
Bucket feeding of colostrum is not
recommended, as training to feed from a
bucket can be associated with erratic
intakes.

The traditional recommendation for

the volume of colostrum to feed at first
feeding to calves is 2 L (2 quarts). How-
ever, only a small proportion of first-
milking colostrum from Holsteins contains
a sufficiently high concentration of
immunoglobulin to provide 100 g IgG in a
2 L volume and higher volumes of col-
ostrum are required to achieve this mass
intake. 17 Possibly the major cause of
failure of transfer of passive immunity
rests with the fact that commercial feed-
ing bottles are made in a 2 L size and this
is consequently the amount of colostrum
that is fed. Some calves fed with a nipple
bottle will drink volumes greater than 2 L
but others will refuse to ingest even 2 L of
colostrum in a reasonable period of time,
and calf rearers may lack the time or
patience to persist with nipple bottle
feeding until the required volume has
been ingested by all calves.

Larger volumes of colostrum can be
fed by an esophageal feeder and single
feedings of large volumes of colostrum
(3.5-4.0 L per 45 kg body weight) result in
the lowest percentage of calves with
failure of transfer of passive immunity by
allowing calves fed colostrum with rela-
tively low immunoglobulin concentrations
to receive an adequate immunoglobulin
mass prior to closure. 12,13,30 Feeding this
volume by an esophageal feeder causes
no apparent discomfort to a minimally
restrained calf.

Channel Island breeds
Jersey cows produce colostrum with a
higher immunoglobulin content than
Holsteins and the feeding of nipple bottle
2.0 L of first milking at birth and again at
12 hours of life results in excellent
circulating concentrations of immuno-
globulin. 31 Three L at each feeding is
recommended where feeding is with an
esophageal feeder.

Beef cows

With beef breeds very effective colostral
immunoglobulin transfer is achieved with

52

PARTI GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

natural sucking. This is believed to be due
to the greater vigor at birth exhibited by
these calves and the higher immuno-
globulin concentrations in beef colostrum,
requiring a smaller volume intake to
acquire an adequate mass. Natural
sucking will give an adequate volume
intake and there is no need to artificially
feed colostrum unless the dam is observed
to refuse nursing or the calf's viability
and sucking drive are compromised. 32,33
The yield of colostrum and colostral
immunoglobulins in beef cows can vary
widely 32 and range beef heifers may
produce critically low volumes of
colostrum. Differences in yield can be due
to breed or to nutritional status, although
undernutrition is not an effect unless it is
very severe. 34

Ewes

Colostrum yield is high in ewes in good
condition at lambing but may be low in
ewes with condition scores of 1.5-2.0. 35

Sows

In sows there is also very effective
colostral immunoglobulin transfer with
natural sucking and piglets average an
intake of 5-7% of body weight in the first
hour of life. 36 There is between-sow
variation in the amount of colostrum and
there can be a large variation in col-
ostrum supply from teat to teat, which
may explain variable health and
performance. During farrowing and for a
short period following, colostrum is
available freely from the udder but
thereafter it is released in ejections during
mass suckling. A strong coordinated
sucking stimulus is required by the piglet
for maximum release of colostrum and
this requires that the ambient tempera-
ture and other environmental factors be
conducive to optimum vigor of the
piglets. Small-birth-weight piglets, late-
birth-order piglets and piglets sucking
posterior teats obtain less colostrum.

All species

In all species a low-volume intake may
also occur because of:

0 Poor mothering behavior, which
may prevent the newborn from
sucking, occurrence of disease or milk
fever

° Poor udder and/or teat

conformation so the newborn cannot
suck normally or teat seeking is more
prolonged. Udder to floor distance is
most critical and low-slung udders
can account for significant delays in
intake. Bottle-shaped teats (35 mm
diameter) also significantly reduce
intake 37

• Delayed and inadequate colostral
intake frequently accompanies
perinatal asphyxia or acidosis due to

the greatly decreased vigor of the calf
in the first few hours of life. Perinatal
asphyxia can occur in any breed and is
greatly increased by matings resulting
in fetal-matemal disproportion and
dystocia

° The newborn may be weak,
traumatized, or unable to suck for
other reasons - a weak sucking
drive can be a result of congenital
iodine deficiency, cold stress or other
factors

° Failure to allow newborn animals to
ingest colostrum may occur under
some management systems.

Efficiency of absorption

After ingestion of colostrum by the new-
born, colostral immunoglobulins are
absorbed by the small intestine, by a
process of pinocytosis, into the columnar
cells of the epithelium. In the newborn
calf this is a very rapid process and
immunoglobulin can be detected in the
thoracic duct lymph within 80-120 minutes
of its being introduced into the duodenum.
The period of absorption varies between
species and with immunoglobulin class
and the mechanism by which absorption
ceases is not well understood but may be
related to replacement of the fetal entero-
cyte. The region of maximum absorption
is in the lower small intestine and peak
serum concentrations are reached by
12-24 hours in all species. Absorption is
not limited to immunoglobulins and
there is a proteinuria during the first
24 hours of life associated with the renal
excretion of low-molecular- weight proteins
such as P-lactoglobulin.

Feeding methods, closure and
immunoglobulin absorption
Under normal conditions complete loss of
the ability to absorb immunoglobulin
(closure) occurs by 24-36 hours after birth
in all species and there is a significant
reduction in absorptive ability (as much
as 50% in some studies but minimal in
others) by 8-12 hours following birth.
The time from birth to feeding is a
crucial factor affecting the absorption of
colostral immunoglobulins by all species,
and any delay beyond the first few hours
of life, particularly after 8 hours, signifi-
cantly reduces the amount of immuno-
globulin absorbed.

The recommendation is that all
neonates be fed colostrum within the first
2 hours of life.

Natural sucking

Natural sucking is the desired method
of intake of colostrum and is the most
efficient, but it is influenced by the suck-
ing drive and vigor of the calf at birth.
Calves that suck colostrum can achieve
very high concentrations of colostral

immunoglobulin and the efficiency of
absorption is best with this feeding
method. However, natural sucking of
dairy calves is commonly associated with
a high rate of passive transfer failure due
to delays in sucking coupled with low
intakes. In one study 25-34% of calves
failed to suck by 6-8 hours of age and
18% of calves did not suck by 18 hours of
age. There may be breed differences in
sucking ability: Jersey calves have better
rates of successful transfer of passive
immunity with natural sucking than do
Holsteins. 38 Many factors influence the
occurrence of delayed sucking but calf
vigor and birth anoxia are the most
important. Conformation of the udder is
significant and the importance of this
increases with parity.

Artificial feeding

In contrast, when calves are fed colostrum
artificially, minimal delays from birth to
the time of colostrum feeding occur
and maximal colostrum immunoglobulin
absorption results. In breeds like American
Holsteins, where colostral immunoglobulin
concentrations tend to be quite low and
maximal efficiency of absorption is
necessary, the logical way to minimize the
effects of closure is to feed the maximum
well-tolerated colostrum volume at the
first feeding within the first few hours of
life. The published literature consistently
reports higher calf serum IgG, concen-
trations and a lower rate of failures in
response to larger colostrum feeding
volumes. 12,13

Other influences

Even with the best available on-farm
colostrum selection methods, large
colostrum-feeding volumes are essential
to minimize failure of transfer of colostral
immunoglobulins in breeds with relatively
low colostral immunoglobulin concen-
trations. The method is particularly
advantageous where time constraints of
other farm activities limit the time
available for calf feeding. The major
detrimental influence on absorptive
efficiency of immunoglobulins is delayed
feeding after birth. Other factors that
affect absorptive efficiency include:

° Perinatal asphyxia or acidosis may
have both direct and indirect effects
on colostral immunoglobulin transfer.
Asphyxia has a major effect on
subsequent sucking drive and
acidemic calves ingest far less
colostrum than calves with more
normal acid-base status at birth. In
carefully controlled colostrum feeding
studies, there was also significant
negative correlation between the
degree of hypercapnia and efficiency
of absorption of colostral

Neonatal infection

immunoglobulins, even in calves
within the 'normal' newborn blood pH
and Pc o 2 ranges. 39 Direct oxygen
deprivation of newborn calves did not
cause a similar effect. 40 Treatment of
calves with an alkalinizing agent and
a respiratory stimulant altered pH and
Pco 2 values towards adult normal
values but did not influence
immunoglobulin absorption
efficiency 39

e In one early study, a mothering
effect was reported where calves
remaining with their dams absorbed
colostral immunoglobulin much more
efficiently than calves removed
immediately to individual box stalls.
However, other studies have shown
much smaller or no effects of
mothering using similar experimental
designs. The different results of these
studies have not been reconciled

° There can be seasonal and

geographical variations in transfer of
immunoglobulins in calves although
these are not always present on farms
in the same area and their cause is
unknown. Where seasonal variation
occurs in temperate climates the
mean monthly serum IgGa
concentrations are lowest in the
winter and increase during the spring
and early summer to reach their peak
in September, after which they
decrease. The cause is not known but
an decrease in sucking drive is
observed in colder months and may
contribute. In subtropical climates,
peak levels occur in the winter
months, while low levels are
associated with elevated temperatures
during the summer months. 41 Heat
stress in late pregnancy will reduce
colostral immunoglobulin
concentration but high ambient
temperature is a strong depressant of
absorption and the provision of shade
will help to obviate the problem
The efficiency of absorption may be
decreased in premature calves that
are born following induced
parturition 42 but the medical
induction of parturition with short-
acting corticosteroids in cattle does
not interfere with the efficiency of
absorption of immunoglobulins in
calves

° The absorption of small volumes
(1-2 L) fed by an esophageal feeder is
usually suboptimal, probably due to
retention of some colostrum in the
immature forestomachs for several
hours. The calf will feel satiated and
not inclined to suck naturally for the
next few hours

° A trypsin inhibitor in colostrum may
serve to protect colostral IgG from

intestinal degradation. It varies in
concentration between colostrums.

The addition of a trypsin inhibitor to
colostrum improves immunoglobulin
absorption 43

° In a study of mare-associated

determinants of failure of transfer
of passive immunity in foals (based
on serum Ig measurements), there
was a trend to increase rates of failure
in foals from mares aged over
12 years but no real association with
age, parity or gestational age of foals
over 325 days. There was an
association with season with a lower
incidence in the late spring compared
with foals bom earlier in the year and
with a foal score based on a veterinary
score of foal health and 'fitness'. 44

Traditionally it has been considered that
the movement of animals, either the dam
just before parturition or the newborn
animal during the first few days of life, is
a special hazard for the health of the calf.
The postulated reason is that the dam
may not have been exposed to pathogens
present in the new environment and thus
not have circulating antibodies against
these pathogens. The newborn animal
may be in the same position with regard
to both deficiency of antibodies and expo-
sure to new infections. While this may
obtain in some situations, the developing
practice of contract-rearing of dairy
heifers away from the farm to be brought
back as close-up springers, and the
practice of purchase of close-up heifers
on to the farm, are not associated with
appreciable increase in mortality in their
calves.

Decline of passive immunity

Passive antibody levels fall quickly after
birth and have usually disappeared by
6 months of age. In the foal, they have
fallen to less than 50% of peak level by
1 month of age, and to a minimum level
between 30 and 60 days. This is the point
at which naturally immunodeficient foals
are highly susceptible to fatal infection.

In calves, the level of IgG declines
slowly and reaches minimum values by
60 days, in contrast to IgM and IgA, which
decline more rapidly and reach minimum
values by approximately 21 days of age.
The half-lives for IgG, IgM and IgA in
calves are approximately 20, 4 and 2 days
respectively and half lives of IgGa, IgGb,
IgG(T) and IgA in foals are approximately
18, 32, 21 and 3.5 days respectively. 45

Immunological competence is present
at birth but endogenous antibody pro-
duction does not usually reach protective
levels until 1 month, and maximum levels
not until 2-3 months of age. The endo-
genous production of intestinal IgA in the
piglet begins at about 2 weeks of age and

does not reach significant levels until
5 weeks of age.

Foals that acquire low concentrations
of immunoglobulins from colostrum may
experience a transitory hypogamma-
globulinemia at several weeks of age as
the levels fall and before autogenous
antibodies develop.They are, as expected,
more subject to infection than normal.

OTHER BENEFITS OF COLOSTRUM

In addition to its immunoglobulin con-
tent, colostrum contains considerably
more protein, fat, vitamins and minerals
than milk and is especially important in
the transfer of fat-soluble vitamins. It has
anabolic effects and lambs that ingest
colostrum have a higher summit metab-
olism than colostrum-deprived lambs.
Colostrum also contains growth-promoting
factors that stimulate DNA synthesis and
cell division including high concen-
trations of insulin-like growth factor
(IGF) -1 46,47

Colostrum contains approximately 106
leukocytes/mL and several hundred
million are ingested with the first feeding
of colostrum. In calves 20-30% of these
are lymphocytes and cross the intestine
into the circulation of the calf. 48 It is
postulated that they have importance in
the development of neonatal resistance to
disease but there is little tangible evidence.
Calves fed colostrum depleted of leuko-
cytes are claimed to be more poorly
protected against neonatal disease than
those fed normal colostrum. 49

ASSESSMENT OF TRANSFER OF
PASSIVE IMMUNITY

Because of the importance of transfer of
colostral antibodies to the health of the
neonate, it is common to quantitatively
estimate the levels of immunoglobulins,
or their surrogates, in colostrum and in
serum in order to predict risk of disease
and to take preventive measures in the
individual or to make corrective manage-
ment changes where groups of animals
are at risk.

Assessment in the individual animal

Where samples are taken from an indivi-
dual animal to determine the risk for
infection, sampling is undertaken early so
that replacement therapy can be given
promptly if there has been inadequate
transfer. IgG is detectable in serum 2 hours
following a colostrum feeding and
sampling at 8-12 hours after birth will
give a good indication of whether early
sucking has occurred and has been
effective in transfer. 50 This type of
monitoring is commonly performed in
foals.There are a number of different tests
that can be used, some of which are quan-
titative and others semi- quantitative. For
foals, these include commercially available

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

tests such as the latex agglutination,
concentration immunoassay and
hemagglutination inhibition tests. These
are semi- quantitative and the relative
value of these tests for this type of
analysis has been evaluated. 51-52 A
glutaraldehyde test for serum is available
commercially for use in the horse and is
reported to correlate well with radial
immunodiffusion (RID) values. 53 In
calves, sampling may be undertaken for
similar reasons but the cost of replace-
ment therapy is limiting.

Monitoring assessment tests on
serum

Sampling to monitor the efficacy of a
farm policy for feeding colostrum, to
evaluate levels in calves to be purchased
or to determine the rates of failure of
transfer of passive immunity in investi-
gations of neonatal disease can be
conducted at any time in the first week of
life after 48 hours with most tests. This is
possible because of the relatively long
half-life of IgG.

Radial immunodiffusion
This test is usually used in research
studies and is the gold standard. It is
available commercially but is expensive
and takes longer to perform than is
desirable for most clinical purposes. An
enzyme-linked immunosorbent assay
(ELISA) for measurement of IgG concen-
tration in horses and in porcine plasma
and colostrum suffers from the same
problems.

Quantitative zinc sulfate test
This is a good predictor of mortality but
requires instrumentation. It has been
used for many years in calves and lambs
and has been validated in horses. 54
Hemolyzed blood samples will give
artificially high readings, and the reagent
must be kept free of dissolved carbon
dioxide. The suggested cut-point is 20
ZST units. Increased test solution concen-
trations to those traditionally used have
been suggested to improve sensitivity. 55

Serum y-glutamyltransf erase activity
Serum y-glutamyltransferase (GGT)
activity has been used as a surrogate for
determining the efficacy of transfer of
passive immunity in calves and lambs.
GGT concentrations are high in the
colostrum of ruminants (but not horses)
and serum GGT activity in calves and
lambs that have sucked or been fed
colostrum are 60-160 times greater than
normal adult serum activity and correlate
moderately well with serum IgG con-
centrations. 56-57 The half-life of GGT from
colostrum is short and serum GGT
activity falls significantly in the first week
of life. Serum GGT values equivalent to a
serum IgG concentration of 10 mg/mL are

200 IU/L on day 1 of life and 100 IU/L on
day 4. Serum GGT concentrations less
than 50 IU/L indicate failure of transfer of
passive immunity. 56-58

Serum total protein

Total protein, as measured by a
refractometer, gives an indirect measure
of the amount of immunoglobulin.
Despite the indirect nature of the test,
there is a reliable correlation between the
refractometer reading and total immuno-
globulin concentration (IgG and IgM)
measured by RID. In healthy calves a
serum total protein of 5.2 g/dL or greater
is associated with adequate transfer of
passive immunity.

Serum total protein has good pre-
dictive value for fate of the newborn, and
the facile and practical nature of the test
and its predictive ability commends it for
survey studies in calves and lambs but not
foals. Cut-points will vary with the environ-
ment 59-60 and the infection pressure to the
calves. The sensitivity of the test is
maximal using a cut point of 5.5 g/dL and
the specificity is maximal at a cut point of
5.0 g/dL. 61 The refractometer can give
false high values in dehydrated calves but
these can be clinically identified and a cut
point of 5.5 g/dL can be used.

Sodium sulfite precipitation and
glutaraldehyde test

Both of these were developed as rapid
field tests to evaluate the immune status
of neonatal calves. An 18% test solution is
used and the development of turbidity is
the determinant of adequate transfer of
passive immunity. The glutaraldehyde
coagulation test is also available for the
detection of hypogammaglobulinemia in
neonatal calves but is less accurate. 61
Neither test is widely used.

ELISA test

An ELISA test is commercially available
and used for calf- side testing.

Monitoring colostrum

There has long been the desire for a
method to select colostrums with high
immunoglobulin concentration for feed-
ing neonates.

Specific gravity

Specific gravity can be used as a measure
of immunoglobulin content of colostrum.
In mares the concentration of immuno-
globulins in colostrum is highly correlated
with the specific gravity of the colostrum,
which in turn is highly correlated with the
serum immunoglobulin levels achieved in
foals. 50-62 Temperature-corrected measure-
ments are most accurate. 63 Measurement
of colostrum specific gravity provides a
rapid and easy method of identifying foals
likely to be at a high risk for failure of
transfer of passive immunity and the

need to provide them with colostrum of a
higher Ig content. It is recommended
that, to prevent failure of transfer of
passive immunity, the colostral specific
gravity should be equal to or greater than
1.060 and the colostral IgG concentration
be a minimum of 3000 mg/dL. 62

In cattle the relation of specific gravity
of colostrum to colostral immunoglobulin
concentration is linear but is better in
Holsteins than in Jerseys 58 The measure-
ment is simple but there is a correction for
temperature, and air trapped in colostrum
taken by a milking machine can give a
false reading if the measurement is taken
too quickly after milking. The cut-point
recommended to distinguish moderate
from excellent colostrum has been set at
1.048 and is based on the amount of
immunoglobulin required for a 2 quart
feeding. Specific gravity is not a perfect
surrogate for immunoglobulin concen-
tration with cattle colostrum. It has good
negative prediction but it will falsely pass
many Holstein colostrums that have low
immunoglobulin concentration and is not
accurate with Jersey colostrum. 64-65 An
analysis of first-milking colostrum in
midwest USA dairies found that specific
gravity differed among breeds and was
influenced by month of calving, year of
calving, lactation number and protein
yield in previous lactation and that it was
more closely associated with colostrum
protein concentration (r = 0.76) than IgG!
concentration (r = 0.53). 66

Glutaraldehyde test

This test for mare colostrum is available
commercially and is reported to have a
high predictive value for colostrums that
contain more than 38 mg/mL of IgG and
have a specific gravity greater than
1.060. 67-68

ELISA

Recently, a cow-side immunoassay kit has
become available commercially in the US.
The kit provided a positive or a negative
response with the cut point being a con-
centration of 50 g/L of IgG in colostrum
and has accuracy sufficient to recommend
its use for rejection of colostrums with
low immunoglobulin concentration. 69

CORRECTION OF FAILURE OF
TRANSFER OF PASSIVE IMMUNITY

Parenteral immunoglobulins
Blood transfusion is commonly used
and the method is described elsewhere in
this text. Purified immunoglobulin prep-
arations are an alternative and are avail-
able commercially in some countries.
Large amounts are required to obtain the
required high serum concentrations of
immunoglobulins and intravenous infusion
can be’ accompanied by transfusion-type
reactions.

Wf'--'-

Neonatal infection

155

AVOIDANCE OF FAILURE OF
TRANSFER OF PASSIVE IMMUNITY

With all species, with the exception of
dairy calves, the common practice is to
allow the newborn to suck naturally. The
policy for avoidance of failure of transfer
of passive immunity with naturally
sucking herds should be to provide
supplemental colostrum by artificial
feeding of those neonates with a high risk
for failure, based on the risk factors
detailed above. In the dairy calf, rates of
failure with natural sucking are so high
that many farms opt to remove that calf at
birth and feed colostrum by hand to
ensure adequate intakes.

Colostrum

Colostrum can be stripped from the dam
and fed fresh or the neonate can be fed
stored (banked) colostrum.

Colostrum for banking
With dairy cows, first- milking colostrum
from a cow with a first- milking yield of
less than 10 kg should be used. The
temptation for the farmer is to store the
leftover from the feeding of large-volume
colostrum. This should not be used as it
has a high probability of containing a low
immunoglobulin concentration.

Colostrum from mares should have a
specific gravity of 1.060 or more and
200 mL can be milked from a mare before
the foal begins sucking.

Storage of colostrum
Colostrum can be kept at refrigerator
temperature for approximately 1 week
without significant deterioration in
immunoglobulins. Storage in plastic
containers also maintains the viability of
cellular components. 26 The addition of
formaldehyde to 0.05% (wt/vol) allows
maintenance at 28° C for 4 weeks without
loss of immunoglobulins as detected by
RID 70 but information on such col-
ostrum's protection efficacy, when fed, is
not available. The addition of 5 g of
propionic or lactic acid per liter extends
the storage life to 6 weeks 30 but, more
commonly, colostrum is frozen for
storage. Frozen colostrum, at -20°C, can
be stored virtually indefinitely and there is
no impairment to the subsequent absorp-
tion of immunoglobulins. Frozen col-
ostrum should be stored in flat plastic
bags in the amount required for a feeding,
which facilitates thawing. Thawing
should be at temperatures below 55°C.
Higher temperatures and microwave
thawing results in the deterioration of
immunoglobulins and antibody in frozen
colostrum and frozen plasma. 71

Cross-species colostrum

Colostrum from another species can be
used to provide immunological protection
where same-species colostrum is not

available. Bovine colostrum can be fed
to a number of different species. While
absorption of immunoglobulins occurs
and significant protection can be
achieved, 72 the use of cross-species
colostrum is not without some risk and
the absorbed immunoglobulins have a
short half-life. Bovine colostrum has been
successfully used for many years to
improve the survival rate of hysterectomy-
produced artificially reared pigs. It has
also been used as an alternate source of
colostral antibody for rearing goats free of
caprine arthritis-encephalitis. Colostrum
from some cows can result in the develop-
ment of a hemolytic anemia, occurring at
around 5-12 days of age, in lambs and
kids because the IgG of some cows
attaches to the red cells and their
precursors in bone marrow, resulting in
red cell destruction by the reticulo-
endothelial system. 73,74 Treatment of the
anemia consists of a blood transfusion.
Bovine colostrum can be tested for 'anti-
sheep'factors by a gel precipitation test on
colostral whey but this test is not
generally available. Bovine colostrum can
provide some protection to newborn foals
against neonatal infections and protection
appears to be due to factors in addition to
the immunoglobulins, which have a short
half-life in foals.

Colostrum supplements

In recent years there has been a move to
develop supplements or even replace-
ments for colostrum to feed calves. These
have been attempted using IgG concen-
trated from bovine colostrum, milk whey,
eggs or bovine serum. The search for
colostrum substitutes or colostrum
replacers has been prompted by the
problem of the variability of IgG concen-
tration in natural colostrum. It has also
been prompted by possible limitations of
availability of high-quality colostrum on
dairy farms as the result of discarding
colostrum from cows that test positive to
disease that can transmit through
colostrum, such as Johne's disease, bovine
leukosis. Mycoplasma bovis. This problem
is confounded by reports that pasteur-
ization of colostrum can have a deleterious
effect on IgG concentration in colostrum
and its subsequent absorption by calves. 27

Lacteal-secretion-based preparations
Colostrum supplements prepared from
whey or colostrum are available com-
mercially in many countries. Depending
upon the manufacturer, they contain
varying amounts of immunoglobulin but
significantly less than first-milking col-
ostrum. The amount of immunoglobulin
contained varies, but the recommendations
for feeding that accompany these pro-
ducts indicate that they will supply
approximately 25% or less of the immuno-

globulin required to elevate calf serum
IgG concentrations above lOOOmg/dL.
There is a further problem in that the
immunoglobulins in products made from
colostrum or whey are poorly absorbed
and trials assessing their ability to increase
circulating immunoglobulins when fed with
colostrum have generally shown little
improvement and no improvement in
health-related parameters. 75-80

There is evidence that their inclusion
with colostrum can impair the efficiency
of colostral immunoglobulin 77 and if they
are fed they should be fed after normal
colostrum. While these milk-protein-
derived products are advertised for
supplementing normal colostrum feed-
ing, they are unfortunately often pro-
moted as replacements and used by
farmers as total substitutes for colostrum.
When fed as the sole source of immuno-
globulin to colostrum -deprived calves,
they achieve circulating concentrations of
immunoglobulin that are lower than
those achieved by natural colostrum
containing equivalent amounts of
immunoglobulin . 76

Bovine-serum-based preparations
Colostrum supplements prepared from
bovine serum are also available com-
mercially but regulations governing the
feeding of blood or blood products to
calves (risk reduction for bovine spongiform
encephalopathy) may limit their avail-
ability in some countries. The absorption
of immunoglobulin from these bovine-
serum-derived commercial products
appears better than from milk-protein-
derived products 80 and consequently they
are also marketed as colostrum replacers.
It has been proposed that the distinction
between a colostrum supplement and a
colostrum replacer should be the immuno-
globulin mass contained in the product,
with a colostrum supplement having less
than 100 g IgG per dose and a colostrum
replacer having sufficient immuno-
globulin mass in a dose to result in a
serum IgG concentration greater than
10 mg/mL following a feeding. 80

A large mass of immunoglobulin is
required for acquisition of adequate
circulating immunoglobulin. Calves fed a
colostrum replacement containing a high
mass (250 g for Holsteins) of an IgG
derived from bovine serum and fed at 1.5
and again at 13.5 hours after birth,
achieved equivalent serum IgG concen-
trations to calves fed normal colostrum
and showed no difference in gain or health
parameters during the first 4 weeks of
life. 81

The IgG in a commercially available
bovine serum colostrum replacer has
been shown to be effectively absorbed
when fed to newborn lambs. The feeding

56

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

of 200 g of IgG in the first 24 hours of life
resulted in a mean plasma concentration
of 18 mg/mL 82

The published literature suggests that
there is little advantage to be gained from
the use of milk-protein- derived colostrum
supplements and their use as colostrum
replacers or substitutes is not recommended,
except where there is no source of natural
colostrum due to factors such as the death
of the dam. The feeding of colostrum-
derived supplements can result in a
modest elevation of circulating IgG,
sufficient to protect against experimental
colisepticemia. If available, the bovine-
serum-derived products would be more
suitable.

The use of colostrum replacers should
be confined to this type of emergency and
there can be little justification for more
widespread use, particularly as there are
limited independent health-related
publications of their efficacy. Also, as men-
tioned above, in addition to immuno-
globulins, natural colostrum contains
various substances important to neonatal
physiology.

Administration of colostrum

Foals

Foals should be allowed to suck naturally.
The specific gravity of the mare's col-
ostrum can be checked at foaling and,
where this is less than 1.060, supple-
mental colostrum may be indicated. Foals
that do not suck, or that have serum IgG
concentrations less than 400 mg/mL at
12 hours of age, or that require supple-
mentation for other reasons, should be
fed colostrum with a specific gravity of
1.060 or more at an amount of 200 mL at
hourly feedings. 50 ' 60

Dairy calves

Assisted natural sucking
Leaving the newborn dairy calf with the
cow is no guarantee that the calf will
obtain sufficient colostrum and a high
proportion fail either to suck early or to
absorb sufficient immunoglobulins from
ingested colostrum. This problem can be
alleviated to some extent by assisted
natural sucking but this can fail because
not all calves requiring assistance are
detected. An alternate approach is to milk
2 L of colostrum from the dam, bottle-
feed each calf as soon after birth as
possible, then leave the calf with the cow
for 24 hours and allow it to suck
voluntarily. While this will not be as
effective as a system based entirely on
artificial feeding of selected colostrum, it
is an approach that is suitable for the
smaller dairy farm.

Artificial feeding systems

With artificial feeding systems, the calf
is removed from the dam at birth and fed

colostrum by hand throughout the whole
absorptive period. Nipple bottle-feeding
can be used with 2 L of colostrum given
every 12 hours (Holstein calves) for the
first 48 hours of life. The first feeding is
usually milked from the cow by hand and
the remaining feedings are from the
colostrum obtained from the cow after
the first machine milking. If care and
patience is taken with feeding, this
system can result in good transfer of
passive immunity in all calves except
those born to dams that have very low
concentrations of immunoglobulin in
their colostrum. Unfortunately, with
American Holsteins this can be a signifi-
cant percentage. An extension from this
system is to nipple bottle-feed at the
same frequency but to feed stored
I colostrum’ selected for its superior j
\ immunoglobulin content. Nipple bottle- j
j feeding of newborn calves requires j
j considerable patience and its success is ;

| very much dependent on the calf feeder I
j and on the availability of the feeder's time ■

| when faced with a calf that has a slow
j intake.

Where the diligence of the calf feeders
j is poor, or where there is a time constraint j
j on their availability, the feeding of a large !
j volume of colostrum (4 L to a 45 kg calf) !

| by esophageal feeder at the initial j
1 feeding immediately after birth can be a j
j successful practice. The large-volume I
; feeding also allows the delivery of an j
; adequate mass of immunoglobulin with I
: colostrum that has low immunoglobulin j
: concentrations and the delivery of j
j colostrum to the gut in its early absorptive \
■ period. The practice usually uses stored
colostrum and the feeding can be |
achieved within a few minutes. It can be
I supplemented by bottle-feeding of a
second feeding at 12 hours of life.

The practice of feeding stored colostrum j
as the sole source of colostrum is limited
to larger dairy herds but it does allow
j the selection of superior colostrum for
feeding with selection based on weight
and specific gravity as detailed above.

: Beef calves i

; Beef calves should be allowed to suck
naturally and force-feeding of colostrum
to beef breeds should not be practiced
unless there is obvious failure of sucking,
i Where colostrum is required, as with j
weak beef calves, calves with edematous 1
tongues and calves that have been sub-
j jected to a difficult birth, it can be
: administered with an esophageal feeder j
; or a stomach tube. ;

I Lambs

j Lambs are allowed to suck naturally but
; there can be competition between siblings
for colostrum and one large single lamb is
: capable of ingesting, within a short period

of birth, all the available colostrum in the
ewe's udder. Lambs require a total of
180-210 mL colostrum/kg body weight
during the first 18 hours after birth to
provide sufficient energy for heat pro-
duction. 35 This amount will usually
provide enough immunoglobulins for
protection against infections. Supple-
mental feeding of colostrum may be
advisable for lambs from multiple birth
litters, lambs that lack vigor and those
that have not nursed by 2 hours following
birth. This can be done with a nipple
bottle or an esophageal feeder.

Piglets

Colostral supplementation is not com-
monly practiced with piglets. An
immunoglobulin dose of 10 g/kg body
weight on day 1 followed by 2 g/kg on
succeeding days for 10 days is sufficient
to confer passive immunity on the col-
ostrum-deprived pig.

REVIEW LITERATURE

Norcross NL. Secretion and composition of colostrum
and milk. J Am Vet Med Assoc 1982; 181:1057.
Gay CC. Failure of passive transfer of colostral
immunoglobulins and neonatal disease in calves:
a review. In: Proceedings of the Fourth
International Symposium on Neonatal Diarrhea,
Saskatoon, Saskatchewan, Canada. Saskatoon:
University of Saskatchewan, 1983: 346-364.
Besser TE, Gay CC. Septicemic colibacillosis and
failure of passive transfer of immunoglobulin in
calves. Vet Clin North Am Food Anim Pract 1985;
1:445-459.

Black L, Francis ML, Nicholls MJ. Protecting young
domestic animals from infectious disease. Vet
Annu 1985; 25:46-61.

Sheldrake RF, Husband AJ. Immune defences at
mucosal surfaces in ruminants. J Dairy Res 1985;
52:599-613.

Staley TE, Bush LJ. Receptor mechanism of the
neonatal intestine and their relationship to
immunoglobulin absorption and disease. J Dairy
Sci 1985; 68:184-205.

Butler JE. Biochemistry and biology of ruminant
immunoglobulins. Prog Vet Microbiol Immunol
1986; 2:1-53.

Carter GK. Septicemia in the neonatal foal. Compend
Con tin Educ Pract Vet 1986; 8:S256-S270.

Morris DD. Immunologic disease of foals. Compend
Contin Educ PractVet 1986; 8:S139-S150.

Mellor D. Meeting colostrum needs of lambs. In Pract
1990; 12:239-244.

Brenner J. Rissive lactogenic immunity in calves: a
review. Israel JVct Med 1991; 46:1-12.

Besser TE, Gay CC. Colostral transfer of
immunoglobulins to the calf. Vet Annu 1993;
33:53-61.

Garry F, Aldridge B, Adams R. Role of colostral
transfer in neonatal calf management: current
concepts in diagnosis. Compend Contin Educ
PractVet 1993; 15:1167-1175.

White DG. Colostral supplementation in ruminants.
Compend Contin Educ Pract Vet 1993;
15:335-342.

Besser TE, Gay CC. The importance of colostrum to
the health of the neonatal calf. Vet Clin North Am
Food Anim Pract 1994; 10:107.

Quigley JD, Drewry JJ. Nutrient and immunity
transfer from cow to calf pre- and postcalving. J
Daily Sci 1998; 81:2779-2790.

Neonatal infection

Weaver DM, Tyler JW, VanMetre D, Hoetetler DE,
Barrington GM. Passive transfer of colostral
immunoglobulins in calves. J Vet Intern Med 2000;
14:569-577.

Barrington GM, Parish SM. Bovine neonatal
immunology. Vet Clin North Am Food Anim Pract
2001; 17:463-476.

Rooke JA, Bland IM. The acquisition of passive
immunity in the newborn piglet. Livestock
Product Sci 2002; 78:13-23.

McGuirk SM, Collins M. Managing the production,
storage, and delivery of colostrum. Vet Clin North
Am Food Anim Pract 2004; 20:593-603.

REFERENCES

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National Dairy Heifer Evaluation Project: Dairy
herd management practices focusing on
preweaned heifers. Fort Collins, CO: USDA:
APHIS: VS, 2002.

2. Besser TE. Vet Immunol Immunopathol 1993;
38:103.

3. Saif LJ, Smith KL. J Dairy Sci 1985; 68:206.

4. Robinson JA et al. EquineVet J 1993; 25:214.

5. Gay CC et al. In: Gyles CL, ed. Escherichia coli in
domestic animals and humans. Wallingford,
Oxfordshire: CAB International, 1994:75.

6. Gay CC. 1983; In: Proceedings of the Fourth
International Symposium on Neonatal Diarrhea,
Saskatoon, Saskatchewan, Canada. Saskatoon:
University of Saskatchewan, 1983; 4:346.

7. Wittum TE, Perino LJ. Am JVet Res 1995; 56:1149.

8. Vtells SJ et al. Prevent \fet Med 1996; 29:9.

9. Donovan GA et al. Prevent Vet Med 1998; 34:31.

10. Ley WB et al. EquineVet Sci 1990; 10:262.

11. Tyler-McGowan JL et al. AustVet J 1997; 75:56.

12. BesserTE, Gay CC.Vet Clin NorthAm Food Anim
Pract 1994; 10:107.

13. BesserTE, Gay CC.Vet Annu 1993; 33:53-61.

14. LeBlanc MM et al. J Am Vet Med Assoc 1992;
200:179.

15. BesserTE et al. J AmVetMed Assoc 1991; 198:419.

16. Chavatte-Fcilmer P et al. Pferdheilkunde 2001;
17:669.

17. Pritchett L et al. J Dairy Sci 1991; 74:2336.

18. Pearson RC et al. Am JVet Res 1984; 45:186.

19. Moore M et al. J Am Vet Med Assoc 2005;
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20. Hostetler D et al. J Appl Res\bt Med 2003; 1:168.

21. V\belchli RO et al. Vet Recl994; 135:16. j

22. Nardone E et al. J Dairy Sci 1997; 80:838. !

23. Perino LJ et al. Am JVet Res 1995; 56:1144, 1149. j

24. Maunsell FP et al. J Daily Sci 1998; 81:1291. j

25. Guy MA et al. J Dairy Sci 1994; 77:3002. j

26. Godden SM et al. J Dairy Sci 2003; 86:1503. j

27. Stott GH et al. J Dairy Sci 1979; 62:1632, 1766, j

1902, 1 908. ;

28. McGuirk SM, Collins M.\fet Clin North Am Food •
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29. Franklin ST et al. J Dairy Sci 2003; 86:2145. ;

30. White DG. Compend Contin Educ Pract Vet 1993; J

15:335. ;

31. Jaster EH. J Dairy Sci 2005; 88:296.

32. Petrie L ct al. Can Vet J 1984; 25:273.

33. Bradley JA, Niilo L. Can Vet J 1984; 25:121. j

34. Hough RL et al. J Anim Sci 1990; 68:2662. ;

35. Mellor DJ. In Pract 1990; 12:239. ;

36. Fraser D, Rushen J. Can J Anim Sci 1992; 72:1.

37. Ventorp M, Michanek P. J Dairy Sci 1992;

75:262. ]

38. Quigley JD et al. J Dairy Sci 1995; 78:893.

39. Ayers MW, BesserTE. Am JVet Res 1992; 53:83.

40. Tyler H, Ramsey H. J Dairy Sci 1991; 74:1953.

41. Mohammed HO et al. Cornell\bt 1991; 81:173.

42. Johnston NE, Stewart JA; AustVet J 1986; 63:191. ;

43. Quigley JD et al. J Dairy Sci 1995; 78:886, 1573.

44. Clabough DL et al. JVet Intern Med 1991; 5:335.

45. Sheoran AS et al. Am JVet Res 2000; 61:1099.

46. Barrington GM, Parish SM. Vet Clin North Am
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47. Blum JW, Baumruckerb CR. Domest Anim
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48. Le Jan C. Vet Res 1996; 27:403.

49. Reidel-Caspari G. Vet Immunol Immunopathol
1993; 35:275.

50. Massey RE et al. Proc Am Assoc Equine Pract
1991; 36:1.

51. Ley WB et al. EquineVet Sci 1990; 10:262.

52. Morris DD et al. Am JVet Res 1985; 46:S294.

53. Jones D, Brook D. J EquineVet Sci 1994; 14:85.

54. LeBlanc MM et al. EquineVet Sci 1990; 10:36.

55. Hudgens KA et al. Am JVet Res 1996; 57:1711.

56. Fbrino LJ et al. Am J Vet Res 1993; 54:56.

57. Tessman RK et al. J Am Vet Med Assoc 1997;
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58. Fhrish SM et al. JVet Intern Med 1997; 11:344.

59. Tyler JW et al. JVet Intern Med 1998; 12:79.

60. Rea DE et al. J Am Vet Med Assoc 1996; 208:2047.

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62. LeBlanc MM et al. J Am Vet Med Assoc 1986;
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63. Dascanio JJ et al. Equine Pract 1997; 19:23.

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66. Morin DE et al. J Dairy Sci 2001; 84:937.

67. Jones D, Brook D. J EquineVet Sci 1994; 14:85.

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75. Abel Francisco SF, Quigley JD. Am JVet Res 1993;
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76. Garry FB et al. J Am Vet Med Assoc 1996; 208:107.

77. Morrin DE et al. J Dairy Sci 1997; 80:747.

78. Arthington JD et al. J Dairy Sci 2000; 83:1463.

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82. Quigley JD et al.\btTherapeut 2002; 3:262

PRINCIPLES OF CONTROL AND
PREVENTION OF INFECTIOUS
DISEASES OF NEWBORN FARM
ANIMALS

The four principles are:

’ Reduction of risk of acquisition of
infection from the environment
> Removal of the newborn from the
infectious environment if necessary
® Increasing and maintaining the

nonspecific resistance of the newborn
Increasing the specific resistance of the
newborn through the use of vaccines.

The application of each of these principles
will vary depending on the species, the
spectrum of diseases that are common on
that farm, the management system and
the success achieved with any particular
preventive method used previously.

REDUCTION OF RISK OF
ACQUISITION OF INFECTION FROM
THE ENVIRONMENT

The animal should be born in an environ-
ment that is clean, dry, sheltered and con-

ducive for the animal to get up after birth,
suck the dam and establish bonding. 1,2
Calving and lambing stalls or grounds,
farrowing crates and foaling stalls should
be prepared in advance for parturition.
No conventional animal area can be
sterilized but it can be made reasonably
clean to minimize the infection rate
before colostrum is ingested and during
the first few weeks of life when the
newborn animal is very susceptible to
infectious disease.

With seasonal calving or lambing there
can be buildup of infection in the birth
area and animals born later in the season
are at greater risk of disease. In these
circumstances it may be necessary to
move to secondary lambing or calving
areas. In northern climates snow may
constrict the effective calving area and
result in a significant buildup of infection.
Buildup of infection pressure must be
minimized by a change to a fresh calving/
lambing area and by the frequent
movement of feed bunks or feed areas.
Any system that concentrates large num-
bers of cattle in a small area increases
environmental contamination and close
confinement of heifers and cows around
calving time is a known risk factor for calf
mortality. 3,4 With large herds both the cow
herd and heifer herd should be broken
into as many subgroups as is practical.
Extensive systems where cows calve out
over large paddocks are optimal and with
more intense systems a group size no
larger than 50 has been suggested. 5

Lambing sheds and calving areas for
beef cattle should be kept free of animal
traffic during the months preceding the
period of parturition. In dairy herds,
maternity pens separate from other
housing functions should be provided
and cleaned and freshly bedded between
calvings. Certainly they should not also
be used as hospital pens.

In swine herds, the practice of batch
farrowing, with all-in all-out systems of
management and disinfection of the
; farrowing rooms, is essential. Sows
■ should be washed prior to entry to the
farrowing area and the floor of the
farrowing crate should be of the type that
minimizes exposure of the piglet to fecal
material at birth.

The swabbing of the navel with
tincture of iodine to prevent entry of
infection is commonly practiced by some
[ producers and seldom by others. In a
heavily contaminated environment it is
recommended; ligation of umbilical
vessels at the level of the abdomen using
plastic clamps available for this purpose
may however be more effective. The
efficiency of the disinfection of the
umbilicus after birth is uncertain. It is
often surprising how many cases of

158

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

omphalophlebitis occur in calves in herds
where swabbing or 'dunking' of the navel
in a solution of tincture of iodine is a
routine practice. Severance of the umbilical
cord too quickly during the birth of foals
can deprive the animal of large quantities
of blood, which can lead to the neonatal
maladjustment syndrome.

When deemed necessary, some
surveillance should be provided for
pregnant animals that are expected to
give birth, and assistance provided if
necessary. In large herds this attention is
concentrated on the heifers and because
these are more susceptible to dystocia
and to neonatal disease they are
preferably calved in a separate group that
can be easily supervised. The major
objective is to avoid or minimize the
adverse effects of a difficult or slow
parturition on the newborn. Physical
injuries, hypoxia and edema of parts of
the newborn will reduce the vigor and
viability of the newborn and, depending
on the circumstances and the environ-
ment in which it is bom, may lead to
death soon after birth.

When possible, every effort should be
made to minimize exposure of the
neonate to extremes of temperature (heat,
cold, snow). Shelter sheds should be built
if necessary. Restricting feeding to
between 4 pm and 6 am can reduce the
number of calves born at night.

In beef herds, the practice of purchasing
dairy bulls to foster on to cows whose
calves have died should be discouraged. If
calves are purchased they should be from
a herd whose health status is known to
the veterinarian and certainly never
through a market. Similarly, colostrum
should be obtained from cows within the
herd and stored frozen for future use.
Colostrum from a dairy herd is a break in
herd biosecurity and may transmit the
agents of leukosis and Johne's disease.
Furthermore, purchased dairy colostrum
is commonly second- or third-milking
colostrum and of limited immunological
value. The use of a commercial colostrum
supplement or replacer is possible,
although they have significant limitations
(see Colostrum substitutes, above).

REMOVAL OF THE NEWBORN FROM
THE INFECTIOUS ENVIRONMENT

In some cases of high animal population
density (e.g. a crowded dairy barn) and in
the presence of known disease it may be
necessary to transfer the newborn to a
noninfectious environment temporarily
or permanently. Adult cows shedding
enteric pathogens are a risk for calf infec-
tion. Thus dairy calves are often removed
from the dam at birth and placed in
individual pens inside or outdoors in
hutches and reared in these pens

separately from the main herd. This
reduces the severity of neonatal diarrhea
and pneumonia and risk for mortality
compared to calves allowed to remain
with the dam. 6-7 Individual housing in
hutches is preferred because this avoids
navel sucking and other methods of
direct-contact transmission of disease.
Humans entering these hutches should
also practice interhutch hygiene. The
prevalence of disease is higher in enclosed
artificially heated barns than in hutches.
However, despite the well-established
value of individual rearing of calves,
animal welfare regulations in several
countries require that there be visual and
tactile contact between calves. The removal
of the cow-calf pair from the main calving
grounds to a 'nursery pasture' after the
cow-calf relationship (neonatal bond) is
well established at 2-3 days of age, has
proved to be a successful management
practice in beef herds. 8 This system moves
the newborn calf away from the main
calving ground, which may be heavily
contaminated because of limited space. It
necessitates that the producer plan the
location of the calving grounds and
nursery pastures well in advance of
calving time. Calves that develop diarrhea
in the calving grounds or nursery pasture
are removed with their dams to a'hospital
pasture' during treatment and conva-
lescence. The all-in all-out principle of
successive population and depopulation
of farrowing quarters and calf barns is an
effective method of maintaining a low
level of contamination pressure for the
neonate. 9

INCREASING THE NONSPECIFIC
RESISTANCE OF THE NEWBORN

Following a successful birth, the next
important method of preventing neonatal
disease is to ensure that the newborn
ingests colostrum as soon as possible. As
detailed above, with natural sucking the
amount which the calf ingests will
depend on the amount available, the
vigor of the calf, the acceptance of the calf
by the dam and the management system
used, which may encourage or discourage
the ingestion of liberal quantities of
colostrum. Beef cows that calve at a
condition score lower than 4 (out of 10)
are at higher risk of having calves that
develop failure of transfer of passive
immunity and the ideal condition score at
calving is 5 to 6. 4

The method of colostrum delivery that
is needed to optimize transfer of passive
immunity to the dairy calf will vary with
the breed of cow, the management level
of the farm and the priority given to calf
health. Owner acceptance of alternate
feeding systems to natural sucking also is
a consideration. The success of the farm

policy for the feeding of colostrum is
easily monitored by one of the tests listed
above, as is the effect of an intervention
strategy.

Newborn male dairy calves are

commonly assembled and transported to
market or to calf-rearing units within a
few days of birth. Studies have repeatedly
shown high rates of failure of transfer of
passive immunity in this class of calf. The
high rates occur either because the
original owner does not bother to feed
colostrum to the calf, knowing it is to be
sold, or because calves are purchased off
the farm before colostrum feeding is
completed. The effects of the transportation
can have a further deleterious effect on
the defense mechanism of the calves and
they are at high risk of disease.

Calf-rearing units should preferably
purchase calves directly from a farm with
an established policy of feeding colostrum
before the calf leaves the farm, and every
effort should be made to reduce the stress
of transportation by providing adequate
bedding, avoiding long distances without
a break and attempting to transport only
calves that are healthy. In some countries
there is now legislation requiring the
feeding of colostrum and limiting the
transport of newborn calves.

The honesty of the stated farm col-
ostrum feeding policy can be monitored by
testing the calves for immunoglobulins.
Where this is not possible and market
calves must be used, the entry immuno-
globulin value should be tested; the
incidence of infectious disease in low-
testing calves will be high unless hygiene,
housing, ventilation, management and
nutrition are excellent. Low-testing calves
should probably be culled. The entry
immunoglobulin of calves entering veal
or other calf-rearing units is a prime
determinant of subsequent health and
performance. The cull cut-point can be
established for an individual farm by
monitoring of individual immunoglobulin
levels and subsequent calf fate.

Following the successful ingestion of
colostrum and establishment of the
neonatal bond, emphasis can then be
given to provision, if necessary, of any
special nutritional and housing require-
ments. Newborn piglets need supplemental
heat, their eye teeth should be clipped
and attention must be given to the special
problems of intensive pig husbandry.
Orphan and weak piglets can now be
reared successfully under normal farm
conditions with the use of milk replacers
containing added porcine immuno-
globulins. Heat is often provided to lambs
for the first day in pen lambing systems.

Milk replacers for the newborn must
contain high-quality ingredients. Human-
grade milk products are preferred to

Neonatal infection

animal-grade products because there is
less heat denaturation. Calves younger
than 3 weeks are less able to digest
nonmilk proteins, and the fats best used
by the calf are high-quality animal source
fats and slightly unsaturated vegetable
oils. 10 ' 11 A 22% crude protein is
recommended for milk replacers comprised
only of milk proteins and 24-26% in
replacers that contain nonmilk protein
sources. The level of fat should be at least
15 %; higher fat concentration will provide
additional energy which may be required
in colder climates. Feeding utensils must
be cleaned and disinfected between each
feeding if disease transmission is to be
minimized. 12

With animals at pasture, the mustering
and close contact associated with manage-
ment procedures such as castration and
docking pose a risk for disease trans-
mission. These procedures should be
performed in yards prepared for the
purpose - preferably temporary yards
erected for this sole purpose in a clean
area.

INCREASING THE SPECIFIC
RESISTANCE OF THE NEWBORN

The specific resistance of the newborn to
infectious disease may be enhanced by
vaccination of the dam during pregnancy
to stimulate the production of specific
antibodies which are concentrated in the
colostrum and transferred to the newborn
after birth. Vaccination of the dam can
provide protection for the neonate against
enteric and respiratory disease. Details are
given under the specific disease headings
in this text. The vaccination of the late
fetus in utero stimulates the production of
antibody but its practical application has
yet to be determined.

REVIEW LITERATURE

Black L, Francis ML, Nicholls MJ. Protecting young
domestic animals from infectious disease. Vet
Annu 1985; 25:46-61.

Brenner J. Passive lactogenic immunity in calves: a
review. Israel JVet Med 1991; 46:1-12.

Vermunt JJ. Rearing and management of diarrhoea in
calves to weaning. AustVet J 1994; 71:33-41.
Rogers GM, Capucille DJ. Colostrum management:
keeping beef calves alive and performing.
Compend Contin Educ PractVet Food Anim Pract
2000; 22(1):S6-S13.

Larson RL, Tyler JW, Schultz LG, Tessman RK,
Hostetler DE. Management strategies to decrease
calf death losses in beef herds. J Am Vet Med
Assoc 2004; 224:42-48.

REFERENCES

1. Nowak R. Appl Anim Behav Sci 1996; 49:61.

2. Ganaba R et al. PreventVet Med 1995; 24:31.

3. Sanderson MW, Dargatz DA. PrevVet Med 2000;
44:97.

4. Larson RL et al. J Am Vet Med Assoc 2004; 224:42.

5. Pence M et al. Compend Contin Educ PractVet
Food Anim Pract 2001; 23(8):S73.

6. Quigley JD et al. J Dairy Sci 1995; 78:893.

7. Wells S] et al. PreventVet Med 1996; 29:9.

8. Radostits OM, Acres SD. Can Vet J 1980; 21:243.

9. Edwards SA et al. BrVet J 1982; 138:233.

10. Heinrichs AJ. Compend Contin Educ Pract Vet

1994; 16:1605.

11. Heinrichs AJ. Compend Contin Educ Pract Vet

1995; 17:433.

12. Lance SE et al. J Am Vet Med Assoc 1992;

201:1197.

OMPHALITIS,

OMPHALOPHLEBITIS AND
URACHITIS IN NEWBORN FARM
ANIMALS (NAVEL-ILL)

Infection of the umbilicus and its associ-
ated structures occurs commonly in
newborn farm animals and appears to be
particularly common in calves. The
umbilical cord consists of the amniotic
membrane, the umbilical veins, the
umbilical arteries and the urachus. The
amniotic membrane of the umbilical cord
is torn at birth and gradually the umbilical
vein and the urachus close, but they
remain temporarily outside the umbilicus.
The umbilical arteries retract as far back
as the top of the bladder.

In many countries regulations govern
the minimal age at which neonatal calves
can be shipped or sent to market and
slaughter. Commonly this can not legally
be done until the calf is in its fifth day of
life. The wetness or dryness of the
umbilicus is used as a surrogate measure
of age in welfare regulations and the
requirement is that the umbilical cord at
the junction with the abdominal skin
should be dry and shriveled. The drying
time varies from 1 to 8 days, with vari-
ation between breeds and a longer drying
period in bull calves. As might be
expected, this measure is only an approxi-
mate surrogate for age but approximately
90% of calves have dry navels by 4 days of
age. 1

Infection of the umbilicus occurs soon
after birth and may result in omphalitis,
omphalophlebitis, omphaloarteritis or
infection of the urachus, with possible
extension to the bladder, causing cystitis.
The majority of infections progress to
sites beyond the umbilicus. 1 There is
usually a mixed bacterial flora including
E. coli, Proteus spp.. Staphylococcus spp., A.
pyogenes, Bacteroides spp, F. necrophorum
and Klebsiella spp. 2,3

Bacteremia and localization with infec-
tion may occur in joints, bone, meninges,
eyes, endocardium and end-arteries of
the feet, ears and tail. The navel can also
be the source of infection leading to
septicemia, arthritis and fever of unknown
origin in neonates with failure of transfer
of passive immunity. 4

Omphalitis

Omphalitis is inflammation of the external
aspects of the umbilicus and occurs
commonly in calves and other species
within 2-5 days of birth and often persists

for several weeks. 5 The umbilicus is
enlarged, painful on palpation and may
be closed or draining purulent material
through a small fistula. The affected
umbilicus may become very large and
cause subacute toxemia. The calf is
moderately depressed, does not suck
normally and is febrile. Treatment consists
of surgical exploration and excision. A
temporary drainage channel may be
necessary.

Omphalophlebitis

Omphalophlebitis is inflammation of the
umbilical veins. It may involve only the
distal parts or extend from the umbilicus
to the liver. Large abscesses may develop
along the course of the umbilical vein and
spread to the liver, with the development
of a hepatic abscess that may occupy up
to one-half of the liver. Affected calves are
usually 1-3 months of age and are
unthrifty because of chronic toxemia. The
umbilicus is usually enlarged with
purulent material; however, in some cases
the external portion of the umbilicus
appears normal-sized. Placing the animal
in dorsal recumbency and deep palpation
of the abdomen dorsal to the umbilicus in
the direction of the liver may reveal a
space -occupying mass.

Ultrasonography may assist in the
diagnosis and can help in formulating a
surgical approach. 6,7 Affected calves and
foals are inactive, inappetent, unthrifty
and may have a mild fever. Parenteral
therapy with antibiotics is usually
unsuccessful. Exploratory laparotomy and
surgical removal of the abscess is
necessary. 8,9 Large hepatic abscesses are
usually incurable unless surgically
removed, but the provision of a drain to
the exterior and daily irrigation may be
attempted if resection is not feasible.

Omphaloarteritis

In omphaloarteritis, which is less com-
mon, the abscesses occur along the
course of the umbilical arteries from
the umbilicus to the internal iliac arteries.
The clinical findings are similar to those
in omphalophlebitis: chronic toxemia,
unthriftiness and failure to respond to
antibiotic therapy. Treatment consists of
surgical removal of the abscesses.

Urachitis

Infection of the urachus may occur
anywhere along the urachus from the
umbilicus to the bladder. The umbilicus is
usually enlarged and draining purulent
material, but can appear normal. Deep
palpation of the abdomen in a dorsocaudal
direction from the umbilicus may reveal a
space-occupying mass. Extension of the
infection to the bladder can result in
* cystitis and pyuria. Contrast radiography
of the fistulous tract and the bladder will

160

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

reveal the presence of the lesion. The
treatment of choice is exploratory
laparotomy and surgical removal of the
abscesses. Recovery is usually uneventful.

CONTROL

The control of umbilical infection depends
primarily on good sanitation and
hygiene at the time of birth. The appli-
cation of drying agents and residual
disinfectants such as tincture of iodine
is widely practiced. However, there is
limited evidence that chemical disinfecting
is of significant value. Chlorhexidine is
more efficient in reducing the number of
organisms than 2% iodine or 1% povidone
iodine. High concentrations of iodine
(7%) are most effective but are damaging
to tissue. 10

REFERENCES

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2. Hathaway SC et al. NZVet J 1993; 41:166.

3. GotoY et al. J Jpn Vet Med Assoc 2003; 56:528.

4. Vaala WE et al. J Am Vet Med Assoc 1988;
193:1273.

5. Virtala AM et al. J Am Vet Med Assoc 1996;
208:2043.

6. Ataller GS et al. J Am Vet Med Assoc 1995; 206:77.

7. Pokar J. PraktTierarzt 2004; 85:646.

8. Baxter GM. Compend Contin Educ Pract Vet
1989; 11:505.

9. Lewis CA et al. J Am Vet Med Assoc 1999; 214:89.

10. Lavan RP. In; Proceedings of the 14th Conference

of the American Association of Equine Practitioners
1994, 14:37.

Clinical assessment and
care of critically ill
newborns

The following discussion focuses on care
and treatment of critically ill foals,
although the principles are applicable to
any species. The increasing availability of
secondary and tertiary care for ill new-
borns has allowed the development of
sophisticated care for newborns of suffi-
cient emotional or financial value. This
level of care, at its most intensive, requires
appropriately trained individuals (both
veterinarians and support staff) and
dedicated facilities. True intensive care of
newborns requires 24-hour monitoring.
The following discussion is not a compre-
hensive guide to intensive care of new-
borns but is rather an introduction to the
general aspects of advanced primary or
secondary care. Sophisticated inter-
ventions, such as mechanical ventilation
and cardiovascular support, are mentioned
but not discussed in detail.

CLINICAL EXAMINATION

Initial assessment of an ill newborn
should begin with collection of a detailed
history including the length of gestation,
health of the dam, parturition and
behavior of the newborn after birth,

including the time to stand and to com-
mence nursing activity. Physical examin-
ation should be thorough, with particular
attention to those body systems most
commonly affected. A form similar to
that in Figure 3.1 is useful in ensuring that
all pertinent questions are addressed
and that the physical examination is
comprehensive.

Examination of ill neonates should
focus on detection of the common causes
of disease in this age group: sepsis, either
focal or systemic; prematurity or dys-
maturity; metabolic abnormalities (such
as hypoglycemia or hypothermia); birth
trauma; diseases associated with hypoxia;
and congenital abnormalities. Detailed
descriptions of these conditions are
provided elsewhere in this chapter.

Sepsis

Sepsis is an important cause of illness in
neonates that can manifest as localized
infections without apparent systemic
signs, localized infections with signs of
systemic illness, or systemic illness with-
out signs of localized infection.

Localized infections without signs of
systemic illness include septic synovitis or
osteomyelitis, or omphalitis. Signs of
these diseases are evident on examination
of the area affected and include lameness,
distension of the joint and pain on
palpation of the affected joint in animals
with synovitis or osteomyelitis, and an
enlarged external umbilicus with or with-
out purulent discharge in animals with
infections of the umbilical structures.
Specialized imaging, hematological and
serum biochemical examinations (see
below) are useful in confirming the
infection.

Systemic signs of sepsis include
depression, failure to nurse or reduced
frequency of nursing, somnolence, recum-
bency, fever or hypothermia, tachypnea,
tachycardia, diarrhea and colic, in
addition to any signs of localized disease.
Fever is a specific, but not sensitive, sign
of sepsis in foals. The presence of petechia
in oral, nasal, ocular or vaginal mucous
membranes, the pinna or coronary bands
is considered a specific indicator of sepsis,
although this has not been documented
by appropriate studies. A similar com-
ment applies for injection of the scleral
vessels. A scoring system ('the sepsis
score') has been developed to aid in the
identification of foals with sepsis. 1

The 'sepsis score' was developed with
the intention of aiding identification of
foals with sepsis, and thereby facilitating
appropriate treatment. A table for
calculation of sepsis score is provided in
Table 3.3. Foals with a score of 12 or
greater are considered to be septic, with a
sensitivity of 94 %. 1 However, the sepsis

score, which was widely used for over a
decade, was not appropriately evaluated
in other clinics until very recently. These
recent studies demonstrate that the sepsis
score has limited sensitivity (67%, 95%
confidence interval (Cl) 59-75%) and
specificity (76%, 95% Cl 68-83%) in foals
less than 10 days of age. 2 The associated
positive and negative likelihood ratios
were 2.76 and 0.43, respectively. 2
Similarly, 49% of 101 foals with positive
blood cultures had a sepsis score of 11 or
less. 3 The low sensitivity of the sepsis
score for detection of sepsis or bacteremia
means that many foals with sepsis are
incorrectly diagnosed. This is an import-
ant shortcoming of the test, as accurate
and prompt identification of foals with
sepsis is assumed to be important for
both prognostication and selection of
treatment. The sepsis score might be use-
ful in some situations, but its short-
comings should be recognized when
using it to guide treatment or determine
prognosis.

Prematurity and dysmaturity

Detection of prematurity is important
because it is a strong risk factor for
development of other diseases during the
immediate postpartum period. The
detection of prematurity is often based on
the length of gestation. However, the
duration of gestation in Thoroughbred
horses varies considerably, with 95% of
mares foaling after a gestation of 327-357
days 4 - the generally accepted 'average'
gestation is 340 days. Ponies have a
shorter gestation (333 days, range
315-350 days). 5 Therefore, a diagnosis of
prematurity should be based not just on
gestational age but also on the results of
physical, hematological and serum
biochemical examination of the newborn.
Factors helping in the determination of
prematurity are listed in Table 3.4. Foals
that are immature (premature) at birth
j typically have low birth weight and small
body size, a short and silky hair coat and
laxity of the flexor and extensor tendons.

: The cranium is rounded and the pinnae
i lack tone (droopy ears). The foals are
j typically weak and have trouble standing,
i which is exacerbated by laxity of the flexor
j tendons and periarticular ligaments.

Dysmature (postmature) foals are typically
; large, although they can be thin, and have
a long hair coat and flexure tendon
contracture. These signs are consistent
; with prolonged gestation combined with
inadequate intrauterine nutrition.
Examination of the placenta, either by
ultrasonographic examination before
birth or by direct examination, including
histologic and microbiologic testing, after
birth is useful in identifying abnormalities
that have significance for the newborn. 5-7

Clinical assessment and care of critically ill newborns

[L .l - " J> - ' t-- X'l > J

! • • ..'7 V

Variable

Number of points to assign
4 3

2

1

Score for
this case

0

1, Historical data

a. Placentitis, vulvar discharge before delivery.

Present

Absent

dystocia, sick dam, induced parturition

b. Gestation length (days)

< 300

300-310

311-330

> 330

2 Clinical examination

a. Petechiation or scleral injection (nontraumatic)

Marked

Moderate

Mild

None

b. Rectal temperature (°C)

> 38.9

<37.8

37.9-38.7

c. Hypotonia, convulsions, coma, depression

Marked

Moderate

Mild

d. Anterior uveitis, diarrhea, respiratory distress,

Present

Absent

swollen joints or open wounds

3, Hemogram

a. Neutrophil count (cells x 10 9 /L)

< 2.0

2. 0-4.0 or 8.0-

-12.0

4.0-8. 0

b. Band neutrophils (cells x 10 9 /L)

> 0.2

0.05-0.2

<0.05

c. Toxic changes in neutrophils

Marked

Moderate

Slight

None

d. Fibrinogen concentration (g/L)

> 6.0

4.1-6. 0

4.0

4. Laboratory data

a. Blood glucose (mmol/L)

< 2.7

27-4.4

>4.4

b. IgG concentration (g/L)

<2.0

2. 0-4.0

1

00

b

> 8.0

c. Arterial oxygen tension (Torr)

< 40

40-50

51-70

>70

d. Metabolic acidosis (base excess < 0)

Present

Absent

Total points for this foal

To calculate the sepsis score, assign foal a score corresponding to the historical, physical examination and laboratory data included in the above table. A score of 1 1
or less predicts the absence of sepsis correctly on 88% of cases whereas a score of 12 or higher predicts sepsis correctly in 93% of cases. For foals less than 12 hours
of age that have nursed or received colostrum, assign a value of 2 for the serum immunoglobulin score. If the foal has not nursed, assign a value of 4.

>4?jri ?.& ©rfer^ iifc> sets©#, Mis

Criterion

OfY’ (6}jf | fl a fslit! L f ri [■ t\V / .'g)h' ;;'pYdi ! pXol flri'; ] ftpjrsti !

Premature

Full term

Physical

Gestational age

320 d

Normally > 330 d

Size

Small

Normal or large

Coat

Short and silky

Long

Fetlock

Overextended

Normal extension

Behavior

First stand

> 120 min

< 120 min

First suck

> 3 h

< 3 h

Suck reflex

Poor

Good

Righting reflexes

Poor

Good

Adrenal activity

Plasma cortisol values over

Low levels (< 30 ng/mL)

Increasing levels (120-140 ng/mL) at 30-60 min postpartum

first 2 h postpartum

Plasma ACTH values over first

Peak values (= 650 pg/mL) at 30 min postpartum

Declining values from peak (300 pg/mL at birth)

2 h postpartum

and declining subsequently

Response to synthetic

Poor response shown by a 28% increase in plasma

Good response shown by a 208% increase in plasma cortisol

ACTH 1 -24 (short-acting

cortisol and no changes in neutrophil:

and widening of neutrophiLlymphocyte ratio

Synacthen), dose

lymphocyte ratio

0.125 mg IM

Hematology

Mean cell volume (fl)

> 39

< 39

White blood cell count (x 10 9 /L)

6.0

8.0

Neutrophiklymphocyte ratio

< 1.0

> 2.0

Carbohydrate metabolism

Plasma glucose levels over first

Low levels at birth (2-3 mmol/L), subsequently

Higher levels at birth (4.1 mmol/L), maintained

2 h postpartum

declining

Plasma insulin levels over first

Low levels at birth (8.6 pU/mL), declining

Higher levels at birth (16.1 pU/mL), maintained

2 h postpartum

Glucose tolerance test (0.5 mg/kg

Slight response demonstrated by a 100% increase

Clear response demonstrated by a 250% increase in plasma

body weight IV)

in plasma insulin at 15 min post-administration

insulin at 5 min post-administration

Renin-angiotensin-aldosterone system

Plasma renin substrate

Higher and/or increasing levels during 15-60 min

Low(< 0.6 pg/mL) and declining levels during 15-30 min

postpartum

postpartum

Acid-base status (pH)

< 7.25 and declining

> 7.3 and maintaining or rising

IM, intramuscularly; IV, intravenously.

162

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

Foal Examination Protocol (age< 1 mon)

The Ohio State University Veterinary Teaching Hospital

Special considerations:

History

Mare

Age:

Clinician:
Student:
Date:

Time:

AM/PM

No of previous foals:

. Problems with previous foals? No Yes

Uterine infectionsA/aginal discharge? No Yes .

liiness during pregnancy? No Yes

Milk dripping? No Yes How long?

Vaccinations? No Yes What/When?

Deworming? No Yes When?

Feeding:

Breeding date: _

Dystocia? No .

Duration of prenancy:

-> on term early overdue ( days)

_Yes

Early cord rupture? No Yes

Placenta completely passed? No Yes

Meconium staining? No Yes

Udder: Normal Abnormal

Premature placental separation? No Yes

Condition of placenta:

Colostrum quality: Normal Low-quality

Foal

Spontaneous breathing? No Yes

Nursing normally? No Yes

Behavior normal? No Yes

Urination? No

Amount: Normal Reduced

Time to stand:

Colostrum/Milk given?

Time to nurse:

_Yes

Medications given? No Yes

Umbilicus treated? No Yes

IgG tested? No Yes

Meconium passed? No Yes Enema given? No Yes

Presenting complaint :

Previous treatment:

The Ohio State University
Form-209046

Foal Examination Protocol

Fig. 3.1 Examples of forms used to document and record historical aspects and findings on physical examination of foals
less than 1 month of age.

Senior Student: Attending Clinician:

Foal Examination Protocol

Fig. 3.1 (Cont'd) Examples of forms used to document and record historical aspects and findings on physical examination
of foals less than 1 month of age.

(See Prematurity, immaturity and dys-
maturity of foals for a complete dis-
cussion of this topic.)

Hypoxia

Hypoxia during late gestation, birth or the
immediate postpartum period has a

variety of clinical manifestations depend-
ing on the tissue or organ most affected.
Signs of central nervous system dys-
function, the so-called 'dummy foals'
or 'barkers and wanderers' are often
assumed to be a result of cerebral hypoxia
during birth. Other signs suggestive of

peripartum hypoxia include colic and
anuria.

Hypoglycemia

Foals that are hypoglycemic because of
inadequate intake, such as through
mismothering, congenital abnormalities

164

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

or concurrent illness, are initially weak
with rapid progression to somnolence
and coma.

DIAGNOSTIC IMAGING

Radiographic and ultrasonographic
examination of neonates can be useful in
determining maturity and the presence of
abnormalities. Prematurity is evident as
failure or inadequate ossification of
cuboidal bones in the carpus and tarsus.
Radiographs of the thorax should be
obtained if there is any suspicion of sepsis
or pneumonia, because thoracic auscul-
tation has poor sensitivity in detecting
pulmonary disease in newborns (see Table
10.2 for definition of radiographic abnor-
malities in foals) . Severity of abnormalities
in lungs of foals detected by radiographic
examination is related to prognosis, with
foals with more severe disease having a
worse prognosis for recovery. 8 Abdominal
radiographs maybe useful in determining
the site of gastrointestinal disease (see
Foal colic).

Ultrasonography is a particularly
useful tool for examination of neonates,
in large part because their small size
permits thorough examination of all
major body cavities. Ultrasonography of
the umbilical structures can identify
omphalitis and abscesses of umbilical
remnants 9 and, when available, is indi-
cated as part of the physical examination
of every sick neonate.

Examination of the umbilical struc-
tures can reveal evidence of infection,
congenital abnormalities and urachal
tears. Examination of the umbilicus can
be achieved using a 7.5 mHz linear probe
(such as that commonly used for repro-
ductive examination of mares) although
sector scanners provide a superior image.
Examination of the umbilical structures
should include examination of the navel
and structures external to the body wall,
the body wall, the umbilical stump as it
enters the body wall and separates into
the two umbilical arteries, the urachus
and apex of the bladder, and the umbilical
vein. The size and echogenicity of each of
these structures should be determined.
For foals less than 7 days of age the intra-
abdominal umbilical stump should be less
than 2.4 cm in diameter, the umbilical
vein less than 1 cm and the umbilical
arteries less than 1.4 cm (usually < 1 cm).
Examination of these structures should be
complete: the umbilical vein should be
visualized in the umbilical stump and
then followed as it courses along the
ventral abdominal wall and into the liver;
the umbilical arteries should be visualized
in the umbilical stump and then as they
separate from that structure and course
over the lateral aspects of the bladder; the
urachus should be visualized from

the external umbilical stump through the
body wall and as it enters the bladder.

Abnormalities observed frequently in
the umbilical structures include overall
swelling, consistent with omphalitis, gas
shadows in the urachus or umbilical
stump, which are indicative of either a
patent urachus allowing entry of air or
growth of gas-producing bacteria, and the
presence of flocculent fluid in the urachus,
vein or artery, which is consistent with
pus. Urachal tears can be observed,
especially in foals with uroperitoneum.

Ultrasonographic examination of the
abdomen is useful in identifying abnor-
malities of gastrointestinal function and
structure, including intestinal distension
or thickening of intestinal wall. Intus-
susceptions are evident as 'donut' lesions
in the small intestine. Gastric outflow
obstruction should be suspected in foals
with a distended stomach evident on
ultrasonographic examination of the
abdomen. Uroperitoneum is readily
apparent as excessive accumulation of
clear fluid in the abdomen. Hemorrhage
into the peritoneum can be detected as
accumulation of echogenic, swirling fluid.
Accumulation of inflammatory fluid, such
as in foals with ischemic intestine, is
detected by the presence of flocculent
fluid.

Ultrasonographic examination of the
chest can reveal the presence of pleural
abnormalities, consolidation of lung
(provided that the consolidated lung is
confluent with the pleura), accumulation
of fluid in the pleural space (hemorrhage
secondary to birth trauma and fractured
ribs, inflammatory fluid in foals with
pleuritis), pneumothorax (usually second-
ary to lung laceration by a fractured
rib 10 ) or congenital abnormalities of the
heart.

Advanced imaging modalities, such as
computed tomography (CT) and mag-
netic resonance imaging (MRI), are

available at referral centers and are
practical in foals and other neonates

I because of the small size of the animals.

i

These modalities are useful in detection
of intrathoracic and intra-abdominal
abnormalities, including abscessation,
gastrointestinal disease and congenital
abnormalities. 11,12 MR] is particularly use-
ful for diagnosis of diseases of the brain
and spinal cord. 13

CLINICAL PATHOLOGY
Serum immunoglobulin
concentration

Serum immunoglobulin G (IgG) concen-
tration, or its equivalent, must be measured
in every ill or at-risk newborn and should
be repeated every 48-96 hours in critically
ill neonates. A variety of tests are available
for rapid detection of failure of transfer of

passive immunity in foals 14-17 and calves. 18
While measurement of serum IgG
concentration is ideally performed by the
gold standard test, a radial immuno-
diffusion, this test requires at least
24 hours to run, whereas the stall side or
chemistry analyzer tests can be run in a
few minutes. The sensitivity and
specificity of a number of these rapid tests
has been determined. Overall, most tests
have high sensitivity (> 80%), meaning
that the few foals that have low concen-
trations of IgG are missed, but poor
specificity (50-70%), meaning that many
foals that have adequate concentrations
of immunoglobulin are diagnosed as
having inadequate concentrations. 15-17
The exact sensitivity and specificity
depends on the test used and the concen-
tration of immunoglobulin considered
adequate. The high sensitivity and low
specificity of most of the available rapid
tests result in a number of foals that do
not need a transfusion receiving one.
However, this error is of less importance
than that of foals that should receive a
transfusion not receiving one.

Serum or plasma concentrations of
IgG should be measured after approxi-
mately 18 hours of age, and preferably
before 48 hours of age - the earlier failure
of transfer of passive immunity is
recognized the better the prognosis for
the foal. Foals that ingest colostrum
within the first few hours of birth have
minimal increases in serum IgG con-
centration over that achieved at 12 hours
of age, 19 suggesting that measurement of
serum IgG concentration as early as
12-18 hours after birth is appropriate.
This early measurement of serum IgG
concentration could be especially import-
ant in high-risk foals. The oldest age at
which measurement of serum IgG is
useful in foals is uncertain, but depends
on the clinical condition of the foal.
Typically, immunoglobulin concentrations
of foals that have adequate concen-
trations of IgG within the first 24 hours
reach a nadir at about 6 weeks of age and
then rise to concentrations similar to
adults over the next 2-3 months.

Hematology

It is important to recognize that the
hemogram of neonates differs from that
of older animals (Table 3.5), as these
differences can impact on the clinical
assessment of the animal. The hematologic
and serum biochemical values of foals
and calves can vary markedly during the
first days and weeks of life and it is import-
ant that these maturational changes are
taken into account when assessing results
of hematological or serum biochemical
examination of foals. Hematological exam-
ination can reveal evidence of hemolytic

Clinical assessment and care of critically ill newborns

165

T a ble 3-5 Hematological values af normal foals and calves

raMnisgtifttt

WBHHISPBW

BlBeSWM

v,.. :, MS-
.

— — —

Variable

Foals
< 12 h

1 week

1 month

Calves
24 h

48 h

3-4 weeks

PCV (%)

42.5 ± 3.4

35.3 ± 3.3

33.9 ± 3.5

34 ±6

32 ±6

35 ± 3

(L/L)

0.43 ± 0.03

0.35 ± 0.03

0.33 ± 0.04

0.34 ± 0.06

0.32 ±0.06

0.35 ±0.03

Plasma protein (g/dL)

6.0 ± 0.8

6.4 ± 0.6

6.1 ± 0.5

6.4 ± 0.7

6.4 ±0.7

6.4 ± 0.3 '

(g/L)

60 ± 8

64 ± 6

61 ± 5

64 ± 7

64 ± 7

64 ± 3

Fibrinogen (mg/dL)

216 ± 70

290 ± 70

400 ± 130

290 ± 105

335 ± 120

285 ± 145

(g/L)

2.16 ± 0.7

2.90 ± 0.7

4.00 ± 1.30

2.90 ± 1.05

3.35 ± 1.20

2.85 ± 1.45

Hemoglobin (g/dL)

15.4 ± 1.2

13.3 ± 1.2

12.5 ± 1.2

10.9 ± 2.1

10.5 ± 1.8

11.3 ± 1.02

(g/L)

154 ± 12

130 ± 12

1 2 5 ± 12

109 ±21

105 ± 18

113 ± 10

Red blood cells (x 10 6 /pL)

10.7 ± 0.8

8.8 ± 0.6

9.3 ± 0.8

8.17 ± 1.34

7.72 ± 1.09

8.86 ± 0.68

(10' 2 /L)

10.7 ± 0.8

8.8 ± 0.6

9.3 ± 0.8

8.17 ± 1.34

7.72 ± 1.09

8.86 ± 0.68

MCV (fL)

40 ± 2

39 ± 2

36 ± 1

41 ± 3

41 ± 3

39 ±2

MCHC (g/dL)

36 ± 2

38 ± 1

37 ± 1

32.1 ± 0.8

32. 6± 1.0

32.8 ± 1.6

(g/L)

360 ± 20

380 ± 10

370 ± 10

320 ± 8

326 ± 10

328 ± 16

MCH (pg)

14 ± 1

15 ± 1

1 4 ± 1

Nucleated cells (1 0 6 /pL)

9500 ± 2500

9860 ± 1800

8150 ± 2030

9810 ± 2800

7760 ± 1950

8650 ± 1690

(10 9 /L)

9.5 ± 2.5

9.86 ± 1.80

8.15 ± 2.03

9.81 ± 2.80

7.76 ± 1.95

8.65 ± 1.69

Neutrophils (1 0 6 /pL)

7950 ± 2200

7450 ± 1550

5300 ±200

6500 ± 2660

41 10 ± 2040

2920 ± 1140

(10 9 /L)

7.95 ± 2.20

7.45 ±1.55

5.30 ± 0.20

6.50 ± 2.66

4.11 ± 2.04

2.92 ± 1.14

Band neutrophils (10 6 /pL)

24 ± 40

0

4 ± 13

310 ±460

210 ±450

10 ± 30

(10 9 /L)

0.02 ± 0.04

0

0.00 ± 0.01

0.31 ±0.46

0.21 ± 0.45

0.01 ± 0.03

Lymphocytes (10 6 /pL)

1350 ± 600

2100 ± 630

2460 ± 450

2730 ± 820

2850 ± 880

5050 ± 800

(10 9 /L)

1.35 ± 0.6

2.10 ± 0.63

2.46 ± 0.45

2.73 ± 0.82

2.85 ±0.88

5.05 ±0.80

Thrombocytes (10 3 /pL)

266 ± 103

250 ± 70

300 ± 80

(10 9 /L)

266 ± 103

250 ± 70

300 ± 80

Serum Fe (pg/dL)

380 ± 60

175 ± 80

1 38 ± 60

71 ±60

127 ± 60

(mg/L)

3.80 ± 0.6

1.75 ± 0.8

1.38 ± 0.6

0.7 ± 0.6

1.27 ±0.6

TIBC (pg/dL)

440 ± 50

385 ± 80

565 ± 65

420 ± 67

(mg/L)

4.40 ± 0.5

3.85 ± 0.8

5.65 ± 0.65

4.2 ± 0.7

UIBC (pg/dL)

55 ±40

210 ± 100

430 ± 85

(mg/L)

0.55 ± 0.4

2.10 ± 1.00

4.30 ± 0.85

Iron saturation (%)

87 ± 9

46 ± 20

25 ± 12

Sources: Harvey JWetal. Equine Vet J 1 984; 1 6:347 ; Adams R et at. Am J Vet Res 1 992; 5 3:944; Tennant B et at. Cornell Vet 1 9 75; 65:543.

disease, bacterial or viral infection, or
prematurity/ dysmaturity (Table 3.4).
Repeated hemograms are often necessary
to monitor for development of sepsis and
responses to treatment.

Foals with sepsis can have a leukocyte
count in the blood that is low, within the
reference range or high. 20 Approximately
40% of foals with sepsis have blood
leukocyte counts that are below the
reference range. Most foals with sepsis
(approximately 70%) have segmented
neutrophil counts that are below the
reference range, with fewer than 15% of
foals having elevated blood neutrophil
counts. Concentrations of band cells in
blood are above the reference range in
almost all foals with sepsis. Some foals
born of mares with placentitis have a very
pronounced mature neutrophilia without
other signs of sepsis - these foals typically
have a good prognosis. Lymphopenia is
present in foals with equine herpervirus-
1 septicemia or Arabian foals with severe
combined immunodeficiency. Thrombo-
cytopenia occurs in some foals with
sepsis. 21 Hyperfibrinogenemia is common
in foals that have sepsis, although the
concentration might not be above the
reference range in foals examined early in
the disease. Hyperfibrinogenemia is com-

mon in foals born of mares with placen-
titis, and reflects systemic activation of the
inflammatory cascade even in foals that
have no other evidence of sepsis. Serum
amyloid A concentrations are above
lOOmg/L in foals with sepsis. 22 Septic
foals also have blood concentrations of
proinflammatory cytokines that are
higher than those in healthy foals. 23
Indices of coagulation are prolonged in
foals with sepsis, and concentrations of
antithrombin and protein C antigen in
plasma are lower than in healthy foals. 23
These abnormalities indicate that coagulo-
pathies are common in septic foals.

Prematurity is associated with a low
neutrophil:lymphocyte ratio (< 1.5:1) in
blood and a red cell macrocytosis (Table
3. 4). 24 A neutrophildymphocyte ratio
above 2:1 is considered normal. Premature
foals that are not septic can have low
blood neutrophil counts but rarely have
immature neutrophils (band cells) or toxic
changes in neutrophils.

Serum biochemistry

Care should be taken in the interpretation
of the results of serum biochemical exam-
inations because normal values for new-
borns are often markedly different to those
of adults, and can change rapidly during

the first days to weeks of life (Table 3.6).
Serum biochemical examination can
reveal electrolyte abnormalities associated
with renal failure, diarrhea and sepsis.
Elevations in serum bilirubin concen-
tration or serum enzyme activities may be
detected. As a minimum, blood glucose
concentrations should be estimated using
a chemical strip in depressed or recumbent
newborns.

Markedly elevated serum creatinine
concentrations are not uncommonly
observed in foals with no other evidence
of renal disease. The elevated serum
creatinine in these cases is a consequence
of impaired placental function during late
gestation, with the consequent accumu-
lation of creatinine (and probably other
compounds). In foals with normal renal
function, which most have, the serum
creatinine concentration should decrease
to 50% of the initial high value within
24 hours. Other causes of high serum
creatinine concentration that should be
ruled out are renal failure (dysplasia,
hypoxic renal failure) and postrenal
azotemia (uroperitoneum).

Sepsis is usually associated with
hypoglycemia, although septic foals can
have nonnal or elevated blood glucose con-
centrations. Hypoglycemia is attributable

16

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

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Variable

Foals
< 12 h

1 week

1 month

Calves
24 h

48 h

3 weeks

Na + (mEq/L) (mmol/L)

148 ± 8

142 ± 6

145 ± 4

145 ± 7.6

149 ± 8.0

140± 6

K + (mEq/L) (mmol/l)

4.4 ± 0.5

4.8 ± 0.5

4.6 ±0.4

5.0 ± 0.6

5.0 ± 0.6

4.9 ± 0.6

Cl (mEq/L) (mmol/L)

106 ± 6

102 ± 4

103 ± 3

100 ±4

101 ± 5.0

99 ± 4

Ca 2+ (mg/dL)

12.8+ 1

12.5 ± 0.6

12.2 ± 0.6

12.3 ± 0.2

12.3 ± 0.3

9.4 ± 0.6

(mmol/L)

3.2 ± 0.25

3.1 ± 0.15

3.05 ± 0.15

3.1 ± 0.1

3.1± 0.1

2.3 ± 0.2

P0 4 “ (mg/dL)

4.7 ± 0.8

7.4 ± 1.0

7.1 ± 1.1

6.9 ± 0.3

7.6 ± 0.2

7.1 ± 6.4

(mmol/L)

1.52 ± 0.26

2.39 ± 0.32

2.29 ± 0.36

2.3 ± 0.1

2.5 ± 0.1

2.3 ± 1.8

Total protein (g/dL)

5.8 ± 1.1

6.0 ± 0.7

5.8 ± 0.5

5.6 ± 0.5

6.0 ± 0.7

6.5 ± 0.5

(g/L)

58 ± 11

60 ±7

58 ± 5

56 ± 5

60 ± 7

65 ± 5

Albumin (g/dL)

3.2 ± 0.3

2.9 ± 0.2

3.0 ± 0.2

(g/L)

32 ± 3

29 ± 2

30 ± 2

Creatinine (mg/dL)

2.5 ± 0.6

1.3 ± 0.2

1.5 ± 0.2

(pmol/L)

221 ± 53

115 ± 18

133 ± 18

Urea nitrogen (mg/dL)

19.7 ± 4.4

7.8 ± 3.4

9.0 ± 3.0

12.6 (7.1-21.2)

(mmol/L)

3.4 ± 1.6

1.6 ± 0.6

1.7 ± 0.5

2 (1. 5-3.6)

Glucose (mg/dL)

1 44 ± 30

162 ± 19

162 ± 22

130 ± 27

1 1 4 ± 19

70 (52-84)

(mmol/L)

8.0 ± 1.6

9.0 ± 1 .0

9.0 ± 1.2

7.23 ± 1.5

6.34 ± 1.1

3.9 (2.9-47)

Total bilirubin (mg/dL)

2.6 ± 1.0

1.5 ± 0.4

0.7 ± 0.2

< 2.5

< 0.9

< 0.6

(pmol/L)

45 ± 17

26 ± 6

12 ± 4

< 42

< 15

< 10

Direct bilirubin (mg/dL)

0.9 ± 0.1

0.5 ± 0.2

0.3 ± 0.2

< 0.6

< 0.3

< 0.3

(pmol/L)

15 ± 2

8.5 ± 3

5 ± 3

< 10

< 5

< 5

GGT (IU/L)

47.5 ± 21.5

49.1 ±21.2

890 ± 200

600 ± 180

70 ± 10

ALK (IU/L)

3040 ± 800

1270 ± 310

740 ± 240

<1150

< 1000

< 770

AST (IU/L)

199 ± 57

330 ± 85

340 ± 55

< 60

< 33

<32

Values are mean ± standard deviation.

ALK , alkaline phosphatase; AST, aspartate aminotransferase; GGT, gammaglutamyl transpeptidase.

Sources: Bauer JE et al. Equine Vet J 1 984; 16:361; Pearson EG et al. J Am Vet Med /Assoc 1 995; 207:1 466; Jenkins SJ et al. Cornell Vet 1 982; 72:403; Dalton RG.

Br W?f J 1967; 123:48; Wise GH et al. J Dairy Sci 1947; 30:983; Diesch TJ et al. NZ Vet J 2004; 52:256 ;

Patterson WH, Brown CM. AmJ Vet Rev 1986; 47:2461;

Thompson JC, Pauli JV. NZ Vet J 1981; 29:223

to failure to nurse whereas hyperglycemia
indicates loss of normal sensitivity to
insulin. Indicators of renal, hepatic or
cardiac (troponin) damage can increase in
foals with sepsis causing organ damage or
failure. 25 Foals with sepsis tend to have
elevated concentrations of cortisol in serum.

Prematurity is associated with low
concentrations of cortisol in plasma or
serum and minimal increase in response to
intramuscular administration of 0.125 mg
of exogenous ACTH (corticotropin). 26
Plasma cortisol concentration of normal,
full-term, foals during the first 24 hours
of life increases from a baseline value
of approximately 40 ng/mL to over
100 ng/mL 60 minutes after ACTH
administration, whereas plasma cortisol
concentrations in premature foals do not
increase from values of slightly less than
40 ng/mL. 26 At 2 and 3 days of age,
plasma cortisol concentrations of full-
term foals increase twofold after ACTH
administration, albeit from a lower resting
value, but do not increase in premature
foals. Blood glucose concentrations of
premature foals are often low, probably
because of inability to nurse.

Blood gas

Arterial blood pH, Pco 2 and Po 2 should
be measured to determine the newborn's
acid-base status and the adequacy of

respiratory function. Foals with hypoxemia
are five times more likely to have pul-
monary radiographic abnormalities. 27
Prolonged lateral recumbency of foals
compromises respiratory function, and
arterial blood samples should be collected
with the foal in sternal recumbency.
Repeated sampling may be necessary to
detect changes in respiratory function and
to monitor the adequacy of oxygen
supplementation or assisted ventilation.

Blood culture

Identification of causative organisms of
sepsis in foals can aid in prognostication
and potentially in selection of therapy,
although there does not appear to be a
relation between antimicrobial sensitivity
of organisms isolated from blood, as
determined by Kirby-Bauer testing, and
survival of foals. Anaerobic and aerobic
blood cultures should be performed as
early in the disease process as possible,
and preferably before initiation of anti-
biotic treatment, although antimicrobials
should not be withheld from a newborn
with confirmed or suspected sepsis in
order to obtain a result from blood culture.
Strict aseptic technique should be used
when collecting blood for culture. Blood
cultures should also be collected if there is
a sudden deterioration in the newborn's
condition.

Gram- negative enteric bacteria are the
most common isolates from blood of
newborn foals, with E. coli the most
common isolate. 3 A. equuli is also a com-
mon isolate from foals. There are important
differences in diseases produced by the
various organisms, with foals with A. equuli
septicemia being twice as likely to die, seven
times more likely to have been sick since
birth, six times more likely to have diarrhea,
five times more likely to have a sepsis score
of more than 11 and three times more likely
to have pneumonia than foals with sepsis
associated with other bacteria. 3

Other body fluids

Synovial fluid should be submitted for
aerobic and anaerobic culture, Gram stain
and cytological examination when signs
of synovitis, such as lameness, joint
effusion or joint pain are present.

Analysis of cerebrospinal fluid (CSF) is
indicated in newborns with signs of
neurologic disease. Samples of CSF
should be submitted for cytological exam-
ination, measurement of total protein
concentration. Gram stain and bacterial
culture.

Urinalysis may provide evidence of
renal failure (casts) or urinary tract infec-
tion (white blood cells).

Abddminal fluid should be collected in
foals with abdominal pain or distension

Clinical assessment and care of critically ill newborns

and should be submitted for cytological
examination and, if uroperitoneum is
suspected, measurement of creatinine
concentration.

TREATMENT

The principles of care of the critically ill
newborn farm animal are that:

o The newborn should be kept in a
sanitary environment to minimize the
risk of nosocomial infections
® Systemic supportive care should be
provided to maintain homeostasis
until the newborn is capable of
separate and independent existence
o There should be frequent and
comprehensive re-evaluations of all
body systems in order to detect signs
of deterioration and allow early
correction

o Provision should be made to ensure
adequate passive immunity to
reduce the risk of secondary
infections or to treat existing
infections. Transfer of passive
immunity should be evaluated using
laboratory methods that measure
serum or plasma immunoglobulin G
concentration.

Tire level of care provided depends upon
the value of the animal and the available
facilities, personnel and expertise. New-
borns of limited financial worth are
usually treated on the farm whereas
valuable foals and calves can be referred
for specialist care. Referral of sick neonates
to institutions and practices with expertise
in provision of critical care to newborns
should be timely and prompt and, when
necessary, should be recommended on
the first visit.

Nursing care

The sophistication of care for critically ill
newborns depends on the facilities and
personnel available, with intensive
management requiring dedicated facilities
and trained personnel available 24 hours
a day. The minimum requirement for
providing basic care of ill newborns is a
sanitary area in which the newborns can
be protected from environmental stress.
Often this means separating the newborn
from its dam.

Excellent nursing care is essential for
maximizing the likelihood of a good out-
come. Critically ill animals might benefit
from constant nursing care. Strict atten-
tion must be paid to maintaining the
sanitary environment in order to minimize
the risk of nosocomial infections. The
newborn should be kept clean and dry
and at an ambient temperature in its
thermoneutral zone. Bedding should
prevent development of decubital ulcers.
Foals should be maintained in sternal
recumbency, or at least turned every

2 hours, to optimize their respiratory
function.

Correction of failure of transfer of
passive immunity

Colostral immunoglobulin
Ideally, adequate transfer of passive
immunity is achieved by the newborn
nursing its dam and ingesting an ade-
quate amount of colostrum containing
optimal concentrations of immuno-
globulins, principally IgG (IgGb) in foals.
Foals need approximately 2 g of IgG per
kilogram of body weight to achieve a
plasma concentration of 2000 mg/dL
(20g/L), therefore a 45 kg foal needs
approximately 90 g of IgG to attain a
normal serum IgG concentration (or
approximately 40 g to achieve a serum
IgG concentration of 800 mg/dL (8 g/L)).
Assuming that colostrum contains on
average 10 000 mg/dL (100 g/L), foals must
ingest at least 1 L of colostrum to obtain
sufficient immunoglobulin. Because
colostral IgG concentration varies con-
siderably (from 2000-30 000 mg/dL),
specific recommendations regarding the
quantity of colostrum to be fed to neo-
natal foals cannot be made with certainty.
However, colostrum with a specific
gravity of more than 1.060 has an IgG
concentration of more than 3000 mg/dL
(30 g/L), 28 suggesting that foals should
ingest at least 1.5 L to achieve serum IgG
concentrations above 800 mg/dL (8 g/L).

Critical plasma IgG concentrations in
foals

There is some debate as to what consti-
tutes a critical serum or plasma IgG con-
centration. Foals that ingest an adequate
amount of colostrum typically have serum
immunoglobulin concentrations during
the first week of life greater than
approximately 2000 mg/dL (20 g/L). 29 ” 31
Both 400 mg/dL (4 g/L) and 800 mg/dL
(8 g/L) have been recommended as con-
centrations below which foals should be
considered to have increased likelihood of
contracting infectious disease. However,
i on a well-managed farm the serum IgG
concentration was not predictive of
morbidity or mortality amongst foals,
suggesting that serum immunoglobulin
concentration in some populations of
foals is not an important risk factor for
infectious disease. 32 The foals in this study
were from an exceptionally well-managed
farm. Other researchers have found that
foals with serum IgG concentration below
800 mg/dL (8 g/L) are at markedly
increased risk of subsequent development
of infectious disease, including sepsis,
pneumonia and septic arthritis. 33 ' 34 It is
likely that there is no single concentration
of IgG in serum that is protective in all
situations and the concentration of IgG in
serum that is desirable in an individual

foal depends on the risk factors for
infectious disease of that foal. Our
opinion is that a minimum serum IgG in
foals free of disease and housed in closed
bands on well-managed farms is
400 mg/dL (4 g/L). For foals at increased
risk of disease, for instance those on large
farms with frequent introduction of
animals and foals that are transported or
housed with foals with infectious disease,
the minimum advisable serum IgG con-
centration is 800 mg/dL (8 g/L). Foals that
have infectious disease should have
serum IgG concentrations of at least
800 mg/dL and it might be advantageous
for these foals to have even higher values,
as indicated by the enhanced survival of
foals with septic disease administered
equine plasma regardless of their serum
IgG concentration. 35 This therapeutic
advantage could be because of the
additional IgG, or because of other factors
included in the plasma. Transfusion of
plasma to sick foals improves neutrophil
function, an important advantage given
that oxidative burst activity of neutrophils
from septic foals is reduced compared to
that in healthy foals. 36

Plasma transfusion

The ability of foals to absorb macro-
molecules, including immunoglobulins,
declines rapidly after birth, being 22% of
that at birth by 3 hours of age, and 1% of
that at birth by 24 hours of age 37 Con-
sequently, by the time that failure of
transfer of passive immunity is recognized
it is no longer feasible to increase serum
IgG concentrations by feeding colostrum
or oral serum products. Foals should then
be administered plasma or serum intra-
venously. The amount of plasma or
serum to be administered depends on the
target value for serum IgG concentration
and the initial serum IgG concentration in
the foal. For each gram of IgG adminis-
tered per kilogram of body weight of the
foal, serum IgG concentration increases
by approximately 8.7 mg/dL (0.87 g/L) in
healthy foals and 6.2 mg/dL (0.62 g/L) in
sick foals. 38 To achieve serum IgG con-
centrations above 800 mg/dL (8 g/L) in
foals with serum IgG concentrations
below 400 mg/dL (4 g/L), they should be
administered 40mL/kg of plasma con-
taining at least 20 g/L of IgG. Similarly
foals with serum IgG concentrations
above 400 mg/dL (4 g/L) but below
800 mg/dL (8 g/L) should be admin-
istered 20 mL/kg of plasma. For 45 kg
foals, these recommendations translate
to administration of 1 or 2 L of plasma,
respectively.

The ideal product for transfusion into
foals with failure of transfer of passive
immunity is fresh frozen plasma
harvested from horses that are Aa and Qa

68

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

antigen-negative -and that do not have
antibodies against either or both of these
red blood cell antigens (see Neonatal
isoerythrolysi). The donor horses should
have been vaccinated against the
common diseases of horses and have
tested negative for equine infectious
anemia. Good-quality commercial pro-
ducts specify the minimum concentration
of IgG in the plasma. Concentrated serum
products that do not need to be frozen until
use are available. These are much more
convenient for field use than are plasma
products that must be frozen until
immediately before transfusion. However,
the IgG concentration of these products is
often not specified, and the manufacturer's
recommendations for dosing often result in
administration of inadequate amounts of
immunoglobulin. Serum products can
produce adequate concentrations of IgG in
foals, but the dose is usually two to three
times that recommended by the manu-
facturer. An adequate dose of concentrated
serum products is approximately 1 L for
some products. 39 The crucial point is that it
is not the volume of plasma or serum that
is administered that is important, but rather
the quantity of immunoglobulin delivered
to the foal. A total of 20-25 g of IgG is
required to raise the serum IgG concen-
tration of a 50 kg foal by 400 mg/dL
(4 g/L). 39

Plasma should be administered intra-
venously - oral administration is likely to
be wasteful, especially in foals more than
a few hours old. Frozen plasma should be
thawed at room temperature or by
immersion in warm (< 100°F, 37°C) water.
Thawing by immersion in water at
temperatures higher than body tempera-
ture can cause denaturation and
coagulation of proteins with loss of
efficacy of transfused immunoglobulins.
Plasma should never be thawed or
warmed using a microwave, as this
denatures the proteins.

Administration of plasma should be
intravenous - intraperitoneal adminis-
tration, such as used in pigs or small
ruminants, has not been investigated in
foals. The thawed plasma should be
administered through a jugular catheter
using a blood administration set contain-
ing a filter (160-270 pm mesh) to prevent
infusion of particulate material. Strict
asepsis should be used. The foal should be
adequately restrained for the procedure,
with some active foals needing moderate
tranquillization. Premedication with
antihistamines or nonsteroidal anti-
inflammatory drugs is usually not
necessary. The plasma should be infused
slowly at first, with the first 20-40 mb
administered over 10 minutes. During
this period the foal should be carefully
observed for signs of transfusion reaction.

which is usually evident as restlessness,
tachycardia, tachypnea, respiratory distress,
sweating or urticaria. If these signs are
observed the transfusion should be
stopped and the foal should be re-
evaluated and treated if necessary. If no
transfusion reactions are noted during the
first 10 minutes, the infusion can then be
delivered at 0.25-1.0 mL/kg/min (i.e.
about lL/h for a 50 kg foal). Rapid infu-
sion can result in acute excessive plasma
volume expansion with the potential for
cardiovascular and respiratory distress.

Serum IgG concentration should be
measured after the infusion to ensure that
an adequate concentration of IgG has
been achieved. Serum IgG can be measured
as early as 20 minutes after the end of the
transfusion. 39

Nutritional support

Provision of adequate nutrition is essen-
tial to the recovery of ill newborns.
Newborn foals have estimated energy
requirements of 500-625 (kj/kg)/d
(120-150 (kcal/kg)/d) and consume
approximately 20% of their body weight
as milk per day. The best food for new-
borns is the dam's milk and newborns
that are able to do so should be encouraged
to nurse the dam. However, if the foal is
unable to nurse or the dam is not avail-
able, then good- quality milk substitutes
should be used. Soy and other plant-
protein-based milk replacers are not
suitable for newborns. Commercial pro-
ducts formulated for foals, calves and lambs
are available. Human enteral nutrition
products supplying 0.7-1 kcal/mL
(2.8-4. 1 kJ/mL) can also be used for
short-term (several days to a week) sup-
port of foals.

It is preferable to provide enteral,
rather than parenteral, nutrition to ill
newborns with normal or relatively nor-
mal gastrointestinal function. Sick neonatal
foals should initially be fed 10% of their
body weight as mare's milk, or a suitable
replacer, every 24 hours, divided into
hourly or 2-hourly feedings. If the foal
does not develop diarrhea or abdominal
distension, then the amount fed can be
increased, over a 24-48-hour period to
20-25% of the foal's body weight (or
150 (kcal/kg)/day; 620 (kj/kg)/day). New-
borns can be fed by nursing a bottle or
bucket or via an indwelling nasogastric
tube such as a foal feeding tube, stallion
catheter, human feeding tube or enema
tube. Every attempt should be made to
encourage the newborn to nurse its dam
as soon as the newborn can stand.
Adequacy of nutrition can be monitored
by measuring blood glucose concentrations
and body weight.

Parenteral nutrition (PN) can be
provided to newborns that are unable to

be fed by the enteral route. This can be
achieved by administration of various
combinations of solutions containing
glucose (dextrose), amino acids and fat. A
commercial product that does not include
lipid has been used successfully for up to
12 days in foals. One product that has
been used successfully for foals is a
solution of amino acids (5%), dextrose
(25%) and electrolytes (Clinimix E, Baxter
Healthcare Corporation, Deerfield, IL).
Lipid emulsion is not added to the prep-
aration. Additional multivitamin supple-
ments including calcium gluconate
(provided 2.5 mmol/L), magnesium
sulfate (6 mEq/L), B vitamin complex
(thiamine 12.5 mg/L; riboflavin 2 mg/L;
niacin 12.5 mg/L; pantothenic acid
5 mg/L; pyridoxine 5 mg/L; cyanocobalamin
5 pg/L), and trace elements (zinc 2 mg/L;
copper 0.8 mg/L; manganese 0.2 mg/L;
chromium 8 pg/L) are added. 40 Adminis-
tration is through a catheter, a single-
lumen 14-gauge over-the-wire catheter
(Milacath), inserted in the jugular vein
with its tip placed in the cranial vena cava.
A double-T extension set is used to allow
concurrent constant rate infusion of
isotonic crystalloid fluids and intravenous
administration of medication in one line
and PN solution in the other. An infusion
pump is used for continuous-rate
infusion of the solutions. The PN solution
should be prepared under aseptic con-
ditions just prior to administration and
used for only a period of 24 hours after
preparation. A 0.22 pm filter is included in
the administration line to remove all
bacteria, glass, rubber, cellulose fibers and
other extraneous material in the PN
solution. The filters and administration
sets are changed with each new bag of
PN solution.

The rate of PN infusion is determined
based on the weight and physical and
metabolic condition of the foal. The
general protocol is based on the assump-
tion that sick foals expend approximately
50 kcal/kg body weight per day (basal
rate) 41 The PN is started at half the basal
rate for 12 hours, increasing to the basal
rate over 24-48 hours, and then in some
foals increased slowly to 75 (kcal/kg) /d if
tolerated by the foal. The clinical con-
dition of the foal is assessed frequently.
Blood glucose concentrations should be
measured every 6-8 hours during the
introduction and weaning of PN until the
blood glucose concentration is stabilized.
Insulin can be administered during hyper-
glycemic crises (»250 mg/dL) at a dose
of 0. 1-0.4 U/kg regular insulin intra-
muscularly, but this is rarely needed.
When a constant rate of PN is achieved
glucose concentrations should be
measured every 8-12 hours, depending
on the clinical condition of the foal. Foals

169

P'

Clinical assessment and care of critically ill newborns

are weaned off the PN as their clinical
condition improves and enteral feeding is
gradually increased. The rate of PN is
halved every 4-12 hours if blood glucose
concentration is stable until half the basal
rate was obtained, at which time the infu-
sion is discontinued if the foal is bright,
alert and nursing well.

PN is supplemented with isotonic fluid
therapy administered intravenously. The
fluid rate and composition are deter-
mined based on clinical condition, packed
cell volume, total protein and serum
electrolyte concentrations (Na, Cl, Ca, K
and HCO ). The composition and rate are
adjusted to maintain normal hydration,
and electrolyte and acid-base status.
During the period that foals receive PN,
enteral feeding is initially withdrawn and
the foals are muzzled or separated from
the mare. Beginning 24 hours after the
institution of PN, 20-40 mL of mare's
milk ('trophic' feeding) is administered
enterally every 4 hours. The trophic
feeding provides nutrition to enterocytes
and stimulates production of lactase in
the small intestine in preparation for
resumption of enteral feeding. As the
foals are weaned off the PN, enteral
feedings are gradually increased from
small trophic feeding every 4 hours to

allowing the foal to nurse from the mare
for 2-5 minutes every 2 hours and
eventually unrestricted nursing from the
mare.

Antimicrobial treatment

Normal newborns are at risk of acquiring
life-threatening bacterial infections, and
the risk increases when they do not ingest
adequate colostrum in a timely fashion or
are subjected to environmental stresses
(see Neonatal infection). Newborns in
which bacterial infection is suspected and
those at high risk of developing an
infection, such as sick newborns with
failure of transfer of passive immunity,
should be administered antimicrobials.
Antimicrobial therapy should not be
delayed pending the results of bacterial
culture and antimicrobial sensitivity
testing.

The choice of antimicrobial is deter-
mined by the likely infecting agent and
clinical experience with antimicrobial
susceptibility of local strains of pathogens.
In general, broad-spectrum antimicrobials
are chosen because it is almost impossible
to predict, based on clinical signs, the
nature of the infecting agent and its
antimicrobial susceptibility. Although
Streptococcus spp. were historically reported

to be the cause of most infections in
neonatal foals, currently infections of
neonatal foals are usually due to Gram-
negative organisms including E. coli,
Klebsiella spp. and Salmonella spp. 3
Because of the wide variety of infecting
agents and their varying antimicrobial
susceptibility, it is possible to make only
general recommendations for antimicrobial
therapy of neonates. A frequently used
antimicrobial regimen is an amino-
glycoside (gentamicin or, more com-
monly, amikacin) and penicillin. 42 Some
commonly used drugs and their doses are
listed in Table 3.7. Dosage of anti-
microbials in foals differs somewhat from
that of adults, and the pharmacokinetics
of drugs in normal foals are often
different from those of the same drug in
sick foals. 43,44 Consequently, higher
dosages administered at prolonged
intervals are often indicated in sick foals,
especially when concentration-dependent
drugs such as the aminoglycosides are
used. 43,44

The response to antimicrobial therapy
should be monitored, using physical
examination and clinical pathology data,
on at least a daily basis. Failure to improve
should prompt a reconsideration of the
therapy within 48-72 hours, and a

In?; ' .• . •' - . ' ;

/TrAAv. ■ . ’ '’AbA ■

Antimicrobial

Dose and route

Frequency

Comments

Amikacin sulfate

25 mg/kg, IM or IV

24 h

Excellent Gram-negative activity, potentially nephrotoxic.
Use with a penicillin

Amoxicillin trihydrate

25 mg/kg, PO

6-8 h

Variable absorption decreasing with age. Limited Gram-
negative spectrum

Amoxicillin-clavulanate

15-25 mg/kg, IV

6-8 h

Enhanced Gram-negative spectrum

Amoxicillin sodium

15-30 mg/kg, IVorIM

6-8 h

Limited Gram-negative spectrum. Use with an
aminoglycoside. Safe

Ampicillin sodium

10-20 mg/kg, IVorIM

6-8 h

Limited Gram-negative spectrum. Use with an
aminoglycoside. Safe

Ampicillin trihydrate

20 mg/kg, PO

6-8 h

Limited Gram-negative spectrum. Variable absorption
decreasing with age

Cefotaxime sodium

1 5-25 mg/kg, IV

6-8 h

Use for bacterial meningitis. Expensive

Cefoperazone sodium

20-30 mg/kg, IV

6-8 h

Use for Pseudomonas sp. infections

Cefpodoxime proxetil

10 mg/kg PO

8-12 h

Broad spectrum and well absorbed by foals after oral
administration

Ceftazidime sodium

20-50 mg/kg

6-8 h

Third-generation cephalosporin. Save for refractory infections

Ceftiofur sodium

10 mg/kg, IV over 15 min

6 h

Broad spectrum. Note higher dose than used in adults

Chloramphenicol palmitate

50 mg/kg, PO

6-8 h

Broad spectrum, bacteriostatic. Human health risk.
Restricted use

Chloramphenicol sodium succinate

50 mg/kg, IV

6-8 h

Broad spectrum, bacteriostatic. Human health risk.
Restricted use

Ciprofloxacin

5 mg/kg, IV

12 h

Broad spectrum. Potentially toxic to developing cartilage

Enrofloxacin

5-7.5 mg/kg, PO or IV

12-24 h

Broad spectrum. Potentially toxic to developing cartilage

Gentamicin sulfate

7 mg/kg, IV or IM

24 h

Good Gram-negative spectrum. Nephrotoxic. Use with a
penicillin

Metronidazole

1 5-25 mg/kg, IV or PO

8-12 h

Active against obligate anaerobes and protozoa only

Oxytetracycline

5 mg/kg, IV

12 h

Variable Gram-negative activity. Safe. Cheap

Procaine penicillin G

20 000-40 000 lU/kg, IM

12 h

Very limited Gram-negative activity. Muscle soreness. Cheap

Sodium or potassium penicillin G

20 000-40 000 lU/kg, IVorIM

6 h

Limited Gram-negative activity. Use with an aminoglycoside

Pivampicillin

15-30 mg/kg, IVorIM

8 h

Ampicillin prodrug

Ticarcillin sodium

50 mg/kg, IV

6 h

Active against Gram-negative organisms. Expensive

Ticarcillin-clavulanate

50 mg ticarcillin/kg, IV

6 h

Extended activity. Expensive

Trimethoprim-sulfonamide

1 5-30 mg/kg, PO, IV

12 h

Cheap. Broad spectrum. Limited efficacy in treating
septicemia in foals

PART 1 GENERAL MEDICINE ■ Chapter 3: Diseases of the newborn

worsening of the newborn's condition may
necessitate changing the antimicrobial
sooner than that. The decision to change
antimicrobial therapy should be guided,
but not determined, by the results of
antimicrobial sensitivity testing of isolates
from the affected newborn. These
antimicrobial susceptibility patterns should
be determined locally, as the results can
vary geographically, although results of
studies are published. 45 The utility of
antimicrobial sensitivity testing in deter-
mining optimal antimicrobial therapy for
foals has not been determined, although
it is likely that, as with mastitis in cows,
sensitivity to antimicrobials determined by
the Kirby-Bauer method will not be use-
ful in predicting efficacy.

Fluid therapy

Fluid therapy of newborns differs from
that of adult animals because of impor-
tant differences in fluid and electrolyte
metabolism in newborns. 46,47 The follow-
ing guidelines are suggested: 47

s Septic shock - sequential boluses of
20 mL/kg delivered over 5-20 minutes
with re-evaluation after each bolus.
Usually, 60-80 mL/kg is the maximum
dose before use of pharmacological
support of blood pressure is
considered. Care should be taken to
avoid fluid overload and the foal
should be re-evaluated after each
bolus and the need for continued
fluid therapy determined. Continuous
infusion of fluid is not indicated
• Maintenance support - this should
be determined based on the ongoing
losses and the clinical status of the
animal. However general
recommendations are:

° First 10 kg body weight
- 100 (mL/kg)/d
,J Second 10 kg body weight
-50 (mL/kg)/d
° Weight in excess of 20 kg
- 25 (mL/kg) /d

Neonates with high ongoing
losses, such as those with diarrhea or
gastric reflux, can have higher fluid
requirements.

Care should be taken to prevent
administration of excess sodium to foals
as they have a limited ability to excrete
sodium. 48 The recommended intake is
2-3 (mEq/kg)/d, and this includes sodium
administered in parenteral fluids. One L of
isotonic sodium chloride provides a 50 kg
foal's sodium requirements for one day. 47

A suitable maintenance fluid for foals
is isotonic dextrose (5%) with supple-
mental potassium (10-40 mEq/L).

Respiratory support

Respiratory failure, evidenced by elevated
arterial Pco 2 and decreased Po 2 , may be

due to depressed central activity, weakness
of respiratory muscles or lung disease.
Regardless of the cause, should the
hypoxemia become sufficiently severe
then oxygenation must be improved by
increasing respiratory drive, increasing
the inspired oxygen tension, or employ-
ing mechanical ventilation. Foals should
always be maintained in sternal recum-
bency to allow optimal respiratory function.

Provision of respiratory support should
be considered when the arterial Po 2 is less
than 60 mmHg (8 kPa) and the arterial
Pco 2 is more than 60 mmHg (8 kPa) in a
foal in sternal recumbency. Pharma-
cological respiratory stimulants have only
a very short duration of action and are of
limited use. Nasal insufflation of oxygen
is achieved by placing a nasopharyngeal
tube and providing oxygen at a rate of
5 L/min.

Mechanical ventilation is useful for
maintaining oxygenation in foals with
botulism, with more than 80% of foals
surviving in one small study. 49 However,
this intervention requires considerable
expertise and sophisticated equipment.
The prognosis is much worse for foals
with diseases of the lungs that require
mechanical ventilation.

Gastroduodenal ulcer prophylaxis

111 neonatal foals are often treated with
antacid drugs in an attempt to prevent the
development or progression of gastro-
duodenal ulcers, although the efficacy of
this approach is unproven. There is a
trend toward not administering antiulcer
medications to foals except for those with
demonstrated gastric ulceration, in part
because of the recognition that critically
ill foals often have gastric pH above 7.0
and administration of ranitidine does not
affect this pH. 50 (See Gastric ulcers in
foals for further discussion.)

COMMON COMPLICATIONS

Complications of the neonate's disease or
its treatment occur frequently:

Entropion is common in critically ill
foals and, although readily treated,
can cause corneal ulceration if
undetected

° Aspiration pneumonia occurs in weak
foals, often as a result of aggressive
bottle feeding or regurgitation of milk
around a nasogastric tube
° Nosocomial infections can be severe
and life-threatening and are best
prevented by strict hygiene and
asepsis

0 Septic synovitis/arthritis occurs as a
consequence of bacteremia and
should be treated aggressively
° Omphalitis and omphalophlebitis
occur and can be an undetected cause
of fever and relapse. These are best

detected by ultrasonographic
examination of the abdomen
° Patent urachus, evident as urine at the
navel, usually resolves with time and
local treatment

° Uroperitoneum as a result of urachal
rupture occurs in critically ill foals and
should be suspected in any ill foal
that develops abdominal distension
° Angular limb deformities and
excessive flexor tendon laxity occur
frequently in ill neonatal foals but
usually resolve with minimal
symptomatic treatment as the foal
recovers its strength.

PROGNOSIS

The prognosis for critically ill neonates
depends on many factors, including the
nature and severity of the disease, facilities
available for care and the expertise of the
personnel caring for the neonate. There is
a consensus that the recovery rate for
severely ill foals has improved over the last
decade because of provision of better care.
There are reports of survival rates of around
80% for foals treated at a specialized
intensive care unit. 51 However, the high
cost of providing care for these animals has
prompted studies to determine outcome,
as a means of deciding whether, financially,
treatment is warranted.

The increased number of foals being
treated intensively has resulted in
prospective studies of outcome. The
prognosis for athletic activity for foals
with septic arthritis is poor. Thoroughbred
foals with septic arthritis have odds of
0.28 (95% Cl of 0.12-0.62) (roughly one-
quarter of the likelihood) for racing as
compared with a cohort of healthy foals. 52
Multisystemic disease, in addition to the
presence of septic arthritis, decreased
the likelihood of racing to l/10th that
of healthy foals (odds ratio 0.12, 95%
Cl 0.02-0. 90). 27 Affected foals that survive
take almost 40% longer to race for the
first time. Approximately 30-48% of
affected Thoroughbred foals eventually
race, compared to approximately 65% of
normal foals. 52,53

Attempts to determine prognostic
indicators for survival of foals have been
partially successful but tend to be most
applicable to the intensive care unit in
which they were developed. 3,23,25,35,54 " 56
The results of these studies are sum-
marized in Table 3.8. The common theme
is that sicker foals are less likely to be
discharged from hospital alive. Charac-
teristics of foals that are more likely to
survive include ability to stand when first
examined, normal birth, white cell count
in blood that is within or above the
reference range, lack of dyspnea, normal
plasma fibrinogen concentration, and
short duration of disease.

Clinical assessment and care of critically ill newborns

Variable

Odds ratio
for survival

Comments

No. foals
(reference)

Dystocia

0.2

Dystocial foals have a decreased chance of survival

109 (25)

Standing at admission

12.1

Foals that are standing when first examined are much more
likely to survive than recumbent foals

65(53) ,

Duration of clinical signs (days)

0.17

Foals with disease of longer duration are less likely to survive

65 (53)

Sepsis score

0.63

Increased sepsis score is associated with greater risk of death

68 (33)

< 7 days of age

8.8

Younger foals are more likely to survive

65 (53)

Respiratory rate (> 60 bpm)

18.8

Foals with high respiratory rates are more likely to survive

65 (53)

Dyspnea

0.25

Foals in respiratory distress are less likely to survive

109 (25)

Rectal temperature subnormal

0.19

Foals with rectal temperature below normal are less likely to survive

90 (52)

Rectal temperature above normal

0.86

Foals with rectal temperature above normal are less likely to survive

90 (52)

Heart rate below normal

0.1

Foals with heart rate below normal are less likely to survive

90 (52)

Heart rate above normal

0.49

Foals with heart rate above normal are less likely to survive

90 (52)

Radiographic evidence of diffuse lung disease

0.28

Foals with radiographic evidence of lung disease in multiple areas of
the lung are less likely to survive

75 (6)

Segmented neutrophil count in blood

1.7

Increased neutrophil count in blood is associated with lower
risk of death

68 (33)

Neutrophil count > 4000 pL
(4.0 x 1 0 9 /L)

37.5

Foals with neutrophil counts in lolood > 4000 pL (4,0 x 1 0 9 /L) are
much more likely to survive are foals with counts < 4000 pL
(4.0 x 1 0 9 /L)

65 (53)

Neutrophil count below normal

0.28

Low neutrophil count in blood is associated with greater risk of death

90 (52)

Neutrophil count above normal

1.5

Increased neutrophil count in blood is associated with lower risk of death

90 (52)

IgG (mg/dL)

1.003

Foals with higher serum IgG on admission are more likely to suivive

68 (33)

Plasma fibrinogen (mg/dL)

0.99

Foals with high fibrinogen concentration are less likely to survive

68 (33)

Red blood cell count

1.8

Foals with higher red cell counts are more likely to survive

68 (33)

Vfenous Po 2 (mmHg)

1.1

Foals with higher venous oxygen tension are more likely t o survive

56 (51)

Anion gap (mEq/l)

0.81

Foals with higher anion gap are less likely to survive

56 (51)

Serum creatinine (mg/dL)

0.20

Foals with higher creatinine concentration are less likely to survive

109 (25)

Odds ratios > 1 are indicative of an increased probability of survival. All variables reported above were statistically significantly associated with survival in the reporting

publication.

REVIEW LITERATURE

McKenzie HC, Furr MO. Equine neonatal sepsis: the
pathophysiology of severe inflammation and
infection. Compend Contin Educ PractVet 2001;
23:661-672.

Sanchez LC. Neonatal Medicine and Surgery. Vet Clin
North Am Equine Pract 2005; 21:241-535.

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3. Stewart AJ et al. JVet Intern Med 2002; 16:464.

4. Rossdale PD, Short RV. J Reprod Fertil 1967;
13:341.

5. Rossdale PD. Equine Vet J Suppl 1993; 14:3.

6. Schlafer DH. Proc Am Assoc Equine Pract 2004;
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7. Renaudin CD et al. Theriogenology 1997; 47:559.

8. Bedenice D et al. JVet Intern Med 2003; 17:876.

9. ReefVB et al. J Am Vet Med Assoc 1989; 195:69.

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17. Davis R, Giguere S. J Am Vet Med Assoc 2005;
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18. McVicker JK et al. Am JVet Res 2002; 63:247.

19. Hofsaess FR. J Equine Vet Sci 2001; 21:158.

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30. Kohn CW et al. J Am Vet Med Assoc 1989; 195:64.

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33. Raidal S. AustVet J 1996; 73:201.

34. Tyler-McGowan CM et al. AustVet J 1997; 75:56.

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38. Wilkins PA, Dewan-Mix S. Cornell Vet 1994; 84:7.

39. McClure JT et al. Equine Vet J 2001; 33:681.

40. Buffington T et al. Manual of veterinary dietetics.
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41. Ousey JC et al. Am JVet Res 1997; 58:1243.

42. Furr M, Mogg TD. Compend Contin Educ Pract
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1 GENERAL MEDICINE

Practical antimicrobial therapeutics

PRINCIPLES OF ANTIMICROBIAL
THERAPY 173

Identification of the infection by clinical
examination 173
Taking samples for diagnosis 174
Antimicrobial sensitivity tests 175
Antibiotic resistance 176

This chapter is not intended as a treatise
on pharmacology, pharmacodynamics
and antibacterial activity of antimicrobial
agents. Other textbooks are available that
deal with those subjects. However, anti-
microbials are the most commonly
employed group of drugs in large animal
practice and their use is recommended on
many occasions in the following chapters.
To avoid repetition, the principles of usage
and considerations for dose schedules and
for the selection of antibacterial agents for
certain circumstances are given here and
in the formulary.

Some of the information or opinions
presented are based on clinical use rather
than experimental evidence. However,
this is often unavoidable, because unfor-
tunately many antimicrobial agents have
in the past been released for use in large
animals with minimal pharmacological or
clinical evaluation in the species con-
cerned. As a result it has been assumed,
often erroneously, that information
obtained from studies in laboratory
animals, dogs and humans can be directly
applied to the ruminant, horse and pig.

Principles of antimicrobial
therapy

The success of antimicrobial therapy
depends upon maintaining, at the site of
infection, a drug concentration that will
result, directly or indirectly, in the death
or control of the infectious organism with
minimal deleterious effect to the host.
In order to achieve this aim the anti-
microbial agent must have activity against
the organism at its site of infection and
it must be administered in such a way as
to maintain an effective inhibitory or
lethal concentration. These principles
apply to therapy in all species and dictate
the choice of antimicrobial agent to be
used. However, in farm animal veterinary
practice there are also other important
considerations

° Cost is critical. This consideration
includes not only the primary cost of

PRACTICAL USAGE OF
ANTIMICROBIAL DRUGS 177

Antibiotic dosage: the recommended
dose 1 77

Routes of administration 178
Drug distribution 181
Duration of treatment 181

the drug but also related factors such
as the ease and frequency of
administration and the duration of
treatment

0 Tissue residue problems and
withdrawal periods must also be
taken into consideration and are a
primary determinant of treatment
strategy

° Animal welfare becomes a
consideration when a decision is
made not to treat an animal because
of concerns about cost or the
occurrence of residues that would
preclude marketing of the animal or
its products in the future
° Antimicrobial resistance and the
risk of contributing to the emergence
and problem of antimicrobial
resistance is a concern that has
increasing attention, not so much
with the therapeutic use of
antimicrobials but certainly with the
prolonged administration of
antimicrobials in animal feeds for
disease prevention.

In the theoretically ideal situation, the
following steps would be taken before
selecting an antimicrobial agent for
therapy.

° First, the site of infection would be
located and the identity of the
infecting organism established by
culture

® Second, the minimal inhibitory
concentration (MIC) of each
antimicrobial agent for the infecting
organism would be identified
0 Third, an initial selection would be
made based on the sensitivity of the
organism and the knowledge of the
capacity of the individual
antimicrobial agents to penetrate to
the site of infection and to achieve
and exceed these concentrations at
nontoxic dose rates
0 Fourth, the dose rates, route of
administration and frequency of
administration required to achieve
these concentrations for each of the
selected antibiotics, in the particular

4

Drug combinations 181
Additional factors determining selection
of agents 182
Drug deterioration 183
Unfavorable response to therapy 183
Drug withdrawal requirements and
residue avoidance 183

animal species being treated, would
then be considered

® Finally, selection of a particular drug
would be based on a consideration of
the potential toxicity to the host, on
the likely relative efficiency of each
drug, on the cost and ease of
administration and, in food animals,
on costs associated with the relative
withholding periods.

It is obvious that for many clinical situ-
ations all these steps cannot be followed
before therapy is instituted. It may take
several days to establish the identity of
the infectious agent unless it can be
ascertained by clinical diagnosis. The
identification of the organism helps in
determining its potential sensitivity but
even without identification the establish-
ment of exact MICs by tube dilution for
each antimicrobial agent also takes
several days, and the results would
frequently be historical by the time that
they were received. Also, a knowledge, for
each antimicrobial agent, of the varying
tissue and organ levels achieved following
varying doses given by different routes of
administration is not easily remembered
and therefore not easily available in large-
animal field situations. Nor, unfortunately,
is complete information of this type avail-
able for each antimicrobial agent in all
large-animal species.

Because of this uncertainty, some
expedients are adopted in clinical anti-
microbial therapy. One of them is the
concept of the recommended dose and
another is the use of disk sensitivity testing,
both of which are discussed later in this
chapter. Regardless of these expedients, it
should be recognized that rational
antimicrobial therapy is based upon the
principles outlined above. These important
principles in antimicrobial therapy are
discussed in greater detail individually.

IDENTIFICATION OF THE
INFECTION BY CLINICAL
EXAMINATION

In infectious disease, clinical examination
aims to identify the nature and site of the

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

infection and its cause. The importance of
making an accurate clinical diagnosis
cannot be overemphasized as the first
prerequisite for successful antimicrobial
therapy. The establishment of a diagnosis
in many instances immediately identifies
the pathogen and previous clinical experi-
ence may suggest the specific antibiotic to
be used and allow a confident prediction
of success of the therapy. Equally, it may
indicate the likelihood of unsuccessful or
prolonged therapy. For example, the
diagnosis of erysipelas or Glasser's
disease in pigs or strangles in horses
immediately identifies the etiological
cause of the infection and the type of
antimicrobial agent that will be required.
It also gives some indication of the likely
ease or difficulty of successful therapy and
of the duration of therapy that might be
required.

The establishment of an accurate
diagnosis is also important in animals
where chemotherapeutic control of further
disease may be required. Thus, in pigs, an
accurate differentiation between the
diarrhea of swine dysentery and that
associated with coliform gastroenteritis
is essential for effective prophylactic
medication.

It is often not possible to establish an
exact diagnosis at the first examination
and yet in almost every instance it is
essential that treatment be instituted at
that time, not only for the wellbeing of
the patient but also for the maintenance
of good client relationships. The lack of a
definitive etiological diagnosis should
never preclude the initiation of therapy
during the period when further tests are
being carried out. Rational therapy in
these circumstances depends very much
on clinical acumen. A detailed examin-
ation leading to a determination of the
site and nature of the infection can
frequently allow an educated guess at the
likely pathogen and allow rational
therapy during the period that specific
diagnosis is being determined by culture.

This approach is frequently used
initially in field situations in large animal
medicine but it requires good clinical
knowledge. Clinicians should be familiar
not only with the individual diseases of
large animals but also with their differ-
ential diagnosis and with the relative
prevalence of each condition in their
area. They should also be familiar with the
types of organism that may produce
infections in various body areas with
similar clinical manifestations and the
relative prevalence of each of these. Thus
peracute mastitis in recently calved cows
is most commonly associated with infec-
tion by staphylococci but can also be
associated with coliform organisms or,
more rarely, Actinomyces (Corynebacterium)

pyogenes or Pasteurella multocida. Treat-
ment must be initiated immediately if the
gland or even the cow is to be saved.
There are subtle clinical and epidemi-
ological differences that may allow some
clinical differentiation between these
agents but frequently treatment must
begin with no sure knowledge of which
agent is involved. There are two
approaches in this type of situation:

® Therapy may be directed at the most
prevalent or likely agent and, in
situations where one particular
infectious agent is the most prevalent
cause of the condition, this is a
rational approach

8 In other situations, where a disease
could be associated with any one of
several different organisms, each with
a different sensitivity, and where
clinical experience suggests that no
one organism is the predominant
infectious agent, it is more common
to initiate therapy with a broad-
spectrum antimicrobial agent or a
combination that will have activity
against all the possibilities. If
indicated, the antibacterial agent
being used for therapy may have to be
changed to a more specific one once
the actual pathogen and its sensitivity
have been determined.

There are also clinical situations where
therapy must begin when there is little
knowledge of the site of infection and
consequently no knowledge of the
identity of the infecting agent.This occurs
where infection, such as abscessation,
occurs in deep-seated and clinically
inaccessible organs such as the liver or
spleen. Also in these situations it may not
be possible to determine the nature and
cause of the disease by laboratory exam-
ination although biochemical examinations
and ultrasound may give some indication
of the site. In these cases therapy is
generally started with a broad-spectrum
antimicrobial agent or a combination of
lesser ones, and the accuracy of the
selection is determined by subsequent
clinical response.

TAKING SAMPLES FOR
DIAGNOSIS

In teaching hospitals, there is ready access
to bacteriology laboratories, which fre-
quently contain automated and rapid
systems for sensitivity testing. However,
in practice the taking of samples for this
purpose is generally restricted and limited
by such factors as the availability of a
diagnostic laboratory, and by cost.
Furthermore, in many cases the results of
culture and sensitivity are historical by the
time they are received. Nevertheless,

information of this type is of value for
future similar cases and it provides preva-
lence data and data of antimicrobial
sensitivity that can be used for back-
ground clinical knowledge and justification
for extralabel drug use in food-producing
animals.

The recognition of when samples
should be taken for microbiological
examination and sensitivity testing comes
with clinical experience. In general, the
approach is different when dealing with
individual sick animals from when dealing
with groups of animals and a contagious
disease. In individual animals, cost and
the time for processing usually limit the
taking of samples to valuable stud animals
and to horses. They should be taken from
individual sick animals with life-
threatening conditions so that, if a
response is not obtained to initial therapy,
the subsequent choice of antimicrobial
agent can be based on laboratory data.
They should also be taken from animals
with disease syndromes that may be
caused by one of several agents or by an
organism that may show variable resist-
ance patterns. Examples would be infec-
tive arthritis in foals or Gram-negative
sepsis. 1 The increasing emergence of
variable resistance patterns in veterinary
pathogens places an increasing importance
on sampling and sensitivity testing and
many practices have now established
their own laboratories for this purpose.

Samples are also frequently taken from
chronic, poorly responsive conditions
to determine the best course of treatment.
In groups of animals where there is
contagious disease, the taking of samples
to establish or confirm the etiological
diagnosis and to determine the best drug
for chemotherapy is most important.
Where there are a large number of
animals at risk it is important to confirm
the initial choice of therapy as soon as
possible so that remedial steps can be
taken if this was incorrect. It is also
important in these situations to have a
confirmed accurate etiological diagnosis
so that control measures can be instigated
to prevent future problems. Thus an
outbreak of diarrhea in postweaned pigs
may be due to coliform gastroenteritis,
salmonellosis or swine dysentery. Clinical
and pathological examination may
eliminate swine dysentery but not
allow complete differentiation between
salmonellosis and coliform gastroenteritis.
An aminoglycoside could be used for the
initial therapy of the outbreak but, at the
same time, samples are taken for culture
and sensitivity to determine the exact
antimicrobial sensitivity of the infectious
agent in case there is resistance to
this antibiotic. Also, by this procedure
the exact etiological diagnosis will be

determined, which will then determine
recommendations for future control of
the disease.

Consideration should be given to the
nature of the sample for examination. In
outbreaks of diarrhea there is little point
in taking fecal samples from chronically
scouring and runted animals. Samples
should be taken from animals at the onset
of diarrhea. The site of sampling can also
have an influence that may affect the
relevance of the results. In animals with
pneumonia, the nasal flora may not
reflect that in the lung and cultures are
best taken as transtracheal aspirates of
the lower respiratory system. 2,3

Similarly, fecal Escherichia coli strains
are not always representative of small-
intestinal strains in scouring calves. 4

ANTIMICROBIAL SENSITIVITY
TESTS

RATIONALE

Antimicrobial sensitivity testing is not
required with all infections because many
organisms are invariably sensitive to one
or more antimicrobial agents and in most
cases these can be used for therapy. The
clinician should be familiar not only with
the spectrum of each antimicrobial drug
but also with the spectrum of sensitivity
for the common organisms involved in
diseases of large animals. Sensitivity
testing is generally reserved for members
of those groups of organisms that show
considerable variation in sensitivity to
individual antimicrobial agents.

There can be considerable area-to-
area variation and spatial and temporal
dustering in the sensitivity patterns of
individual organisms. 5 ^ 7 It is wise to
establish the broad patterns of general
sensitivity or resistance for these groups
in any practice area and to monitor any
change periodically so that therapy can be
guided by this information. This also can
provide information justifying the
extralabel use of antimicrobials in food-
producing animals.

The purpose of sensitivity testing is

to attempt to determine if the organism
under consideration is likely to be suscep-
tible to the action of an antimicrobial
agent at the drug levels that can be
achieved using the usual therapeutic dose
rates. In clinical terms, organisms are con-
sidered to be either sensitive or resistant
to the action of an antimicrobial. How-
ever, with many organism-antimicrobial
associations, resistance or susceptibility is
not an all-or-none phenomenon but is
dependent upon drug concentration.
Organisms that may be resistant to low
levels of an antimicrobial agent are
frequently susceptible to its action at
higher concentrations. Thus an organism

Principles of antimicrobial therapy

175

that is susceptible to the action of
benzylpenicillin at a concentration of
0.1 pg/mL would be considered sensitive
because equivalent levels of benzyl-
penicillin can be easily achieved in the
blood and tissues. One that was sus-
ceptible only at a concentration above
5 pg/mL might be considered resistant,
even though it is possible to achieve and
maintain this concentration of benzyl-
penicillin in the tissues with high and
frequent dosing.

SENSITIVITY TEST METHODS
Tube sensitivity tests

Sensitivity tests may be quantitative or
qualitative. Tube sensitivity tests, using
serial dilutions of the antimicrobial drug
against a standard dose of the test
organism, provide quantitative infor-
mation in terms of an exact MIC of the
drug being tested. The MIC is the lowest
antibiotic concentration that prevents the
growth of bacteria within a defined
period of time and under the conditions
of the test. Tube sensitivity testing is the
gold standard. With most antibiotics, a
mean plasma level 2-5 times the MIC
needs to be sustained through the dosing
interval for effective therapy. These tests
are laborious and time-consuming and
are seldom used in practice situations for
these reasons.

Disk sensitivity tests
Disk sensitivity tests provide more
limited qualitative information. They are
generally a valuable adjunct in the choice
of an antimicrobial agent for therapy,
particularly for systemic diseases. How-
ever, the limitations of the usual method
of testing, and the limitations of inter-
pretation should be recognized by the
clinician.

The Kirby-Bauer technique is the
most commonly used method of disk
diffusion sensitivity testing. With this
technique, disks are impregnated with a
standard amount of antibiotic that
diffuses into the media to produce a zone
of inhibition of growth. With a standard
concentration of antibiotic in the disk and
standard antibiotic sensitivity test media
and test conditions, the concentration of
the diffused antibiotic at any given
distance from the disk is relatively
predictable and constant. There is a linear
relationship between the diameter of the
zone of inhibition and the log 2 of the
MIC. For each antibiotic MIC, break-
points have been established and
corresponding zone size breakpoints
established above or below which an
organism is classified as resistant, suscep-
tible or of intermediate sensitivity.

Although the Kirby-Bauer disk sensi-
tivity testing system has a quantitative
genesis the results are qualitative -

especially as used in most practice
laboratories. MIC breakpoints are specific
values used to assign bacteria to one of
three classifications - susceptible, inter-
mediate and resistant.

The MIC breakpoints and thus the
published reference zone sizes for resist-
ance and susceptibility are often based on
the pharmacokinetic properties of each
antimicrobial in humans. These frequently
have limited relationship to their pharma-
cokinetic properties in animals, particularly
ruminants. 8

Also, a single antimicrobial considered
to be representative of its class is used to
test sensitivity to that class of anti-
microbials, but commonly this represen-
tative is not the antibiotic agent present in
commercially available antibiotic treat-
ments for livestock. 8 Further, the use of
specific zone diameters to establish resist-
ance and susceptibility assumes a standard
test with standard media and under
standard conditions. These conditions are
frequently not met in veterinary practice
laboratories.

Despite these limitations, disk sensitivity
tests can be used as a guide to the selec-
tion of antimicrobials for therapy in large-
animal veterinary practice. They are of
particular value in selecting a choice of
antibiotic with organisms that exhibit
variable patterns of resistance and where
this pattern for any one antibiotic is
essentially bimodal in distribution. 9 They
may have limited value in the testing of
organisms where the sensitivities are
clustered around the MIC breakpoint.
However, there is a lack of validation for
susceptibility testing being predictive for
treatment outcome in almost all large-
animal diseases as the breakpoints have
not been validated. 8,10

There should not be over-reliance on
the results of testing for sulfonamide sensi-
tivity, as these are frequently misleading
and a good clinical response can be
achieved with therapy even though the
sensitivity test suggests resistance.

Frequently, with disk sensitivity tests,
the organism proves sensitive to a
number of different antimicrobial agents.
The selection of one of these for therapy is
based on such factors as ease of admin-
istration and cost. The relative efficacy of
any one of the agents cannot be
determined by comparison of the size of
the zones of inhibition.

Microtiter techniques

The development of semiautomated
microtiter methodology for direct MIC
determinations allows many reference
diagnostic laboratories and teaching
hospitals to determine MIC concen-
trations directly in bacterial sensitivity
testing. The results are more directly

176

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

applicable to rational therapy and, in
particular, have more relevance than
disk diffusion tests for determining the
sensitivity of organisms that cluster
around the MIC breakpoint for a given
antibiotic . 9,11

OTHER CONSIDERATIONS

The antimicrobial sensitivity of an organ-
ism can vary considerably depending
upon the species of animal from which
it is isolated. E. coli isolates from pigs
generally show a greater degree of anti-
biotic resistance than those isolated from
adult cattle. Similarly, Campylobacter spp.
isolates from pigs show substantially
different antibiotic sensitivity patterns
from those isolated from sheep. Isolates
from the same species may also vary
significantly in sensitivity, so that E. coli
isolated from mastitis in cattle generally
have a broader sensitivity pattern than
those isolated from enteric disease in
calves. In addition, there are area differ-
ences and changes with time. Low levels
of antibiotic fed for growth-promoting
purposes may influence sensitivity patterns,
and in herds where growth promoters are
being used it is generally wise not to use
the same drug or members of the same
group for therapeutic purposes without
prior testing.

REVIEW LITERATURE

Woolcock JB, Mutimer MD. Antibiotic sensitivity
testing: caeci caecos ducentes? Vet Res 1983;
113:125-128.

Prescott JG, Baggot JD. Antimicrobial susceptibility
testing and antimicrobial drug dosage. J Am Vet
Med Assoc 1985; 187:363-368.

Baggot JD, Prescott JF. Antimicrobial selection and
dosage in the treatment of equine bacterial
infections. Equine Vet J 1987; 19:92-96.

Wilcke JR. Therapeutic decisions. Choosing appropriate
antimicrobial therapy. Probl Vet Med 1990;
2:279-289.

Dow SW, Papich MG. Keeping current on develop-
ments in antimicrobial therapy. Vet Med 1991;
86:600-609.

Constable PD, Morrin DE. Treatment of clinical
mastitis: Using antimicrobial susceptibility testing
profiles for treatment decisions. Vet Clin North
Am Food Anim Pract 2003; 19:139-155.

REFERENCES

1. Brewer BD, Koterba AM. Compend Con tin Educ
Equine Pract 1990; 12:1773.

2. Spurlock SL. Equine Pract 1989; 11:6.

3. Thomas A et al. Vet Res Commun 2002; 26:333.

4. Constable PD. J Vet Intern Med 2004; 18:8.

5. Gunn GL, Low JC. Vet Rec 2003; 152:537.

6. Singer RS et al. J Am Vet Med Assoc 1998;
212 : 1001 .

7. Dunlop RH et al. PrevVet Med 1998; 34:265, 283.

8. Constable PD. Proceedings of the 37th Annual
Convention of the American Association of
Bovine Practitioners 2004; 37:11.

9. Libal MC et al. Proc Am Assoc Vet Lab Diagn
1986; 29:9.

10. Constable PD, Morrin DE. J Am Vet Med Assoc
2002; 221:103.

11. Libal MC. Am J Vet Res 1985; 46:1200.

ANTIBI OTIC RE SIST ANCE

Antimicrobial resistance is a natural
biological phenomenon and the intro-
duction of antibiotics into clinical use has
almost invariably been followed by the
emergence of resistance to these drugs in
bacterial populations . 1 When a microbial
population is exposed to an antibiotic, the
more susceptible organisms will succumb,
and antimicrobial use in human medicine
and in agriculture naturally must result in
the selection of antimicrobial-resistant
phenotypes. This occurs in nonpathogens
as well as pathogens . 2 Resistance is
generally slow to reverse or is irreversible.

There are a number of mechanisms
whereby resistance is engendered. Resist-
ance that results from spontaneous
mutation of chromosomal genes encoding
a target site is probably of limited import-
ance in clinical settings. It occurs more
frequently with certain antibacterials, i.e.
rifampin, and may be combated by the
inclusion of a second antibacterial in j

I

the treatment regimen. Plasmid- and i
j transposon-determined drug resistance is
of much more importance in clinical
situations and has led to widespread
i multiresistance patterns in certain
| bacterial populations.

Plasmids are extrachromosomal genetic
elements that replicate independently of
the chromosome. They can be transferred
within, and in some cases between,
bacterial species and may also act as
vectors for transposons.They may encode
for single or multiple patterns of antibiotic
resistance and, increasingly, multiple
patterns of resistance are emerging. With
veterinary pathogens, plasmid-determined
I resistance is particularly important in the
: Enterobacteriaceae, Staphylococcus aureus
] and to some extent in Pasteurella spp . 3 " 5

Virtually all antibiotics given in
therapeutic doses cause marked changes
in the microflora of sites in the host
normally colonized by bacteria. There is
suppression of the sensitive flora with
subsequent selection and colonization by
resistant bacteria. In pigs, there is some
evidence that therapeutic use of anti-
biotics in individual animals does not
j greatly influence herd flora resistance
. patterns but in-feed medication of
: postweaned pigs selects for antibiotic
; resistance that maintains in finisher pigs . 6
: The feeding of antibiotics for growth
!. promotion and the feeding of antibiotic-
i treated milk to calves will select for
: resistance among organisms within the
\ alimentary tract. These resistant organisms
can persist in the animal and in the
environment and subsequently form part
; of the normal colonizing flora of other
animals, so that it is not unusual to isolate
organisms, E. coli for example, that are

resistant to one or more antibiotics even
though the animal from which they were
isolated had never received antibiotic
medication . 7,8

There is a higher prevalence of
antibiotic-resistant E. coli in the normal
intestinal flora of young animals than
adults . 9 The prevalence is higher in young
animals reared intensively, such as veal
calves and pigs, and in environments
where antibiotic usage has exerted
selection pressure. The prevalence falls
with increasing age and the intestinal
flora of adults generally shows a broader
sensitivity pattern. Although many of
these resistant organisms are not patho-
gens, they contribute a pool of R plasmids
that can be transmitted to pathogens, and
therapy decisions should take into
account what antibiotics are in routine
use on the farm as growth-promoting
additives. Tetracyclines and neomycin are
commonly incorporated in calf milk
replacers with the label claim that they
are growth promoters and aid in the
control of calf diarrhea. However, there
are no published studies that support
health benefits . 10 There are studies that
show improved growth of calves on
medicated milk replacers compared with
control calves but this difference is lost
after weaning and not of any production
benefit.

Feeding antimicrobials to livestock and
poultry to reduce disease and promote
weight gain has been standard practice in
developed countries for several decades
but is engendering increasing concern
and the occurrence of antimicrobial
resistance is beginning to be considered
to be a societal issue. The concern is that
! antimicrobial use in food-producing
i animals may affect human health by the
i presence of drug residues in foods, and by
' promoting the presence of antibiotic-
resistant strains in animals that can
| subsequently infect humans through food
or from effluent contamination of the
environment . 11 " 13 The consequences of
this also include an increased risk for
j resistant pathogens to be transferred to
I humans by direct contact with animals.
Although many of the growth-promoting
antibiotics used in animals are not the
same as those used for human therapy,
antimicrobial exposure can initiate bacterial
: resistance to compounds of dissimilar
] structures . 14

i There is a particular risk to farmers,

! farm workers and veterinarians from
; exposure to contamination in the farm
environment . 13,15 " 17 and a risk from trans-
j fer of resistant bacteria through farm food
; and via environmental contamination
from farm effluents . 18

[

Public and medical concern about the
ways in which antimicrobials are used in

Practical usage of antimicrobial drugs

177

IP

agriculture has particularly been aroused
by the development of vancomycin-
resistant enterococci in humans associated
with the use of the related drug avoparcin
as a growth-promoter in animal feeds. 19
In response to concerns about the emerg-
ence of antimicrobial resistance, Sweden
banned all growth -promoting antibiotics
in 1986. This was followed by a ban on
avoparcin and virginiamycin in Denmark
in 1995 and 1998. Finally, the European
Union (EU) banned the use of avoparcin
in 1997 and bacitracin, spiramycin, tylosin
and virginiamycin for growth promotion
in 1999. The effects of these bans on the
antibiotic resistance of flora in animals
and humans will take some time to
determine. There has been an apparent
reduction in vancomycin resistance in
fecal enterococci isolated from humans
and animals. 20-21 There has also been an
apparent increase in morbidity and
mortality among pigs, associated with
enteric infections, diarrhea and chronic
infections due to Lawsonia intracellularis.
This increase in animal disease since the
ban has resulted in a substantial increase
in the use of therapeutic antibiotics for
food animals in Europe, primarily tetra-
cyclines, trimethoprim/sulfonamides and
macrolides. 21

With respect to the emergence of anti-
biotic resistance in zoonotic organisms, a
particular concern has been plasmid-
determined multiple antibiotic-resistant
strains of salmonella that have emerged
and caused rapidly spreading epidemics
of disease in young calves in England and
Europe 22 These multiple resistance patterns
have been associated with particular
phage types and biotypes of Salmonella
typhimurium and Salmonella dublin.

Preventing the spread of multiresistant
organisms is not easily achieved and there
are examples of spread involving virtually
every major pathogenic bacterial group. 23
An example is the emergence and spread
of S. typhimurium DT 104, in which mul-
tiple antibiotic resistance is chromosomally
determined. A pathogen of a variety of
different animal species, including humans,
this organism spread globally in the
1990s. Because of the advanced salmonella
surveillance system in the UK, this
organism was first recognized as causing
outbreaks of disease in cattle and humans
in the UK and its emergence was initially
attributed to the use of antimicrobials in
cattle. There is however no evidence in
support of this 24 and its spread was due to
its colonizing ability, not to selection by
the feeding of antimicrobials. The history
of the emergence and spread of this
organism, which was unrelated to the use
of antimicrobials in livestock and related
more to the colonizing ability of DT104,
should act as a brake on proposals to use

changing patterns of antimicrobial resist-
ance as a measure of the risk of the use of
antimicrobials in livestock.

Plasmid-determined multiple patterns
of resistance are likely to increase in
organisms in environments where selec-
tion pressure is high as a result of
frequent antibiotic usage. The use of
antibiotics in agriculture is an obvious
target to reduce this selection, and is
frequently blamed for the problem of
developing antibiotic resistance in human
pathogens. Nosocomial infection with
antibiotic-resistant animal pathogens is
an emerging problem in veterinary
hospitals and procedures for limiting their
spread are available. 25

Whereas the major concern has been
directed at antibiotic use for growth
promotion there are also moves, in some
countries, to restrict the use of certain
antimicrobials, e.g. fluoroquinolones, from
therapeutic use in farm animals.
However, a European survey of anti-
microbial susceptibility among zoonotic
and commensal bacteria from food-
producing animals found that, although
there was variation among European
countries in the resistance of enteric
organisms, this largely involved the older
antimicrobials, and that resistance to the
newer compounds used to treat humans
was low. 26 Equally, a study of mastitis
pathogens over a 7-year period in the USA
showed no trend towards increased resist-
ance and reported a reduction of resistance
to beta-lactam antimicrobials for several
Gram-positive mastitis pathogens. 27

REVIEW LITERATURE

Saunders JR. Genetics and evaluation of antibiotic
resistance. Br Med Bull 1984; 40:54-60.

Hinton M. The ecology of Escherichia coli in animals
including man with particular reference to drug j
resistance. Vet Rec 1986; 119:420-426.

Pohl P, Lintermann P. R plasmid reservoirs and |
circulation. In: Rico RG, ed. Drug residues in \
\ animals. Veterinary Science and Comparative j
Medicine A Series. New York: Academic Press, 1986. j
| Corpet DE. Microbiological hazards for humans of ;
antimicrobial growth promoter use in animal j
production. Rev Med Vbt 1996; 147:851-862. i

| National Research Council. The use of drugs in food j
animals: benefits and risks. Washington, DC: j

National Academy Press, 1998:211. j

| Tallefson L, Angulo FJ, Fedorka-Cray PJ. National ,
; surveillance for antibiotic resistance in zoonotic i

enteric pathogens. Vet Clin North Am Food Anim
Pract 1998; 14:141-150. i

; Bailar JC, Travers K. Review of assessments of the \
human health risk associated with the use of ;
antimicrobial agents in agriculture. Clin Infect Dis
2002; 34(Suppl 3):S135-S143.

Wise R, Soulsby EJL. Antibiotic resistance - an ’
■ evolving problem. Vet Rec 2002; 151:371-372. ;

BesserTE, Hancock D, Davis M. The veterinarians role ;
in controlling the emergence and dissemination
of drug-resistant bacteria. J Vet Med Educ 2003;
i 30:136-139.

Thiele-Bruhn S. Pharmaceutical antibiotic compounds
in soils - a review. J Plant Nutr Soil Sci 2003;
166:145-167.

Rooklidge SJ. Environmental antimicrobial contami-
nation from terraccumulation and diffuse pollution
pathways. Sci Total Environ 2004; 325:1-13.

REFERENCES

1. Kayser FH.Vet Microbiol 1993; 35:257.

2. Schrocder CM et al. Emerg Infect Dis 2002;
8:1409.

3. Hinckley LS et al. J Am Vet Med Assoc 1985;
187:709.

4. Boyce JR, Morter RL. Am J Vet Res 1986; 47:1204.

5. Libal M et al. J Am Vet Med Assoc 1982; 180:908.

6. Dunlop RH et al. Prev Vet Med 1998; 34:265,
283.

7. Gellin G et al. Appl Environ Microbiol 1989;
55:2287.

8. Hinton M et al. J Appl Bacteriol 1985; 58:131.

9. Khachatryan AR et al. Appl Environ Microbiol
2004; 70:752.

10. Constable PD. In: Proceedings of the Annual
Conference of the American Association of
Bovine Practitioners 2003; 37:137.

11. Corper DE.Vet Microbiol 1993; 35:199.

12. Gorbach SL. Vet Hum Toxicol 1993; 35(Suppl
1):13.

13. Rooklidge SJ. Sci Total Environ 2004; 325:1.

14. Courvalin P. Emerg Infect Dis 2001; 7:489.

15. Hamscher G. Environ Health Perspect 2003;
111:1590.

16. Haller M et al. J Chromatogr A 2002; 952:111.

17. Meyer M et al. Sci Total Environ 2000; 248:181.

18. Thiele-Bruhn S. J Plant Nutr Soil Sci 2003;
166:145.

19. Lu K et al. Emerg Infect Dis 2004; 10:679.

20. Aarestrup FM et al. Antimicrob Agents
Chemother 2001; 45:2054.

21. Casewell M et al. J Antimicrob Chemother 2003;
52:159.

22. Threlfall EJ. Soc Appl Bacteriol Symp Ser 1992;
21:S96.

23. Tenover FC. Clin Infect Dis 2001; 33 (Suppl
3):S108.

24. Hancock D et al. In: Brown C, Bolin CA, eds.
Emerging diseases of animals. Washington, DC:
ASM Press, 2000; 217-243.

25. Brewer BD, Koterba AM. Compend Contin Educ
Equine Pract 1990; 12:1773.

26. Bywater R et al. J Antimicrob Chemother 2004;
53:744.

27. Makovec JA, Ruegg PL. J Am Vet Med Assoc 2003;
222:1582.

Practical usage of
antimicrobial drugs

ANTIBIOTIC DOSAGE: THE
RECOMMENDED DOSE

Theoretically, there is no set dose for any
antimicrobial agent. The concentration of
an antimicrobial drug required for effec-
tive activity against different micro-
organisms varies and these requirements
could be met by varying the dose rate of
the drug. However, this is an impractical
situation and in practice one works from
the recommended dose. The rec-
ommended dose is one that will give
blood and tissue levels that will be
effective against very susceptible organisms,
with minimal side effects to the host. In
* this respect the recommended dose
should be considered as a minimum dose.

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

If one is dealing -with organisms that
require higher concentrations of the
drug for therapeutic effectiveness, the
recommended dose can be exceeded.
With low-toxicity antibacterials this dose
may be exceeded severalfold and with
drugs such as benzyl penicillin this is a
frequent therapeutic ploy. However, with
antibacterials that have toxic potential the
recommended dose should only be
exceeded with caution and frequently it is
wise to search for a different antimicrobial
agent to which the organism is more
sensitive.

Similarly, the recommended dose may
be exceeded in an attempt to increase the
concentration gradient in sensitive infec-
tions where necrotic tissue produces long
diffusion paths. The recommended dose
may also be exceeded for management
reasons, as in the case of the treatment of
sheep with footrot or mycotic dermatitis,
where only a single treatment is adminis-
tered for practical purposes.

The label dose is the dose stated on
the label of the drug and is the legal dose
that can be used for that product. The
label states the required withdrawal
periods for avoidance of tissue or milk
residues. The recommended doses given
in the sections on individual diseases are
based on our expectations of therapeutic
efficiency, and may exceed the label
dose recommendations for certain drugs.
The problem of persisting tissue residues
should be recognized when label
recommendations are exceeded and
withdrawal periods should be adjusted
accordingly.

Label dose levels and dose intervals for
many of the antimicrobial agents used in
large animals are frequently too low and
too long. In many cases, there are no
obvious pharmacological reasons for
these dosing regimes. Unfortunately,
pharmacokinetic studies of the earlier
antimicrobial agents released for use in
large animal species were limited at the
time of their release and it would appear
that in many instances the label dose
established at that time was inadequate.
Some estimate of the dose required for an
antimicrobial drug can be obtained by a
comparison of the MICs required for
activity against various organisms with
the blood and tissue levels of the drug
obtained at various dose levels. Usually,
levels 3-5 times the MIC are considered
necessary for effective therapy, and it is
generally considered desirable to main-
tain these levels over the treatment period,
especially with bacteriostatic antimicrobials,
although this is probably not essential.

The ultimate proof for dose levels and
dose intervals of an antimicrobial is by
clinical trials of its efficacy in the treat-
ment of infectious disease. It is apparent

that antimicrobial drugs are effective in
many diseases in large animals at the
dose rates and intervals currently in use.
Nevertheless, as the results of pharma-
cokinetic studies in farm animals become
available it is quite probable that they will
suggest changes in the dose levels and
intervals for several of the antimicrobial
drugs in use, which may result in more
efficacious therapy and lead to label doses
that have a broader spectrum of activity
against disease.

ROUTES OF ADMINISTRATION

INTRAVENOUS INJECTION

Intravenously administered antibiotics
attain high and immediate blood and
tissue levels. This route should be used in
the treatment of septicemia and other
life-threatening diseases. The concen-
trations obtained are much higher than
those obtained with equivalent doses of
the same drug given intramuscularly or
orally, and consequently greater diffu-
sion concentrations are achieved at sites
of infection. For this reason this route of
administration may also be used in an
attempt to increase the drug concentration
in areas where the antibiotic normally
achieves only low concentrations, and
where areas of necrosis increase the
length of the diffusion pathway. Intra-
venous administration may also be
indicated in chronic infections such as
corynebacterial pneumonia in foals,
where high diffusion concentrations are
required in order to penetrate the abscess
areas and the capsular material of the
organism.

An initial intravenous loading dose
may combat the development of step-
wise resistant mutants. Because of the
initial higher blood and tissue levels, the
intravenous route may also be used for
the treatment of infections that are only
moderately sensitive to the antibacterial
drug being used. This is because effective
concentrations may be achieved by
repeated intravenous dosing which would
not be achieved by equivalent doses given
intramuscularly or orally.

For practical reasons the intravenous
route of administration is used for low-
concentration, high-volume antimicrobial
agents such as sulfamethazine and
oxytetracycline. It is also preferred to the
intramuscular route in racehorses where
there is a need to avoid muscular sore-
ness. The need to avoid muscle damage
in beef cattle close to marketing may also
dictate intravenous administration.

Administration by this route is not
without its dangers. Acute toxic reactions
either to the drug or to its vehicle
are more common when intravenous
administration is used. Drugs specifically

formulated for intravenous use should be
used, or the manufacturer's recommen-
dations on the advisability of the use of
this route for any preparation should be
followed. Severely toxemic terminal cases
may die immediately following injection,
and in the owner's mind death may be
attributed to the therapy.

Injections should be given slowly and
not as a bolus. Therapy by repeated intra-
venous administration is generally
restricted to hospital situations and can
be expensive because of the added cost of
the intravenous preparations. In field situ-
ations an initial intravenous loading dose
followed by sustaining intramuscularly
administered doses is frequently indi-
cated in the treatment of infectious
diseases and is sound therapeutic policy.

The jugular vein is used in all species
except the pig, where the inaccessibility
of superficial veins other than the ear
veins makes the jugular route of adminis-
tration generally impractical. Perivascular
reactions and intravascular thrombosis
are a hazard with this route, especially
following the administration of irritant
drugs such as sulfonamides and
tetracyclines.

INTRAMUSCULAR INJECTION

Intramuscular injection is the most com-
monly used method for antimicrobial
administration in large animals. Where
possible this route should be avoided in
meat-producing animals, especially
with irritant preparations. Lesions can be
detected at slaughter 12 months after the
intramuscular injection of long-acting
tetracyclines. 1 If the drug must be given
intramuscularly in a meat-producing
animal it should be given in the muscles
of the neck, as scar tissue and blemish
are more likely to be detected at this site
in the cutting process after slaughter and
they can be trimmed. With certain anti-
biotics, drug residues may persist at these
sites for long periods, and the label
recommendation for withdrawal or with-
holding time should be followed. 2

Irritant drugs should be used with care
in horses, or avoided, as this species more
commonly develops severe reactions at
the site of injection. The development of
such reactions is usually an indication to
change to alternative therapy. Oil-based
vehicles frequently produce severe
reactions at the site of injection in horses
and should not be used.

There is evidence, for some antibiotics
at least, that the site of intramuscular
administration can influence the rate of
absorption, the bioavailability and the
subsequent pharmacokinetics of the
administered antibiotic. In both cattle and
horses, irtjection in the neck gives more
favorable pharmacokinetic parameters

than does injection into the gluteal or
shoulder muscles. 3-5 Injection into the
dewlap gives the poorest bioavailability.
These differences presumably result from
differences in the spread of the injected
drug within and between the muscles and
differences in blood supply. With inter-
muscular spread there is a greater absorp-
tion area and less compromise of capillary
and lymphatic structures. 5 Injection into
tire side of the neck of horses is con-
sidered to be malpractice in some
countries. When irritant preparations must
be given to horses it is wise to inject them
into the muscle of the chest between the
forelegs, as reactions in this area have less
tendency to spread and are more accessible
to drainage and treatment.

At all sites, care should be taken to
ensure that the injection is not inadvertently
given intravascularly, by applying nega-
tive pressure to the syringe prior to
injection. In adult animals no more than
10 mL should be given at any injection
site. Large injection volumes can result in
the formation of encapsulated antibiotic-
filled cysts in muscle. 2 Label directions of
the maximum amount to be given at any
one site should not be exceeded.

With most antimicrobial drugs, except-
ing the repository forms and drugs of an
irritant nature, peak blood concentrations
are obtained within 30-120 minutes of
injection. However, the bioavailability of
drugs given by intramuscular injection is
markedly influenced by their formulation
and irritant nature. This is especially
marked with oxytetracycline preparations.

INTRAPERITONEAL INJECTION

Intraperitoneal injection is occasionally
used for antimicrobial administration,
especially in cattle close to market size,
and where intravenous administration for
various reasons may be impractical. It is
also occasionally used in pigs with
diarrhea, where the antibacterial drug is
combined with fluids for rehydration. In
cattle the injection is given in the right
flank midway between the last rib and the
tuber coxae and at least 10 cm ventral to
the lateral processes of the lumbar verte-
brae so as to avoid retroperitoneal and
perirenal deposition of the drug. An
aseptic injection technique should be
used. Animals with peritonitis are also
occasionally additionally treated by this
route of injection. In horses with peritonitis
the peritoneal cavity can be drained
through a cannula inserted in the ventral
midline as used for abdominal para-
centesis, and the antimicrobial agent is
injected via this route. Intraperitoneal
injection may also be used for the
parenteral administration of the tetra-
cycline group in acutely toxemic animals or
in animals with severe respiratory distress

Practical usage of antimicrobial drugs

135

where intravenous injection may result in
collapse and even death.

SUBCUTANEOUS INJECTION

Subcutaneous injection has not been
commonly used in large-animal practice
but concerns regarding lesions in meat
following intramuscular injections is
leading to a greater use of this route.
Providing the drug is not deposited in a
fat depot, this route provides a reasonable
alternative to intramuscular injection. 6
With irritant preparations there is a
danger of excessive reaction and the
occurrence of sterile abscesses. Very small
animals (piglets) are often treated by this
route.

ORAL ADMINISTRATION

Oral administration of antimicrobial agents
is generally restricted to preruminant
animals, young foals and pigs. The
blood and tissue levels achieved following
oral administration are considerably less
than those achieved by an equivalent
dose of the same antimicrobial agent
given parenterally, and for this reason the
oral dose rate is generally 2-5 times
greater than the parenteral dose. Oral
drugs are less reliable because absorption
characteristics may vary with the volume
of ingesta, the presence or absence of
gastric and intestinal stasis or hyper-
motility and the nature of the ingesta,
which variably bind the orally administered
drug. For example, oxytetracycline and
trimethoprim have a much lower bio-
availability to calves when administered
in milk, rather than in water, because of
the high degree of binding to milk. 7 There
is some evidence that the oral adminis-
tration of antibiotics to calves in glucose-
glycine-electrolyte solutions is associated
with more favorable absorption charac-
teristics. The aminoglycoside and poly-
myxin groups of antimicrobial agents are
not absorbed from the alimentary tract
and benzylpenicillin is largely destroyed
within the stomach.

The oral route is the easiest method for
administration, and where the cost of
revisits is a significant consideration this
route is often chosen for continuing
medication, as it is within the capability
of any owner. In general, however, systemic
infections are better treated by parenteral
injection and certainly treatment should
be initiated by this route. The oral route is
the one of choice for the treatment of
enteric infections. Experimental studies
have shown that the oral administration
of antibiotics to healthy neonatal calves
may induce villous atrophy within the
intestine and a malabsorption diarrhea. 8
This occurred particularly with neomycin
and to a lesser extent with tetracycline
and ampicillin. Although this does not
negate the use of antibiotics for specific

therapy of enteritis in young calves (when
this is indicated), it does suggest that
prophylactic use of oral antibiotics has a
risk in young calves.

Prolonged oral medication at thera-
peutic levels may result in superinfection
in all animal species. Commonly a yeast,
staphylococcus or Pseudomonas aeruginosa
is involved. It occurs most commonly in
calves given courses of differing anti-
microbial agents. It is more common
following medication involving tetra-
cyclines and usually a treatment period of
at least 2 weeks is required for its
development.

Antimicrobial drugs are seldom given
orally to ruminant animals. Exceptions are
the use of sulfonamides, especially as
sustaining medication following initial
parenteral treatment, and low-level anti-
biotic therapy to feedlot animals to reduce
the incidence of liver abscess and respir-
atory disease. Blood levels following oral
administration in ruminants are variable
and frequently not achieved until
12-18 hours after dosing. Also, many
antibacterials are destroyed or inactivated
within the rumen. Orally administered
antimicrobials cause a significant disruption
of the ruminal flora and by itself this may
result in a syndrome of ruminal stasis,
anorexia and depression. If antibacterial
agents are given orally to ruminants, the
course should be followed by re-
establishment of the ruminal flora by cud
transfer.

Contamination of feedstuffs
Antibiotic contamination of rations is a

potential problem in feed mills that
process medicated and nonmedicated
feeds consecutively. The inadvertent feed-
ing of antibiotics to cattle and horses can
result in clinical disease and the cause
may not be immediately apparent to the
investigating clinician. This can occur
when cattle and horses are fed medicated
pig feed, but may also occur when regular
rations become contaminated with
antibiotics. Residual carryover of medicated
material into other feedstuffs can occur
with feed-mixers of various types and
also via residues in conveyors, hoppers
and trucks. The risk for feedstuffs being
contaminated can be quite high and the
most common contaminating drugs are
chlortetracycline, sulfonamides, penicillin
and ionophores. 9

Within 24 hours of being fed medicated
feed, dairy cattle show anorexia, rumen
stasis and subsequently pass custard-
consistency feces containing undigested
fiber. There is a precipitous fall in milk
production. Dullness, muscle fasciculation,
ketosis, hypocalcemia and recumbency
have also been observed. Affected cattle
usually recover when placed on non-

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

medicated feed, but milk production may
be adversely affected for the remainder of
the lactation. Feeds contaminated with
dimetridazole, lincomycin and tylosin
have been incriminated, 10 ' 11 although
there is debate as to the role of tylosin in
this syndrome. 12 The carryover of medi-
cated material into other feeds can also
create violative tissue residues at
slaughter. 9 Sulfonamide contamination of
swine rations is a particular problem. 13

The use of orally administered anti-
microbial agents in horses over 3 months
of age should be approached with great
care. Their use can be followed by
diarrhea, which is often intractable and
results in chronic debilitation or death.
Clindamycin and lincomycin carry a high
risk and are probably totally contra-
indicated but macrolides, tetracyclines,
tylosin and metronidazole are also associ-
ated with risk in stressed horses.

Water medication of pigs

The oral route is the most common and
convenient one for group medication of
pigs. The antibacterial agent may be
incorporated in the water or in the feed.
For the treatment of disease in pigs, water
medication is preferred as sick pigs may
drink, whereas they frequently will not
eat. Also, water medication can usually be
started immediately, whereas the
mixing of an antibacterial agent with the
diet for piggeries purchasing prepared
diets may take 1-2 days. Antibiotic
bioavailability is also less in pelleted
feeds. 14

In outbreaks of contagious disease in
pigs, the sick pigs within the group are
usually initially treated individually by
parenteral injection followed by mass
medication of the water supply. Large
swine units usually have facilities for in-
line medication; small swine units may
not. With pigs using troughs, water
medication is no problem. However, with
automatic watering systems, medication
must be through the header tank, if this
can be isolated, or more commonly the
water is turned off and medicated water is
provided for the pigs via portable 200 L
drums with a drinking bowl or nipple
drinker inserted in the side.

In determining the concentration of
antibiotic required in the water, the total
daily dose of the drug is computed by
multiplying the total weight of the group
of pigs in kilograms by the daily dose of
the drug in milligrams per kilogram. This
dose must then be added to the amount
of water that will be consumed in one
day. It is obvious that this amount will
vary according to climatic conditions and
to the nature of the disease in the pigs.
For example, diarrheic pigs may drink
more than normal quantities. In practice.

a rule of thumb of 10% body weight water
consumption of pigs between weaning
and market age has been found to be
satisfactory, with estimates of 15% for
situations in which high water consump-
tion can be expected. The total daily dose
is thus added to the number of liters of
water equivalent to 10-15% of the esti-
mated total body weight of the group. In
pregnant sows, water consumption is
usually 5-8 L/d, but lactating sows may
drink 15-20 L/d. When there is doubt as
to the exact water consumption the medi-
cation can be added to the lower estimate
and, when consumed, fresh water provided
for the remainder of the day. Water medi-
cation is generally continued for a period
of at least 5 days. Antibiotics may
deteriorate rapidly in water and a fresh
j mix should be prepared each day. Most
I drugs for water medication have label
| directions.

Water medication in cattle

There are some major limitations in the
mass medication of water supplies of
i cattle.The daily amount of water consumed
I is usually directly proportional to the
amount of dry matter intake. Anorexia or
inappetence will result in a marked
decrease in water intake to mere main-
j tenance requirements. Depending on the
| drug used, the palatability of the medi-
j cated water may affect intake. With large
i drinking water tanks that are replenished
on a continuous basis, or even two or
; three times daily, it is difficult to deter-
| mine how much drug should be added on
a daily basis in order to maintain a
reasonably steady concentration. On a
theoretical basis, automatic in-line water
medicators should provide a uniform
concentration of drug in the water supply.
However, some medicators are extremely
unreliable and regular surveillance and
servicing may be necessary. In countries
where below-freezing temperatures occur
during the winter months, the medication
of water supplies may be difficult and
impractical under certain management
conditions.

Dietary medication
This is generally used for long-term
disease control. In many countries, the
amount of an antimicrobial that can be
added to a feed is restricted to the
approved label level and the veteri-
narian has no legal right to alter this
concentration. The drug is usually added
at the feed mill.

OTHER ROUTES

Other routes of administration may be
used to increase the level of antibacterial
drug in areas where diffusion following
parenteral administration of the drug may
be limited and when high local levels are

required. These include intra-articular,
intrapleural and subconjunctival injection.
Non-irritant preparations should be used
with strict aseptic technique. In most
cases these treatments should be sup-
ported by parenteral treatment. The indi-
cations are described in the special
medicine section.

Intramammary infusion of drugs is
dealt with under mastitis.

Intratracheal administration of anti-
biotics has its advocates for the treatment
of pneumonia in cattle. In theory, this
could result in higher levels of antibiotics
at the site of infection, although with
many pneumonias diffusion through the
affected lung must be minimal. The anti-
biotics are administered in sterile
physiological saline equivalent to 2.0 mL/kg
body weight. An extensive study has
shown variation in absorption and per-
sistence between antibiotics administered
by this route, when compared to parenteral
administration, but has concluded that
there is no potentially useful advantage to
its use. 15

The local administration of antibiotics
may not always be the preferred route
despite historical precedence. For example,
in the treatment of the genital tract, it
has been shown that parenteral adminis-
tration of antibiotics achieves tissue
concentrations of drug in all areas of the
genital tract, whereas intrauterine infu-
sion results in comparable concentrations
only in the endometrium and uterine
secretions. Local and/or parenteral
administration may be indicated in
different cases of genital tract infection. 16

REVIEW LITERATURE

George MH, Tatum JD, Smith GC, Cowman GL.
Injection-site lesions in beef subprimals: Incidence,
palatability, consequences and economic impact.
Compend Contin Educ Food Anim Pract 1997;
19(2):S84-S93.

REFERENCES

1. George MI I et al. J Anim Sci 1995; 73:3510.

2. Mawhinney H et al. AustVet J 1996; 74:140.

3. Hoffman B et al. Dtsch Tierarztl Wochenschr
1986; 93:310.

4. NouwsJM,VreeTB.Vet Q 1983; 5:165.

5. Firth EC et al. Am J Vet Res 1986; 47:2380.

6. Gilman JM et al. J Vet Pharmacol Ther 1987;
10 : 101 .

7. Groothuis DG, van Miert ASJPAM. Vet Q 1987;
9:91.

8. Mero KN et al.Vet Clin North Am Food Anim
Pract 1985; 1:581.

9. Lynas L et al. Food Addit Contamin 1998; 15:162.

10. Crossman PJ, Payser MR. Vet Rec 1981; 108:285.

11. Anon. Vet Res 1984; 114:132.

12. MacKinnon JD et al.Vet Rec 1984; 115:278.

13. Rosenburg MC. J Am Vet Med Assoc 1985;
187:704.

14. Mevius DJ et al.Vet Q 1986; 8:274.

15. Hjerpe CA. Bovine Pract 1979; 14:18.

16. Guslafsson BK. J Am Vet Med Assoc 1984;
185:1194.

Practical usage of antimicrobial drugs

181

drug distribution
absorption

Antibiotics of the aminoglycoside group
and polymyxins are not absorbed from
the alimentary tract and if circulating
levels of these antibiotics are required
they must be given by parenteral injec-
tion. Where both intestinal and systemic
levels are required, as may be the case in
neonatal colibacillosis, these drugs should j
be given both orally and parenterally. j
Benzylpenicillin and methicillin are j
destroyed by acid pH and significant blood !
levels are not achieved following oral j
administration but blood levels are achieved j
with ampicillin and amo>4cillin. Certain j
sulfonamides (phthalylsulfathiazole, j
phthalylsulfacetamide, sulfaguanidine j
and succinyl sulfathiazole) are not j
absorbed from the alimentary tract. The !
remaining antibiotics and sulfonamides j
are absorbed following oral adminis- j
tration in preruminant calves and lambs j
and in pigs and horses. However, in
general, blood and tissue levels obtained ;
are considerably lower than those
achieved with equivalent doses given
parenterally. Whey feeding (calcium) will
inhibit the absorption of tetracylines
in pigs.

DISTRIBUTION

Factors governing the distribution of
antimicrobial agents in the body fluids are
complex, and distribution should be
considered as involving a multi-
compartmental system with all body
compartments being in contact directly or
indirectly with the blood. The occurrence
of exchange, and its rate, between the
blood and the various tissue compart-
ments is governed by the factors that
influence the diffusion of solutes, such as
the concentration of the drug and the
volume of blood flow through the tissues
and the volume of the tissue. It is also
considerably influenced by the extent of
protein binding of the drug in blood and
in the tissues, the ionization constant of
the drug, pH differences in the compart-
ments, and the lipid solubility of the drug.
Drug distribution is also influenced by
age and the disease state of the animal.

In most diseases infection occurs in the
extravascular tissue compartments and it
is the concentration of the unbound drug
at these sites that determines the efficacy
of therapy. The majority of antibiotics
diffuse relatively freely in extracellular
fluids but sulfonamides, the chloram-
phenicol group, tetracyclines, fluoro-
quinolones and macrolides have a
distribution that more closely approximates
total body water, and they can enter cells.

There are several so-called barriers to
antimicrobial diffusion and these include
the brain and cerebrospinal fluid, serous

cavities, joints and synovial fluid, the eye
and the placenta and fetus. In general
sulfonamides, the tetracyclines and
chloramphenicol have some ability to
penetrate these barriers in the normal
state, whereas penicillin may not.
Erythromycin has the ability to penetrate
intracellularly and across most barriers
but will not produce effective levels in the
brain or cerebrospinal fluid. Members of
the aminoglycoside group of antibiotics
generally achieve effective levels in
synovial fluid and the pleural and
peritoneal fluid but not in the brain or
eye. The importance of these barriers,
especially those of serous cavities and
synovia, in the presence of inflammation
is open to doubt and effective therapy can
often be achieved by the use of antibiotics
that do not in normal situations reach
these areas unless they are inflamed. An
exception to this rule is infections
involving the eyes where, in order to
achieve effective levels, high circulating
levels of the antimicrobial agent are
required and intravenous injection to
achieve this is usually necessary. Lipophilic
drugs diffuse into tears and parenterally
administered erythromycin, oxytetracycline
and gentamicin, for example, may achieve
bacteriostatic concentrations in tears. In
many areas, especially joints and the
peritoneal, pleural and pericardial
cavities, high levels of the required anti-
microbial agent can be achieved by local
administration.

Almost all antimicrobial agents are
excreted via the kidney, and the urine
usually contains high levels of them. This
feature is not of great significance in large
animals, where urinary tract infections are
comparatively rare, but violative residue
levels can persist in the kidney for long
periods with drugs such as the amino-
glycosides. Penicillins and tetracyclines
have a significant enterohepatic cycle, and
erythromycin also may obtain significant
levels in bile.

REVIEW LITERATURE

Baggot JD. Principles of drug distribution in domestic
animals. Philadelphia: WB Saunders, 1977.

Baggot JD. Factors involved in the choice of routes of
administration of antimicrobial drugs. J Am Vet
Med Assoc 1984; 185:1076-1082.

Koritz GD. Relevance of peak and trough concen-
trations to antimicrobial therapy. J Am Vet Med
Assoc 1984; 185:1072-1075.

Short CR, Clark CR. Calculation of dosage regimens
of antimicrobial drugs for the neonatal patient.
J Am Vet Med Assoc 1984; 185:1088-1093.

Riviere JD. Veterinary clinical pharmacokinetics.
Compend Contin Educ PractVet 1988; 10:24-30,
314-328.

Koritz GD. Practical aspects of pharmacokinetics for
the large animal practitioner. Compend Contin
Educ PractVet 1989; 11:202-204.

Prescott JF. Antimicrobial chemotherapy. In: Biberstein
EL, Mian CZ, eds. Review of veterinary microbiology.
Boston, MA: Blackwell Scientific, 1990.

Riviere JD. Pharmacologic principles of residue
avoidance for veterinary practitioners. J Am Vet
Med Assoc 1991; 198:809-816.

DURATION OF TREATMENT

For certain infectious diseases there is an
established regimen of therapy that” is
known from clinical experience to be
therapeutically effective. Where such
\ regimens are known they are stated in the
j treatment section for the individual
[ diseases in the Special Medicine section.

\ As a rule of thumb in undifferentiated
j diseases, therapy should be continued for
1 at least a 3-5- day period, or longer if
l there is evidence of chronic infectious
j disease with localization. An alternative
| rule of thumb is that treatment should be
j continued for at least 1 day beyond the
I return of body temperature to normal,
j especially if bacteriostatic antibiotics are
1 being used. Chronic pyogenic processes
1 may require treatment for a 2-4-week
| period or even longer.

DRUG COMBINATIONS

Combinations of antimicrobial drugs are
frequently used in veterinary practice.
Combinations of antimicrobial agents are
used either to achieve a synergistic
j effect in the case of a single infection, or
to achieve a broad spectrum of activity
in the case of infections involving more
than one agent. Combinations may also
be of value in combating the emergence
of resistant mutants during therapy.

The combination of two drugs may
result in indifference, where the effect is
either that of the single most effective
drug or is equal to the sum of the effects
of the two individual drugs, or it may
result in synergism or antagonism.
There are, however, no hard and fast rules
for combinations that will result in any of
these effects. Knowledge of these effects
results largely from laboratory animal
studies and from some human thera-
peutic trials. From these trials it is evident
that the occurrence of synergism is very
much dependent on the type of infectious
organism, and to some extent the site of
infection, and, whereas two drugs may
show a synergistic effect with one type of
infection, the effect may be indifferent or
even occasionally antagonistic with other
infective agents. Antagonism is equally
not easily predictable but the drugs that
most commonly result in antagonistic
effect when combined with others are the
tetracycline group, chloramphenicol and
the macrolide groups.

A traditional approach has been that
combinations of bactericidal drugs will
generally result in an indifferent effect or
in synergism; combinations of bacteriostatic
drugs generally give an indifferent effect,

•iJk

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

j Table 4.1 Mode of action of
antimicrobial drugs •:

Bactericidal

Bacteriostatic

antimicrobials

antimicrobials

Beta-lactams

Sulfonamides - all

Penicillins

Trimethoprim

Cephalosporins

Methotrexate

Semisynthetic penicillins

Pyrimethamine

Ampicillin

Tetracyclines

Amoxicillin

Macrolides

Cloxacillin

Erythromycin

Methicillin

Oleandomycin

Carbenicillin

Spiramycin

Aminoglycosides

Tylosin

Streptomycin

Carbomycin

Neomycin

Lincomycin

Gentamicin

Chloramphenicol

Paromomycin

Tobramycin

Glycopeptides

Vancomycin

Rifampin

Bacitracin

Polymyxins

Fluoroquinolones

Florphenicol

whereas combinations of a bactericidal
with a bacteriostatic drug may result in
antagonism (Table 4.1). This approach is,
however, too general for validity as
interactions are specific to individual
infections and are dose-dependent.

In farm animals, synergistic activity
between penicillin and streptomycin has
been demonstrated in the therapy of
mycotic dermatitis and footrot in sheep.

The synergism between amino-
glycoside and beta-lactam antimicrobials
is widely used in the approach to the
therapy of sepsis in neonates. Carbenicillin
and gentamicin in combination can be of
value in therapy against P. aeruginosa,
Klebsiella and Proteus spp., and tylosin
and oxytetracycline can be of value in
treating infection with Mannheimia and
Pasteurella spp. Trimethoprim and
sulfonamide combinations are of special
value in treating several infectious
diseases in large animals. Rifampin and
erythromycin show in-vitro synergism
against Rhodococcus equi, as does a
combination of gentamicin and penicillin.
Tiamutilin and tetracycline show in-vitro
synergism against several swine respir-
atory pathogens and herd studies show a
measured response in the control of
respiratory disease greater than that
achieved by chlortetracycline alone.

Drug combinations are also used for
broad-spectrum therapy. An accurate
diagnosis with consequent recognition of
the likely infectious organism allows
specific antibacterial therapy and obviates
the need for broad-spectrum antibacterial
therapy. However, there are clinical situ-
ations where broad-spectrum therapy,
including the possibility of combined

drug therapy, is indicated. These include
such problems as the acute septicemia,
where a number of different organisms,
with differing antibacterial sensitivities,
can produce identical clinical disease, and
those infections associated with organisms
that have a varying sensitivity depending
upon the isolate. The requirement for
immediate treatment without knowledge
of the bacterial sensitivity dictates the use
of antimicrobial drugs designed to obtain
a broad spectrum of activity.

The availability of broad-spectrum
drugs such as ampicillin or amoxicillin
and trimethoprim-potentiated sulfon-
amides has lessened the need to use drug
combinations but the latter may still be
necessary in certain situations and are
fully indicated. Although antagonism has
not been demonstrated in clinical
veterinary situations it is wise to avoid
bacteriostatic and bactericidal drug
combinations.

Fixed-dose combinations are avail-
able commercially for some antibiotics
but they are not recommended for use

and are gradually being withdrawn from
the market or being declared not legal for
use in food-producing animals. Fixed-
dose combinations suffer from the
deficiency that the dose level of any one
of the drugs in the combination is
dictated by the level of the other. Also, the
excretion rates of the two drugs may be
markedly different. The most common of
these, fixed-dose penicillin/streptomycin
combinations, suffer from this deficiency.

Where combinations of antibacterial
drugs are used they should be given
individually and at their respective
recommended doses and repeats. Some
antibiotics are physically incompatible
when mixed together. The incompatibility
may rest with the drugs or their vehicles
and may be visible, as with crystalline
benzylpenicillin and neomycin, or it may
be inapparent, as with gentamicin and
carbenicillin. The two drugs should
be given separately at separate sites.
Incompatibilities can also occur with
antibiotics and intravenous fluid solutions
- especially those containing protein
hydrolysates.

Antibiotics may influence the activity
of other drugs. In particular, chloram-
phenicol and tetracyclines inhibit liver
microsomal metabolism and may signifi-
cantly increase the half-life of drugs
metabolized by this mechanism, such as
digitalis or barbiturates, with resultant
potential toxicity.

REVIEW LITERATURE

Reilly PEB, Issacs JP. Adverse drug interactions of

importance in veterinary practice. Vet Rec 1983;

112:29-33.

Whittem T, Hanlon D. Dihydrostreptomycin or

streptomycin in combination with penicillin G in

dairy cattle therapeutics: a review and re-analysis
of published data. NZ Vet J 1997; 45:178-184,
223-229.

McKenzie HC, Furr MO. Aminoglycoside antibiotics
in neonatal foals. Compend Contin Educ PractVet
2003; 25:457-469

ADDITIONAL FACTORS
DETERMINING SELECTION OF
AGENTS

In addition to the considerations of
bacterial sensitivity to the antimicrobial
agent, there are other important factors
that dictate the selection of the anti-
microbial agent to be used in a particular
case. In most clinical situations several
agents would be effective and a choice
needs to be made amongst them.

COST

This is a major factor and includes not
only the primary cost of the drug but also
the ancillary costs that may be associated
with its administration. This is a most
important factor in agricultural animals
but of less importance with pleasure
horses. The importance of the primary
cost of the drug is obvious. For example,
in most countries a 5 -day course of
treatment with procaine benzylpenicillin
will cost considerably less than one with,
for example, oxytetracycline. If there is no
specific indication for the use of the more
expensive drug then the less expensive
one should be used. The ancillary costs
associated with repeat visits to administer
the drug may also be important. The
practice of dispensing drugs for continuing
intramuscular therapy varies between
countries and veterinary practices and has
an influence on this consideration.

EASE OF ADMINISTRATION

This is a further factor that influences the
nature of the drug and treatment used. In
general, one avoids starting a course of
therapy with an antibacterial such as
tetracycline, which may require daily
intravenous administration, in favor of
one that can be administered more simply
- unless there are good therapeutic reasons
for choosing the former. In situations
where facilities are poor, where mustering
or yarding is difficult, or where mass
medication is required, long-acting
repository preparations may be indicated.
Irritant preparations are avoided where
possible.

TOXICITY

This is always a consideration when
dealing with infections that may require
high dose rates of antimicrobial drugs, or
in chronic infections that require a pro-
longed course of therapy. Where a choice
is available, antimicrobial agents with a
low incidence of toxic side effects at high
doses are chosen. As in all clinical situ-
ations involving large animals it is

Practical usage of antimicrobial drugs

183

essential to make an assessment of the
case and to attempt a prognosis. The
possible cost and duration of treatment
should be estimated and the owner
advised of this. When examined in this
light the decision may be against treat-
ment and for salvage slaughter.

BACTERICIDAL OR BACTERIOSTATIC

antimicrobials

Antibiotics are either primarily bactericidal
or primarily bacteriostatic in their activity
(Table 4.1). Some of the bactericidal group
are bacteriostatic at low concentration.
Both classes rely on intact and effective
body defense mechanisms for full effect.
Although in terms of clinical response
little if any difference can be detected
between the two groups in most diseases,
in certain situations it is probably
advisable to choose a bactericidal anti-
biotic for therapy. This is especially true
when dealing with acute septicemic
infection where there is frequently a
significant leukopenia, and quick maximal
bactericidal effect is required. There is
also the need to prevent subsequent
localization.

Bactericidal antimicrobials are also
indicated for antibacterial treatment of
secondary infection in granulocytopenic
syndromes such as bracken fern poison-
ing or chronic furazolidone poisoning in
calves. Bactericidal antibiotics are also
preferable in the treatment of heavily
capsulated organisms, such as Klebsiella
spp. and R. equi, which show anti-
phagocytic activity. Infections in which
significant intracellular parasitism
occurs are a problem. The majority of
antimicrobials that diffuse relatively freely
into cells are bacteriostatic in activity and,
although the disease may be controlled by
their use, infection may still persist in a
latent carrier state.

Antimicrobials prohibited from use in
animajs intended for food in the USA

• Chloramphenicol

• Dimetridazole

• Ipronidazole

• Other nitroimidazoles

• Furazolidone, nitrofurazone, other
nitrofurans

• Sulfonamide drugs in lactating dairy
cattle (except approved use of

su If adimethoxine, sulf abromomethazine
and sulfamethoxypyridazine)

• Fluoroquinolones

• Glycopeptides (example: vancomycin)

DRU G DETERIORATION

Many antibacterials lose their activity
rapidly when kept under adverse con-
ditions. Quality control in terms of
purity, efficacy and freedom from toxicity

costs money but for these reasons it is
preferable to purchase from known
reputable companies and follow their
recommendations with respect to storage
and expiration periods. The use of
cheap antibacterial preparations, often
purchased in bulk and simply packaged,
and distributed with little consideration
for factors influencing drug stability, often
results in poor therapeutic results.
Crystalline or dry preparations that
require reconstitution to a solution before
parenteral administration are frequently
presented this way because their activity
degenerates rapidly once they are in
solution. Therefore, once they have been
prepared they should be used imme-
diately, or the manufacturer's recommen-
dations should be followed regarding
storage. Attention should be paid to the
length of activity expected following
reconstitution. 1 Temperature and exposure
to sunlight can be important factors in
antibiotic stability and become especially
important in farm ambulatory practice:
car cold boxes should be used to store
antibiotic preparations and other sensi-
tive drugs.

UNFAVORABLE RESPONSE TO
THERAPY

In clinical cases that do not respond to
antimicrobial therapy the initial consider-
ation should be that the wrong anti-
microbial agent has been chosen for
therapy. This is especially true of infec-
tious conditions of undetermined etiology
where the drug has been chosen on the
basis of an educated guess. In these
circumstances adequate time should be
given for an evaluation of the efficacy of
the treatment before a change is made. In
general a 3- day period of treatment is
allowed for this evaluation provided there
is no marked deterioration in the clinical
state or further elevation of temperature
during this period. If there is no response
to initial therapy then, in the case of
conditions of undetermined etiology, it is
generally best to change to an entirely
different class of antimicrobial agent.
However, the possibility of viral or non-
infectious etiology should always be
considered in these cases and the case
and diagnosis should be reviewed before
any change is made.

In any situation where there is a poor
response to therapy the usual causes of
this failure should be considered in any
further adjustments to therapy or future
therapy of similar cases. The first and
most obvious of these is that the organism
is either insensitive to the drug or that it
is not susceptible to the level of the
drug that is being used for therapy. There
are two possible approaches. The first is to

increase the dose rate and dose frequency
and/or to change the route of adminis-
tration so that higher and possibly
effective levels will be achieved, bearing
in mind the possible toxic consequences.
The second, and safer, approach is to
change the antimicrobial agent being
used. This problem can be avoided if the
organism and its potential sensitivity
can be identified, either by clinical
examination or by appropriate sampling
with culture and sensitivity testing. The
development of resistance during anti-
microbial treatment of an individual
animal is not a recognized problem in
large-animal medicine.

Another common cause of poor
response is that the infection is situated
in an area to which the drug is poorly
accessible. If this is associated with an
area behind a barrier to the entry of the
antibiotic, such as the joints or the eye, it
may be necessary to resort to higher dose
rates and frequency, or intravenous
administration of the drug, or to ancillary
local treatment into this area. Alter-
natively, another drug with superior
penetrability may be used.

Organisms must be actively meta-
bolizing in order for antimicrobial agents
to exert their effect. This feature can result
in poor response to therapy or relapse
following discontinuation of therapy in
chronic infections such as endocarditis
or where there is excessive necrotic or
fibrotic tissue associated with the infec-
tion. In these instances, dormant organ-
isms and the long diffusion tracks make
effective cure difficult and high anti-
microbial levels sustained over longer
periods are required. In purulent con-
ditions surgical drainage, where possible,
is an essential adjunct to antimicrobial
therapy.

The importance of ancillary and sup-
portive therapy to counteract the effects
of shock, toxemia and dehydration that
may be associated with infection cannot
be overemphasized and frequently such
therapy may markedly influence the out-
come of a case. It is obvious, for example,
that 3 mL of antibiotic will do little to
counter the effects of a 4 L fluid deficit in
a scouring calf.

DRUG WITHDRAWAL
REQUIREMENTS AND RESIDUE
AVOIDANCE

In most countries there are requirements
for the withdrawal of antimicrobial agents
from the feed for specified periods prior
to slaughter, and animals or their milk
cannot be marketed for certain periods
. following antimicrobial therapy.

Antibiotic contamination of food pro-
ducts can be a public health risk.

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

although proven risk for toxicity or allergy
from antibiotics in humans is minuscule.
An example would be allergic reactions to
antibiotic residues - particularly penicillin.
There are also commercial considerations
where residues of antibiotics in milk can
cause considerable problems in the
manufacture of milk products. Effects on
starter cultures for cheese and yoghurt
can be particularly deleterious and can
result in downgrading or total loss of
large quantities of manufacturing milk.

The purpose of withdrawal require-
ments is to ensure that meat and milk for
human consumption is wholesome and
does not contain violative residues of
drugs.The public's concern for the whole-
someness of the food that it consumes
will determine the food that it buys.
Cooperative quality assurance programs
involving both the producer and the
veterinarian are a major answer to this
concern.

A withdrawal period is the time
during which the animal must be held
free of the drug before it can be marketed.
In the case of milk, the term withholding
period is commonly used and defines the
period during which milk cannot be sent
for human consumption following the
treatment of the animal with a drug. A
tolerance for the pharmacologically
active ingredient in tissues is set by
regulatory authorities for each drug. The
tolerance level is the level below which
tissue concentrations must fall before
they are considered safe for human
consumption, and there is a large margin
of safety . 2

The required withdrawal and with-
holding periods will vary between anti-
microbial agents and also with the same
antimicrobial agent depending upon the
amount of drug given; factors such as age
and the disease state of the animal
are also important. Unfortunately, the
required withdrawal and withholding
periods to ensure freedom of food
products from violative drug residues are
not known for the variety of dose con-
centrations and dose intervals of the
various antimicrobials that could be used
in clinical practice - nor are they likely to
be known in the near future. In many
countries this has led to regulations that
limit the quantity of antibiotics in drug
products. Label instructions explaining
product usage and drug withdrawal
times are required. These label instruc-
tions include what is generally called the
label dose.

The label dose and extralabel use

The label dose (and dose interval) is a
dose of an antimicrobial for which the
specific withdrawal and withholding
periods have been established, and these

are stated in conjunction with the label
dose. The label dose is the officially
approved or legal dose rate for that drug.

When an antimicrobial is used, it is
incumbent upon the practitioner to notify
the owner that the animal cannot be
marketed (or milk sent for human
consumption) before the accompanying
withdrawal (or withholding) period has
expired. The practitioner may be legally
liable if a violation occurs and this
notification has not been given.

In the USA the label dose of a drug
also includes use only in the species of
animal for which the drug is labeled, the
class of animal (lactating versus non-
lactating dairy cow), the disease con-
ditions indicated by the label, the route of
injection, the amount of drug to be
injected at one site and the number of
repeat treatments that can be given. These
label directions, and the need to follow
them, are directed primarily at lay users of
these drugs and lay users may not use the
drug in a nonlabel fashion. The label
directions should also be followed by the
veterinarian whenever possible.

Requirements for extralabel use of
drugs in the USA

• Extra label use of drugs (ELDU) is
permitted only by or under the
supervision of a veterinarian

• ELDU is allowed only for US Food and
Drug Administration (FDA)-approved
animal and human drugs

• A valid veterinarian-client-patient
relationship is a prerequisite for all ELDU

• ELDU must be for therapeutic purposes
only (animal's health is suffering or
threatened), not drugs for production
use

• Rules apply to dosage form drugs and
drugs administered in water - ELDU in
feed is prohibited

• ELDU is not permitted if it results in a
violative food residue, or any residue
that may present a risk to public health

• FDA prohibition of a specific ELDU
precludes such use

Extralabel use

There are times where extralabel use of
drugs is necessary and veterinarians
can do this where they have established
a proper veterinarian-client-patient
relationship . 3 It is the intention that the
label dose should be one that is
therapeutically effective for that drug.
However, this is not always the case, and
the label dose should not be confused
with the term 'recommended dose' as
used elsewhere in this book. There are
also circumstances where, although the
label dose may be therapeutically efficient
in many cases, it is not for the particular
case in hand. In fact, optimal therapeutic

dose regimes often require extralabel use
of the drug . 4,5 In these situations, anti-
microbial drugs may need to be used at
dose concentrations and dose intervals
different from the label dose. Extralabel
use of the drug may be therapeutically
necessary for the successful treatment
of the problem, but it is not officially
approved and the establishment of the
required withdrawal period is entirely
incumbent upon the veterinarian. The
withdrawal period in these circumstances
cannot always be extrapolated from that
for the label dose . 2

Definition of valid veterinarian-dient-
patient relationship (American
Veterinary Medical Association)

An appropriate veterinarian-client-patient

relationship will exist when:

1 . The veterinarian has assumed the
responsibility for making medical
judgments regarding the health of the
animal(s) and the need for medical
treatment, and the client (owner or
other caretaker) has agreed to follow
the instructions of the veterinarian

2. There is sufficient knowledge of the
animal(s) by the veterinarian to initiate
at least a general or preliminary
diagnosis of the medical condition of
the animal(s). This means that the
veterinarian has recently seen and is
personally acquainted with the keeping
and care of the animal(s) by virtue of an
examination of the animal(s) and/or by
medically appropriate and timely visits
to the premises where the animal(s) are
kept, and

3. The practicing veterinarian is readily
available for followup in case of adverse
reactions or failure of the regimen of
therapy

WITHDRAWAL PERIODS

Label dose withdrawal periods are

determined from pharmacokinetic studies
of excretion following administration of
the label dose. However, the rate of drug
elimination from the body can be
influenced by drug dose and dose fre-
quency. For example, the metabolism and
excretion half-life of sulfonamides in
cattle is dose-dependent. With repeated
dosing of antibiotics such as tetracycline
and the aminoglycosides, there is
deposition of the antibiotic in certain
tissues and following cessation of drug
administration there is a slow release
from these tissues and a long washout
period . 6,7 During this washout period
there are decreasing concentrations of the
drug in tissues and in milk, which,
although not of therapeutic importance,
are sufficiently high to be violative. This
presents a dilemma to the veterinarian
trying to establish withdrawal periods.

The occurrence of significant washout
periods following prolonged therapy with
antibiotics has only recently been
recognized and there are few data on
their duration at different dose concen-
trations and dose frequencies. A further
problem is that most pharmokinetic para-
meters have been determined in healthy
animals and altered physiology in diseased
animals can markedly alter elimination
half-lives; there is also considerable
animal-to-animal variation. 2 Rather than
try to guess the possible withdrawal
period for an extralabel use, computer-
based data information banks with easy
access are established to provide this
information. 8 One of these is the Food
Animal Residue Avoidance Databank
(FARAD), which provides recommen-
dations for withdrawal intervals for extra -
label drug use based on analysis of
published pharmacokinetic data, foreign
and domestic label drug withdrawal
intervals and established maximum
residue limits. Another, the Veterinary
Antimicrobial Support System (VADS),
aims to provide information on optimal
therapeutic regimens against pathogens
in cattle and swine using approved drugs
and treatment regimens but also providing
infonnation on extralabel regimens that
might be required in the face of a
refractory pathogen.

RESIDUE TESTING

Currently, the only way to attempt to
ensure nonviolation with extralabel use of
antimicrobials is to test for residues. 9-10
There are a very large number of testing
systems becoming available, which vary
in their method of detection of the
presence of antibiotics. 11 " 14 Tests such as
the Swab Test on Premises (STOP), Calf
Antibiotic and Sulfa Test (CAST), Live
Animal Swab Test (LAST), Fast Anti-
microbial Screen Test (FAST) (which has a
higher sensitivity and shorter analytical
time and has largely replaced the use of
STOP and CAST), the Delvotest-P, the
Charm Inhibition Assay and the Charm
Farm and Disk Assays are based on
the inhibition of growth of Bacillus
stearothermophilus var. calidolactes or
Bacillus stearothermophilus. While relatively
cheap and easy to perform, they have a
risk for false-positive results due to
inhibition of growth by inhibitory sub-
stances other than antibiotics in milk,
particularly substances in milk from
inflamed mammary glands. 12,13,13 ' 17 They
are sensitive for detecting penicillin and
its derivative compounds but less sensi-
tive to other classes of antibiotic. Other
commercially available tests use a variety
of different immunological detection
methods and test for a single antibiotic or
class of antibiotics.

Practical usage of antimicrobial drugs

185

TESTING FOR COMPLIANCE

Most countries have a monitoring pro-
gram to detect the occurrence of residues
in meat. In the USA, sampling is such as
to provide a 95% probability of finding a
violative residue when 1% of the popu-
lation is violative. The occurrence of
violative residues in red meat is very low
as the prevalence of infectious disease is
low in the period before slaughter.
Feedlot cattle can have a high prevalence
of disease in the early feeding period but
there is a substantial subsequent period
on-feed before the animals are slaughtered,
which exceeds the withholding period of
most drugs used for treatment of disease
occurring during the early feeding period.
Violative drug residues occur pre-
dominantly in cull dairy cows and in bob
veal calves.

The concentrations for the various
antibiotics that are violative are not stated
in this chapter for two reasons. First, they
vary from country to country. Secondly,
the violative concentrations tend to be
set by the sensitivity of the detection
assay used by the regulatory authority
and, as assay technology improves, legally
acceptable minimal concentrations will
be lowered. Local regulatory publi-
cations should be consulted for current
requirements.

Assay techniques can be remarkably
sensitive. An example is the occurrence of
violative residues of chloramphenicol in
the milk, blood and urine of cows that
had teat or skin lesions sprayed with a 5%
chloramphenicol solution 18 - an illegal
drug for use in animals for food in most
countries.

CAUSES OF RESIDUE VIOLATIONS IN
MILK

In a retrospective study of reasons for the
presence of violative antibiotic residues in
milk 19 failure to withhold milk for the
full withdrawal period and accidental
inclusion of treated milk in the ship-
ment were the most common. Accidental
inclusion of treated milk can occur when
there is inadequate identification of
treated cows. The veterinarian should
work with the producer to establish a
system that easily identifies cows whose
milk is subject to a withholding period.
Colored leg markers are one system and
are immediately visible to the milker.

Contamination of recorder jars and
milking equipment with the high con-
centration of antibiotic secreted in milk in
the first milking after treatment is a
further reason for residue violations.
Treated cows should be milked last in
large dairies, or milked with separate
equipment, and are preferably kept separate
as a hospital string.

Common causes of antibiotic residues
in milk

Other reasons for residue violations
include short dry periods, where dry
cow therapy has been used but the cow
has calved earlier than expected. The infu-
sion of dry cow treatments into the
udder of heifers prior to calving for the
prevention of summer mastitis has also
been followed by the presence of violative
residues for as long as 26 days. 9 A less
common cause is the accidental milking
of dry cows, where the latter are not kept
as a separate group, and the withholding
of milk from only treated quarters. 19 The
use of dry cow infusion preparations for
treatments during lactation can occur by
mistake if drugs intended for the treat-
ment of lactating cows are not kept in a
separate storage area from other drugs.

The risk for residues is higher for
farms that have higher frequency of
antibiotic usage and for those that use
part time labor. 10 The use of records to
document treatments and the day of exit
from the withholding period is an import-
ant preventive measure. Sulfonamides,
tetracyclines, penicillins, aminoglycosides,
cephalosporin and chloramphenicol have
been found in milk in the USA. 20

CAUSES OF RESIDUE VIOLATIONS IN
BEEF CATTLE

Violative drug residues occur predomi-
nantly in cull dairy cows and in bob veal
calves. 21 In one study 22 the primary
reasons for violations in this group were:

c Failure to observe the withdrawal
periods (61%)

° Use of an unapproved drug (10%)

J The feeding to calves of milk or
colostrum from a treated cow (9%).

A greater risk for residues occurs in
herds that feed larger volumes of
colostrum, possibly reflecting
contamination from dry cow therapy;
waste milk, discarded from treated
cows and fed to calves, is also a

• Extended usage or excessive dosage

• Failure to observe withdrawal times

• Poor records of treatment

• Prolonged drug clearance

• Failure to identify treated animals

• Contaminated milking equipment

• Milker or producer mistakes

• Products not used according to label
directions

• Lack of advice on withdrawal period

• Withholding milk from treated quarters
only

• Early calving or short dry periods

• Purchase of treated cows

• Use of dry cow therapy for lactating
cows

• Milking dry cows

6

PART 1 GENERAL MEDICINE ■ Chapter 4: Practical antimicrobial therapeutics

risk 23-24 especially if extralabel doses of

antimicrobials are used for udder

infusions 25

® Exceeding the label dose (6%).

The major drugs involved with residues in
meat are neomycin, streptomycin, peni-
cillin, oxytetracycline, gentamicin and
sulfamethazine, with intramuscular injec-
tion being the route of administration in
60% of the residue cases, oral adminis-
tration in 28% and intramammary
infusion in 9%. 21,22 The use of orally
administered antimicrobial boluses in
calves that were subsequently slaughtered
as bob veal calves is also a problem.

CAUSES OF RESIDUE VIOLATIONS IN
SWINE

Similar causes are recorded for the
occurrence of violative residues in pigs
but an additional problem in pigs is tissue
residues resulting from antibiotic inclu-
sions in feeds for growth promotion and
disease control purposes. Sulfonamides
are a particular problem. Nonobservance
of the required withdrawal period can
result in the rejection of market batches of
animals with a substantial financial loss to
producers. If feed inclusions have been for
the purposes of medication, the prescribing
veterinarian may be liable if adequate
information on withdrawal periods has
not been given.

There is also a problem with
sulfonamide residues resulting from
carryover of sulfonamides from medi-
cated to nonmedicated feeds at the feed
mill or on the farm. 26 Mistakes in feed
delivery, feed mixing sequences, ingre-
dient contamination and contamination
within the bulk feed distribution system,
and delivery augers can cause residual
contamination. 26,27 Carryover concen-
trations of sulfamethazine (sulfadimidine)
of greater than 2g per tonne in the
finisher ration can result in violative
residues in the liver at slaughter. 28 The use
of granular forms of sulfamethazine
markedly reduces the potential for
carryover. 29

A further source of contamination in
the piggery is environmental contami-
nation. Manure and pooled urine from
swine fed 100 g per tonne of sulfa-
methazine contains sufficient drug to
contaminate swine to violative levels
when contact with the material is main-
tained and this can continue for 6-7 weeks
when pens are not cleaned after a drug is
withdrawn from the feed. 27 Dried urine
has the potential for airborne contami-
nation of pigs. Sulfamethazine is stable in
manure and flush water for long periods
and coprophagy by pigs can lead to
significant intake of the drug. In order to
avoid the risk of this occurring, it is
recommended that, 3 days after the medi-

cated feed has been withdrawn, the pens
should be thoroughly cleaned or the pigs
moved to new housing. Water medication
can also lead to buildup of residues in the
water delivery system, so the watering
systems should be flushed. Pigs destined
for slaughter can be tested on the farm
prior to shipping using commercially
available testing systems, which can also
be used for detection of the occurrence of
sulfonamides in feed and water. 27

TYPE OF THERAPY

In the USA veterinarians are responsible
for a very minor proportion of detected
residue violations. 30 Possible causes of
violations resulting from veterinary therapy
include the selection of an inadequate
withdrawal period following extralabel
use of an antimicrobial and treatment
modalities that may not be considered a
risk. The local infusion of antibiotic
solutions into the uterus of cows may
result in circulating concentrations of
antibiotic and residues in body tissues
and in milk. This results from the absorp-
tion of the antibiotic through the endo-
metrium and from the peritoneal cavity
following passage through the fallopian
tubes. 31 Similarly, following infusion of
antibiotic solutions into one quarter of
the udder, low concentrations of the
antibiotic can occur in milk secreted from
the remaining quarters. Gentamicin is
generally considered not to be absorbed
from the mammary gland but more
than 87% of an intramammary dose of
gentamicin is absorbed from the inflamed
udder. 32

APPROVED DRUGS

Whenever possible, approved anti-
microbials should be used for therapy at
label dose and a known withdrawal time
in order to comply with regulatory
requirements and to minimize the possi-
bility of antibiotic residues in meat and
milk. It may be necessary to use non-
approved antimicrobial drugs in certain
circumstances and in minor species. The
use of an approved antibiotic in a minor
species for which it is not approved
constitutes an extralabel use of the drug.
The legality of the use of unapproved
drugs, or of approved drugs in minor
species for which they are not approved,
is questionable. If such use is contem-
plated it is probably wise to have culture
and sensitivity data indicating that the use
of the unapproved drug is therapeutically
necessary. Certain nonapproved antibiotics
are totally banned for use in food-
producing animals in some countries (e.g.
in the USA: chloramphenicol, the

nitroimidazoles, sulfamethazine in dairy
cattle over 20 months of age, furazolidone
and the use of fluoroquinolones in an

extralabel fashion) and local regulations
should be followed. The use of sulfa-
methazine in food- producing animals
may be banned in some countries. The
American Association of Bovine Practi-
tioners has passed a voluntary moratorium
on the use of aminoglycosides in cattle.

REVIEW LITERATURE

Bevill RF. Factors influencing the occurrence of drug
residues in animal tissues after the use of
antimicrobial agents. J Am Vet Med Assoc 1984;
185:1124.

Bishop JR, White CH. Antibiotic residue detection in
milk - a review. J Food Pract 1984; 47:647.

Bishop JR et al. Retention data for antibiotics
commonly used for bovine infections. J Dairy Sci
1984; 67:437.

Sundloff SF. Drug and chemical residues in livestock.
Vet Clin North Am Food Anim Pract 1989;
5:424-430.

Riviere JD. Pharmacologic principles of residue
avoidance for veterinary practitioners. J Am \fet
Med Assoc 1991; 198:809-816.

Payne MA. The rational use of antibiotics in dairies.

Vet Med 1993; 88:161-169.

Nicholls TJ et al. Food safety and residues in
Australian agricultural produce. Aust Vet J 1994;
71:393-396.

Hung E,Tollefson L. Microbial food borne pathogens.
Vet Clin North Am Food Anim Pract 1998;
14:1-176.

Sundberg P. Food safety: Antimicrobial residues.

Compend Contin Educ Pract Vet 2000; 22(9):S118.
Food Animal Residue Avoidance Databank Home-
page. Available on line at: http://www.farad.org/.
Accessed May 19 2005.

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30. Gibbons SN et al. J Am Vet Med Assoc 1996;
209:589.

31. AyliffeTR, Noakes DE.Vet Rec 1986; 118:243.

32. Sweeney RW et al. J Vet Pharmacol Ther 1996;
19:155.

PART 1 GENERAL MEDICINE

Diseases of the alimentary tract - I

PRINCIPLES OF ALIMENTARY TRACT
DYSFUNCTION 189

Motor function 1 89
Secretory function 191
Digestive function 191
Absorptive function 191

MANIFESTATIONS OF ALIMENTARY
TRACT DYSFUNCTION 191

Abnormalities of prehension,
mastication and swallowing 191
Drooling of saliva and excessive
salivation 192

Vomiting and regurgitation 1 92
Diarrhea, constipation and scant
feces 193
Ileus 193

Alimentary tract hemorrhage 194
Abdominal pain 194
Tenesmus 195
Shock and dehydration 195
Abdominal distension 195
Abnormal nutrition 195

SPECIAL EXAMINATION 195

Nasogastric intubation 195
Medical imaging 196
Endoscopy 197

Exploratory laparotomy (celiotomy) 197
Tests of digestion and absorption 197
Abdominocentesis for peritoneal
fluid 199

Intestinal and liver biopsy 203

PRINCIPLES OF TREATMENT IN
ALIMENTARY TRACT DISEASE 203

Relief of abdominal pain 203
Relief of distension 203
Replacement of fluids and
electrolytes 203

Correction of abnormal motility 204
Relief of tenesmus 204
Reconstitution of rumen flora and
correction of acidity or alkalinity 204

DISEASES OF THE BUCCAL CAVITY
AND ASSOCIATED ORGANS 205

Diseases of the muzzle 205
Stomatitis 205
Diseases of the teeth 207
Parotitis 208

Diseases of the pharynx and
esophagus 209

Pharyngitis 209
Pharyngeal obstruction 210
Pharyngeal paralysis 211
Esophagitis 211
Esophageal obstruction 212

DISEASES OF THE NONRUMINANT
STOMACH AND INTESTINES 215

Equine colic (adult horses) 215
Colic in the pregnant and
postparturient mare 229
Colic in foals 230
Gastric dilatation in the horse 233
Gastric impaction in horses 234
Gastric ulcers 234
Gastric (gastroduodenal) ulcer in
foals 234

Gastric ulcer in adult horses 237
Intestinal obstruction in horses 241
Small-intestinal obstruction in
horses 241
Anterior enteritis 245
Diseases of the cecum 246
Displacement and volvulus of the large
(ascending) colon 248
Impaction of the large intestine of the
horse 252

Enteroliths and fecaliths 253
Sand colic 254
Right dorsal colitis 255
Small colon obstruction 255
Spasmodic colic 256
Intestinal tympany in horses 257
Verminous mesenteric arteritis 257
Gastritis 258

Acute gastric dilatation in pigs 259
Acute gastric torsion in sows 259
Intestinal reflux 259
Intestinal obstruction in pigs 259
Impaction of the large intestine of
pigs 259

Intestinal tympany in pigs 260
Enteritis 260

Acute diarrhea of adult (nonsuckling)
horses 268

Chronic undifferentiated diarrhea of
horses 272

Acute diarrhea of suckling foals 274

Intestinal hypermotility 277

Dietary diarrhea 277

Intestinal or duodenal ulceration 279

Diverticulitis and ileitis of pigs 279

Rectal prolapse 279

Rectal stricture 279

CONGENITAL DEFECTS OF THE
ALIMENTARY TRACT 280

Harelip and cleft palate 280
Atresia of the salivary ducts 280
Agnathia, micrognathia and
brachygnathia 280

Persistence of the right aortic arch 280
Choanal atresia 280
Congenital atresia of the intestine and
anus 280

NEOPLASMS OF THE ALIMENTARY
TRACT 281

Mouth 281

Pharynx and esophagus 281
Stomach and rumen 281
Intestines 282

DISEASES OF THE PERITONEUM 282

Peritonitis 282
Rectal tears 287
Retroperitoneal abscess 290
Abdominal fat necrosis 290
Tumors of peritoneum 290

Principles of alimentary
tract dysfunction

The primary functions of the alimentary
tract are the prehension, digestion and
absorption of food and water and the
maintenance of the internal environ-
ment by modification of the amount and
nature of the materials absorbed.

The primary functions can be divided
into four major modes and, corre-
spondingly, there are four major modes of
alimentary dysfunction. There may
be abnormality of motility, secretion,
digestion or absorption. The procedure

in diagnosis should be to determine
which mode or modes of function are
disturbed before proceeding to the deter-
mination of the site and nature of the
lesion and ultimately of the specific cause.

MOTOR FUNCTION

NORMAL GASTROINTESTINAL
MOTILITY

The form and function of the small
intestine of farm animals is similar
between species but the stomachs and
large intestines vary considerably . 1 The
motility patterns in both the small and
large intestine are similar among the

species. In the small intestine, the funda-
mental unit of electrical activity is the
slow wave, which is a subthreshold
fluctuation in membrane potential. Slow
waves are constantly propagated from
the stomach to the rectum. When an
additional stimulus causes the membrane
potential to exceed the excitation thres-
hold, a spike or electrical response activity
occurs, which is usually accompanied by
contraction. Almost all spike activity in
the intestine is superimposed on slow
waves, which are important in controlling
, frequency and velocity at which spiking
events occur. The spiking activity, also
known as the migrating myoelectric

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

development is always the same and
alimentary tract disease is the major cause
of visceral and, more specifically, of
abdominal pain. The most important
mechanism is stretching of the wall of
the viscus, which stimulates free pain
endings of the autonomic nerves in the
wall. Contraction does not of itself cause
pain but does so by causing direct and
reflex distension of neighboring segments.
Thus spasm, an exaggerated segmenting
contraction of one section of intestine,
will result in distension of the imme-
diately oral segment of intestine when a
peristaltic wave arrives. When there is
increased motility for any reason, excessive
segmentation and peristalsis cause
abdominal pain, and the frequent occur-
rence of intermittent bouts of pain
depends upon the periodic increases in
muscle tone that are typical of alimentary
tract wall. Other factors that have some
stimulating effect on the pain end organs
are edema and failure of local blood
supply, such as occurs in local embolism
or in intestinal accidents accompanied by
twisting of the mesentery. A secondary
mechanism in the production of abdomi-
nal pain is the stretching and inflammation
of serous membranes.

Clinically, abdominal pain can be
detected by palpation and the eliciting of
pain responses. However, it is unknown if
the response elicited is due to involve-
ment of underlying organs or to referred
pain. It is difficult to decide if referred
pain occurs in animals. In humans it is
largely a subjective sensation, although
often accompanied by local hyperalgesia.
There are no known examples of referred
pain that are of diagnostic importance in
animals and a local pain response on
palpation of the abdomen is accepted as
evidence of pain in the serous membranes
or viscera that underlie the point of
palpation.

complex, is the myoelectric pattern in the
stomach and small intestine of fasted
nonruminants, fed and fasted ruminants,
and pigs and horses fed ad libitum . 2 There
are three phases of the migrating myo-
electric complex:

° The quiescent phase, in which very
little spike activity occurs
° The irregular phase, characterized by
intermittent spike activity
® The activity front, characterized by
intense, continuous spike activity . 2

There is very little muscle contraction
or transit of gut contents during the
quiescent phase. During the irregular
phase, contractions mix the intestinal
contents and propel them in an aboral
direction. The activity front is accompanied
by intense muscular contraction that
obliterates the lumen, preventing back-
flow of content as it propagates, or
migrates, down the intestine. In non-
ruminants, and pigs and horses fed
periodically, feeding abolishes the migrating
myoelectric complex for several hours. It
is replaced by the fed pattern, charac-
terized by intermittent spike activity
resembling the irregular phase.

Normal cecal and colonic myoelectric
activities, like those of the small intestine,
are characterized by slow waves and
spikes. However, unlike the small intestine,
the patterns of spikes vary greatly with
the species and the area of the large
intestine . 2

Abnormalities of stomach and intestinal
motility represent the most common
consequence of gastrointestinal tract
disease. Disruption in gastrointestinal
tract motility can result in:

° Hypermotility or hypomotility
° Distension of segments of the tract
° Abdominal pain
° Dehydration and shock.

HYPERMOTILITY AND
HYPOMOTILITY

The most important functions of alimentary
tract motility are the peristaltic movements
that move ingesta from the esophagus to
the rectum, the segmentation movements
that chum and mix the ingesta, and the
tone of the sphincters. In ruminants these
movements are of major importance in the
forestomach. Prehension, mastication
and swallowing are other functions of
alimentary tract motility that are essential
for normal function. Eructation of ruminal
gases is an additional crucial function of
motility in ruminants.

Abnormal motor function may take
the form of increased or decreased
motility. Peristalsis and segmenting
movements are usually affected equally
and in the same manner. Motility depends
upon stimulation via the sympathetic and

parasympathetic nervous systems and is
thus dependent upon the activity of the
central and peripheral parts of these
systems, and upon the intestinal muscu-
lature and its intrinsic nervous plexuses.
Autonomic imbalance, resulting in a
relative dominance of one or other
system, is manifested by hypermotility or
hypomotility, and can arise as a result of
stimulation or destruction of hypothalamic
centers, the ganglia, or the efferent or
afferent peripheral branches of the system.
Debility, accompanied by weakness of the
musculature, or severe inflammation,
such as occurs in acute peritonitis or after
trauma, or infarction, results in atony of
the intestinal wall. Less severe inflam-
mation, such as occurs in mild gastritis
and enteritis, may result in an increase in
muscular activity and increased propulsive
activity. Increased motility causes diarrhea,
decreased motility causes constipation, and
both have deleterious effects on digestion
and absorption.

Increased irritability at a particular
intestinal segment increases its activity
and disturbs the normal downward
gradient of activity that insures that the
ingesta is passed from the esophagus to
the rectum. Not only is the gradient
towards the rectum made steeper, thus
increasing the rate of passage of ingesta
in that direction, but the increased
potential activity of an irritated segment
may be sufficiently high to produce a
reverse gradient to the oral segments so
that the direction of the peristaltic waves
is reversed orally to the irritated segments.

DISTENSION

One of the major results of abnormality of
motility is distension of the tract. This
occurs in a number of disturbances,
including the rapid accumulation or
inefficient expulsion of gas, complete
occlusion of the lumen by intestinal
accident or pyloric or ileocecal valve
obstruction, and engorgement on solid or
liquid feeds. Fluids, and to a lesser extent
gas, accumulate because of their failure to
pass along the tract. Much of the
accumulated fluid represents saliva and
gastric and intestinal juices secreted during
normal digestion. Distension causes pain
and, reflexly, increased spasm and motility
of adjoining gut segments. Distension also
stimulates further secretion of fluid into the
lumen of the intestine and this exaggerates
the distension. When the distension passes
a critical point, the ability of the muscu-
lature of the wall to respond diminishes,
the initial pain disappears, and a state of
paralytic ileus develops in which all
muscle tone is lost.

ABDOMINAL PAIN

Visceral pain may arise in any abdominal
viscus or organ but the mode of its

DEHYDRATION AND SHOCK

An immediate effect of distension of the
stomach or small intestine by the accumu-
lation of saliva and normal gastric and
intestinal secretions is the stimulation of
further secretion of fluid and electrolytes
in the oral segments. The stimulation is
self-perpetuating and creates a vicious
cycle resulting in loss of fluid and electro-
lytes to the point where fatal dehydration
can occur. The dehydration is accompanied
by acidosis or alkalosis depending on
whether the obstruction is in the intestine
and accompanied by loss of alkali, or in
the stomach and accompanied by a large
loss of acid radicals. The net effect is the
same whether the fluid is lost by vomiting
or is retained in the gut.

The same cycle of events occurs in
ruminants that gorge on grain but here

the precipitating mechanism is not
distension but a gross increase in osmotic
pressure of the ingesta due to the
accumulation of lactic acid. Dehydration
is also of major importance in diarrhea,
irrespective of the cause. An important
additional factor in the production of
shock, when there is distension of ali-
mentary segments, is a marked reflex
depression of vasomotor, cardiovascular
and respiratory functions. In diarrhea in
calves in which there is no septicemia nor
toxemia associated with bacteria, the end-
point in the phase of dehydration can be
cardiac failure due to severe metabolic
acidosis. Renal ischemia leading to uremia
may result from decreased circulating
blood volume and also contribute to a
fatal outcome. These matters are dis-
cussed in detail in the section in Chapter
2 on disturbances of body fluids, electro-
lytes and acid-base balance.

SECRETORY FUNCTION

Diseases in which abnormalities of
secretion occur are not generally recognized
in farm animals. In humans, and to a
lesser extent in small animals, defects of
gastric and pancreatic secretion produce
syndromes that are readily recognized,
but they depend upon clinical patho-
logical examination for diagnosis. If they
do occur in farm animals, they have so far
only been recognized as aberrations of
motility caused by the defects of secretion.
However, it is reasonable to assume that
some neonates may be deficient in lactase
activity, which results in dietetic diarrhea.
Undigested lactose causes diarrhea by its
hyperosmotic effect, and some of the
lactose may be fermented in the large
intestine, the products of which fermen-
tation may exaggerate the diarrhea. A
deficiency of lactase activity has been
suspected in foals affected with diarrhea
of undetermined origin but the definitive
diagnosis has not been made. The
intestinal lactase activity of foals is at its
highest level at birth and gradually
declines until the fourth month of age,
and then disappears from adults before
their fourth year.

DIGESTIVE FUNCTION

The ability of the alimentary tract to
digest food depends on its motor and
secretory functions and, in herbivores, on
the activity of the microflora that inhabits
the forestomachs of ruminants or cecum
and colon of Equidae. The flora of the
forestomachs of ruminants is capable of
digesting cellulose, of fermenting the
end-products of other carbohydrates to
volatile fatty acids and converting
nitrogenous substances to ammonia and
protein. In a number of circumstances, the

Manifestations of alimentary tract dysfunction

191

activity of the flora can be modified so
that digestion is abnormal or ceases.
Failure to provide the correct diet, pro-
longed starvation or inappetence, and
hyperacidity as occurs in engorgement on
grain all result in impairment of microbial
digestion. The bacteria, yeasts and
protozoa may also be adversely affected
by the oral administration of antibiotic
and sulfonamide drugs, or drugs that
drastically alter the pH of the rumen
content.

Diseases of the stomach of ruminants
are presented in Chapter 6. Information
about the digestive and absorptive
capacities of the equine gut is not exhaus-
tive but some basic data are available. 1,3
The rate of passage of ingesta through the
stomach and intestines is rapid but varies
widely depending on the physical charac-
teristics of the ingesta, dissolved material
passaging more rapidly than particulate
material; 75% of a liquid marker can be
emptied from the stomach in 30 minutes
and be in the cecum at 2 hours. Passage
through the large bowel is much slower,
especially in the latter part of the colon
where much of the fluid is absorbed.
There is an obvious relationship between
the great activity of the small intestine and
the effect of a complete obstruction of it:
the pain is very severe and often
uncontrollable with standard analgesics,
fluid loss into the obstructed parts is
rapid, and dehydration, loss of electro-
lytes and disturbances of acid-base
balance are acute, severe and life-
threatening.

ABSORPTIVE FUNCTION

Absorption of fluids and the dissolved
end-products of digestion may be
adversely affected by increased motility or
by disease of the intestinal mucosa. In
most instances, the two occur together
but, occasionally, as with some helminth
infestations, lesions occur in the intestinal
wall without accompanying changes in
motility.

Manifestations of
alimentary tract
dysfunction

Inanition is the major physiological effect
of alimentary dysfunction when the
disease is a chronic one, dehydration is
the major effect in acute diseases, and
shock is the important physiological
disturbance in hyperacute diseases. Some
degree of abdominal pain is usual in most
diseases of the alimentary tract, the
severity varying with the nature of the
lesion. Other manifestations include
abnormalities of prehension, mastication

and swallowing, and vomiting, diarrhea,
hemorrhage, constipation and scant
feces.

ABNORMALITIES OF
PREHENSION, MASTICATION AND
SWALLOWING

Prehension is the act of grasping for food
with the mouth (lips, tongue, teeth). It
includes the ability to drink. Causes of
faulty prehension include:

® Paralysis of the muscles of the jaw or
tongue

0 Malapposition of incisor teeth due to:

° inherited skeletal defect (inherited
displaced molar teeth, inherited
mandibular prognathism, inherited
congenital osteopetrosis)

® rickets

® Absence of some incisor teeth
s Pain in the mouth due to:

° stomatitis, glossitis
» foreign body in mouth
° decayed teeth, e.g. fluorosis
* Congenital abnormalities of tongue
and lips:

o inherited harelip
® inherited smooth tongue of cattle.

A simple examination of the mouth usually
reveals the causative lesion. Paralysis is
indicated by the behavior of the animal as
it attempts to ingest feed without success.
In all cases, unless there is anorexia due
to systemic disease, the animal is hungry
and attempts to feed but cannot do so.

Mastication may be painful and is
manifested by slow jaw movements inter-
rupted by pauses and expressions of pain
if the cause is a bad tooth, but in a painful
stomatitis there is usually complete
refusal to chew. Incomplete mastication is
evidenced by the dropping of food from
the mouth while eating and the passage
of large quantities of undigested material
in the feces.

Swallowing is a complex act governed
by reflexes mediated through the glosso-
pharyngeal, trigeminal, hypoglossal and
vagal nerves. It has been described endo-
scopically and fluoroscopically in the
horse. The mechanism of the act includes
closure of all exits from the pharynx, the
creation of pressure to force the bolus into
the esophagus, and involuntary move-
ments of the musculature of the eso-
phageal wall to carry the bolus to the
stomach. A defect in nervous control of
the reflex or a narrowing of the lumen of
the pharynx or esophagus may interfere
with swallowing. It is difficult to differ-
entiate clinically between physical and
functional causes of dysphagia (difficulty
in eating/swallowing).

Dysphagia is manifested by forceful
attempts to swallow accompanied initially

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

by extension of the head, followed by
forceful flexion and violent contractions
of the muscles of the neck and abdomen.
Inability to swallow is usually caused by
the same lesions as dysphagia, but in a
greater degree. If the animal attempts to
swallow, the results depend on the site of
the obstruction. Lesions in the pharynx
cause regurgitation through the nostrils
or coughing up of the material. In the
latter instance, there is danger that some
of the material may be aspirated into the
lungs and cause acute respiratory and
cardiac failure or aspiration pneumonia.
When the obstruction is at a low level in
the esophagus, a large amount of material
may be swallowed and then regurgitated.
It is necessary to differentiate between
material regurgitated from the esophagus
and vomitus: the former is usually slightly
alkaline, the latter acid.

CAUSES OF DYSPHAGIA AND
INABILITY TO SWALLOW

° Foreign body, tumor or inflammatory
swelling in pharynx or esophagus
° Painful condition of pharynx or
esophagus

° Esophageal dilatation due to paralysis
c Esophageal diverticulum
° Esophageal spasm at site of mucosal
erosion (achalasia of cardia not
encountered) .

DROOLING OF SALIVA AND
EXCESSIVE SALIVATION

Drooling saliva from the mouth, distinct
from frothing such as occurs during
convulsions, may be caused by pain in the
mouth and by an inability to swallow.
Excessive salivation is caused by stimu-
lation of saliva production by systemic
toxins, especially fungal toxins, or by hyper-
thermia. With systemic poisonings the
increased salivation is often accompanied
by lacrimation.

LOCAL CAUSES OF DROOLING

" Foreign body in mouth or pharynx
Ulceration, deep erosion or vesicular
eruption of the oral mucosa
° Inability to swallow (esophageal
abnormality).

SYSTEMIC CAUSES OF EXCESSIVE
SALIVATION

<> Fbisonous trees - Oleander spp.,
Andromeda spp. (rhododendron)

< Other poisonous plants - kikuyu
grass (or an attendant fungus)

° Fungal toxins, e.g. slaframine and
those causing hyperthermia, e.g.
Claviceps purpurea, Acremonium
coenophialum
° Iodism

-> Watery mouth of lambs
° Sweating sickness
° Methiocarb poisoning.

VOMITING AND REGURGITATION

VOMITING

Vomiting is the forceful ejection of
contents of the stomach and the proximal
small intestine through the mouth and is
a complex motor disturbance of the
alimentary tract. It is a vigorously active
motion signaled by hypersalivation,
retching and forceful contractions of the
abdominal muscles and diaphragm.
Vomiting is essentially a protective mech-
anism with the function of removing
excessive quantities of ingesta or toxic
materials from the stomach. It occurs in
two forms: projectile and true vomiting.

Projectile vomiting

This is not accompanied by retching
movements and large amounts of fluid
material are ejected with little effort. It is
almost always as a result of overloading of
the stomach or forestomach with feed or
fluid.

True vomiting

As it occurs in monogastric animals like
the dog and cat, true vomiting is
accompanied by retching movements
including contraction of the abdominal
wall and of the neck muscles and exten-
sion of the head. The movements are
commonly prolonged and repeated and
the vomitus is usually small in amount
and of porridge-like or pasty consistency.
It is most commonly a result of irritation
of the gastric mucosa. Vomiting is com-
monly designated as being either
peripheral or central in origin depending
on whether the stimulation arises centrally
at the vomiting center or peripherally by
overloading of the stomach or inflam-
mation of the gastric mucosa, or by the
presence of foreign bodies in the pharynx,
esophagus or esophageal groove. Central
stimulation of vomiting by apomorphine
and in nephritis and hepatitis are typical
examples but vomiting occurs rarely, if at
all, in these diseases in farm animals.

Vomiting may have serious effects on
fluid and electrolyte balance because of
the losses of gastric and intestinal contents
during vomiting. Aspiration pneumonia
or laryngeal obstruction are potential
serious consequences of vomiting. Exam-
ination of any suspected vomitus to
determine its site of origin should always
be carried out.

True vomiting is rare in farm animals

except in pigs with gastroenteritis and
some systemic diseases. True vomiting
does not occur in ruminants but abnormal
regurgitation does occur (see below under
Regurgitation). True vomiting is not a
feature of gastric disease in the horse
for two reasons. First, the strong cardiac
sphincter inhibits the release of stomach
contents; in horses rupture of the stomach

is more likely to occur before vomiting
takes place. Secondly, the soft palate
and epiglottis combine to effect a seal
between the oral and nasal parts of the
pharynx so that any vomited stomach
contents must be discharged through the
nasal cavities and not through the mouth.
Spontaneous nasal regurgitation or vomit-
ing does occur occasionally, as manifested
by the production of green stomach
contents at the nostrils. This suggests
extreme gastric distension or a dilated
esophagus and cardiac sphincter and
perhaps some underlying neurological
deficit. Thus vomiting of large quantities of
materia] in the horse is usually a terminal
event and suggests gastric rupture.

REGURGITATION

Regurgitation is the expulsion through
the mouth or nasal cavities of feed, sali\a
and other substances that have not yet
reached the stomach. In most cases it is
due to abnormalities of the esophagus
that interfere with swallowing. A com-
mon example in large animals is the
regurgitation of feed, saliva, and perhaps
blood-stained fluid from the esophagus
of the horse with esophageal obstruction.
Esophagitis is also a common cause of
regurgitation.

Ruminants regurgitate rumen contents
as part of rumination but the material is
not expelled from the mouth nor into the
nasal cavities. The regurgitation of rumen
contents through the mouth does occur in
cattle occasionally, is abnormal, and is a
dramatic event. It is most commonly
associated with loss of tone of the cardia
or inflammation of the cardia (see
examples below).

Nasogastric regurgitation or gastric
reflux occurs in the horse. Stomach
contents flow into the esophagus, and
usually into the nasopharynx and nasal
cavities, as a result of distension of the
stomach with fluid (which usually
originates in the small intestine). This
involuntary process is usually slow and
gradual, unlike true vomiting. Gastric
reflux in the horse can be elicited by
nasogastric intubation. Spontaneous
efflux of stomach contents is indicative of
high-volume and high-pressure fluid
distension of the stomach. On other
occasions the presence of sequestrated
gastric fluids can be confirmed only by the
creation of a siphon, using the nasogastric
tube to infuse a volume of fluid then
disconnecting its supply in order to
retrieve the nasogastric reflux.

Causes of vomiting and regurgi-
tation include:

° Terminal vomiting in horses with

acute gastric dilatation
° 'Vomiting' in cattle is really

regurgitation of large quantities of

rumen contents through the mouth.
Causes include:

o third- stage milk fever (loss of tone
in the cardia)

o arsenic poisoning (acute
inflammation of the cardia)

° poisoning by plants including
E upatorium rugosum, Geigeria spp.,
Hymenoxis spp., Andromeda spp..
Oleander spp., Conium maculatum
o veterinary administration of large
quantities of fluids into the rumen
(regurgitation occurs while the
stomach tube is in place)
o use of a large-bore stomach tube
o cud-dropping: a special case of
regurgitation usually associated
with abnormality of the cardia
o Vomiting in pigs may be due to:

° transmissible gastroenteritis
° acute chemical intoxications
0 poisoning by the fungus Fusarium
sp., which also causes off-feed
effects suspected to be analogous
to nausea in humans
o Regurgitation - in all diseases causing
dysphagia or paralysis of swallowing.

DIARRHEA, CONSTIPATION AND
SCANT FECES

Diarrhea and constipation are the most
commonly observed abnormalities in

fecal consistency, composition and fre-
quency of defecation.

DIARRHEA

Diarrhea is the increased frequency of
defecation accompanied by feces that
contain an increased concentration of
water and decrease in dry matter content.
The consistency of the feces varies from
soft to liquid.

Abnormalities of peristalsis and
segmentation usually occur together and
when there is a general increase in
peristaltic activity there is increased caudal
fbw, resulting in a decrease in intestinal
transit time and diarrhea. Because of a lack
of absorption of fluid the feces are usually
softer than normal, the dry matter content is
below the normal range, and the total
amount of feces passed per day is increased.
The frequency of defecation is usually also
increased. Common causes of diarrhea are:

" Enteritis, including secretory
enteropathy

0 Malabsorption, e.g. due to villous
atrophy and in hypocuprosis (due to
molybdenum excess)

0 Neurogenic diarrhea as in excitement
0 Local structural lesions of the
stomach or intestine, including:

0 ulcer, e.g. of the abomasum or
stomach

0 tumor, e.g. intestinal
adenocarcinoma

Manifestations of alimentary tract dysfunction

° Indigestible diet, e.g. lactose
intolerance in foals

0 Carbohydrate engorgement in cattle
° In some cases of ileal hypertrophy,
ileitis, diverticulitis and adenomatosis
° Terminal stages of congestive heart
failure (visceral edema)

° Endotoxic mastitis in cattle
(splanchnic congestion)

° Chronic and acute undifferentiated
diarrhea in horses
° Vagus indigestion in cows causes
pasty feces but bulk is reduced. These
cases may be mistaken initially for
other causes of diarrhea.

Malabsorption syndromes
Malabsorption syndromes are being
recognized with increased frequency in
monogastric farm animals. For example,
in recently weaned pigs, there is villous
atrophy with a resulting loss in secretory
and absorptive function. Inefficient diges-
tion originating in this way may or may
not be manifested by diarrhea, but in
malabsorption there is usually diarrhea.
There is always failure to grow or main-
tain body weight, in spite of an apparently
normal appetite and an adequate diet. In
horses, the lesions associated with mal-
absorption, which may be with or without
diarrhea, include villous atrophy, edema
and/or necrosis of the lamina propria of
the gut wall, and nodular tracts and
aggregations of eosinophils indicating
damage by migrating strongyle larvae. It
is possible also that some cases are
caused by an atypical reaction of tissue to
unknown allergens (possibly helminths)
and are probably an abnormal immuno-
logical response. A common accompani-
ment in the horse is thin hair coat, patchy
alopecia and focal areas of scaling and
crusting. The pathogenesis is unknown.
Special tests are now detailed for the
examination of digestive efficiency in the
horse. These are listed in the next section
under special tests. Increased venous
pressure in the portal circuit caused by
congestive heart failure or hepatic fibrosis
also causes diarrhea.

The question of whether or not
enteritis in animals causes intestinal
hypermotility and increased peristalsis,
resulting in diarrhea, remains unresolved.
If hypermotility and increased peristalsis
cause diarrhea, antimotility drugs may be
indicated in some causes of acute infec-
tious diarrhea. Current concepts on the
pathophysiology of the common diarrheas
associated with infectious agents (such as
enterotoxigenic Escherichia coli) indicate
that there is a net increase in the flow of
intestinal fluid into the lumen and a
decrease in outflow back into the systemic
circulation, which causes distension of the
intestine with fluid. The hydraulic effect of

the distension can cause diarrhea and
hypermotility is probably not necessary.
In addition, because of the temporary
malabsorption that exists in infectious
enteritides, and the presence of infectious
agents and enterotoxins in the lumen of
the intestine, the emphasis should be on
evacuation of the intestinal contents and
not on the use of anticholinergic drugs to
inhibit evacuation. Furthermore, it is
unlikely that the anticholinergics will
have any significant effect on the
secretory-absorptive mechanisms that
have been altered by an enteropathogen.

CONSTIPATION

Constipation is the decreased frequency
of defecation accompanied by feces that
contain a decreased concentration of
water. The feces vary in consistency from
being hard to dry and of small bulk. True
constipation as it occurs in humans is
usually characterized by failure to
defecate and impaction of the rectum
with feces. When the motility of the
intestine is reduced, the alimentary transit
time is prolonged and constipation or
scant feces occurs. Because of the increased
time afforded for fluid absorption, the
feces are dry, hard and of small bulk and
are passed at infrequent intervals. Consti-
pation may also occur when defecation is
painful, as in cattle with acute traumatic
reticuloperitonitis.

SCANT FECES

Scant feces are small quantities of feces,
which may be dry or soft. Scant feces occur
most commonly in cattle with abnor-
malities of the forestomach or abomasum
resulting in the movement of only small
quantities of ingesta into the small and
large intestines (an outflow abnormality).
The details are available in Chapter 6.
When there is complete intestinal stasis the
rectum may be empty except for blood-
tinged, thick, pasty material.

Common causes of constipation or
scan t feces are:

° Diseases of the forestomach and
abomasum causing failure of outflow
0 Impaction of the large intestine in the
horse and the sow
0 Severe debility, as in old age
0 Deficient dietary bulk, usually fiber
•“ Chronic dehydration
0 Partial obstruction of large intestine
° Painful conditions of the anus
” Paralytic ileus
0 Grass sickness in horses
° Chronic zinc poisoning in cattle
n Terminal stages of pregnancy in cows.

ILEUS (ADYNAMIC AND
DYN AMI C ILEUS)

Ileus is a state of functional obstruction

of the intestines or failure of peristalsis.

194

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

It is also known as paralytic ileus or
adynamic ileus. Dynamic or mechanical
ileus is a state of physical obstruction. In
paralytic ileus there is loss of intestinal
tone and motility as a result of reflex
inhibition. This can occur in acute
peritonitis, excessive handling of viscera
during surgery, and prolonged and severe
distension of the intestines as in intestinal
obstruction or enteritis. Ileus can also be
caused by acid-base imbalance, dehy-
dration, electrolyte imbalances such as
hypocalcemia and hypokalemia, and
toxemia. Ileus can affect the stomach,
causing delayed gastric emptying and
subsequent dilatation with fluid and gas.
The effect of ileus on the intestines is to
cause failure of orocaudal movement of
fluid, gas and ingesta and accumulation of
these substances, which results in
intestinal distension and varying degrees
of abdominal pain, dehydration and a
marked reduction in the amount of feces.
Distension of the abdomen, fluid-
tinkling, fluid-splashing sounds, and
pings on percussion of the abdomen are
common clinical findings. Impaction of the
large intestine of horses is a form of ileus.

Postoperative ileus of the large
intestine is a common complication of
surgical treatment for colic in the horse.
The clinical findings include gastric reflux
because of gastric distension with fluid,
absence of or minimal intestinal peristaltic
sounds, an absence of feces, abdominal
pain, distended loops of intestine pal-
pable per rectum, and varying degrees
of shock and dehydration as a result of
intestinal fluid sequestration and a
decrease in fluid absorption. Infarction
of the intestinal wall associated with an
acute mechanical obstruction of the
intestine also results in ileus. In thrombo-
embolic colic due to verminous mesenteric
arteritis in the horse, large segments of
the large colon and cecum can become
infarcted, resulting in irreversible ileus.

The etiology and pathogenesis of ileus
in farm animals are not well understood.
Sympathetic hyperactivity is thought to
be a factor. The gastroileal reflex is one
example of the influence of the activity of
one part of the digestive tract on that of
another; inhibition of gastric motility
when the ileum is distended is called
ileogastric reflex. Immediate cessation of
all intestinal movement (adynamic ileus)
follows distension of an intestinal
segment, rough handling of the intestine
during abdominal surgery or peritoneal
irritation. Adynamic ileus operates through
three pathways: general sympathetic
discharge of the peripheral reflex pathway
through the iliac and mesenteric plexuses,
and the intramural plexuses. The
treatment of ileus depends on the original
cause. Physical obstruction of the intestines

and torsion of the stomach must be
corrected surgically. Postoperative ileus in
the horse is difficult to manage and the
case fatality rate is high. 2 Fluid therapy
and gastric reflux decompression using a
nasogastric tube are standard recommen-
dations. Nonsteroidal anti-inflammatory
drugs (NSAIDs) are used to control
abdominal pain. Xylazine is contra-
indicated because of its depressant effect
on gastric and intestinal motility.

ALIMENTARY TRACT
HEMORRHAGE

Hemorrhage into the stomach or intestine
is a common occurrence in farm animals.
The main causes are:

° Gastric or abomasal (rarely duodenal)
ulcers

® Severe hemorrhagic enteritis
» Structural lesions of the intestinal
wall, e.g. adenomatosis, neoplasia
° Infestation with blood-sucking
nematodes, e.g. bunostomiasis
° Local vascular engorgement or

obstruction as in intussusception and
verminous thrombosis.

Hemorrhage into the stomach results in
the formation of acid hematin, which
makes vomitus a dark brown color like
coffee grounds, and feces have a black
or very dark brown, tarry appearance
(melena). The change in appearance of
the feces caused by hemorrhage into the
intestine varies with the level at which the
hemorrhage occurs. If the blood originates
in the small intestine, the feces may be
brown-black, but if it originates in the
colon or cecum, the blood is unchanged
and gives the feces an even red color.
Hemorrhage into the lower colon and
rectum may cause the voiding of feces
containing or consisting entirely of clots
of whole blood.

Hemorrhage into the pharynx is
unusual, but when it occurs the blood
may be swallowed and appear in the feces
or vomitus. If there is any doubt about the
presence of blood in the feces or vomitus,
biochemical tests should be performed.
The hemorrhage may be sufficiently
severe to cause anemia and, in parti-
cularly severe cases, acute peripheral
circulatory failure. In cattle the most
sensitive test is one using a dilute
alcoholic solution of guaiac as the test
reagent. It is capable of detecting a daily
blood loss into the abomasum of as small
a volume as 70 mL. Transit time of blood
from abomasum to rectum in normal
cows varies from 7-19 hours.

ABDOMINAL PAIN

The pain associated with diseases of the
abdominal viscera causes similar signs

regardless of the viscus or orgap involved
and careful clinical examination is necess-
ary to locate the site of the lesion. The
manifestations of abdominal pain vary
with the species, horses being particularly
sensitive, but comprise largely of abnor-
malities of behavior and posture. Pain as a
systemic state is presented in general terms
in Chapter 2, including its effects on body
systems and methods for its detection.

Readily identifiable syndromes of
abdominal pain referable to the alimentary
tract include the following.

Horses

0 Acute pain: Pawing, flank-watching,
rolling

o Subacute pain: Lesser degree of flank-
watching, often excessive pawing,
lying down frequently without rolling,
stretching out as if to urinate, males
may extrude the penis, walking
backwards, dog-sitting posture, lying
on back, impulsive walking
° Peritoneal pain: Rigidity of the
abdominal wall, pain on palpation.

Cattle

° Acute pain: Downward arching of
back with treading of the hind feet,
lying down (rolling is uncommon).
Calves will lie down and bellow with
severe abdominal pain, as in
abomasal torsion

° Subacute pain, including peritoneal
pain: Back arched upwards, grunting
on walking or lying down, grunting
on deep palpation of the abdomen,
immobility.

DIFFERENTIAL DIAGNOSIS

The disease states likely to be mistaken for
the above categories of alimentary tract
pain are:

• Acute pain: Paresthesia, e.g. in
photosensitive dermatitis of cows;
pleuropneumonia in the horse; uterine
torsion in the mare and cow; snakebite
in horses; urticaria as in milk allergy in
cows; renal and urethral colic;
compulsive walking, e.g. in hepatic
disease; lead poisoning; dysuria or
obstruction of urinary tract generally;
laminitis and lactation tetany in mares

• Subacute pain: Encephalopathy, possibly
hepatic insufficiency

COMMON CAUSES OF ALIMENTARY

TRACT PAIN

Horses

° Acute pain: All causes of intestinal
obstruction, gastric dilatation, enteritis
generally, colitis X, rarely
salmonellosis

° Subacute pain: Thromboembolic colic,
impaction of the large intestine, ileal
hypertrophy.

Special examination

195

Cattle

• Acute pain: Intestinal obstruction,
especially by phytobezoars; poisoning
by kikuyu grass, Andromeda sp..
Oleander sp., water hemlock

(I Cicuta sp.)

• Subacute pain: Traumatic
reticuloperitonitis and peritonitis
generally. Abomasal volvulus.

tenesmus

Tenesmus, or persistent straining, is com-
mon in many diseases of the organs of the
pelvic cavity; therefore it is not necessarily
a diagnostic sign of disease in the lower
alimentary tract. It is sometimes associated
with frequent defecation caused by
neurological stimulation of peristalsis.
Common causes of tenesmus are listed by
species below.

Cattle

8 Lower alimentary tract disease, e.g.
colitis and proctitis caused by
coccidiosis

6 Genital tract disease, e.g. severe
vaginitis, retained placenta

• Estrogen toxicity in steers, e.g.
estrogen implantation, fusariotoxicosis

6 4-aminopyridine poisoning,
methiocarb poisoning
0 Lower spinal cord lesions - spinal
cord abscess, rabies
e Idiopathic.

Horses

6 Tenesmus does not usually occur
except during parturition.

Pigs

0 Constipation in parturient sows; also
dystocia.

SHOCK AND DEHYDRATION

Acute rapid distension of the intestine or
stomach causes reflex effects on the heart,
lungs and blood vessels. The blood
pressure falls abruptly, the temperature
falls below normal and there is a marked
increase in heart rate. In acute intestinal
accidents in horses that terminate fatally
in 6-12 hours, shock is the major cause of
death. There appears to be some species
difference in the susceptibility to shock
because similar accidents in cattle rarely
cause death in less than 3-4 days; acute
ruminal tympany is an exception and may
exert its effects rapidly, causing death in a
very short time after its onset. Less severe
distension, vomiting and diarrhea cause
clinically recognizable dehydration and
abnormalities of electrolyte concentration
and acid-base balance. Determination of
the relative importance of shock and
dehydration in a particular case at a
particular time is one of the challenges in
gastroenterology. The subject is considered

in detail under the heading of equine
colic and under enteritis.

ABDOMINAL DISTENSION

Distension of the abdomen is a common
manifestation of disease of the alimentary
tract. Generally, abdominal distension
associated with the alimentary tract is
caused by distension of viscera with gas
or fluid. The degree of abdominal dis-
tension depends on the viscera that are
distended, the species involved and the
age of the animal. Abdominal distension
is most pronounced when large viscera of
adult cattle and horses are distended.
Distension of the small intestines in adult
cattle and horses may not be detectable
clinically. On the other hand, distension
of the small intestine with fluid in calves
and foals often causes noticeable abdomi-
nal distension.

Occasional cases of abdominal dis-
tension are due to pneumoperitoneum,
which usually follows abdominal surgery.
In ruminants the most common causes
are distension of the rumen, abomasum,
cecum and large intestine, the details of
which are presented in Chapter 6.
Abdominal distension in horses and pigs
is usually due to distension of the large
intestine. Gastric dilatation of the horse
does not cause abdominal distension.
Ascites is a cause in all species.

Abdominal distension may be sym-
metrical, asymmetrical or more pronounced
dorsally or ventrally on one or both sides.
The severity can vary from mild and
barely detectable to so severe that the
skin over the abdominal wall has
sufficient tension that it cannot be picked
up or'tented'. Determination of the cause
of the distension requires careful exam-
ination of the abdomen by inspection,
palpation, percussion and simultaneous
auscultation. Rectal palpation is used to
determine the location and nature of
distended viscera. Diseases of other body
systems that cause abdominal distension
and must be considered in the differential
diagnosis include advanced pregnancy
and hydrops allantois.

The alimentary tract diseases of simple-
stomached animals in which abdominal
distension may be a manifestation are:

° Intestinal tympany - due to excessive
gas production caused by abnormal
fermentation in the large intestine of
horses and pigs

0 Obstruction of the large intestine - in
horses and pigs as a result of their
torsion or miscellaneous constrictions
caused by adhesions, usually as a
result of peritonitis

° Retention of the meconium - in foals.
This is often accompanied by severe
distension of the colon and abdomen.

Obstruction of the small intestine may
cause abdominal distension but not to the
degree that occurs in distension of the
large intestine. In all the above diseases,
acute abdominal pain is common.

ABNORMAL NUTRITION

Failure of normal motor, secretory, diges-
tive or absorptive functions causes
impairment of nutrient supply to body
tissues. Inanition or partial starvation
results and the animal fails to grow, loses
body weight or shows other signs of
specific nutritional deficiencies. Ancillary
effects include decreased appetite when
gut motility is decreased; in many cases
where motility is increased and there is
no toxemia, the appetite is increased and
may be voracious.

Special examination

The general aspects of the clinical exam-
ination of the alimentary tract and
abdomen of farm animals are described in
Chapter 1 under Clinical examination.
Some additional or special examination
techniques and procedures are included
here.

NASOGASTRIC INTUBATION
RUMEN OF CATTLE

Examination of the rumen contents is
often essential to assist in determination
of the state of the rumen environment
and digesta. Passage of a stomach tube
into the rumen will determine the
patency of the esophagus and if there is
increased intraruminal pressure associ-
ated with a frothy or free-gas bloat. In a
free-gas bloat, large quantities of gas are
usually released within a minute. In a
frothy bloat, the ruminal end of the tube
may become occluded by the froth and
very little if any gas is released. Moving
the tube back and forth within the rumen
and blowing air into the tube to clear the
ruminal end may result in the release of
some gas.

When the tube is in the rumen, some
rumen juice can be siphoned or pumped
out and collected in an open beaker for
field and laboratory analysis. The color,
depending on the feed to a limited extent,
will be green, olive-green or brown-
green. In cattle on pasture or being fed
good quality hay, the color is dark green.
When silage or straw is the diet the color
is yellow-brown. In grain overload the
color is milky-gray, and in rumen stasis
of long duration with putrefaction, the
color is greenish-black. The consistency
; of the rumen contents is normally
slightly viscid, and watery rumen content
is indicative of inactive bacteria and

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

protozoa. Excess froth is associated with
frothy bloat as in primary ruminal
tympany or vagus indigestion. The odor
of the rumen contents is normally aromatic
and, although somewhat pungent, not
objectionable to the nose. A moldy,
rotting odor usually indicates protein
putrefaction, and an intensely sour odor
indicates an excess of lactic acid
formation, due to grain or carbohydrate
engorgement. The pH of the rumen
juice varies according to the type of feed
and the time interval between the last
feeding and taking a sample for pH
examination. The normal range, however,
is between 6.2 and 7.2. The pH of rumen
juice should be examined immediately
after the sample is obtained, using a wide
range pH (1-11) paper. High pH values
(8-10) will be observed when putrefaction
of protein is occurring in the rumen or if
the sample is mixed with saliva. Low pH
values (4-5) are found after the feeding of
carbohydrates. In general, a pH below 5
indicates carbohydrate engorgement;
this pH level will be maintained for
between 6-24 hours after the animal has
actually consumed the carbohydrate diet.
Microscopic examination of a few drops
of rumen fluid on a glass slide with a low-
power field will reveal the level of proto-
zoon activity. Normally 5-7 protozoons
are active per low-power field. In lactic
acidosis the protozoa are usually absent
or a few dead ones are visible.

DECOMPRESSION OF DISTENDED
RUMEN

In adult cattle with severe abdominal
distension due to gross distension of the
rumen it is difficult, if not impossible, to
assess the status of the abdomen. To
determine if the rumen is distended
and/or to relieve the pressure a large-bore
stomach tube should be passed (Colorado
Kingman Tube: 2 m long and 3 cm inside
diameter). In vagus indigestion, the
rumen may be grossly distended with
fluid contents, which will gush out
through a large-bore tube. In some cases
100-150 L of rumen contents may be
released. If no contents are released the
contents may be frothy or mushy and the
rumen end of the tube will plug almost
instantly. Rumen lavage may then be
attempted using a water hose to deliver
20-40 L of water at a time followed by
back drainage using gravity flow. After the
rumen is partially emptied it is usually
possible to more accurately assess the
rumen and the abdomen.

DECOMPRESSION OF THE HORSE'S
STOMACH

Attempts to pass a nasogastric tube in the
horse will usually detect complete or
partial obstruction of the esophagus. In
gross distension of the stomach in the

horse, there is an immediate rush of fluid
contents as soon as the cardia is passed
(gastric reflux). The technique of gastric
decompression is therapeutic and diag-
nostic. Gastric distension is a highly
distressing feature of some colic cases
and the mere pain relief of gastric
decompression facilitates the clinical
examination. The retrieval of significant
volumes (2 L or more) of sequestrated
gastric fluid is also an extremely specific
indicator of intestinal obstruction,
especially small intestinal obstruction,
and a reasonably specific indicator that
surgical intervention is necessary.

MEDICAL IMAGING

RADIOGRAPHY

Because of their large size, and the
presence of substantial amounts of gas in
the large intestine, abdominal radio-
graphy has not been used routinely as a
diagnostic aid in mature horses with
abdominal pain. Similarly, in mature
cattle the sheer size of the abdomen and
the gas in the rumen has not favored
abdominal radiography except for
identifying the presence of metal objects
in the reticulum. Esophageal radiography
is, however, useful for the diagnosis of
disorders of swallowing in horses.

Foals, calves and small horses are too
small to be palpated per rectum, and
abdominal radiography, with and without
contrast media, has been used diag-
nostically in colic of foals. A standard
lateral abdominal radiography is a valu-
able diagnostic aid in the foal with colic. 4
The site of the lesion, whether gastric,
small or large intestinal, or a combination
of all three, can be determined from the
radiographs. The sensitivity of radio-
graphy in detecting gastrointestinal
lesions in neonatal foals was found to be
96%; the specificity was 71%. 4

Knowledge of the radiographic appear-
ance of the normal neonatal abdomen is
important before lesions can be reliably
detected. The standing lateral radio-
graphic of the normal abdomen of the
neonatal foal is characterized by:

A gas cap over fluid and ingesta in
the stomach

Small collections of gas in the small
intestine in the cranial and mid-
central abdomen

Gas caps over fluid and ingesta in the
cecum and large colon, seen in the
caudodorsal abdomen
Small amounts of gas in the small
colon and inconsistent gas in the
rectum, seen at the pelvic inlet.

Abdominal radiography has also been
used for the diagnosis of enterolithiasis
and sand accumulation as causes of colic 3

The technique provides a high positive-
predictive value and is cost-effective in
high-prevalence areas.

ABDOMINAL ULTRASONOGRAPHY

Abdominal ultrasonography has been
used to identify small intestine intus-
susceptions, large colon displacements,
abdominal viscera and neoplasms. The
technique may require only several
minutes in the hands of an experienced
clinician.

Horse

Abdominal ultrasonography is a diag-
I nostic aid that is used for evaluation of
j equine colic and to assist in differentiation
j of medical from surgical colics.

It is accurate in identifying horses
: with abnormal small intestines. 5 Ultra-
; sonographic findings of edematous small
intestine without motility provides an
indication of primary small-intestine
disease (obstruction or strangulation) and
justifies surgical intervention. Detecting
increased thickness of the wall of the
large intestine during ultrasonography is
a reproducible and accurate preoperative
test for large -colon torsion in horses with
surgical colic localized to the large colon. 6
Strangulating lipomas and epiploic
foramen entrapments were diagnosed
more often than any other primary small
intestine lesion. Detection of distended or
edematous small intestine by rectal
palpation provided a sensitivity of 50%, a
specificity of 98% and a positive pre-
dictive value of 89% for small intestine
strangulation obstructions. 5 The duodenum
of the horse can be evaluated by ultra-
sonography. 7 Normally it does not contain
any gas and the accumulation of fluid and
gas associated with colic may be useful.
The technique has been used to detect
intestinal sand accumulations. 8 Gastro-
intestinal activity patterns have been
evaluated in healthy horses using B mode
and Doppler ultrasonography. 9 The
anatomy and biometric analysis of the
thoracic and abdominal organs in healthy
foals from birth to age 6 months have
been evaluated with ultrasonography. 10

Cattle

Abdominal ultrasonography is an ideal
diagnostic aid for the investigation of
gastrointestinal diseases, the most com-
mon of which include traumatic reticulo-
peritonitis, left and right displacement of
the abomasum, ileus of the small intestine,
and dilatation and displacement of the
cecum. 11,12 The various divisions of the
small intestine can be differentiated from
one another with the exception that the
ileum cannot be differentiated from
jejunum. 13 In normal cows, in which the
intestine'is full of ingesta, all parts of the
intestine have a relatively large diameter.

Special examination

197

In cows with ileus, the loops of intestine
proximal to the ileus are distended and
those distal to the ileus are empty.

ENDOSC OPY

gastroenteroscopy

Fiberoptic gastroduodenoscopy is a

practicable procedure in a sedated horse
that has had no feed for 12-24 hours. A
275 x 13.5 cm fiberoptic instrument is
passed via a nostril to the stomach, which
is then distended with air. The control of
the objective of the endoscope is quite
difficult and entry into the pylorus
particularly so, so that examination of the
duodenum is not possible in all horses.

LAPAROSCOPY

In this procedure a laparoscope is passed
through an incision in the abdominal wall
of either the left or right paralumbar
fossa. 14 Feed must be withheld for
36 hours, analgesia is provided during the i
procedure, and abdominal insufflation j
with carbon dioxide is required in order to ]
separate the viscera for viewing. Laparo- j
scopy in standing horses is a valuable j
diagnostic aid for examination of the struc- I
tures in the dorsal regions of the abdomen.

In the standing horse, the anatomic
structures of importance that can be i
viewed in the left half of abdomen are the :
hepatic duct, left lateral and quadrate
lobes of the liver, stomach, left kidney
with associated nephrosplenic ligament,
segments of the jejunum, descending
colon and ascendingcolon, left side of the
male and female reproductive tracts,
urinary bladder, vaginal ring and
mesorchium. The important structures
observable in the right side of the
abdomen are the common hepatic duct,
left lateral, quadrate and right lobes of the
liver, caudate process of the liver,
stomach, duodenum, right dorsal colon,
epiploic foramen, omental bursa, right
kidney, base of the cecum, segments of
jejunum, descending colon and ascending
colon, urinary bladder, right half of the
male and female reproductive tracts, and
rectum. 14

In the dorsally recumbent horse under
general anesthesia, with laparoscopy the
main structures of diagnostic relevance in
the caudal region of the abdomen are the
urinary bladder, mesorchium, ductus
deferens (left and right), left and right
vaginal rings, insertion of the prepubic
tendon, random segments of jejunum and
descending colon, the pelvic flexure of the
ascending colon, body of the cecum and
cecocolic fold. The main structures
observed in the cranial region of the
abdomen are the ventral surface of the
diaphragm, falciform ligament and round
ligaments of the liver, ventral portion of
the left lateral, left medial, quadrate and

right lateral lobes of the liver, spleen, right
and left ventral colons, sternal flexure of
the ascending colon, apex of the cecum,
and stomach. 15 Alterations in cardiovascular
and respiratory functions in response to
the pneumoperitoneum and various
positional changes indicated a need for
continuous and thorough anesthetic
monitoring and support.

EXPLORATORY LAPAROTOMY
(CELIOTOMY)

An exploratory laparotomy is useful for
palpating and inspecting the abdominal
viscera as a diagnostic aid in cattle, sheep 1
and horses of all ages. Cost and time
are important factors but if abdominal
disease is suspected and other diagnostic
techniques cannot identify the location
and nature of the abnormality, a laparotomy
is highly desirable.

TESTS OF DIGESTION AND
ABSORPTION

Digestion and absorption of nutrients are
complex, interrelated functions of the
gastrointestinal tract. Failure in one or more
of normal motility, enzymic digestion of
food and absorption of simple sugars, fat
and protein by the small intestine can result
in inadequate assimilation of nutrients
from the gastrointestinal tract. Tests of
small intestinal digestion, absorption or
both have been devised for use in mono-
gastrics. These tests take advantage of the
rapid appearance in blood of products of
digestion, or of compounds that are readily
absorbed without digestion.

Indications for these tests include:

Weight loss of undetermined cause
that is suspected to be due to failure
of absorption of food by the small
intestine

Diarrhea of suckling foals that is
suspected to be due to failure of the
foal to digest lactose (lactase
deficiency)

Suspected protein-losing enteropathy
of older foals and adult horses.

Low serum protein and albumin concen-
trations with small intestinal disease can
be due to failure of digestion of proteins
and absorption of amino acids or leakage
of plasma proteins into the intestine.
Regardless of the mechanism, some horses
with protein -losing enteropathy have
abnormal tests of intestinal digestion and
absorption of sugars. Contraindications
include the presence of obstructive
lesions of the gastrointestinal tract, risk of
worsening the disease process by the
period of fasting required for most of the
tests (such as in ponies with hyperlipemia),
or known adverse reactions of the animal
to any of the test substances.

Interpretation of the test is based on
the concentration of the variable of
interest (usually glucose or xylose) in
blood over a period of time after adminis-
tration of the test meal (usually by
nasogastric intubation). Concentration of
the metabolite or marker of interest" in
blood is plotted against time and the
shape of the curve, highest concentration
attained, time to attain the highest con-
centration, and elevation over baseline
values (i.e. those measured immediately
before administration of the test meal) is
compared against values obtained from
clinically normal horses or foals. Blood
concentrations of glucose or xylose that
are lower than expected (so called 'flat
curve') can be indicative of alterations in
j gastrointestinal function that hinder
propulsion, digestion or absorption of
nutrients. Thus, tests of digestion and
absorption alone rarely provided suffi-
cient information to make a definitive
diagnosis of the functional disorder. The
exception to this rule is the modified
lactose tolerance test in foals (see below).
Interpretation of the results of oral tests of
absorption is often confounded by factors
that alter gastrointestinal function, such
as feed withholding or enteritis, or con-
ditions that alter removal of the test
compound from blood, such as reduced
insulin sensitivity. This is particularly the
■ case for tests that depend on measure-
ment of blood glucose concentration.
Blood glucose concentrations are deter-
mined in the absorptive state by the
difference in rates of absorption of
glucose from the small intestine into
blood and removal of glucose from blood
by uptake into muscle, adipose tissue and
metabolically active tissues. Conditions
that enhance glucose uptake from the
blood can result in low peak blood
glucose concentrations, and conditions
that decrease insulin sensitivity (as is seen
in fat horses) can result in high blood
glucose concentrations. The use of D-xylose
as an indicator of small intestinal absorp-
tion is intended to avoid these effects of
variable glucose disposal. Therefore, the
values obtained with oral tests of absorp-
tion and digestion should be interpreted
with caution and should be considered in
light of all clinical and laboratory data
available for the animal.

GLUCOSE ABSORPTION TEST

The oral glucose tolerance test is one of
the simplest tests of small intestinal
absorptive capacity to perform. However,
because of the many factors that affect
blood glucose concentration, including
factors not related to small-intestinal
absorptive capacity, results of the test can
on occasion be difficult to interpret. 16 Oral
glucose tolerance testing can produce

198

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

abnormal results 'in horses with diseases
that do not involve the small intestine,
such as lower motor neurone disease
or polysaccharide storage myopathy. On
the other hand, the oral glucose tolerance
test is often used because of the ready
availability of glucose for oral adminis-
tration and routine nature of measure-
ment of blood glucose concentrations.

The main indications for performing
oral glucose tolerance testing include
unexplained weight loss believed to be
associated with gastrointestinal disease,
and suspected protein-losing enteropathy.
Contraindications are those listed above.
In addition, care should be exercised in
performing the test in horses at increased
risk of laminitis, as rapid passage of
unabsorbed glucose into the large colon
and cecum can cause laminitis.

Horses for oral glucose tolerance
testing are first fasted for 12-18 hours.
Access to water should be provided.
Glucose is given by stomach tube at
1 g/kg body weight (BW) of anhydrous
glucose (or comparable) as a 10-20%
solution in water. Blood for measurement
of glucose concentration is collected
immediately before, and every 30 minutes
for 4-6 hours after glucose adminis-
tration. Some protocols involve less
frequent (hourly) collection of blood. One
protocol requires collection of blood
samples before and 120 minutes after
administration of glucose. This last
protocol is not recommended as early or
delayed peaks in blood concentration are
not detected. The blood glucose concen-
tration in the normal horse increases by at
least 85% (from 90 up to 180 mg/dL
(5.0 to 10.0 mmol/L)) with peak blood
concentrations attained 90-150 minutes
after administration of glucose. Horses
with partial malabsorption have increases
in blood glucose concentration of 15-85%
of baseline values, and horses with
complete malabsorption have no increase
or less than 15% increase in blood
glucose concentration by 2 hours. 17 Blood
concentrations of glucose in normal
horses return to resting values in approxi-
mately 6 hours. The shape of the curve is
affected by the horse's previous diet, the
curve being much lower in horses fed on
stored feeds such as hay and grain
compared to horses eating pasture of
clover and grass.

Horses with weight loss and complete
failure of absorption of glucose are likely
to have extensive infiltrative disease of the
small intestine such as lymphosarcoma or
granulomatous enteritis. 17 Of 25 horses
with partial failure of glucose absorption,
18 (62%) had structural abnormalities of
the small intestine. Clearly abnormal
results of the oral glucose tolerance test
therefore appear to be fairly specific for

severe and widespread small-intestinal
disease. Care should be taken when
interpreting results that deviate only
marginally from normal values.

STARCH DIGESTION TEST

A suitable test for the evaluation of
gastric, small-intestinal and pancreatic
function is the starch digestion test. The
test relies on the presence of amylase in
the small intestine with subsequent
cleavage of starch into glucose, which is
then absorbed into the blood. The horse is
fasted for 18 hours and then given com
starch (1 kg in 4 L of water or 2 g/kg BW)
by stomach tube. A pretreatment blood
sample is matched with others taken at
15, 30, 60, 90 and 120 minutes and then
hourly to 6 hours.

In the normal horse there is an
increase in blood glucose levels of about
30 mg/dL (1.7 mmol/L) (from 90 up to
120 mg/dL (5.0-6. 7 mmol/L)), with the
peak occurring at 1-2 hours and the curve
returned to pretreatment level at 3 hours. 18
The test can be affected by the diet of the
horse prior to testing.

LACTOSE DIGESTION TEST

Newborn animals rely on ingestion of
milk sugar (lactose) as an important
source of energy until weaning. Lactose is
digested in the proximal small intestine
by lactase, a disaccharidase present in the
brush border of intestinal epithelial cells
that cleaves lactose into glucose and
galactose. Loss of small-intestinal pro-
duction of lactase, such as occurs in some
bacterial and viral enteritides including
rotavirus infection, results in failure to
cleave lactose and passage of the sugar to
the hind gut. Fermentation of lactose in
the hind gut causes acute and sometimes
severe osmotic diarrhea. A prime indi-
cation for the oral lactose tolerance test is
therefore acute diarrhea in neonates
being fed milk. The test not only has
diagnostic usefulness because a positive
test (i.e. demonstration of lactose
intolerance) provides a clear indication for
feeding lactose-free milk or providing
supplemental lactase in the animal's diet.

An oral lactose digestion test has been
j devised for foals. Lactose (1 g/kg BW) is
| given by stomach tube in a 20% solution
! to a foal that has been fasted for 2-4 hours.
I In foals and young horses up to 3 years of
j age there is a rise in blood glucose levels
I from 86 ± 11 mg/dL (4.8 ±0.1 mmol/L)

| up to 153 ± 24 mg/dL (8.5 ± 1.3 mmol/L),
| with a peak achieved in 90 minutes, and
the level returns to pretreatment levels in
5 hours. In foals of 1-12 weeks of age the
plasma glucose concentration should rise
by at least 35 mg/dL (1.9 mmol/L) and
peak within 40 minutes of the adminis-
tration of the lactose. With this test no
changes in blood sugar levels occur in

horses over 4 years of age. Instead there is
abdominal discomfort followed by
diarrhea, with feces the consistency of
cow feces for the next 24 hours. Sucrose
and maltose are readily digested by the
intestine of the adult horse, but not by
newborn foals. Maximum levels of the
relevant intestinal disacchaxidases (sucrase
and maltase) are not achieved until
7 months of age. The oral lactose diges-
tion test is likely to be of value as a
monitor of epithelial damage in young
horses. In humans the ability to hydrolyze
lactose is one of the first functions of the
intestinal mucosa to be lost where there is
epithelial damage in the gut. It is also one
of the last functions to return in the
recovering patient. The loss of intestinal
lactase may be the pathogenetic basis
of the diarrhea that occurs in rotavirus
infections in neonates. Lactase digestion
is impaired in calves with mild diarrhea. 19
Calves with acute diarrhea are in a
catabolic state and respond with a larger
increase in plasma glucose concentration
to a given amount of glucose than do
healthy calves.

A modification of the oral lactose
tolerance test in foals includes a second
evaluation in foals in which there is
failure of blood glucose concentrations to
increase by the appropriate amount after
oral administration of lactose. At least 8
hours after the first test, foals are fed a
meal of lactose-free milk, or of milk to
which lactase has been added. Blood
glucose concentrations are measured and
an increase of at least 35 mg/dL
(1.9 mmol/1) is interpreted as evidence of
lactase deficiency. Such animals can then
be maintained on a diet of lactose-free
milk. Diarrhea usually resolves in
24 hours, but returns within hours of
feeding milk containing lactose.

XYLOSE ABSORPTION TEST

D-xylose is used to evaluate small
intestinal absorptive function because it is
not metabolized by tissues, which is an
advantage over the oral glucose tolerance
test. D-xylose absorbed from the intestinal
tract is excreted unchanged in the urine
within 15 hours of dosing. 20 Concen-
trations of D-xylose in blood are therefore
dependent only upon the rate of absorp-
tion from the intestine and rate of
excretion into the urine. However, the
compound is more expensive than
glucose and measurement of D-xylose in
blood requires a particular analysis that
might not be readily available. Indications
for the test are the same as those for the
oral glucose tolerance test described
above.

D-xylose, at a dose rate of 0.5 g/kg BW
as a 10% solution, is administered by
stomach tube after a starve of 18 hours. 21

Special examination

.709

A maximum blood xylose level of 30 mg/dL
(2.0 mmol/L) at 1.5 hours is a normal
result in adult horses. In normal foals the
peak blood concentration of xylose is
reached in 30-60 minutes and the level
attained varies with age, being highest
(47 mg/dL (3.14 mmol/L)) at 1 month of
age and lowest (19 mg/dL (1.25 mmol/L))
at 3 months (the pretreatment reading
should be zero). In abnormal horses the
xylose curve is flat (a peak of 7-13 mg/dL
(0.5 mmol/L) at 60-210 minutes) contrasted
with a peak of 20 mg/dL (1.3 mmol/L) at
60 minutes in normal horses. As an initial
checking test, one postdosing sample at
2 hours is recommended.

Interpretation of the test is influenced
by the customary diet of tested animals and
feed deprivation. Horses receiving a high
energy diet have a lower absorption curve
than horses on a low energy diet. The test is
also affected by the duration of deprivation
of feed. 20 In mares deprived of feed for 72
and 96 hours, the rate of D-xylose absorp-
tion and the maximum concentrations of
D-xylose in plasma were reduced. 22 For
example, apparent low absorption can be
caused by increased transit time through
the gut, due perhaps to excitement.

Low blood concentrations of xylose
occur in horses with small intestinal
infiltrative disease, such as lympho-
sarcoma or granulomatous enteritis. 20 The
test appears to be quite specific (low false-
positive rate) for small intestinal disease,
but the sensitivity (false-negative rate) is
unknown.

A D-xylose absorption curve has been
determined for cattle.The xylose (0.5 g/kg
BW) is deposited in the abomasum by
abomasocentesis, and a peak of blood
glucose is attained in about 90 minutes.

SUCROSE ABSORPTION TEST

The sucrose absorption test differs from the
other tests in this section in that abnormal
results are associated with detection of
sucrose in blood or urine of horses. Sucrose
is not normally absorbed intact - it is
usually cleaved by disaccharidases in the
small intestine into glucose and fructose,
which are then absorbed. Intact sucrose is
absorbed across compromised gastric
mucosa and detection of sucrose in blood
or urine indicates the presence of gastric
ulceration, as mammals neither synthesize
nor metabolize sucrose. 23,24 The sucrose
absorption test involves administration of
250 g of sucrose to an adult horse that has
been fasted overnight. Blood samples for
measurement of serum sucrose concen-
tration are collected at 0, 15, 30, 45, 60 and
90 minutes after dosing. Alternatively, a
urine sample is collected 2 hours after
dosing (the bladder must be emptied
immediately before dosing). Peak serum
sucrose concentrations occur 45 minutes
after administration and peak values
correlate with the severity of gastric
ulceration. Horses with minimal lesions
have serum sucrose concentrations of
103 pg/pL, whereas horses with the most
severe lesions have concentrations of
3400 pg/pL. 24

RADIOACTIVE ISOTOPES

A technique used for determining
whether a protein-losing enteropathy
is present is based on the examination
of feces for radioactivity after the intra-
venous administration of a radioactive
agent. 51 Cr 13 C-labeled plasma protein has
been used for this purpose. Similarly,
administration of radioactively labeled
leukocytes reveals the presence of small-
intestinal inflammatory disease in
horses. 4,25 The testis quite specific, in that,
false-positive tests are uncommon, but
not very sensitive.

ABDOMINOCENTESIS FOR
PERITONEAL FLUID

Peritoneal fluid reflects the patho-
physiological state of the parietal and
visceral mesothelial surfaces of the
peritoneum. Collection of a sample of
peritoneal fluid is a useful aid in the
diagnosis of diseases of the peritoneum
and the abdominal segment of the ali-
mentary tract. 22 It is of vital importance in
horses in the differential diagnosis
and prognosis of colic and in cattle in the
diagnosis of peritonitis.

EQUINE AND BOVINE PERITONEAL
FLUID

Normal peritoneal fluid is a transudate
with properties as summarized in Tables
5.1 and 5.2. It has functions similar to
those of other tissue fluids. It contains
mesothelial cells, lymphocytes, neutrophils,
a few erythrocytes and occasional mono-

}lj|jj|

jjBlji

. ■ ■■

ft tm

Classification
of fluid

Physical

appearance

Total Specific

protein g/dL gravity

Total RBC
x 10 6 /pl

Total WBC
x 10 6 /pl

Differential
WBC count

Bacteria

Particulate
matter
(plant fiber)

Interpretation

Normal

Amber,
crystal clear
1-5 mL per
sample

0. 1-3.1 (1.6) 1.005-1.015

Does not clot

Few from
puncture of
capillaries
during
sampling

0.3-5.3

Polymorpho-
nuclear and
mononuclear
cells, ratio 1:1

None

None

Increased
amounts in
late gestation,
congestive
heart
failure

Moderate

inflammation

Amber to
pink, slightly
turbid

2.8-73 (4.5) 1.016-1.025

May clot

0. 1-0.2

2.7-40.7(8.7)

Nontoxic

neutrophils,

50-90%.

Macrophages

may

predominate
in chronic
peritonitis

None

None

Early stages of

strangulation,

destruction of

intestine;

traumatic

reticuloperitonitis;

ruptured

bladder;

chronic peritonitis

Severe

inflammation

Sero-

sanguineous,
turbid, viscous
10-20 mL
per sample

3. 1-5.8 (4.2) 1.026-1.040

Commonly

clots

0.3-0. 5

2.0-31.1 (8.0)

Segmented

neutrophils,

70-90%

Presence of

(toxic)

degenerate

neutrophils

containing

bacteria

Usually

present

May be
present

Advanced stages
of strangulation
obstruction; acute
diffuse peritonitis;
perforation of
abomasal ulcer;
rupture of uterus,
stomachs or
intestine

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

cte ri st j "c-spf Vh u irie

"e'iTdke'aiewrf ibises-’.*

j2- | - , w

Disease

Protein

concentration

Total nucleated cell
count (TNCC)

Cytological comments

Other variables

Coments

Normal horse

< 2.1 g/dL

< 21 g/L

< 9 x 10 9 cells/L

< 9 x 10 3 cells/|jL
(TNCC is usually
substantially lower
in clinically normal
horses)

Approximately 50%
each of nondegenerate
neutrophils and
mononuclear cells

Lactate < 1 mmol/L
(always < plasma (lactate));
Glucose < 2.0 mmol/L
different from blood
glucose; pH > 7.45;
fibrinogen < 300 mg/dL
(3 g/L)

Creatinine = serum

creatinine

No red blood cells

Clear and slightly yellow.
Not malodorous. Culture
does not yield growth

Normal late-
gestation mare

< 2.5 g/dL

< 25 g/L

< 0.9 x 10 9 cells/L

< 900 cells/pL

< 40% neutrophils. No
degenerative changes.

< 20% lymphocytes

Fluid usually readily
obtained. Clear and
slightly yellow

Normal post-
partum
(< 7 d) mare

< 2.5 g/dL

< 25 g/L

< 5.0 x 10 9 cells/L
<5.0x1 0 3 cells/|jL

< 50% neutrophils. No
degenerative changes.

< 10% lymphocytes

Fluid usually readily
obtained. Clear and
slightly yellow

Dystocia but
clinically normal
mare (1 d)

< 2.5 g/dL

< 25 g/L

2.7 x 10 9 (3.9) cells/L*
2.7 x 10 3 (3.9) cells/pL

50-90% nondegenerate
neutrophils, 40%
mononuclear cells and
10% lymphocytes

Fluid clear and yellow.
Essentially normal fluid
with small increases in
TNCC and protein
concentration

Dystocia and
clinically
abnormal
mare (uterine
rupture,
vaginal tear)

4.4 (1 .3) g/dL*
44 (13) g/L

27 x 10 9 (35) cells/L*
27 x 10 3 (35) cells/pL

70-100% neutrophils,
some of which are
degenerate, <10%
mononuclear cells and
<10% lymphocytes

Increased red blood
cell count.

Fluid yellow or
serosa nguinous and
cloudy. Can be
malodorous. Culture
can yield variety of
bacteria. Red cell count
in mares with middle
uterine artery rupture is
high with normal TNCC

Peritonitis,

septic

5.2 (4.0-6.0) g/dL*
50 (40-60) g/L

131 (7-700) x 10 9 cells/L 1
131 (7-700) x 10 3 cells/pL

Almost all neutrophils,
many of which have
degenerative changes.
Some neutrophils
contain bacteria in
many cases. Plant
material with rupture
of intestine

pH < that of blood;
glucose < blood
(difference < 2.0 mmoW.
or 50 mg/dL);
peritoneal glucose
< 30 mg/dL

(1.5 mmol/L); fibrinogen
> 200 mg/dL (2.0 g/L)

Fluid usually dark yellow,
brown, or serosanguinous.
Can be green if
severe rupture of
intestine or
stomach. Cloudy.
Malodorous. Culture
yields bacteria

Peritonitis,

nonseptic (e.g.

nonstrangulating,

nonischemic

obstructive

lesion of

the bowel)

2.7 ( 0.7-4.9) g/dL 1
27 (7-49) g/L

13 (0.4-51 6) x 10 9 cells/L 1
13 (0.4-516) x 10 3 cell s/p L

Mostly neutrophils
(> 50%). Nondegenerate.
No bacteria detected.

No plant or foreign
material

No abnormalities.
pH > that of blood

Fluid yellow and clear.
Not malodorous. No
bacteria isolated
on culture

Strangulating

intestinal

lesion or

ruptured

intra-abdominal

viscus

5.2 (4.0-6. 0) g/dL 1 "
50 (40-60) g/L

131 (7-700) x 10 9 cells/L 1
131 (7-700) x 10 3 cells/pL

Almost all neutrophils,
many of which have
degenerative changes.
Some neutrophils
contain bacteria in
many cases. Plant
material with rupture
of intestine

Lactate 8.5 ±
5.5 mmol/L

Serosanguinous fluid.
Cloudy if ruptured.

Nonstrangulating

obstruction

Lactate 2.1 ±
2.1 mmol/L

Peritonitis due
to Actinobacillus
equuli

2. 5-8.4 g/dL
25-84 g/L

46-810 xIO 9 cells/L
46-81 0 x 10 3 cells/pL

> 80% neutrophils most
of which do not have
signs of degeneration.
Low numbers of Gram-
negative pleomorphic
rods, both intra-
and extracellular

Cream, orange, brown or
red fluid. Turbid. Not
malodorous. Growth
of Actinobacillus equuli
on culture

Intra-abdominal

abscess

> 2.5 g/dL

> 25 g/L

> 10 x 10 9 cells/L

> 1 0 x 1 0 3 cells/pL

> 80% nondegenerate
neutrophils. Usually no
bacteria detected on
Gram stain

>

Yellow to white. Slightly
cloudy. Culture will
occasionally yield x
causative bacteria
(usually Streptococcus
equi)

Special examination

201

Sfete.-T£: iSnpf'siK-

Swr:- : . Vat: 7 ; a >

V-'-- •: ''.A ■ : -

Disease

Protein

concentration

Total nucleated cell
count (TNCC)

Cytological comments

Other variables

Coments

Hemoperitoneum

3.2-6 .3 g/dL
32-63 g/L

< 10 x 10 9 cells/L

< 10 x 10 3 cells/pL

Differential similar to blood.
Mostly nondegenerate
neutrophils. Erythrophages
and hemosiderophages as
hemorrhage resolves

High red cell count
(2 .4-8.6 x 10’ 2 cells/L,
2.4-8 6 x 10 6 cells/pL)

Serosanguinous to
frankly bloody

Intra-
abdominal
neoplasia
(lymphosarcoma,
gastric
squamous
cell carcinoma)

< 2.5 g/dL

< 25 g/L

< 10 x 10 9 cells/L

< 1 0 x 10 3 cells/pL

Abnormal cells not
detected in most cases.
Care should be taken
not to mistake reactive
lymphocytes for
neoplastic lymphocytes

Clear and yellow. Often
subjective assessment of
increased quantity
(increased ease of
collection of a
large quantity of fluid)

Uroperitoneum

< 2.5 g/dL

< 25 g/L

«< 10 x 10 9 cells/L
«< 1 0 x 1 0 3 cells/pL

Normal differential. Might
see calcium carbonate
crystals in adult horses
with uroperitoneum

Creatinine > serum
creatinine concentration
Urea nitrogen > serum
urea nitrogen
concentration
Potassium > serum
potassium concentration

Large amount of fluid.
Clear to very pale yellow.
Uriniferous odor

* mean (SD). ’ median (range).

Data from Frazer G. eta/. Theriogenology 1997 ; 48:919 ; van Hoogmoed L. etal. J Am Vet Med Assoc 1996; 209:1280; van Hoogmoed L. etal. J Am Vet Med Assoc
1999; 214:1032; Pusterla N et at. J Vet Intern Med 2005; 19:344; Latson KM et at. Equine Vet J 2005; 37:342; Matthews S et at. Aust Vet J 2001; 79:536.

cytes and eosinophils. The following
general comments apply:

<■ It can be examined in terms of
physical characteristics, especially
color, translucence, specific gravity,
clotting time, biochemical
composition, cell volume, cell
morphology and cell type
Examination of the fluid may help in
determining the presence in the
peritoneal cavity of:

peritonitis (chemical or infectious)
infarction of a segment of gut wall
perforation of the alimentary tract
wall

rupture of the urinary bladder
leakage from the biliary system
intraperitonea 1 hemorrhage
peritoneal neoplasia
The reaction of the peritoneum varies
with time and a single examination
can be dangerously misleading. A
series of examinations may be
necessary, in acute cases at intervals
of as short as an hour
A significant reaction in a peritoneal
cavity may be quite localized, so a
normal sample of fluid collected at
one point in the cavity may not be
representative of the entire cavity
Changes in peritoneal fluid, especially
its chemical composition, e.g. lactate
level, may be a reflection of a systemic
change. The examination of a
concurrently collected peripheral
blood sample will make it possible to
determine whether the changes are
in fact restricted to the peritoneal
cavity

As in any clinicopathological exam-
ination the results must be interpreted
with caution and only in conjunction
with the history and clinical findings.

Specific properties of peritoneal fluid
(normal and abnormal)

Color

Normal fluid is crystal clear, straw-
colored to yellow. Turbidity indicates
the presence of increased leukocytes and
protein, which may include fine strands of
fibrin.

A green color suggests food material;
intense orange-green indicates rupture
of the biliary system. A pink-red color
indicates presence of hemoglobin, degener-
ated erythrocytes, entire erythrocytes and
damage to vascular system by infarction,
perforation or hydrostatic pressure. A red-
brown color indicates the late stages of
necrosis of the gut wall, the presence of
degenerated blood and hemoglobin and
damage to gut wall with hemorrhage.

Whole blood, clear fluid streaked
with blood or heavily bloodstained fluid
indicate that the sample has been collected
from the spleen or a blood vessel or that
there is hemoperitoneum. Rupture of the
uterus or bladder or dicoumarol poisoning
are also possibilities.

A dark green sample containing
motile protozoa with very few leukocytes
and no mesothelial cells indicates that the
sample has been collected from the gut
lumen. Enterocentesis has little apparent
clinical affect in normal horses, although
an occasional horse will show a transient
fever. However, puncture of a devitalized
loop of intestine may lead to extensive

leakage of gut contents and a fatal
peritonitis. The effect of enterocentesis of
normal gut on peritoneal fluid is con-
sistently to increase the neutrophilic
count, which persists for several days.

Cellular and other properties
Surgical manipulation of the intestinal
tract during exploratory laparotomy or
intestinal resection and anastomosis in
the horse results in a significant and rapid
postoperative peritoneal inflammatory
reaction. 26 Manipulation of the viscera
causes injury to the mesothelial surfaces.
Total and differential nucleated cell
counts, red blood cell numbers, and total
protein and fibrinogen concentrations
were all elevated on the first day after the
surgery and remained elevated for up to
7 days in a study of this phenomenon. 26

In cattle, exploratory celiotomy and
omentopexy results in an increase in the
total nucleated cell count by a factor of
5-8, minor increases in specific gravity
and increases in total protein concentration
by a factor of up to 2. These changes
appear by two days after surgery and
continue to increase through to day 6. 27,28

Particulate matter in peritoneal fluid
suggests either fibrin clots/strands or gut
contents caused by leakage from a
perforated or ruptured gut wall.

High specific gravity and high
protein content are indicative of vascular
damage and leakage of plasma protein, as
in peritonitis or mural infarction.

The volume and viscosity of fluid
varies. A normal flow is 1-5 mL per
sample. A continuous flow with 10-20 mL
per sample indicates excess fluid due to

202

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

ruptured bladder or. ascites (clear yellow),
acute diffuse peritonitis (yellow, turbid),
infarction or necrosis of gut wall (thin,
red-tinged). The higher the protein
content, as the peritoneal fluid shifts from
being a transudate to an inflammatory
exudate, the higher the viscosity becomes.
Highly viscous fluid may clot.

Cells

A rapid staining method, using a modified
Wright's stain, gives a stained slide ready
for examination within 5 minutes. The
value of the technique is in indicating the
number of leukocytes and other cells
present, and in differentiating the types
of cell.

An increase in total white cell count

of the fluid including a disproportionate
number of polymorphonuclear cells indi-
cates acute inflammation, which may
have an infectious origin or else be sterile.
An increase in mononuclear phagocytes
from the peritoneum is an indication of
chronic peritonitis. Degenerate and toxic
neutrophils suggest the probability of
infection being present.

An increase in the number of meso-
thelial cells with the distinctive presence
of actively dividing mitotic figures sug-
gests neoplasia.

Bacteria found as phagocytosed
inclusions in leukocytes, or by culture
of fluid, indicate an infective peritonitis,
which may arise by hematogenous spread,
in which case the infection is likely to be
a specific one. If there has been leakage
from a peritoneal abscess the same
comment applies, but if there is leakage
through a segment of devitalized or
perforated bowel wall there is likely to be
a mixed infection and possibly particulate
matter from bowel contents.

Entire erythrocytes, often accompanied
by some hemoglobin, indicate either
hemoperitoneum, in which case there
should be active phagocytosis of erythro-
cytes, or that the sample has been
inadvertently collected from the spleen.
The blood is likely to be concentrated if
there has been sufficient time for fluid
resorption across the peritoneum. Splenic
blood has a higher packed cell volume
(PCV) also, but there is no erythrophago-
cytosis evident in the sample. A PCV of
less than 5% in peritoneal fluid suggests
extravasation of blood from an infarcted
or inflamed gut wall; one of more than
20% suggests a significant hemorrhage.

Abdominocentesis in horses

In the horse the recommended site for
paracentesis is on the ventral midline,
25 cm caudal to the xiphoid (or midway
between the xiphoid and the umbilicus).
Following surgical preparation and sub-
cutaneous infiltration of an anesthetic, a
stab incision is made through the skin

and subcutaneous tissues and into the
linea alba. A 9 cm long blunt-pointed
bovine teat cannula, or similar metal
catheter, with the tip wrapped in a sterile
swab to avoid blood and skin contami-
nation, is inserted into the wound and
manipulated until the incision into the
linea alba can be felt. With a quick thrust the
cannula is pushed through the linea alba
into the peritoneal cavity. A 'pop' is often
heard on entry into the peritoneal cavity.
Failure to incise into the linea alba first will
cause many cannulas to bend and break.

In mosthorses (about 75%) a sample of
fluid is readily obtained. In others it takes a
moment or two before the fluid runs out,
usually spurting synchronously with the
respiratory movements. Applying suction
with a syringe may yield some fluid if there
is no spontaneous flow. Normal fluid is
clear, yellow and flows easily through
an 18-gauge needle. Two samples are
collected, one in a plain tube and one in a
tube with an anticoagulant. In case the
fluid clots readily a few drops should be
placed and smeared out on a glass slide
and allowed to dry for staining purposes.

In peritonitis, the total leukocyte count
will increase markedly, but wide variation
in the total count can occur between
horses with similar conditions, and in the
same horse within a period of hours.
Variations are due to the nature and stage
of the lesion and to the total amount of
exudate in the peritoneal cavity, which
has a diluting effect on the total count.
Total leukocyte counts ranging from
10 000-150 000 pL have been recorded in
peritonitis and in infarction of the intestine
in horses. Experimentally, the intravenous
injection of endotoxin into horses causes
marked changes in the peripheral blood
cellular components but there are no
changes in the total white cell count of
the peritoneal fluid. 29

In healthy foals the reference values
for peritoneal fluid are different than in
adult horses. 30 The maximum peritoneal
fluid nucleated cell counts in foals are
much lower than in adult horses (1.5 x
10 9 /L versus 5.0 x 10 9 /L. Nucleated cell
counts greater than 1.5 x 10 9 /L should be
interpreted as elevated.

Peritoneal fluid abnormalities in mares
within a week of foaling should be
attributed to a systemic or gastrointestinal
abnormality not due to the foaling
event. 31 The nucleated cell count, protein
concentration, fibrinogen concentration
and specific gravity of peritoneal fluid from
recently foaled mares should be normal;
however, differential cell counts may be
abnormal for up to 1 week after foaling.

Risks

Abdominocentesis is not without some
danger, especially the risk of introducing

fecal contents into the peritoneal cavity
and causing peritonitis. This appears to be
of major importance only if there are
loops of distended atonic intestine situated
on the ventral abdominal wall. This is a
common occurrence in the later stages of
intestinal obstruction that is still amenable
to surgery. Puncture of a devitalized loop
of intestine may cause a leakage of
intestinal contents and acute diffuse
peritonitis, which is rapidly fatal.
Penetration of a normal loop of intestine
occurs often enough to lead to the con-
clusion that it appears to have no ill-
effects. If a sample of peritoneal fluid is an
important diagnostic need in a particular
case and the first attempt at paracentesis
causes penetration of the gut, it is
recommended that the attempt be
repeated, if necessary two or three times,
at more posterior sites. Repeated abdomi-
nocentesis does not cause alterations in
peritoneal fluid constituents and any
significant changes are likely due to
alterations in the disease state present. 32
The technique most likely to cause
bowel penetration is the use of a sharp
needle instead of the blunt cannula
recommended, and forcibly thrusting the
cannula through the linea alba without a
prior incision. When the suggested
incision is made in the linea alba, the
cannula can be pushed gently through
whilst rotating it.

Abdominocentesis in cattle

The choice of sites for paracentesis is a
problem because the rumen covers such a
large portion of the ventral abdominal
wall and avoiding penetration of it is diffi-
cult. Cattle have a low volume of peritoneal
fluid, and failure to obtain a sample is not
unusual. 27 The most profitable sites are
those that, on an anatomical basis, consist
of recesses between the forestomachs,
abomasum, diaphragm and liver. These
are usually caudal to the xiphoid sternum
and 4-10 cm lateral to the midline.
Another recommended site is left of the
midline, 3-4 cm medial and 5-7 cm
cranial to the foramen for the left sub-
cutaneous abdominal vein. A teat cannula
similar to the one described for use in the
horse is recommended but, with care and
caution, a 16-gauge 5 cm hypodermic
needle may also be used. The needle or
cannula is pushed carefully and slowly
through the abdominal wall, which will
twitch when the peritoneum is punc-
tured. When this happens the fluid will
usually run out into a vial without the aid
of a vacuum. However, if it does not, a
syringe may be used and the needle may
be moved backwards and forwards in a
search for fluid, with the piston of the
syringe Withdrawn. A further site is the
right caudoventral abdominal wall medial

to the fold of the flank, using a 3.8 cm,
15 -gauge needle. 27

In calves, a reliable technique includes
the use of sedation with intravenous
xylazine hydrochloride and diazepam. The
animal is placed in left lateral recumbency
with the right hind limb pulled dorsally and
caudally. One site slightly dorsal and caudal
to the umbilicus is prepared together with
another site in the center of the inguinal
region. The site is prepared with local
anesthetic and a 14-gauge needle is
introduced and directed slightly caudally
and toward the midline while keeping it
parallel to the inner abdominal wall once
the peritoneal cavity is entered. 33 A 3.5
gauge urinary catheter (1.2 mm x 56 cm
sterile feeding tube) is inserted through
the needle and a 3 mL sterile syringe is
attached to the catheter. Gentle suction is
applied. The fluid is placed in a 2 mL tube
containing tri-potassium EDTA. A 14-
gauge over-the-needle catheter can also be
used, followed by insertion of a 3.5 French
feeding tube. If fluid cannot be obtained
from the first site, the inguinal site is used
using the same basic technique and with
the catheter directed slightly cranially
toward the midline.

Failure to obtain a sample does not
preclude the possibility that peritonitis
may be present: the exudate may be very
thick and contain large masses of fibrin,
or the peritonitis may be localized. Also,
animals that are dehydrated may have
less peritoneal fluid than normal. Most
animals from which samples cannot be
obtained, however, are in fact normal. In
animals in which peritonitis is strongly
suspected for clinical reasons, up to four
attempts at paracentesis should be made
before aborting the procedure. The fluid
should be collected into an anticoagulant,
preferably EDTA, to avoid clotting.

Abnormal peritoneal fluid in cattle is a
highly sensitive indicator of peritoneal
disease, but not a good indicator of the
nature of the disease. The most pronounced
abnormalities occur in acute diseases of
the peritoneum; chronic peritonitis may
be accompanied by peritoneal fluid which
is almost normal.

Examination of the fluid should take
into account the following characteristics:

0 Large amounts (10-20 mL) of
serosanguineous fluid suggests
infarction or necrosis of the gut wall
° Heavily bloodstained fluid, whole
blood or fluid with streaks of blood
through it are more likely to result
from puncture of a blood vessel or
from bleeding into the cavity, as in
dicoumarol poisoning or with a
neoplasm of the vascular system
0 The same sort of bloodstained fluid as
above may accompany a ruptured

Principles of treatment in alimentary tract disease

109

uterus or bladder or severe congestive
heart failure

® Large quantities of yellowish-colored
turbid fluid suggests acute diffuse
peritonitis. The degree of turbidity
depends on the number of cells and
the amount of fibrin present
® Particulate food material in the
sample indicates perforation or
rupture of the gut, except that
penetration of the gut with the
instrument during collection may be
misleading. Such samples are usually
heavily fecal in appearance and
contain no mesothelial cells
® Laboratory examination is necessary
to derive full benefit from the sample.
This will include assessment of: the
number and type of leukocytes
present - the number is increased in
peritonitis, neutrophils predominating
in acute peritonitis and monocytes in
chronic forms; the number of
erythrocytes present; whether
bacteria are present inside or outside
the neutrophils; and total protein
content.

The significant values for these items are
included in Table 5.1.

Reference values for peritoneal fluid
constituents of normal adult cattle may be
inappropriate for interpretation of perito-
neal fluid analysis in calves of up to
8 weeks of age. 34 The peritoneal fluid
nucleated cell count and mononuclear
cell counts are higher in calves, and the
eosinophil counts are lower than in adult
cows.

INTESTINAL AND LIVER BIOPSY

An intestinal biopsy may be obtained
from an exploratory laparotomy but is
costly and time-consuming. Rectal biopsy
is easily done and of low cost. It is a
valuable diagnostic aid for evaluating
certain intestinal diseases of the horse. 35
Biopsy specimens are taken using minimal
restraint and unaided by proctoscopic
visualization in the standing horse. A
rectal biopsy forceps is used to obtain the
biopsy from the floor of the rectum
approximately 30 cm proximal to the anal
sphincter.

The technique for liver biopsy is
presented in Chapter 7.

Principles of treatment in
alimentary tract disease

Removal of the primary cause of the
disease is essential but a major part of the
treatment of diseases of the alimentary
tract is supportive and symptomatic. This
is aimed at relieving pain and distension.

replacement of fluids and electrolytes,
correcting abnormal motility and relieving
tenesmus and reconstitution of the
digestive flora if necessary. Specific treat-
ment for individual diseases is presented
with each disease throughout this book.
General principles are outlined here..

RELIEF OF ABDOMINAL PAIN

The relief of abdominal pain is of prime
importance from the humane aspect, to
prevent the animal from self-injury'
associated with falling and throwing itself
against a wall or other solid objects, and
to allay the concerns of the owner. No
single analgesic is completely satisfactory
for every situation. Non-narcotic and
narcotic analgesics are in general use and
are discussed under the heading of pain,
and under the individual diseases. The
analgesics used in the important subject
of equine colic are presented under that
heading.

RELIEF OF DISTENSION

The relief of distension of the gastro-
intestinal viscera is a critical principle in
order to minimize shock and to prevent
rupture of the viscus. Relief of distension
of the stomach of the horse with colic
is accomplished by nasogastric intu-
bation. Distension due tc bloat in cattle
can be relieved by stomach tube or
trocarization of the rumen. Relief of
distension may be possible by medical
means alone with the use of laxatives and
purgatives when there is accumulation of
ingesta without a physical obstruction.
Surgical intervention is often necessary
when the distension is associated with a
physical obstruction. In functional dis-
tension (paralytic ileus), relief of the atony
or spasm can be effected by the use of
drugs such as metoclopramide. Distension
due to intestinal or gastric accidents
requires surgical correction.

REPLACEMENT OF FLUIDS AND
E LECTROLYTES

Replacement of fluid and electrolytes lost
in gastrointestinal disease is one of the
most important principles of treatment. In
gastric or intestinal obstruction, or when
diarrhea is severe, it is necessary to
replace lost fluids and electrolytes by the
parenteral administration of large quan-
tities of isotonic glucose-saline or other
physiologically normal electrolyte solutions.
The amount of fluid lost may be very large
and fluids must be given in quantities to
replace losses and to support continuing
losses and maintenance requirements. In
acute, severe dehydration in horses, such
as occurs in acute intestinal obstruction,
the amount of fluid required before and

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

during surgery ranges from 50-100 mL/kg
BW per 24 hours. It is critical that
administration of fluid be commenced at
the earliest possible time because of the
need to maintain homeostasis and thus
ameliorate the almost impossible task of
restoring animals to normal before surgery
is to be attempted. Details of fluid therapy
are given in the section on disturbances of
water, electrolytes and acid-base balance
in Chapter 2.

In young animals the need is much
greater still and amounts of 100 mL/kg BW,
given slowly intravenously, are commonly
necessary and not excessive. The treatment
of shock is also presented in Chapters 2
and 9 and includes the administration of
fluids, plasma or blood and NSAIDs. The
use of intravenous hypertonic saline
followed by the ingestion of large quan-
tities of water by the animal is another
aspect of fluid therapy in gastrointestinal
disease (see Chapter 2).

CORRECTION OF ABNORMAL
MOTILITY

INCREASED MOTILITY

When motility is increased, the adminis-
tration of atropine or other spasmolytics
such as dipyrone or proquamezine is
usually followed by disappearance of
the abdominal pain and a diminution
of fluid loss. Meperidine, butorphanol
and pentazocine inhibit regular cyclic
myoelectric activity in the jejunum. 36
There is a need for some scientific clinical
investigation into the desirability of
treating intestinal hypermotility, if it does
exist in enteritis for example, and the
efficacy of anticholinergics. Loperamide
has an antidiarrheal effect in experimentally
induced diarrhea in calves but the
mechanism of action does not involve
changes in intestinal motility.

DECREASED MOTILITY

When gastrointestinal motility is decreased,
the usual practice is to administer para-
sympathomimetic drugs or purgatives,
usually combined with an analgesic.
Prokinetic drugs such as metoclopramide :
hydrochloride and cisapride monohydrate i
increase the movement of ingesta through S
the gastrointestinal tract. 37 They are useful [
because they induce coordinated motility i
patterns.

Metoclopramide

Metoclopramide, acting in the upper
gastrointestinal tract, increases acetyl-
choline release from neurons and
increases cholinergic receptor sensitivity
to acetylcholine. It is a dopamine antagonist
and stimulates and coordinates esophageal,
gastric, pyloric and duodenal motor
activity. It increases lower esophageal
sphincter tone and stimulates gastric

contractions, while relaxing the pylorus and
duodenum. This results in accelerated
gastric emptying and reduced esophageal
reflux. The transit time of ingested material
from the duodenum to the ileocecal valve is
reduced, due to increased jejunal peristalsis.
It has little or no effect on colonic motility.
The pharmacokinetics of metoclopramide
in cattle have been studied 38

Metoclopramide crosses the blood-
brain barrier, where its dopamine
antagonist activity at the chemoreceptor
trigger zone can result in an antiemetic
effect. It can also result in involuntary
activity including tremors, restlessness
and aggressive behavior characterized by
charging and jumping walls. This can be
reversed by the use of an anticholinergic
such as diphenhydramine hydrochloride
intravenously at 0. 5-2.0 mg/kg BW.

Indications for metoclopramide include
reflux esophagitis and gastritis, chronic
gastritis associated with delayed empty-
ing, abomasal emptying defects in
ruminants, gastric stasis following gastric
dilatation and volvulus surgery, and post-
operative ileus. It is contraindicated in
animals with physical obstruction of the
gastrointestinal tract.

In horses, the dose is 0.125-0.25 mg/kg
BW diluted in multiple electrolyte
solution and given intravenously over
60 minutes. 37 It is used for stimulating
equine gastric and small intestinal activity
at dose rates of 0.25 mg/kg BW per hour
when there is intestinal hypomotility. 39
Given as continuous intravenous infusion
of 0.04 (mg/kg)/h it can decrease the inci-
dence and severity of persistent post-
operative ileus following resection and
anastomosis of the small intestine in
horses without serious side effects. 40

In cattle and sheep metoclopramide is
used at 0.3 mg/kg BW subcutaneously
every 6-8 hours. Metoclopramide did not
alter cecocolic myoelectrical activity in
cattle. 41

Cisapride

Cisapride promotes gastrointestinal
motility by enhancing the release of
acetylcholine from postganglionic nerve
endings of the myenteric plexus. Cisapride
is more potent and has broader prokinetic
activity than metoclopramide by increasing
the motility of the colon as well as the
esophagus, stomach and small intestine. 37
It is does not have dopaminergic effects
and does not have either the antiemetic
or the extrapyramidal effects of meto-
clopramide. Cisapride is useful for
the treatment of gastric stasis, gastro-
esophageal reflux and postoperative ileus.
In horses, cisapride increases left dorsal
colon motility and improves ileocecal
junction coordination. The suggested
dose is 0.1 mg/kg BW orally every 8 hours.

Cisapride may have some value in the
clinical management of cecal dilatation in
cattle. 42

Xylazine and naloxone
While xylazine is used for alleviation of
visceral pain in horses and cattle, it is not
indicated in cecal dilatation in cattle
because it reduces the myoelectric activity
of the cecum and proximal loop of the
ascending colon. 42 Naloxone, a widely
used opiate antagonist with a high
affinity for p receptors, is also not indi-
cated for medical treatment of cecal
dilatation when hypomotility must be
reversed.

Bethanechol, neostigmine
Bethanechol is a methyl derivative of
carbachol and classified as a direct-acting
cholinomimetic drug. Its action is more
specific on the gastrointestinal tract
and urinary bladder. Neostigmine, a
cholinesterase inhibitor, is an indirect-
acting cholinergic drug with motor-
stimulating activities but only on the
gastrointestinal tract. Bethanechol at
0.07 mg/kg BW intramuscularly may be
useful for medical treatment of cecal
dilatation in cattle in which hypomotility
of the cecum and proximal loop of the
ascending colon must be reversed. 41
Neostigmine at 0.02 mg/kg BW intra-
muscularly increased the number of pro-
pagated spike sequences but they were
uncoordinated. 41

REL IEF OF TENE SMU S

Tenesmus can be difficult to treat effec-
tively. Long-acting epidural anesthesia
and sedation are in common use. Combi-
nations of xylazine and lidocaine may be
used. Irrigation of the rectum with water
and the application of topical anesthetic
in a jelly-like base are also used.

RECONSTITUTION OF RUMEN
FLORA AND CORRECTION OF
ACiDlIY OR ALKALINITY

When prolonged anorexia or acute
indigestion occurs in ruminants, the
rumen flora may be seriously reduced. In
convalescence, the reconstitution of the
flora can be hastened by the oral adminis-
tration of a suspension of ruminal contents
from a normal cow, or of dried ruminal
contents, which contain viable bacteria
and yeasts and the substances necessary
for growth of the organisms.

The pH of the rumen affects the growth
of rumen organisms, and hyperacidity,
such as occurs on overeating of grain, or
hyperalkalinity, such as occurs on over-
eating of protein-rich feeds, should
be corrected by the administration of
alkalinizinj* or acidifying drugs as the case
may be.

Diseases of the buccal cavity and associated organs

205

REVIEW LITERATURE

Roussel AJ. Intestinal motility. Compend Contin Educ
PractVet 1994; 16:1433-1142.

Dowling PM. Prokinetic drugs: metoclopramide and
cisapride. Can Vet J 1995; 36:115-116.

Navarre CB, Roussel AJ. Gastrointestinal motility and
disease in large animals. J Vet Intern Med 1996;
10:51-59.

references

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2. Navarre CB, Roussel AJ. J V?t Intern Med 1996;
10:51.

3. Yarbrough TB et al. J Am \fet Med Assoc 1994;
205:592.

4. Fischer AT et al. Vet Radiol 1987; 28:42.

5. Klohnen A et al. J Am Vet Med Assoc 1996;
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6. Phase AP et al. Vet Radiol Ultrasound 2004;
45:220.

7. Kirberger RM et al. V?t Radiol Ultrasound 1995;
36:50.

8. Korolainen R, Ruohoniemi M. Equine Vet J 2002;
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9. Mitchell CF et al. Can V?t J 2005; 46:134.

10. Aleman M et al. Equine Vet J 2002; 34:649.

11. Braun U.\fct J 2003; 166:112.

12. Braun U.Vet J 2002; 150:75.

13. Braun U, Marmier O. Vet Recl995; 136:239.

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15. Galuppo LD et al. Am J Vet Res 1996; 57:923.

16. Kronfeld DS et al. J Am Vet Med Assoc 2005;
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17. MairTS et al. Equine Vht J 1991; 23:344.

18. Van Amstel SR et al. J S Aft Vet Assoc 1984;
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19. Gutzwiller A, Blum JW. Am JVet Res 1996; 57:560.

20. Freeman DE et al. Am JVet Res 1989; 50:1609.

21. Brown CM. BrVet J 1992; 148:41.

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31. Hoogmoed L et al. J Am Vet Med Assoc 1996;
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33. Burton S et al.Vet Clin Pathol 1997; 26:38.

34. Anderson DE et al. Am JVet Res 1995; 56:973.

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Diseases of the buccal
cavity and associated
organs

DISEASES OF THE MU ZZLE

The congenital defect of harelip may be
contiguous with a cleft palate. Severe
dermatitis with scab formation, develop-

ment of fissures, and sloughing and
gangrene of the skin of the muzzle are
common lesions in cattle affected with
photosensitive dermatitis, bovine malig-
nant catarrh, bovine virus diarrhea and
rinderpest.

In sheep severe lesions of the muzzle
are less common, but occur in bluetongue
and ecthyma.

In pigs, only the vesicular diseases -
vesicular exanthema of swine, swine
vesicular disease, and foot-and-mouth
disease - cause such lesions on the snout
and on other sites. The lesions are vesicular
initially and confusion has arisen in
recent years because of isolated incidents
in Australia and New Zealand in which
such outbreaks occurred but in which no
pathogenic agent was identified.

STOM ATITIS

Stomatitis is inflammation of the oral
mucosa and includes glossitis (inflam-
mation of the tongue), palatitis (lampas)
(inflammation of the palate) and gingivitis
(inflammation of the mucosa of the gums).
Clinically it is characterized by partial or
complete loss of appetite, smacking of the
lips and profuse salivation. It is commonly
an accompaniment of systemic disease.

ETIOLOGY

Stomatitis may be caused by physical,
chemical or infectious agents, the last
being the largest group of causes. The
agents are listed under these group head-
ings below.

Physical agents

Trauma while dosing orally with a
balling gun

° Laceration of the tongue 1
° Foreign body injury
° Malocclusion of teeth
° Sharp awns or spines on plants. The
commonest lesions are on the gums
of cattle and sheep just below the
corner incisors where tough grass is
pulled around the corner of the
incisor arcade. In spear grass country
the alveoli are often stuffed full of
grass seeds. Very young animals, e.g.
1-6-week-old lambs, are particularly
susceptible to traumatic injury from
abrasive feed. 2 Among the most
dramatic lesions are those in the
mouths of horses. They are large
(2-3 cm long and 5 mm wide) and
linear in shape. They may be caused
by eating hairy caterpillars that infest
pasture, or by the awns in hay or chaff
made from triticale (a hybrid of wheat
and rye) and a yellow bristle grass
( Setaria lutescens). Foxtail awns can
cause multiple painful nodules on the >
lips of horses that have eaten hay
contaminated with the awns

° The strength and thickness of the awn
in dwarf barley cultivars used to make
silage fed to feedlot cattle in some
regions is associated with mouth
lesions. The incidence of tongue
lesions in slaughter cattle in some
areas can be about 19% and the'
incidence is higher in cattle finished
on silage from semidwarf rough awn
(29.3%) compared to normal-stem
rough awn (.13.5%) and normal-stem
smooth awn barley (11. 8%) 3

o Eating frozen feed and drinking hot
water are recorded, but seem highly
improbable

o Ulcers of the soft palate of horses may
be due to mechanical trauma
associated with dorsal displacement
of the soft palate. 4

Chemical agents

o Irritant drugs, e.g. chloral hydrate,
administered in overstrong
concentrations

* Counterirritants applied to skin, left
unprotected and licked by the animal,
including mercury and cantharides
compounds

o Irritant substances administered by
mistake, including acids, alkalis and
phenolic compounds

° Manifestation of systemic poisoning,
e.g. chronic mercury poisoning.
Poisoning with bracken, Heraclum
mantegazzianum, furazolidone and
some fungi ( Stachybotrys , Fusarium
spp. and mushrooms) cause a
combination of focal hemorrhages
and necrotic ulcers or erosions. They
are a common cause of confusion
with vesicular or erosive disease

* Lesions associated with uremia
syndrome in horses.

Infectious agents

Cattle

<f Oral necrobacillosis associated with
Fusobacterium necrophorus

° Actinobacillosis of the bovine tongue
is not a stomatitis, but there may be
one or two ulcers on the dorsum and
sides of the tongue and on the lips.
Characteristically, there is initially an
acute diffuse myositis of the muscle of
the tongue, followed by the
development of multiple granulomas
and subsequently fibrosis and
shrinkage

<=■ Ulcerative, granulomatous lesions
may occur on the gums in cases of
actinomycosis

o Stomatitis with vesicles occurs in
foot-and-mouth disease and in
vesicular stomatitis

a Erosive, with some secondary

ulcerative, stomatitis occurs in bovine
viral diarrhea (mucosal disease),
bovine malignant catarrh, rinderpest

6

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

and rarely in bluetongue. Cases of
infectious bovine rhinotracheitis in
young calves may have similar lesions
® Proliferative lesions occur in papular
stomatitis, proliferative stomatitis and
rare cases of rhinosporidiosis and
papillomatosis where the oral mucosa
is invaded

® Oral mucosal necrosis in bovine
sweating sickness

0 Nondescript lesions varying from
erosions to ulcers occur late in the
stages of many of the above diseases
when secondary bacteria have
invaded the breaches in the mucosa.

In some cases the involvement goes
deeper still and a phlegmonous
condition or a cellulitis may develop.
Thus, lesions that were initially
vesicular are converted to what look
like bacterial ulcers. Secondary
infection with fungi, especially
Mon Hi a spp., may also occur.

Sheep

0 Erosive lesions in bluetongue,
rinderpest and peste de petits
ruminantes

0 Vesicular lesions rarely in foot and
mouth disease

° Granulomatous lesions due to
ecthyma are not unusual in the
mouth, especially in young lambs.
Similarly, oral lesions occur in bad
cases of sheep pox, ulcerative
dermatosis, coital exanthema and
mycotic dermatitis.

Horses

° Cheilitis and gingivitis (inflammatory
nodules of the lips and gums caused
by plant awns)

0 Vesicular lesions in vesicular
stomatitis

® Plerpesvirus infections are commonly
accompanied bv small (1 mm
diameter) vesicles surrounded by a
zone of hyperemia. The lesions are in
groups and at first glance appear to
be hemorrhages

° Lingual abscess associated with
Actinobacillus spp.

Pigs

0 The vesicular diseases: foot and
mouth disease, vesicular stomatitis,
vesicular exanthema of swine and
swine vesicular disease.

Bullous stomatitis

° Bullous stomatitis has been reported
in the horse and may be associated
with a paraneoplastic pemphigus
syndrome. 5

Many other causes of stomatitis have
been suggested but the relationship of
these conditions to the specific diseases
listed above is unknown. It is common to

find stomatitides that cannot be defined
as belonging to any of these etiological
groups. An example is necrotic glossitis
reported in feeder steers in the USA in
which the necrotic lesions are confined to
the anterior part of the tongue.

PATHOGENESIS

The lesions of stomatitis are produced by
the causative agents being applied directly
to the mucosa, or gaining entrance to it by
way of minor abrasions, or by localization
in the mucosa from a viremia. In the first
two instances, the stomatitis is designated
as primary. In the third, it is usually
described as secondary because of the
common occurrence of similar lesions in
other organs or on other parts of the
body, and the presence of a systemic
disease. The clinical signs of stomatitis are
caused by the inflammation or erosion of
the mucosa and the signs vary in severity
with the degree of inflammation.

CLINICAL FINDINGS

There is partial or complete anorexia
and slow, painful mastication. Chewing
movements and smacking of the lips are
accompanied by salivation, either frothy
and in small amounts, or profuse and
drooling if the animal does not swallow
normally. The saliva may contain pus or
shreds of epithelial tissue. A fetid odor is
present on the breath only if bacterial
invasion of the lesion has occurred.
Enlargement of local lymph nodes may
also occur if bacteria invade the lesions.
Swelling of the face is observed only in
cases where a cellulitis or phlegmon has
extended to involve the soft tissues. An
increased desire for water is apparent and
the animal resents manipulation and
examination of the mouth.

Toxemia may be present when the
stomatitis is secondary to a systemic
disease or where tissue necrosis occurs.
This is a feature of oral necrobacillosis and
many of the systemic viremias. In some
of the specific diseases, lesions may
be present on other parts of the body,
especially at the coronets and muco-
cutaneous junctions.

Several different lesions of the oral
cavity may be present and their charac-
teristic appearances are as follows. The
importance of vesicular diseases such as
foot-and-mouth disease means that the
recognition and differentiation of these
lesions assumes major importance.

Erosions are shallow, usually discrete,
areas of necrosis, which are not readily
seen in the early stages. They tend to
occur most commonly on the lingual
mucosa and at the commissures of the
mouth. The necrotic tissue may remain in
situ but is usually shed, leaving a very
shallow discontinuity of the mucosa with
a dark red base that is more readily seen.

If recovery occurs, these lesions heal very
quickly.

Vesicles are thin-walled swellings
1-2 cm in diameter filled with clear serous
fluid. They are very painful and rupture
readily to leave sharp-edged, shallow
ulcers.

Ulcerative lesions penetrate more
deeply to the lamina propria and are
painful, as in necrotic stomatitis in calves
associated with F. necrophorus. In lambs
the tongue may be swollen and contain
many microabscesses infected with
Actinomyces (Corynebacterium) pyogenes.
There is an accompanying abscessation of
the pharyngeal lymph nodes. 2

Proliferative lesions are characterized
by an abnormality raised above the
surface of the mucous membrane as in
oral papillomatosis. Traumatic lesions
are usually solitary and characterized by a
discontinuity in the mucous membrane
often with evidence of healing and the
presence of granulation tissue.

Catarrhal stomatitis is manifested by
a diffuse inflammation of the buccal
mucosa and is commonly the result of
direct injury by chemical or physical
agents. Mycotic stomatitis is characterized
by a heavy, white, velvety deposit with
little obvious inflammation or damage to
the mucosa.

Deformity of or loss of tissue at the

tip of the tongue may result in a chronic
syndrome of chewing and swallowing food
in such a way that food is always oozing
from between the lips. In sheep this may
cause permanent staining of the hair
around the mouth, creating an appearance
similar to that of a tobacco- chewer. Loss
of the tip is usually the result of predator
attack on a newborn or sick lamb.

Laceration of the tongue can result in
complete or partial, severance of the
organ, with the severed portion protruding
from the oral cavity. In cattle, glossectomy
interferes with prehension and the animal
is unable to eat. Excessive loss of saliva is
common because of interference with
swallowing.

Ulceration of the soft palate of

horses may occur in 16% of horses with
dorsal displacement of the soft palate and
is characterized clinically by reduced
exercise tolerance, respiratory noise
during light exercise or racing, dysphagia
and coughing after exercising. 4 The ulcers
can be viewed by upper respiratory airway
video-endoscopy. Bullous stomatitis in
the horse is characterized by intact or
ruptured vesicles on the peripheral margin
of the tongue, the sublingual region and
the mucosa of the oral cavity and lips.

CLINICAL PATHOLOGY

Material collected from lesions of stomatitis
should be examined for the presence of

Diseases of the buccal cavity and associated organs

207

pathogenic bacteria and fungi. Transmission
experiments may be undertaken with
filtrates of swabs or scrapings if the
disease is thought to be due to a viral
agent.

NECROPSY FINDINGS

The oral lesions are easily observed but
complete necropsy examinations should
be carried out on all fatally affected animals
to determine whether the oral lesions are
primary or are local manifestations of a
systemic disease.

DIFFERENTIAL DIAGNOSIS

• Particularly in cattle, and to a less extent
in sheep, the diagnosis of stomatitis is
most important because of the
occurrence of oral lesions in a number
of highly infectious viral diseases. The
diseases are listed under etiology and
their differentiation is described under
their specific headings elsewhere in this
book

• Careful clinical and necropsy
examinations are necessary to define
the type and extent of the lesions if any
attempt at field diagnosis is to be made

• In cattle, lymphoma of the ramus of the
mandible may spread extensively
through the submucosal tissues of the
mouth causing marked swelling of the
gums, spreading of the teeth, inability
to close the mouth and profuse
salivation. There is no discontinuity or
inflammation of the buccal mucosa but
gross enlargement of the cranial lymph
nodes is usual

• The differentiation of causes of
hypersalivation must depend on a
careful examination of the mouth (the
causative gingivitis is often surprisingly
moderate in horses) and an awareness
of the volume of increased saliva output
caused by toxic hyperthermia, e.g. in
fescue and ergot poisonings

• Poisoning by the mycotoxin slaframine
also causes hypersalivation

TREATMENT

Affected animals should be isolated and
fed and watered from separate utensils if
an infectious agent is suspected. Specific
treatments are described under the
headings of the individual diseases.
Nonspecific treatment includes frequent
application of a mild antiseptic collutory
such as a 2% solution of copper sulfate, a
2% suspension of borax or a 1% suspen-
sion of a sulfonamide in glycerin. Indolent
ulcers require more vigorous treatment
and respond well to curettage or
cauterization with a silver nitrate stick or
tincture of iodine.

In stomatitis due to trauma, the teeth
may need attention. In all cases, soft,
appetizing food should be offered and
feeding by stomach tube or intravenous
alimentation may be resorted to in severe,
prolonged cases. If the disease is infec-

tious, care should be exercised to insure
that it is not transmitted by the hands or
dosing implements.

REFERENCES

1. Mohammed A et al.Vet Rec 1991; 128:355.

2. Rossiter DL et al. J Am Vet Med Assoc 1984;
185:1552.

3. Karren DB et al. Can J Anim Sci 1994; 74:571.

4. Gille D, Lavoie JR Equine Pract 1996; 18:9.

5. Williams MA et al. J Am Vet Med Assoc 1995;
207:331.

DISEASES OF THE TEETH

Surgical diseases of the teeth of animals
are presented in textbooks of surgery.
Some of the medical aspects of diseases
of the teeth of farm animals are described
here.

ETIOLOGY

The causes may be congenital or acquired.

Congenital defects

° Inherited

° Malocclusion of sufficient degree to
interfere with prehension and
mastication

® Red -brown staining of inherited
porphyrinuria of cattle
° Defective enamel formation on all
teeth combined with excessive
mobility of joints in inherited defect
of collagen metabolism in
Holstein/Friesian cattle identified as
bovine osteogenesis imperfecta. The
teeth are pink and obviously deficient
in substance. This defect is also
recorded in a foal with severe
epitheliogenesis imperfecta. 1

Dental fluorosis

The teeth are damaged before they erupt
and show erosion of the enamel. See the
section on fluorosis.

Enamel erosion

The feeding of acidic byproduct feed such
as sweet potato cannery waste, which is
acidic because of the presence of lactic
acid, can cause erosion of the enamel of
the incisors of cattle. 2,3 Exposure of incisor
teeth in vitro to a supernatant of cannery
waste or lactic acid at pH 3.2 results in
removal of calcium from the surface
enamel of bovine teeth. Neutralizing the
cannery waste to a pH of 5.5 does not
cause detectable etching of the teeth.
Feeding cattle with heavily compacted
silage is also associated with loss of
incisor enamel and severe incisor wear. 4

Premature wear and loss of teeth in
sheep (periodontal disease)

Premature loss of incisor teeth or 'broken
mouth' causes concern because of the
early age at which affected sheep have to
be culled. Broken mouth is a chronic >
inflammatory disease of the tissue sup-
ports of the tooth. 5 Between 60% and

70% of ewes sold at slaughter iif England
and Scotland have loose or missing incisor
teeth. 6 Broken mouth is geographically
specific and it seems that once the disease
is established on a particular farm, the
animals are permanently susceptible. 7
Many sheep are culled before the end of
their useful reproductive life because of
broken mouth. The problem is particularly
severe in New Zealand and the hill
country in Scotland. 8 The cause is
uncertain but environmental factors that'
result in periodontal disease are probably
important. Bacteroides gingivalis, an
organism that is found in plaque from
sheep's teeth, has been found with
increased frequency in diseased compared
to unaffected animals. 8 The depths of the
gingival crevice of sheep are heritable and
it is possible that deeper crevices may
already be harboring greater numbers of
periodontally pathogenic bacteria so that
when the animals are exposed to a
broken-mouth environment they may be
more prone to the changes. 9 While
nutrition and mineral deficiencies influence
dental development and tooth eruption of
sheep, there is no significant difference in
calcium or phosphorus status between
control and affected populations of sheep.
Low planes of nutrition have delayed
eruption of the permanent dentition and
retarded mandibular growth but these
changes are not seen in broken mouth in
sheep. The occurrence of this periodontal
disease is higher on some soil types than
on others. The ingestion of irritating
materials such as sand and spiny grass
seeds 10 has been suggested as causes, but
they are considered to be secondary
complications in a pre-existing disease.

Another dental disease of sheep is also
recorded on an extensive scale in New
Zealand. 11 There is excessive wear of
deciduous incisors but no change in the
rate of wear of the molar teeth. The incisor
wear is episodic and is not due to any
change in the supportive tissues, nor is
there any change in the intrinsic resist-
ance to wear of the incisor teeth. 12 The
disease is not related to an inadequate
dietary intake of copper or vitamin D and
is thought to be caused by the ingestion
of soil particles. 13 The two New Zealand
diseases do not occur together and have
no apparent effect on body condition

14

score.

Dentigerous cysts have been described
in ewes in the South Island of New
Zealand with a prevalence of 0.91%. 15

PATHOGENESIS

There are some limitations to the use of
number of incisors for determining age in
sheep. 16 In mixed-age female sheep
flocks, the median age when two, four, six
and eight incisors come into wear is 15,

IS

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

23, 30 and 42 monfhs of age, respectively. 16
Errors will be made by assuming that all
sheep gain a pair of permanent incisors at
annual intervals between 1.5 and 4.5 years
of age.

In periodontal disease or broken-
mouth disease of sheep the primary
lesion is an acute gingivitis around
permanent incisors and premolars at the
time of their eruption. This subsides
leaving a chronic gingivitis and an
accumulation of subgingival plaque. On
some farms, for reasons not understood,
this gingivitis penetrates down into the
alveoli, causing a severe periodontitis and
eventual -shedding of the teeth. 17 The
severity of the ginghdtis can vary between
farms. 18 The disease is episodic in nature,
with discrete acute inflammatory incidents
leading to periodontal injury that may
resolve by healing. 8 The balance between
repair and the various short- and long-
term acute episodes probably accounts for
the large variation in incidence and
age onset of tooth loss both within and
between flocks. 4 The inflammatory
periodontal disease markedly affects the
tooth's mobility. 19 Collagen fibrils sup-
porting the tooth become abnormal. The
deepened periodontal pocket resulting j
from inflammation removes the major j
area of support for the tooth and abnormal j
loads are applied to fibers deeper within j
the tissue. 20 While the incisor teeth are I
usually most severely affected, the cheek j
teeth are also involved. 5 In some unusual :
circumstances the gingivitis appears to i
arise from heavy deposits of dental :
calculus. 21 In the Scottish disease there :
is local alveolar bone loss but no
accompanying general skeletal deficiency. 6

CLINICAL FINDINGS

The most obvious evidence of broken-
mouth disease is incisor tooth loss, which
usually occurs when sheep are between
3.5 and 6.6 years; normal sheep without
broken mouth will retain their teeth
beyond 7 years of age. Several dental
health indices can assist to assess the
amount of gingivitis, tooth movement,
gum recession and pocketing. 5 Gingivitis
is characterized by redness and edema of
the attached gingiva. Bleeding from the
gingivae is also a feature. Clinical
gingivitis is evident as soon as the
permanent teeth erupt. Chronic gingivitis
results in a downward retreat of the gum
margin, loss of its normal, scalloped
shape and fibrosis of the gingiva. Within a
year prior to tooth loss, tissue damage
around the incisors leads to deepening of
the gingival sulcus and the formation of
pockets which are readily detected by the
use of graduated dental measuring probes.
The normal sulcus is 0.5-1.0 mm deep
labially and up to 4 mm deep lingually;

pockets may be over 1.0 cm in depth prior
to tooth loss. Crown lengthening, pro-
trusion, hemorrhages, loosening and
lingual periodontitis are characteristic. If
sheep affected with broken mouth
periodontal disease are examined over a
12-month period, only a few animals
undergo clinically significant destruction. 8
The relationship between periodontal
disease and body condition score in sheep
is variable. 14

Secondary starvation occurs even with
a plentiful feed supply. Inspection of the
mouth may reveal the worn or damaged
incisor teeth but the molar teeth are not
easily inspected in the living animal and
tooth lesions can be missed. Since it is
common to find that both incisors and
molars are all affected, damage to incisors
should lead the clinician to suspect that
molar disease is also present.

Cattle fed sweetpotato cannery waste
develop black, stained teeth with severe
enamel erosion. 3

An abattoir survey of dental defects in
cull cows, all over 30 months of age found
that 14.6% had one or more missing
incisors, most of which were acquired
losses. 22 Rotation and overlapping of
rostral teeth were common, as was
attrition. Congenitally absent first lower
premolars, other missing teeth, large and
often multiple interdental spaces and a few
cases of macrodontia, cavitation, multiple
defects and fractures were observed in
cheek tooth arcades. There were also some
unusual patterns of premolar and molar
attrition, often attributable to malocclusion,
one result of which was the formation of a
hook at the posterior extremity of the i
third maxillary molar.

CLINICAL PATHOLOGY

On bacteriological examination spirochetes i
and Fusobacterium spp. are present.

TREATMENT AND CONTROL

There is no reliable treatment and control
for broken mouth in sheep. The use of
dental prosthetics glued to the incisors
when the ewe has three pairs of incisors
in place is being investigated. The use of
antimicrobials has been proposed to con-
trol the gingivitis but there is no apparent
effect on the periodontal disease. Cutting
the incisor teeth of ewes to control pre-
mature tooth loss has been explored but
the practice has been banned in the UK. 23

REVIEW LITERATURE

Spence JA, Aitchison GU. Early tooth loss in sheep: a

review. \fetAnnu 1985; 25:125-133.

Spence J, Aitchison G. Clinical aspects of dental

disease in sheep. In Pract 1986; 8:128.

REFERENCES

1. Dubielzig RR et al. Vet Rathol 1986; 23:325.

2. Rogers GM et al. Am JVet Res 1997; 58:498.

3. Rogers GM et al. J Am Vet Med Assoc 1999;

214:681.

4. Smith A J et al.VetRec 1992; 130:352, 455, 479.

5. Spence JA et al. ResVet Sci 1988; 45:324.

6. Aitchison GU, Spence JA. J Comp Pathol 1984,
94:285, 95:505.

7. Frisken KW et al. ResVet Sci 1989; 46:147.

8. Laws A J et al. NZVet J 1988; 36:32.

9. Laws AJ et al. ResVet Sci 1993; 54:379.

10. Anderson BC et al. J Am Vet Med Assoc 1984;
184:737.

11. Thurley DC. NZVet J 1984; 32:25, 33:25, 157.

12. Erasmuson AF. NZ \fet J AgricRes 1985; 28:225.

13. Millar KRetal. NZVet J 1985; 33:41.

14. Orr MB, Chalmers M. NZVet J 1988; 36:171.

15. Orr MB, Gardner DG. NZVet J 1996; 44:198.

16. Bray A et al. Proc NZ Soc Anim Prod 1989;
49:303.

17. Morris PL et al. NZVet J 1985; 33:87, 131.

18. Thurley DC. J Comp Pathol 1987; 97:375.

19. Moxham BJ et al. ResVet Sci 1990; 48:99.

20. Shore RC et al. ResVet Sci 1998; 47:148.

21. Baker JR, Britt DP. Vet Rec 1984; 115:411.

22. Ingham B. Vet Rec 2001; 148:739.

23. Barber DML, Waterhouse A. Vet Rec 1988; 123:598.

PAR OTIT IS

Fhrotitis is inflammation of any of the
salivary glands.

ETIOLOGY

Parotitis may be parenchymatous, when
the glandular tissue is diffusely inflamed,
or it may be a local suppurative process.
There are no specific causes in farm
i animals, cases occurring only sporadically
| and due usually to localization of a blood-
| borne infection, invasion up the salivary
| ducts associated with stomatitis, irritation
1 by grass awns in the duct, or salivary
calculi. 1 Avitaminosis A often appears to
be a predisposing cause.

Local suppurative lesions are caused
usually by penetrating wounds or exten-
sion from a retropharyngeal cellulitis or
lymph node abscess. Neoplasia of the
parotid glands of cattle examined at
slaughter has been described. 2

PATHOGENESIS

In most cases only one gland is involved.
There is no loss of salivary function and
the signs are restricted to those of
inflammation of the gland.

CLINICAL FINDINGS

In the early stages, there is diffuse enlarge-
ment of the gland accompanied by warmth
and pain on palpation. The pain may
interfere with mastication and swallowing
and induce abnormal carriage of the head
and resentment when attempts are made
to move the head. There may be marked
local edema in severe cases. Diffuse
parenchymatous parotitis usually subsides
with systemic and local treatment within
a few days, but suppurative lesions may
discharge externally and form permanent
salivary fistulae.

CLINICAL PATHOLOGY

Bacteriological examination of pus from
discharging abscesses may aid the choice
of a suitable antibacterial treatment.

Diseases of the pharynx and esophagus

03

NECROPSY FINDINGS

Death occurs rarely and necropsy findings
are restricted to local involvement of the
gland or to primary lesions elsewhere in
the case of secondary parotitis.

DIFFERENTIAL DIAGNOSIS

• Careful palpation is necessary to
differentiate the condition from
lymphadenitis, abscesses of the throat
region and metastases to the parotid
lymph node in ocular carcinoma or
mandibular lymphoma of cattle

• Acute phlegmonous inflammation of
the throat is relatively common in cattle
and is accompanied by high fever,
severe toxemia and rapid death. It may
be mistaken for an acute parotitis but
the swelling is more diffuse and causes
pronounced obstruction to swallowing
and respiration

treatment

Systemic treatment with sulfonamides or
antibiotics is required in acute cases,
especially if there is a systemic reaction.
Abscesses may require draining and, if
discharge persists, the administration of
enzymes either parenterally or locally. A
salivary fistula is a common sequel.

REFERENCES

1. Misk NA, Nigam JM. Equine Pract 1984; 6:49.

2. Bundza A. J Comp Pathol 1983; 93:629.

Diseases of the pharynx
and esophagus

PHARYNGITIS

Pharyngitis is inflammation of the pharynx
and is characterized clinically by cough-
ing, painful swallowing and a variable
appetite. Regurgitation through the nostrils
and drooling of saliva may occur in severe
cases.

ETIOLOGY

Phaiyngitis in farm animals is usually
traumatic. Infectious pharyngitis is
often part of a syndrome with other more
obvious signs.

Physical causes

Injury while giving oral treatment
with balling or drenching gun 1 or
following endotracheal intubation. 2
The administration of intraruminal
anthelmintic coils to calves under a
minimum body weight have also been
associated with pharyngeal and
esophageal perforation 3
u Improper administration of a reticular
magnet, resulting in a retropharyngeal
abscess

0 Accidental administration or ingestion
of irritant or hot or cold substances

• Foreign bodies, including grass and
cereal awns, wire, bones, gelatin
capsules lodged in the pharynx or
suprapharyngeal diverticulum of pigs.

Infectious causes

Cattle

° Oral necrobacillosis, actinobacillosis
as a granuloma rather than the more
usual lymphadenitis
° Infectious bovine rhinotracheitis
° Pharyngeal phlegmon or

intermandibular cellulitis is a severe,
often fatal, necrosis of the wall of the
pharynx and peripharyngeal tissues
without actually causing pharyngitis.

F. necrophorum is a common isolate
from the lesions.

Horses

° As part of strangles or anthrax
° Viral infections of the upper
respiratory tract, including equine
herpesvirus-1, Hoppengarten cough,
parainfluenza virus, adenovirus,
rhinovirus, viral arteritis, influenza-
1A/E1 and 1A/E2, cause pharyngitis
° Chronic follicular pharyngitis with
hyperplasia of lymphoid tissue in
pharyngeal mucosa giving it a
granular, nodular appearance with
whitish tips on the lymphoid follicles.
An exaggerated form of the disease is
a soft tissue mass hanging from the
pharyngeal roof and composed of
lymphoid tissue.

Pigs

As part of anthrax in this species and
in some outbreaks of Aujeszky's
disease.

PATHOGENESIS

Inflammation of the pharynx is attended
by painful swallowing and disinclination
to eat. If the swelling of the mucosa and
j wall is severe, there may be virtual obstruc-
i tion of the pharynx. This is especially so
! if the retropharyngeal lymph node is
enlarged, as it is likely to be in equine viral
infections such as rhinovirus.

In balling-gun-induced trauma of feed-
lot cattle treated for respiratory disease with
boluses of sulfonamides, perforations of
the pharynx and esophagus may occur
with the development of periesophageal
diverticulations with accumulations of
ruminal ingesta, and cellulitis. 1 Improper
administration of a magnet to a mature cow
can result in a retropharyngeal abscess. 4

Pharyngeal lymphoid hyperplasia in
horses can be graded into four grades
(I— IV) of severity based on the size of the
lymphoid follicles and their distribution
over the pharyngeal wall.

CLINICAL FINDINGS

The animal may refuse to eat or drink or it
may swallow reluctantly and with evident

pain. Opening of the jaws to examine the
mouth is resented and manual compression
of the throat from the exterior causes
paroxysmal coughing. There may be a
mucopurulent nasal discharge, some-
times containing blood, spontaneous
cough and, in severe cases, regurgitation
of fluid and food through the nostrils.
Oral medication in such cases may be
impossible. Affected animals often stand
with the head extended, drool saliva and
make frequent, tentative jaw movements.
Severe toxemia may accompany the local
lesions, especially in oral necrobacillosis
and, to a less extent, in strangles. Empyema
of the guttural pouches may occur in
horses. If the local swelling is severe,
there may be obstruction of respiration
and visible swelling of the throat. The
retropharyngeal and parotid lymph nodes
are commonly enlarged. In 'pharyngeal
phlegmon'in cattle there is an acute onset
with high fever (41-41. 5°C, 106-107°F),
rapid heart rate, profound depression and
severe swelling of the soft tissues within
and posterior to the mandible to the point
where dyspnea is pronounced. Death
usually occurs 36^18 hours after the first
signs of illness.

In traumatic pharyngitis in cattle,

visual examination of the pharynx through
the oral cavity reveals hyperemia, lymphoid
hyperplasia and erosions covered by
diphtheritic membranes. Pharyngeal
lacerations are visible, and palpation of
these reveals the presence of accumulated
ruminal ingesta in diverticulae on either
1 side of the glottis. 1 External palpation of
the most proximal aspect of the neck
reveals firm swellings, which represent
the diverticula containing rumen contents.
A retropharyngeal abscess secondary to
an improperly administered magnet can
result in marked diffuse painful swelling
of the cranial cervical region. 4 Ultra-
: sonographic examination of the swelling
i may reveal the magnet within the abscess. 4

Palpation of the pharynx may be
performed in cattle with the use of a gag
; if a foreign body is suspected, and endo-
: scopic examination through the nasal
cavity is possible in the horse.

Most acute cases recover in several
days but chronic cases may persist for
! many weeks, especially if there is ulcer-
ation, a persistent foreign body or abscess
: formation. Pharyngitis has become one of
: the most commonly recognized diseases
; of the upper respiratory tract of the horse.

\ Chronic pharyngitis after viral infections
i is relatively common and results in a
break in training, which is inconvenient
I and costly. On endoscopic examination
there may be edema in early and relatively
; acute cases. In long-standing cases there
: is lymphoid infiltration and follicular
hyperplasia. This is more common and

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

more severe in young horses, who also
suffer more attacks of upper respiratory
tract disease. The condition does not
appear to diminish racing performance or
respiratory efficiency. If secondary bacterial
infection is present a purulent exudate is
seen on the pharyngeal mucosa and in
the nostrils. Affected horses cough
persistently, especially during exercise, are
dyspneic and tire easily. Guttural pouch
infections may occur secondarily. An
occasional sequel is aspiration pneumonia.

CLINICAL PATHOLOGY

Nasal discharge or swabs taken from
accompanying oral lesions may assist in
the identification of the causative agent.
Moraxella spp. and Streptococcus
zooepidemicus can be isolated in large
numbers from horses with lymphoid
follicular hyperplasia grades III and IV.

NECROPSY FINDINGS

Deaths are rare in primary pharyngitis
and necropsy examinations are usually
undertaken only in those animals dying
of specific diseases. In 'pharyngeal
phlegmon' there is edema, hemorrhage
and abscessation of the affected area and
on incision of the area a foul-smelling
liquid and some gas usually escape.

DIFFERENTIAL DIAGNOSIS

• Pharyngitis is manifested by an acute
onset and local pain

• In pharyngeal paralysis, the onset is
usually slow

• Acute obstruction by a foreign body
may occur rapidly and cause severe
distress and continuous, expulsive
coughing - but there are no systemic
signs

• Endoscopic examination of the
pharyngeal mucous membranes is often
of diagnostic value

TREATMENT

The primary disease must be treated,
usually parenterally, by the use of anti-
microbials. 'Pharyngeal phlegmon' in
cattle is frequently fatal and early treat-
ment, repeated at short intervals, with a
broad-spectrum antimicrobial is necessary.

Pharyngeal lymphoid hyperplasia is not
generally susceptible to antimicrobials or
medical therapy. Surgical therapy including
electrical and chemical cautery is indicated
and has been successfully applied.

REFERENCES

1. Adams GP, Radostits OM. Can Vet J 1988; 29:389.

2. Brock KA. J Am Vet Med Assoc 1985; 187:944.

3. West HJ et al.Vet Rec 1996; 139:44.

4. Braun U et al.Vet Radiol Ultrasound 1999; 40:162.

PHARYNGEAL OBSTRUCTION

Obstruction of the pharynx is accompanied

by stertorous respiration, coughing and
difficult swallowing.

ETIOLOGY

Foreign bodies or tissue swellings are the
usual causes.

Foreign bodies

These include bones, corn cobs and
pieces of wire. While horses are con-
sidered discriminating eaters in comparison
to cattle, they will occasionally pick up
pieces of metal while eating. 1

Tissue swellings

Cattle

° Retropharyngeal lymphadenopathy or
abscess due to tuberculosis,
actinobacillosis or bovine viral
leukosis

0 Fibrous or mucoid polyps. These are
usually pedunculated because of
traction during swallowing and may
cause intermittent obstruction of air
and food intake.

Horses

° Retropharyngeal lymph node

hyperplasia and lymphoid granulomas
as part of chronic follicular pharyngitis
syndrome

° Retropharyngeal abscess and cellulitis
0 Retropharyngeal lymphadenitis
caused by strangles

° Pharyngeal cysts in the subepiglottic
area of the pharynx, probably of
thyroglossal duct origin, and fibroma;
also similar cysts on the soft palate
and pharyngeal dorsum, the latter
probably being remnants of the
craniopharyngeal ducts
° Dermoid cysts and goitrous thyroids.

Pigs

° Diffuse lymphoid enlargement in the
pharyngeal wall and soft palate
° Food and foreign body impaction in
the suprapharyngeal diverticulum.

PATHOGENESIS

Reduction in caliber of the pharyngeal
lumen interferes with swallowing and
respiration.

CLINICAL FINDINGS

There is difficulty in swallowing and
animals may be hungry enough to eat
but, when they attempt to swallow, can-
not do so and the food is coughed up
through the mouth. Drinking is usually
managed successfully. There is no dila-
tation of the esophagus and usually little
or no regurgitation through the nostrils.
An obvious sign is a snoring inspiration,
often loud enough to be heard some
yards away. The inspiration is prolonged
and accompanied by marked abdominal
effort. Auscultation over the pharynx
reveals loud inspiratory stertor. Manual
examination of the pharynx may reveal

the nature of the lesion but an examin-
ation with a fiberoptic endoscope is likely
to be much more informative. When the
disease runs a long course, emaciation
usually follows. Rupture of abscessed
lymph nodes may occur when a nasal
tube is passed, and can result in aspiration
pneumonia.

In horses with metallic foreign bodies
in the oral cavity or pharynx, the clinical
findings include purulent nasal discharge,
dysphagia, halitosis, changes in phonation,
laceration of the tongue and stertorous
breathing. 1 In case studies, most horses
were affected with clinical signs for more
than 2 weeks and had been treated
with antimicrobials with only temporary
improvement. 1

CLINICAL PATHOLOGY

A tuberculin test may be advisable in
bovine cases. Nasal swabs may contain
S. equi when there is streptococcal lymph-
adenitis in horses.

NECROPSY FINDINGS

Death occurs rarely and in fatal cases the
physical lesion is apparent.

DIFFERENTIAL DIAGNOSIS

• Signs of the primary disease may aid in
the diagnosis in tuberculosis,
actinobacillosis and strangles

• Pharyngitis is accompanied by severe
pain and commonly by systemic signs
and there is usually stertor

• It is of particular importance to
differentiate between obstruction and
pharyngeal paralysis when rabies occurs
in the area. Esophageal obstruction is
also accompanied by the rejection of
ingested food but there is no respiratory
distress. Laryngeal stenosis may cause a
comparable stertor but swallowing is
not impeded. Nasal obstruction is
manifested by noisy breathing but the
volume of breath from one or both
nostrils is reduced and the respiratory
noise is more wheezing than snoring

• Radiography is useful for the
identification of metallic foreign bodies’

TREATMENT

Removal of a foreign body may be
accomplished through the mouth. Treat-
ment of actinobacillary lymphadenitis
with iodides is usually successful and
some reduction in size often occurs in
tuberculous enlargement of the glands
but complete recovery is unlikely to occur.
Fhrenteral treatment of strangles abscesses
with penicillin may effect a cure. Surgical
treatment has been highly successful in
cases caused by medial retropharyngeal
abscess.

REFERENCE

1. Kiper ML et al. J Am \£t Med Assoc 1992; 200:91.

Diseases of the pharynx and esophagus

PHARYNGEAL PARALYSIS

Pharyngeal paralysis is manifested by
inability to swallow and an absence of
signs of pain and respiratory obstruction.

ETIOLOGY

Pharyngeal paralysis occurs sporadically,
due to peripheral nerve injury, and in
some encephalitides with central lesions.

Peripheral nerve injury

° Guttural pouch infections in horses
° Trauma to the throat region.

Secondary to specific diseases

a Rabies and other encephalitides
° Botulism

® African horse sickness
• A series of unexplained fatal cases in
horses.

PATHOGENESIS

Inability to swallow and regurgitation are
the major manifestations of the disease.
There may be an associated laryngeal
paralysis, accompanied by 'roaring'. The
condition known as 'cud-dropping' in
cattle may be a partial pharyngeal paralysis
as there is difficulty in controlling the
regurgitated bolus, which is often dropped
from the mouth. In these circumstances,
aspiration pneumonia is likely to develop.

CLINICAL FINDINGS

The animal is usually hungry but, on
prehension of food or water, attempts at
swallowing are followed by dropping of
the food from the mouth, coughing and
the expulsion of food or regurgitation
through the nostrils. Salivation occurs
constantly and swallowing cannot be
stimulated by external compression of the
pharynx. The swallowing reflex is a
complex one controlled by a number of
nerves and the signs can be expected to
vary greatly depending on which nerves
are involved and to what degree. There is
rapid loss of condition and dehydration.
Clinical signs of the primary disease may
be evident but, in cases of primary
pharyngeal paralysis, there is no systemic
reaction. Pneumonia may follow aspir-
ation of food material into the lungs
and produces loud gurgling sounds on
auscultation.

In'cud-dropping'in cattle, the animals
are normal except that regurgitated boluses
are dropped from the mouth, usually in
the form of flattened disks of fibrous food
material. Affected animals may lose
weight but the condition is usually
transient, lasting for only a few days. On
the other hand, complete pharyngeal
paralysis is usually permanent and fatal.

CLINICAL PATHOLOGY

The use of clinicopathological examin-
ations is restricted to the identification of
the primary specific diseases.

NECROPSY FINDINGS

If the primary lesion is physical, it may be
detected on gross examination.

DIFFERENTIAL DIAGNOSIS*

• In all species, often the first clinical
impression is the presence of a foreign
body in the mouth or pharynx and this
can only be determined by physical
examination

• Pharyngeal paralysis is a typical sign in
rabies arid botulism but there are other
clinical findings that suggest the
presence of these diseases

• Absence of pain and respiratory
obstruction are usually sufficient
evidence to eliminate the possibility of
pharyngitis or pharyngeal obstruction

• Endoscopic examination of the guttural
pouch is a useful diagnostic aid in the.
horse

TREATMENT

Treatment is unlikely to have any effect.
The local application of heat may be
attempted. Feeding by nasal tube or intra-
venous alimentation may be tried if
disappearance of the paralysis seems
probable.

ESOPHAGITIS

Inflammation of the esophagus is
accompanied initially by clinical findings
of spasm and obstruction, pain on
swallowing and palpation, and regurgi-
tation of bloodstained, slimy material.

ETIOLOGY

Primary esophagitis caused by the
ingestion of chemical or physical irritants
is usually accompanied by stomatitis and
pharyngitis. Laceration of the mucosa by
a foreign body or complications of naso-
gastric intubation may occur. 1 Nasogastric
intubation is associated with a higher risk
of pharyngeal and esophageal injury
when performed in horses examined for
colic. 1 This may be related to the use of
larger- diameter nasogastric tubes to
provide more effective gastric decom-
pression, the longer duration of intu-
bation in some horses, or the presence of
gastric distension resulting in increased
resistance to tube passage at the cardia. 1
In a series of six horses with esophageal
trauma the lesions were detected 5 and
20 cm from the cranial esophageal
opening. 1

The administration of sustained-
release anthelmintic boluses to young
calves that are not large enough for the
size of the bolus used may cause
esophageal injury and perforation. 2,3 The
boluses are 8.5 cm in length and 2.5 cm in
diameter and the calves 100-150 kg. The
minimum body weight for these boluses
is 100 kg but in the study some calves

were younger than the recommended age
and were also fractious when handled,
which may have contributed to the
injury. 2 Death of Hypoderma lineatum
larvae in the submucosa of the esophagus
of cattle may cause acute local inflam-
mation and subsequent gangrene.

Inflammation of the esophagus occurs
commonly in many specific diseases,
particularly those that cause stomatitis,
but the other clinical signs of these
diseases dominate those of esophagitis.

PATHOGENESIS

Inflammation of the esophagus combined
with local edema and swelling results in a
functional obstruction and difficulty in
swallowing. Traumatic injury to the
esophagus results in edema, hemorrhage,
laceration of the mucosa and possible
perforation of the esophagus, resulting in
periesophageal cellulitis, which spreads
proximally and distally along the eso-
phagus in fascial planes from the site of
perforation. Perforation of the thoracic
esophagus can result in severe and fatal
pleuritis. There is extensive edema and
accumulation of swallowed or regurgitated
ingesta along with gas. The extensive
cellulitis and the presence of ingesta
results in severe toxemia, and dysphagia
may cause aspiration pneumonia.

CLINICAL FINDINGS

In the acute injury of the esophagus, there
is salivation and attempts to swallow,
which cause severe pain, particularly in
horses. In some cases, attempts at swallow-
ing are followed by regurgitation and
coughing, pain, retching activities and
vigorous contractions of the cervical and
abdominal muscles. Marked drooling of
saliva, grinding of the teeth, coughing and
profuse nasal discharge are common in
the horse with esophageal trauma with
complications following nasogastric
intubation. 1 Regurgitation may occur and
the regurgitus contains mucus and some
fresh blood. If the esophagitis is in the
cervical region, palpation in the jugular
furrow causes pain and edematous tissues
around the esophagus may be palpable. If
perforation has occurred, there is local
pain and swelling and often crepitus.
Local cervical cellulitis may cause rupture
to the exterior and development of an
esophageal fistula, or infiltration along
fascial planes with resulting compression
obstruction of the esophagus, and toxemia.
Perforation of the thoracic esophagus may
lead to fatal pleurisy. Animals that recover
from esophageal traumatic injury are
commonly affected by chronic esophageal
stenosis with distension above the
stenosis. Fistulae are usually persistent
but spontaneous healing may occur. In
Specific diseases such as mucosal disease
and bovine malignant catarrh, there are

2

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

no obvious clinical findings of esophagitis,
the lesions being mainly erosive.

Endoscopy of the esophagus will
usually reveal the location and severity of
the lesion. Lateral cervical radiographs
may reveal foreign bodies and extensive
soft tissue swelling with pockets of gas.

CLINICAL PATHOLOGY

In severe esophagitis of traumatic origin a
marked neutrophilia may occur, suggest-
ing active inflammation.

NECROPSY FINDINGS

Pathological findings are restricted to those
pertaining to the various specific diseases in
which esophagitis occurs. In traumatic
lesions or those caused by irritant sub-
stances, there is gross edema, inflammation
and, in some cases, perforation.

DIFFERENTIAL DIAGNOSIS

• Esophagitis must be differentiated from
pharyngitis, in which attempted
swallowing is not as marked and
coughing is more likely to occur.
Palpation may also help to localize the
lesion; however, pharyngitis and
esophagitis commonly occur together

• When the injury is caused by a foreign
body, it may still be in the esophagus
and, if suitable restraint and anesthesia
can be arranged, the passage of a
nasogastric tube or endoscope may
locate it. Complete esophageal
obstruction is accompanied by bloat in
ruminants, by palpable enlargement of
the esophagus and by less pain on
swallowing than in esophagitis,
although horses may show a great deal
of discomfort

• In cattle perforation of the esophagus is
not uncommon. There is a persistent,
moderate toxemia, a moderate fever
and a leukocytosis. Edema and swelling
are prominent in surrounding fascial
planes, but may cause only slight
physical enlargement, which is easily
missed on a routine examination

TREATMENT

Feed should be withheld for 2-3 days and
fluid and electrolyte therapy may be
necessary for several days. Parenteral
antimicrobials are indicated, especially
if laceration or perforation has occurred.
Reintroduction to feed should be
monitored carefully and all feed should be
moistened to avoid the possible accumu-
lation of dry feed in the esophagus, which
may not be fully functional.

REFERENCES

1. Hardy J etal.J Am Vet Med Assoc 1992; 201:483.

2. Mannion PA et al.Vet Rec 1997; 140:331.

3. West HJ et al.Vet Rec 1996; 139:44.

ESOPHAGEAL OBSTRUCTION

Esophageal obstruction may be acute or
chronic and is characterized clinically by

inability to swallow, regurgitation of feed
and water, continuous drooling of saliva,
and bloat in ruminants. Acute cases are
accompanied by distress. Horses with
choke commonly regurgitate feed and
water and drool saliva through the nostrils
because of the anatomical characteristics
of the equine soft palate.

ETIOLOGY

Obstruction may be intraluminal by
swallowed material or extraluminal due
to pressure on the esophagus by surround-
ing organs or tissues. Esophageal paralysis
may also result in obstruction.

Intraluminal obstructions

These are usually due to ingestion of
materials that are of inappropriate size and
that then become lodged in the esophagus:

o Solid obstructions, especially in cattle,
by turnips, potatoes, peaches, apples,
oranges, etc.

15 g gelatin capsules in Shetland
ponies 1

° The most common type of esophageal
obstruction in horses is simple
obstruction due to impaction of
ingesta. 2 Feedstuffs are a common
cause of obstruction in horses allowed
to eat immediately after a race or
workout. Improperly soaked
sugarbeet pulp, inadvertent access to
dry sugarbeet pulp and cubed and
pelleted feed are especially risky for
horses when eaten quickly. The horse
eats ravenously and swallows large
boluses without properly insalivating
them. The bolus lodges at the base of
the neck or the cardia. Similar
obstructions occur when horses are
turned into stalls containing fresh
bedding, including shavings
° Foreign bodies in horses include
pieces of wood, antimicrobial boluses
and fragments of nasogastric tubes. 3 A
nasogastric tube inserted into a horse
may break if the animal is startled and
jumps, or in some cases the tube
becomes weakened from overuse and
breaks if left in place over a period of
time 3

° A trichobezoar caused esophageal
obstruction in a cow; 4 it may have
been regurgitated rather than
ingested because of the lack of teeth
marks on the trichobezoar.

Extraluminal obstructions

r Tuberculous or neoplastic lymph
nodes in the mediastinum or at the
base of lung

0 Cervical or mediastinal abscess
« Persistent right aortic arch
a Thymoma.

Esophageal paralysis

This may be due to congenital or acquired

abnormalities of the esophagus and

there are many examples of such abnor-
malities, which interfere with swallowing
and cause varying degrees of obstruction,
even though it may be possible to pass a
stomach tube through the esophagus into
the stomach or rumen.

Esophageal paralysis, diverticulum
or megaesophagus has been recorded in
horses and in cattle. 5 Congenital hyper-
trophy of esophageal musculature and
esophagotracheal fistula has been found
in calves. Congenital esophageal ectasia is
recognized in foals, 6 caused by degener-
ation of musculature and reduced
ganglion cells in the myenteric plexus.
Congenital esophageal dysfunction has
also occurred in foals with no detectable
histopathological lesion but with pro-
longed simultaneous contractions through-
out the esophagus.

Megaesophagus

Megaesophagus is a dilatation and atony
of the body of the esophagus usually
associated with asynchronous function of
the esophagus and the caudal esophageal
sphincter. It occurs sporadically in cattle,
and in horses with pre-existing esophageal
disease. 2 It is usually a congenital con-
dition, causing regurgitation and aspiration
pneumonia. A mild esophagitis has been
observed in some cases and congenital
stenosis of the esophagus in a foal has
been associated with megaesophagus. 7

Esophageal strictures

These arise as a result of cicatricial or
granulation tissue deposition, usually as
result of previous laceration of the
esophagus. They may occur in the adult
horse with a history of previous obstruc-
tion. Esophageal strictures resulting in
obstruction occur in foals from 1-6 months
of age without any history of foreign
body. 8 An esophageal stricture has also
been described in a goat. 9

Other causes of obstruction
° Carcinoma of stomach causing
obstruction of cardia
• Squamous cell carcinoma of the
esophagus of a horse 10
° Esophageal hiatus hernia in cattle
° Fhraesophageal cyst in a horse 11
° Combined esophageal and tracheal
duplication cyst in a young horse 12
° Esophageal duplication in a horse 12
c Tubular duplication of the cervical
portion of the esophagus in a foal 13
° Cranial esophageal pulsion (pushing
outward) diverticulum in a horse 14
° Esophageal phytobezoar in a horse 15
o Esophageal mucosal granuloma 11
■ Traumatic rupture of the esophagus
from an external injury (e.g. a kick) or
duhing treatment using a nasogastric
tube

o Esophageal paralysis may also be
associated with lesions of
encephalitis, especially in the brain
stem. 16

PATHOGENESIS

An esophageal obstruction results in a
physical inability to swallow and, in cattle,
inability to eructate, with resulting bloat.
In acute obstruction, there is initial spasm
at the site of obstruction and forceful,
painful peristalsis and swallowing move-
ments. Complications of esophageal
obstruction include laceration and rupture
of the esophagus, esophagitis, stricture and
stenosis, and the development of a
diverticulum.

Acquired esophageal diverticula

may occur in the horse. A traction diver-
ticulum occurs following periesophageal
scarring and is of little consequence. An
esophageal pulsion diverticulum is a
circumscribed sac of mucosa protruding
through a defect in the muscular layer of
the esophagus. Causes that have been
proposed to explain pulsion diverticula
include excessive intraluminal pressure
from impacted feed, fluctuations in
esophageal pressure and external trauma. 15
Complications associated with esophageal
diverticula include peridiverticulitis, pul-
monary adhesions, abscesses and medias-
tinitis. Esophageal stricture and subsequent
obstruction secondary to impaction of a
diverticulum may also occur.

In megaesophagus, the esophagus is
dysfunctional, dilated and filled with
saliva, feed and water. This results in
regurgitation and may lead to aspiration
pneumonia. It may be congenital or
secondary to other lesions and has been
associated with gastric ulceration in a foal. 17

Using esophageal manometry, the
normal values for esophageal pressure
profiles in healthy horses, cows and sheep
have been recorded. 18 The body of the
equine and bovine esophagus has two
functionally different regions: the caudal
portion and the remainder of the
esophageal body (cranial portion).

CLINICAL FINDINGS
Acute obstruction or choke

Cattle

The obstruction is usually in the cervical
esophagus just above the larynx or at the
thoracic inlet. Obstructions may also
occur at the base of the heart or the
cardia. The animal suddenly stops eating
and shows anxiety and restlessness. There
are forceful attempts to swallow and
regurgitate, salivation, coughing and
continuous chewing movements. If
obstruction is complete, bloating occurs
rapidly and adds to the animal's dis-
comfort. Ruminal movements are con-
tinuous and forceful and there may be a
systolic murmur audible on auscultation

Diseases of the pharynx and esophagus

213

of the heart. However, rarely is the bloat
severe enough to seriously affect the
cardiovascular system of the animal, as
occurs in primary leguminous bloat.

The acute signs, other than bloat,
usually disappear within a fewhours. This
is due to relaxation of the initial eso-
phageal spasm and may or may not be
accompanied by onward passage of the
obstruction. Many obstructions pass on
spontaneously but others may persist for
several days and up to a week. In these
cases there is inability to swallow,
salivation and continued bloat. Passage
of a nasogastric tube is impossible.
Persistent obstruction causes pressure
necrosis of the mucosa and may result in
perforation or subsequent stenosis due to
fibrous tissue construction.

Horse

In the horse with esophageal obstruction
due to feed, the obstruction may occur at
any level of the esophagus from the upper
cervical region all the way to the thoracic
portion. The ingestion of large quantities
of grain or pelleted feed can cause
obstruction over a long portion of the
esophagus.

The clinical findings vary with the
location, nature, extent and duration of
the obstruction. Typically the major
clinical finding is dysphagia with nasal
reflux of saliva, feed and water.
Affected horses will usually not attempt
further eating but will drink and attempt
to swallow water. External palpation of
the cervical esophagus may reveal a
firm cylindrical swelling along the
course of the neck on the left side when
the esophagus is obstructed with feed. In
cases of foreign body obstruction such as
a piece of wood, there may be no palpable
abnormality.

Horses with acute esophageal obstruc-
tion are commonly difficult to handle
because they are panicky and make
forceful attempts to swallow or retch.
They may vigorously extend and flex their
necks and stamp their front feet. In some
horses it may be difficult to pass a naso-
gastric tube because they resist the
procedure. During these episodes of
hyperactivity they may sweat profusely,
tachycardia may be present and they may
appear to be in abdominal pain. Such
clinical findings on first examination may
resemble colic but attempted passage of a
nasogastric tube as part of the examin-
ation of a horse with colic reveals the
obstruction.

Passage of a nasogastric tube is

necessary to make the diagnosis and to
assess the level of the obstruction. 19 The
level of obstruction can be approximated
by the amount of tube that has been
passed. Care must be taken not to push

the tube more than gently to avoid injury
to the esophagus. Occasionally, a foreign
body or bolus of feed will move distally
into the stomach as the tube is gently
advanced.

The nature of the obstruction can be
assessed more adequately with a fiber-
optic endoscope but visualization of the
entire esophagus of an adult horse
requires an endoscope of 2.5 m length.
The endoscope allows determination of
the rostral but not the distal limit of the
obstruction. If radiographic equipment is
available, standing lateral radiographs of
the cervical and thoracic esophagus along
with contrast media may be required to
determine the extent and nature of an
obstruction.

Persistent obstruction may occur in the
horse and death may occur in either
species from subsequent aspiration
pneumonia or, when the obstruction
persists, from dehydration. In foals with
esophageal obstruction the clinical
findings include nasal reflux of saliva,
feed and milk, reluctance to eat solid feed
and dyspnea if aspiration pneumonia has
occurred. 8 Unthriftiness occurs if the
obstruction has been present for a few
weeks. Affected foals may have had several
episodes of choke within the previous few
weeks from which they appeared to
recover spontaneously. 8 Passage of a
nasogastric tube may be possible in some
and not in others.

Chronic obstruction

No acute signs of obstruction are evident
and in cattle the earliest sign is chronic
bloat, which is usually of moderate
severity and may persist for several days
without the appearance of other signs.
Rumen contractions may be within the
normal range. In horses and in cattle in
which the obstruction is sufficiently
severe to interfere with swallowing, a
characteristic syndrome develops. Swallow-
ing movements are usually normal until
the bolus reaches the obstruction, when
they are replaced by more forceful move-
ments. Dilatation of the esophagus may
cause a pronounced swelling at the base
of the neck. The swallowed material
either passes slowly through the stenotic
area or accumulates and is then regurgi-
tated. Projectile expulsion of ingested
material occurs with esophageal diverticula,
but water is retained and there is no
impedance to the passage of the stomach
tube. In the later stages, there may be no
attempt made to eat solid food but fluids
may be taken and swallowed satisfactorily.

When there is paralysis of the
esophagus, as in megaesophagus, regur-
gitation does not occur but the esophagus
! fills and overflows, and saliva drools from
the mouth and nostrils. Aspiration into

214

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

the lungs may follow. Passage of a stomach
tube or probang is obstructed by stenosis
but may be unimpeded by paralysis.

Complications following esophageal
obstruction

Complications following an esophageal
obstruction are most common in the horse
and include esophagitis, mucosal ulceration
in long-standing cases, esophageal perfor-
ation and aspiration pneumonia. Mild cases
of esophagitis heal spontaneously. Circum-
ferential full-thickness mucosal ulceration
may result in a stricture, which will be
clinically evident in 2-5 weeks and may
require surgical correction. Esophageal
perforation may occur and is characterized
by diffuse cellulitis of the periesophageal
tissues, often with subcutaneous emphy-
sema. A fistula may develop.

CLINICAL PATHOLOGY

Laboratory tests are not used in diagnosis
although radiographic examination is
helpful to outline the site of stenosis,
diverticulum or dilatation, even in animals
as large as the horse. Radiological exam-
ination after a barium swallow is a
practicable procedure if the obstruction is
in the cervical esophagus. Viewing of the
internal lumen of the esophagus with a
fiberoptic endoscope has completely
revolutionized the diagnosis of esophageal
malfunction. Biopsy samples of lesions
and tumor masses can be taken using the
endoscope. 10 Electromyography has been
used to localize the area of paralysis of the
esophagus in a cow with functional
megaesophagus. 20

TREATMENT
Conservative approach

Many obstructions will resolve sponta-
neously and a careful conservative
approach is recommended. If there is a
history of prolonged choke with consider-
able nasal reflux having occurred, the
animal should be examined carefully for
evidence of foreign material in the upper
respiratory tract and the risk of aspiration
pneumonia. It may require several hours
of monitoring, re-examination and
repeated sedation before the obstruction
is resolved. During this time, the animal
should not have access to feed and water.

Sedation

In acute obstruction, if there is marked
anxiety and distress, the animal should be
sedated before proceeding with specific
treatment. Administration of a sedative
may also help to relax the esophageal
spasm and allow passage of the impacted
material. For sedation and esophageal
relaxation in the horse, one of the follow-
ing is recommended:

° Acepromazine 0.05 mg/kg BW
intravenously

DIFFERENTIAL DIAGNOSIS

• The clinical findings of acute esophageal
obstruction in cattle and horses are
usually typical but may be similar to
those of esophagitis, in which local pain
is more apparent a nd there is often an
accompanying stomatitis and
pharyngitis

• The excitement, sweating, and
tachycardia observed in acute choke in
the horse often suggests colic. Passage
of the nasogastric tube reveals the
obstruction. The use of a fiberoptic
endoscope will usually locate the
obstruction for visualization and
obstructions are easiest to see when the
endoscope is being withdrawn rather
than advanced

Chronic obstruction

• Differentiation of the causes of chronic
obstruction may be difficult. A history of
previous esophagitis or acute
obstruction suggests cicatricial stenosis.
Contrast radiography of the esophagus
is valuable in the investigation of horses
with dysphagia, choke and nasogastric
reflux . 21 The use of the sedative
detomidine can affect the function of
the esophagus and make interpretation
of barium swallowing studies difficult 22

• Persistent right aortic arch is rare and
confined to young animals

• Mediastinal lymph node enlargement is
usually accompanied by other signs of
tuberculosis or lymphomatosis

• Chronic ruminal tympany in cattle may
be caused by ruminal atony, in which
case there is an absence of normal
ruminal movements

• Diaphragmatic hernia may also be a
cause of chronic ruminal tympany in
cattle and is sometimes accompanied by
obstruction of the esophagus with
incompletely regurgitated ingesta. This
condition and vagus indigestion,
another cause of chronic tympany, are
usually accompanied by a systolic
cardiac murmur but passage of a
stomach tube is unimpeded. Dysphagia
may also result from purely neurogenic
defects. Thus, an early paralytic rabies
'choke' is often suspected, with dire
results for the examining veterinarian

• Equine encephalomyelitis and botulism
are other diseases in which difficulty is
experienced with swallowing

• Cleft palate is a common cause of nasal
regurgitation in foals

° Xylazine 0.5-1. 0 mg/kg BW
intravenously

° Detomidine 0.01-0.02 mg/kg BW
intravenously

° Romifidine 0.04-0.12 mg/kg
intravenously. 19

For esophageal relaxation, analgesia and
anti-inflammatory effect hyoscine: dipyrone
0.5:0.22 mg/kg BW intravenously can
be used and for analgesia and anti-
inflammatory effect flunixin meglumine
1.1 mg/kg BW intravenously or phenyl-

butazone 2-4 mg/kg intravenously are
suggested. For analgesia butorphanol
0.02-0.1 mg/kg intravenously may be
administered.

Pass a stomach tube and allow
object to move into stomach

The passage of the nasogastric tube is
always necessary to locate the obstruc-
tion. Gentle attempts may be made to
push the obstruction caudad but care
must be taken to avoid damage to the
esophageal mucosa. A fiberoptic endoscope
can be used to determine the presence of
an obstruction, its nature and the extent
of any injury to the esophageal mucosa.

If the above simple procedures are
unsuccessful it is then necessary to pro-
ceed to more vigorous methods. In cattle,
it is usual to attempt further measures
immediately, partly because of the
animal's distress and the risk of self-injury
and partly because of the bloat. However,
rarely is the bloat associated with
esophageal obstruction life-threatening.
The important decision is whether to pro-
ceed and risk damaging the esophagus or
wait and allow the esophageal spasm to
relax and the obstruction to pass spon-
taneously.This problem is most important
in the horse. Attempts to push the
obstruction too vigorously may injure the
mucosa, causing esophagitis and even
esophageal perforation. Alternatively,
leaving a large obstruction in place may
restrict the circulation to the local area of
mucosa and result in ischemic necrosis.
Complications such as strictures and
diverticula may occur but are uncommon.
As a guide in the horse it is suggested that
conservative measures, principally sedation,
waiting and lavaging the esophagus, be
continued for several hours before
attempting radical procedures such as
general anesthesia and manipulation or
esophagotomy.

Removal by endoscope

If a specific foreign body, such as a piece
of wood, is the cause of the obstruction, it
may be removed by endoscopy. The
foreign body must be visible endoscopically
and suitable forceps or a snare through
the scope are required. In some cases,
impacted feed anterior to the foreign
object must be lavaged out before the
object is retrieved.

Manual removal through oral cavity
in cattle

Solid obstructions in the upper esophagus
of cattle may be reached by passing the
hand into the pharynx with the aid of a
speculum and having an assistant press
the foreign body up towards the mouth.
Because o£ slippery saliva, it is often
difficult to grasp the obstruction sufficiently
strongly to be able to extricate it from the

Diseases of the nonruminant stomach and intestines

215

esophagus. A long piece of strong wire
bent into a loop may be passed over the
object and an attempt made to pull it up
into the pharynx. The use of Thygesen's
probang with a cutting loop is a simple
and effective method of relieving choke in
cattle that have attempted to swallow
beets and other similar-sized vegetables
and fruits. If both methods fail, it is
advisable to leave the object in situ and
use treatments aimed at relaxing the
esophagus. In such cases in cattle it may
be necessary to trocarize the rumen and
leave the cannula in place until the
obstruction is relieved. However,
this should not be undertaken unless
specifically required.

General anesthesia in the horse

In horses, attempts to manually remove
solid obstructions from the cranial
portion of the esophagus require a
general anesthetic, a speculum in the
mouth and a manipulator with a small
hand. The fauces are much narrower in
the horse than in the cow and it is only
with difficulty that the hand can be
advanced through the pharynx to the
beginning of the esophagus. Fragments of
nasogastric tubes have been retrieved
from the esophagus of horses using
sedation with xylazine and butorphanol
intravenously and the use of a fiberoptic
endoscope. 23

Esophageal lavage in the horse

Accumulations of feedstuffs, which occur
most commonly in the horse, can be
removed by careful lavage or flushing of
the obstructed esophagus. Lavage may be
performed in the standing horse or in
lateral recumbency under general
anesthesia. Small quantities of warm
water, 0.5-1 L each time, are pumped
through a nasogastric tube passed to the
point of obstruction, and then the tube is
disconnected from the pump and the
liquid material is allowed to siphon out
through the tube by gravity flow. Return
of the fluid through the oral cavity and
nostrils is minimized by ensuring that the
tube is not plugged by returning material
and by using only small quantities of fluid
for each input of the lavage. Throughout
the procedure, the tube is gently mani-
pulated against the impaction. The use of
a transparent tube assists in helping to
see the amount and nature of the material
coming through the tube. This is repeated
many times until the fluid becomes clear.
This procedure may require a few hours
but perseverance will be successful. After
each lavage the tube can be advanced
caudad a few centimeters and eventually
all the way to the stomach. Following
relief of the obstruction the horse will
become relaxed and phonate its pleasure.
Care must be taken to avoid overflowing

the esophagus and causing aspiration
into the lungs. This is a constant hazard
whenever irrigative removal is attempted
and the animal's head must always be
kept as low as possible to avoid aspir-
ation. Following relief of obstruction the
horse can be offered water to drink, and a
wet mash of feed for a few days.

In the recumbent horse under general
anesthesia, lavage is similar. A cuffed
endotracheal tube is used to maintain an
airway and to prevent aspiration of foreign
material. Lavage under general anesthesia
provides relaxation of the esophagus,
which may enhance the procedure and
allow a greater volume of water to be
used.

Surgical removal of foreign bodies

Surgical removal by esophagostomy may
be necessary if other measures fail.
Gastrotomy may be necessary to relieve
obstructions of the caudal portion of
the esophagus adjacent to the cardia. 24
Although stricture or fistula formation is
often associated with esophageal surgery,
complications do not occur in every case;
healing by secondary intention is
common. 6

Repeated siphonage in chronic cases

In chronic cases, especially those due to
paralysis, repeated siphonage may be
necessary to remove fluid accumulations.
Successful results are reported in foals
using resection and anastomosis of
the esophagus and in a horse using
esophagomyotomy, but the treatment of
chronic obstruction is usually unsuccessful.

Cervical esophagostomy
alimentation

Alimentation of horses with esophageal
ruptures can be attempted by various
means. Maintenance of nasogastric tubes
through the nostrils is difficult but
possible. Tube feeding through a cervical
esophagostomy has some disadvantages,
but it is a reasonably satisfactory pro-
cedure in any situation where continued
extraoral alimentation is required in the
horse. However, the death rate is higher
than with nasogastric tube feeding. When
the obstruction is due to circumferential
esophageal ulceration, the lumen is
smallest at about 50 days and begins to
dilate at that point so that it is normal
again at about 60 days.

REFERENCES

1. Undvall RL, Kingrey BW. J Am Vet Med Assoc
1985; 133:75.

2. Felge K et al. Can\£t J 2000; 41:207.

3. Baird AN, True CK. J Am Vet Med Assoc 1989;
194:1098.

4. Patel JH, Brace DM. Can Vet J 1995; 36:774.

5. Bargai U et al. Vet Radiol 1991; 32:255.

6. Wilmot L et al. Can Vet J 1989; 30:175.

7. Clabough DL et al. J Am Vet Med Assoc 1991;
199:483.

8. Knottenbelt DC et al.\bt Rec 1992; 131:27.

9. Fleming SA et al. J Am Vet Med AsSftc 1989;
195:1598.

10. Campbell -Beggs CL et al. J Am Vet Med Assoc
1993; 202:617.

11. Shiroma JT et al. Vet Radiol Ultrasound 1994;
35:158.

12. Peek SI 7 et al. Equine Vet J 1995; 27:475.

13. Gaughan EM et al. J Am Vet Med Assoc 1992;
201:748.

14. Murray RC, Gaughan EM. Can\fet J 1993; 34:365.

15. MacDonald MH et al. J Am Vet Med Assoc 1987;
191:1455.

16. Scott PR et al. Vet Rec 1994; 135:482.

17. Murray MJ et al. J Am Vet Med Assoc 1988;
192:381.

18. Clark ES et al. Am J Vet Res 1987; 48:547.

19. Hillyer M. In Pract 1995; 17:450.

20. Pearson EG et al. J Am Vet Med Assoc 1994;
205:1767.

21. Greet TRC. In Pract 1989; 11:256.

22. WatsonTDG, Sullivan M.Vet Rec 1991; 129:67.

23. DiFranco B et al. J Am Vet Med Assoc 1992;
201:1035.

24. Orsini JA et al. J Am Vet Med Assoc 1991; 198:295.

Diseases of the
nonruminant stomach and
intestines

Only those diseases that are accompanied
by physical lesions, such as displacement
or strangulation, or disturbances of
motility, such as ileus, are presented.
Diseases associated with functional
disturbances of secretion are not recog-
nized in animals. Deficiencies of biliary
and pancreatic secretion are dealt with in
the chapter on diseases of the liver. Those
diseases of the stomach and intestines
peculiar to ruminants are dealt with
separately in Chapter 6.

EQUINE COLIC (ADULT HORSES)

GENERAL PRINCIPLES

Gastrointestinal disease causing signs of
abdominal pain in horses is commonly
referred to as colic. Colic is a frequent and
important cause of death and is con-
sidered the most important disease
of horses encountered by practicing
veterinarians. It is estimated to cost the
horse industry in the USA approximately
$115 000 000 annually. 1-3

ETIOLOGY

Several classification systems of equine
colic have been described including a
disease-based system (Table 5.3) classifying
the cause of colic as:

° Obstructive

° Obstructive and strangulating
° Nonstrangulating infarctive
° Inflammatory (peritonitis, enteritis).

Colic cases can also be classified on the
basis of the duration of the disease: acute
? (< 24-36 h), chronic (> 24-36 h) and
recurrent (multiple episodes separated

6

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Synopsis

Etiology See Tables 5.4, 5.5, 5.6 and 5.7
Epidemiology Incidence of 2-30 cases
per 100 horse years, mortality of 0. 5-0.7
cases per 100 horse years and case fatality
rate of 7-13%. Any age predisposition is
weak, although certain diseases (e.g.
meconium impaction, strangulation by
pedunculated lipoma) have specific age
distributions. Consumption of a diet high
in concentrate increases the risk of colic, as
does a poor parasite control program
Clinical signs Signs of abdominal pain
include agitation, flank watching, flank
biting, pawing, frequent lying down,
kicking at the abdomen, frequent attempts
to urinate or defecate, and rolling.
Tachycardia is common. Normal gut sounds
are absent and replaced by tympanitic
sounds. Abdominal distension may
develop. Reflux through a nasogastric tube
may occur. Rectal examination may reveal
abnormalities

Clinical pathology Few changes have
diagnostic significance but many are used
to monitor the severity of the disease.
Hemoconcentration, azotemia and
metabolic acidosis are frequent findings.
Peritoneal fluid may have increased protein
and leukocyte concentration
Lesions Consistent with the particular
disease

Diagnostic confirmation Physical
examination, exploratory laparotomy,
necropsy

Treatment Analgesia (Table 5.7),
correction of fluid, acid-base and
electrolyte abnormalities (Ch. 2), gastric
decompression via nasogastric intubation,
administration of fecal softeners or
lubricants (Table 5.8), surgical correction of
the lesion

Control Parasite control. Ensure adequate
roughage in the diet

by periods of > 2 days of normality).
Another classification system is anatom-
ically based and is listed in Table 5.4.
Regardless of the classification system
used, some estimates are that fewer than
20% of colic cases seen in the field have a
definitive diagnosis. 2,4 Horses with acute
transient colic relieved by analgesics are
often referred to as having 'spasmodic
colic'. 5 Spasmodic or gas colic was
the cause of 35% of horses with colic
examined in the field by veterinarians. 6
Large-colon impaction (20%) and
undiagnosed (13%) were the other largest
diagnostic categories. 6

EPIDEMIOLOGY

Most studies of the epidemiology of colic
do not provide details of specific diseases
but rather consider colic as one disease.
This inclusion of many diseases into one
category, while maximizing the statistical
power of the studies, is unfortunate
because it can obscure important details
regarding the occurrence and risk factors
of individual diseases. Furthermore, much
of the information related to incidence,
treatments and outcome of horses with
colic is derived from studies of horses
examined at referral centers. Horses
examined at these centers are in all likeli-
hood not representative of horses with
colic that are not referred for examin-
ation by specialists, this being the
majority of horses with colic. Details of
the epidemiology of specific etiological
entities are included under those head-
ings. Only general principles are included
here.

Occurrence

Equine colic occurs worldwide, although
there are regional differences in the types
of colic, and is a common and important
disease of horses. For cases of equine colic
recognized in the field, as distinct from
those referred for specialized treatment,
the incidence rate ranges between 3.5
and 10.6 cases per 100 horse years,

I although individual farms may experience
I rates as high as 30 or more cases per
j 100 horse years . 2 ' 3,7,8 Mortality due to
j colic ranges between 0.5 and 0.7 deaths
j per 100 horse years, representing 28% of
j overall horse deaths (2.5 deaths per 100
\ horse years). 2,4,8 The case fatality rate is
i 6-13% of field cases. 2 ' 4,8 Approximately
j 1-2% of colic events in the USA and the
: British Isles result in surgery. 3,8 It should
| be borne in mind that these estimates of
incidence and mortality are highly
j influenced by the population of horses
studied and may be biased or unduly
influenced by inclusion of farms or groups
of horses with an extremely high, or low,
; incidence of colic.

Risk factors

i Risk factors for colic can be categorized
; as: 1) intrinsic horse characteristics;

2) those associated with feeding practices;

: 3) management; 4) medical history, and;
5) parasite control. 9

Horse characteristics
Age

There are conflicting results of studies
that examine the association of colic and
age. The conflicting results might be the
result of varying study populations, study
design, presence of varying confounding

Type of colic

Etiology

Lesion

Typical clinical signs

Diagnosis

Simple obstruction

Luminal obstruction

Impaction of stomach,

Mild to moderate pain, heart

Usually subacute course.

(not infarctive)

ileum or large intestine
with dry ingesta
Concretion-type body,
e.g. fecalith, meconium,
phytobezoar, enterolith,
foreign body, sand colic,
congenital atresia

rate mildly increased initially,
moderate dehydration
Mild to moderate pain,
moderate dehydration

Diagnosis on rectal exam or
Imaging. Exploratory celiotomy
Subacute to acute course.
Diagnosis on rectal exam or
imaging. Exploratory celiotomy

Mural blockage

Hematoma, neoplasm,
idiopathic muscular
hypertrophy

Pain, moderate dehydration

Rectal exam, reflux through
nasogastric tube. Exploratory
celiotomy

Extramural blockage

Large colon displacement

Mild to moderate pain,
mild dehydration, abdominal
distension

Rectal exam. Exploratory
celiotomy

Functional

Spasm (spasmodic colic)
Paralytic ileus

Gastric reflux (acute gastric
dilatation, gastric ulcer,
anterior enteritis)

Moderate to severe pain,
moderate to severe signs
of hypovolemia

Rectal exam, gut sounds,
nasogastric intubation,
ultrasonographic examination

Inflammation

Infectious (e.g. Salmonella

Peritonitis

Mild pain, fever, toxemia,

Leukocytosis, abdominal

(irritation of
peritoneal pain
receptors)

spp., Actinobacillus equuli),
chemical irritation (urine,
ingesta)

Enteritis

tachycardia, hypovolemia

paracentesis, diarrhea

Diseases of the nonruminant stomach and intestines

217

—

SBIMlilBSlllMtt

'mmSSBSX^m^sS0m

Type of colic

Etiology

Lesion Typical clinical signs

Diagnosis

Simple infarction
(no obstruction)

Infarction. Ischemia

Thromboembolic colic Mild to severe pain, toxemia,

(verminous arteritis), arterial Possibly blood loss
occlusion (pedunculated
lipoma around mesentery),
detachment of mesentery
(traumatic or congenital)

Abdominal paracentesis, total
white cell count. Exploratory
celiotomy

Obstruction plus
infarction

Intestinal accidents

Intussusception Intractable pain followed by

Torsion profound depression,

Strangulation (epiploic toxemia, severe tachycardia,

foramen, diaphragmatic, hypovolemia

inguinal hernias, mesenteric

tear or congenital defect,

pedunculated lipoma)

Rectal exam. Abdominal
paracentesis, PCV, total
white cell count, nasogastric
intubation, ultrasonographic
examination

Stomach Gastric dilatation

Primary

Secondary to outflow obstruction, pyloric stenosis, ileus or anterior enteritis
Gastric impaction
Gastroduodenal ulceration
Small intestine Volvulus

Intussusception
Ileocecal
Jejunojejunal
Infarction or ischemia
Thromboembolic disease
Disruption of blood supply by mesenteric tear

Strangulation, including entrapment through the epiploic foramen, mesenteric rents (including cecocolic fold, splenic
ligament, uterine ligaments, spermatic cord), Merkel's diverticulum and hernias (diaphragmatic, inguinal/scrotal, umbilical).
Strangulation by pedunculated lipoma
Luminal obstruction
Foreign bodies
Ascarids

Luminal compression
Lipomas

Intramural masses such as Pythium spp. and neoplasms (adenocarcinoma, lymphoma, eosinophilic enteritis)

Adhesions

Enteritis

Cecum Impaction

Rupture and perforation
Intussusception
Cecocolic
Cecocecal
Cecal torsion

Infarction (thromboembolic disease, necrotizing enterocolitis)

Typhilitis

Tympany

Ascending (large) colon Impaction

Intestinal tympany
Volvulus

Displacement, including left dorsal (reno- or nephrosplenic), right dorsal, cranial displacement of pelvic flexure
Infarction (verminous mesenteric arteritis, necrotizing enterocolitis)

Luminal obstruction
Sand accumulation
Enterolith

Right dorsal ulcerative colitis
Colitis

Necrotizing enterocolitis

Descending (small) colon Impaction

Luminal obstruction
Fecalith
Enterolith

Luminal compression
Pedunculated lipoma
Intramural hematoma
Perirectal abscess

Perirectal tumor (melanoma) 5

Avulsion of mesocolon and rectal prolapse in mares at parturition
Strangulation

8

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

factors, and interpretation of data.
Confounding factors are those that alter
with the age of the horse, such as use,
feeding and management of horses, and
mask an effect of age or give the
impression of an effect of age when in fact
such an effect is not present. 9,10 Horses
2-10years of age are 2.8 times more likely
to develop colic that horses less than
2 years. 11 One large-scale study reported
that foals less than 6 months of age had
an incidence of 0.2 cases of colic per
100 horses per year, while horses more
than 6 months of age had incidence of
approximately 4-6 colic-affected horses
per 100 horse years, with the incidence
varying to a limited extent among older
age groups. 3 Other studies have not
found a similar effect of age. 4 However,
each age group has a particular set of
diseases unique or common to it. New-
born foals may have congenital colon or
anal atresia, or meconium impaction
(see Colic in foals), diseases that do not
affect older horses, whereas strangu-
lating or obstructive lesions caused by
pedunculated lipomas are found only in
older horses. 12

Sex

There is no overall effect of sex on risk of
colic 4,11 but certain diseases are restricted
by sex. For instance, inguinal hernias
occur only in males, whereas entrapment
of intestine in the mesometrium is
restricted to mares, for obvious reasons.

Breed

There is a consistent finding that Arabian
horses are at increased risk of colic, but
the reason for this apparently greater risk
has not been determined. 4,6,9,10 Thorough-
breds are reported to be at increased risk
of colic, independent of their use. 3,11

Diet and feeding practices
Horses at pasture are at a lower risk of
developing colic than are stabled horses
fed concentrate feeds. 11,13,14 The risk of
colic increases with the amount of con-
centrate fed, such that a horse fed 5 kg of
concentrated feed per day has 6 times as
great a risk of developing colic as a horse
not fed concentrate. 11 However, another
report did not detect an effect of diet
composition on risk of colic. 6 Changes to
the horse's diet through changes in
quantity and quality of feed, feeding
frequency, or time of feeding increase the
risk of colic by 2-5 times. 6,11,13,15

Management

Watering

Horses without constant access to water
are at increased risk of developing colic, 14
whereas horses with access to ponds
or dams have a reduced risk of colic
compared to horses provided with
water from buckets or troughs. 11,14 This

might represent a confounding effect of
pasturing, in that horses with access to
dams are probably at pasture and benefit
from the lower risk of colic associated
with that management practice. Alter-
natively, horses provided with water from
buckets may be at greater risk of having
periods when water is not available. 14

Housing

Increased duration of stabling per day is
associated with an increased risk of
colic. 6,13 Horses cared for by their owner
and horses in stables with large numbers
of horses are less likely to develop colic. 8

Exercise

Overall, there appears to be an increased
risk of colic among horses that are under-
taking physical activity or that have a
recent change in the amount of physical
activity. However, the finding of this
association should be considered in the
context of other differences that exist
between active and inactive horses, such as
in feeding practices, housing (stabling
versus pasture), and transportation.

Weather and climate

Despite the widespread belief that colic

is associated with changes in weather,

particularly thunderstorms, there is

no conclusive evidence of such an

association. 9,10

Medical history

Horses with a history of colic are more
likely to have another episode, and horses
that have had colic surgery are approxi-
mately five times more likely to have
another episode of colic than are horses
that have not had colic. 6,15 There is no
association between dental care and
incidence of colic or recent vaccination
and colic. 6,9

Parasite control

Inadequate parasite control programs
have been estimated to put horses at
2-9 times greater risk of developing colic, 7
although other studies have not demon-
strated a relationship between anthelmintic
administration and colic. 8,10 The presence
of tapeworms is associated with a 3 times
greater risk of ileal impaction. 16 A recent
large-scale study in the USA found an
increased incidence of colic in horses on
farms on which rotation of anthelmintics
was practiced. 3 This apparently paradoxical
finding may be because farms with a
higher incidence of colic are more likely
to alter rotate anthelmintics as a result of
having more horses with colic. 3

The apparently conflicting results of
some of the epidemiologic studies should
not deter veterinarians from recommending
effective parasite control programs for
horses, given the clear association at an
individual level of presence of tapeworms.

cyathostomes and/or large strongyles and
ileocecal disease, diarrhea and ill thrift,
and verminous arteritis, respectively.

Importance

Losses caused by colic in horses are due
almost entirely to death of the patient.
However, the cost of treatment and the
emotional trauma to the owners of their
horse being afflicted with a potentially
fatal disease are important consider-
ations. A 1989 survey of veterinarians in
the USA rated colic the most serious
medical disease in horses, ahead of viral
respiratory disease 1 and recent studies
estimated the cost of colic to the horse
industry in the USA at $115 000 000
annually. 3

PATHOGENESIS

The pathogenesis of equine colic is
variable depending on the cause and
severity of the inciting disease. A horse
with a strangulating lesion involving 50%
of its small intestine has a much more
rapidly evolving disease, with severe
abnormalities, than does a horse affected
with mild spasmodic colic or impaction of
the pelvic flexure of the large colon. While
equine colic often involves changes in
many body systems, notably the gastro-
intestinal, cardiovascular, metabolic and
endocrine systems, there are several
features and mechanisms that are com-
mon to most causes of colic and that
depend only on the severity of the disease
for the magnitude of their change. The
features common to severe colic, and
often present to a lesser degree in milder
colics, are pain, gastrointestinal dysfunction,
intestinal ischemia, endotoxemia, compro-
mised cardiovascular function (shock)
and metabolic abnormalities.

Pain

Pain is the hallmark of gastrointestinal
disease in horses and is attributable to
distension of the gastrointestinal tract
and stimulation of stretch receptors in the
bowel wall and mesentery, stretching of
mesentery by displaced or entrapped
bowel, and inflammation and irritation of
the bowel, peritoneum or mesentery. The
intensity of the pain is often, but not
always, related to the severity of the
inciting disease. Horses with mild impac-
tion of the large colon of short duration
(< 24 h) often have very mild pain,
whereas a horse with a strangulating lesion
of the small intestine will have very severe
pain.

Gastrointestinal pain has an inhibitory
effect on normal gastrointestinal function,
causing a feedback loop in which the pain
inhibits normal gut motility and function,
allowing accumulation of ingesta and
fluid, resulting in distension and further
pain. Horses can respond very violently to

abdominal pain and may injure them-
selves when rolling or thrashing.

Gastrointestinal dysfunction

Colic is almost invariably associated with
impaired gastrointestinal function, usually
alterations to motility or absorptive
function. Gastrointestinal motility may be
increased, as is presumed to be the case in
spasmodic colic, altered in its character or
coordination, as in some cases of
impaction colic, or absent, such as in ileus
secondary to inflammation or ischemia of
the bowel or to the presence of endo-
toxemia. Increased or uncoordinated
gastrointestinal motility probably causes
pain through excessive contraction of
individual segments of bowel or dis-
tension of bowel because of the loss of
normal propulsive activity. Ileus is
associated with fluid distension of the
small intestine and stomach and fluid and
gas distension of the large colon, both of
which cause severe pain and can lead to
gastric or colonic rupture. The absorptive
function of the intestine may be
decreased by inflammation or ischemia,
which results in distension of the small
intestine or large colon, pain and
potentially rupture of the stomach or colon.

Impairment of the barrier function of
the gastrointestinal mucosa by inflam-
mation or ischemia can result in leakage
of endotoxin into peritoneal fluid and
endotoxemia 17 (see Endotoxemia).

ischemia of the intestinal wall

Ultimately, most forms of lethal colic
involve some degree of ischemia of the
intestine, with subsequent loss of barrier
function, evident in its most extreme form
as rupture of the viscus, endotoxemia,
bacteremia, cardiovascular collapse and
death. Ischemia may be the result of
impaired blood flow to or from the
intestine because of torsion or volvulus of
the intestine, entrapment of the intestine
and associated mesentery in rents or
hernias, strangulation such as by a
pedunculated lipoma, or thromboembolic
disease. Ischemia may also result from
severe gastrointestinal distension, such as
occurs in the terminal stage of severe
colon impaction. Mild ischemia probably
impairs normal intestinal motility and
function. The role of reperfusion injury in
pathogenesis of ischemic disease is
uncertain at this time.

Endotoxemia

Death in fatal cases of colic in which the
affected viscus ruptures secondary to
distension, or when ischemia and/or
infarction damages a segment of bowel
wall, is due to the absorption of endo-
toxins from the gut lumen into the
systemic circulation. 17 (See Endotoxemia).
Endotoxin absorption causes increased

Diseases of the nonruminant stomach and intestines

219 “

concentrations of tumor necrosis factor
and interleukin 6 in peritoneal fluid and
blood concentrations 17

Rupture of the stomach or intestine is
also a characteristic termination of dis-
tension of the intestine in the horse. The
resulting deposition of large quantities of
highly toxic ingesta or fecal contents into
the peritoneal cavity causes profound
shock and death within a few hours.

Shock

The usual cause of death in severe colic
is cardiovascular collapse secondary to
endotoxemia and hypovolemia. In less
severe colic, hypovolemia and cardio-
vascular dysfunction may contribute to
the development of the disease, and rapid
correction of hypovolemia is central to the
effective treatment of colic.

Hypovolemia is due to the loss of
fluid and electrolytes into the lumen of
the gastrointestinal tract or loss of protein
from the vascular space with subsequent
reduction in the circulating blood volume.
Hypovolemia impairs venous return to
heart and therefore cardiac output, arterial
blood pressure and oxygen delivery to
tissues. Not surprisingly, measures of
circulatory status are good predictors of the
outcome of colic (see Prognosis, below).

Cardiorespiratory function is impaired
if there is severe distension of gut, such as
in large-colon torsion, because of restricted
respiration by pressure on the diaphragm
and reduced venous return to the heart
because of pressure on the caudal vena
cava.

Coagulation and fibrinolysis

Severe colic, especially that involving
ischemia or necrosis of intestine, is associ-
ated with abnormalities in coagulation and
fibrinolysis characterized by hyper-
coagulation of blood and decreases in rate
of fibrinolysis. 18-21 Disseminated intra-
vascular coagulation is common among
horses with ischemia or necrosis of the
gut and is a good prognostic indicator of
survival. 19,20 Changes in coagulation and
fibrinolysis include decreases in anti-
thrombin activity and fibrinogen concen-
tration and increases in prothrombin
time, activated partial thromboplastin
time and concentration of thrombin-
antithrombin complexes in plasma. 19-21

Overview of the pathogenesis of
common colics

Simple obstructive

Simple obstructive colics are those in
which there is obstruction to the aboral
passage of ingesta but no ischemia or
strangulation of bowel. In the terminal
stages there is often ischemia caused by
distension of the intestine.

Small-intestinal obstructive lesions
include ileal hypertrophy, ileocecal

intussusception and foreign-body-obstruc-
tion of the lumen. The course of the disease
is often 24-72 hours, and sometimes
longer depending on the extent of the
obstruction, partial obstructions having
much less severe signs and disease of
longer duration. The principal abrior-
mality is reduced aboral flow of ingesta,
with subsequent distension of intestine
cranial to the obstruction, causing pain
and, if the distension is severe, gastric
rupture.

Large intestinal obstructive lesions
include impaction and simple (non-
strangulating) displacements of the large
colon. The course of disease is prolonged,
often more than 72 hours! Signs of
abdominal pain are due to distension of
the bowel. There is progressive distension
with fluid and gas and ultimately ischemia
of the bowel and rupture.

Obstructive and strangulating
Diseases that cause both obstruction and
strangulation as an initial event, such as
torsion of the small intestine or volvulus
of the large colon, result in severe and
unrelenting pain that is little relieved with
analgesics. Obstruction causes distension
and strangulation causes ischemia, loss of
barrier function and endotoxemia. These
diseases have a short course, usually less
than 24 hours and sometimes as short as
6 hours, and profound clinical signs.
Endotoxemia and cardiovascular collapse
are characteristic of these diseases.

Infarctive

Infarctive diseases, such as thrombo-
embolic colic, are characterized by
ischemia of the intestinal wall with sub-
sequent alterations in motility and
absorptive and barrier functions. Ileus
causes distension of the intestines and
stomach and altered barrier function
causes endotoxemia. The course of the
disease is usually less than 48 hours and is
terminated by cardiovascular collapse and
death.

Inflammatory

Inflammation of the intestine or
peritoneum alters gastrointestinal motility
and absorptive function leading to accu-
mulation of fluid and ingesta, distension
and abdominal pain.

CLINICAL FINDINGS

The bulk of the following description is
generally applicable to severe acute colic.
Clinical findings characteristic of each
etiological type of colic are dealt with
under their individual headings. The
purposes of the clinical examination are
diagnostic - .to determine whether the
pain is due to gastrointestinal tract
disease and, if so, to determine the nature
of the lesion - and prognostic, to provide
some estimate of the likely outcome of

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

the disease. Veterinary clinicians are able
to accurately predict the site of lesions
(small versus large intestine), type
of lesion (simple obstructive versus
strangulating or infarctive) and outcome. 22
The ability to predict these events
increases with training and experience. 22

Accurate diagnosis of the cause of
the colic has some prognostic usefulness,
but assessment of the horse's physio-
logical state by measurement of heart and
respiratory rates, mucous membrane color
and refill time, arterial blood pressure,
hematocrit and serum total protein con-
centration, and other measures, allows
more accurate prognostication. Further-
more, the cause of colic is determined in
only approximately 20% of field cases.

Visual examination

Behavior

Pain is manifested by pawing, stamping
or kicking at the belly or by restlessness
evident as pacing in small circles and
repeatedly getting up and lying down,
often with exaggerated care. Other signs
are looking or nipping at the flank,
rolling, and lying on the back. Often the
penis is protruded without urinating or
with frequent urination of small volumes.
Continuous playing with water without
actually drinking (sham drinking) is
common.

Pain may be continuous or, more
commonly, intermittent with bouts of
pain lasting as long as 10 minutes inter-
spersed with similar periods of relaxation.
In general the intensity of the pain is of
about the same severity for the duration
of the illness; sudden exacerbations may
indicate a change in the disease status or
the development of another abnormality,
such as a horse with impaction of the
large colon developing a displacement of
the colon or horses with diarrhea
developing necrotizing enteritis. Horses
in the terminal phase of the disease may
have a marked diminution of pain
associated with relief of pressure after
rupture of distended bowel and depression
caused by toxemia and shock. Pain
responses in colic may be so severe, and
uncontrolled movements so violent, that
the horse may do itself serious injury.
Other causes of pain, such as pleuritis or
rhabdomyositis, can be confused with
colic, although a horse that goes down
and rolls almost certainly has alimentary
tract colic.

Posture

The posture is often abnormal, with the
horse standing stretched out with the
forefeet more cranial and the hindfeet
more caudal than normal - the so-called
'saw-horse' stance. Some horses lie down
on their backs with their legs in the air.

suggesting a need to relieve tension on
the mesentery.

Abdomen size

Distension of the abdomen is an
uncommon but important diagnostic
sign. Symmetrical, severe distension is
usually caused by distension of the colon,
sometimes including the cecum, second-
ary to colon torsion, or impaction of the
large or small colon and subsequent fluid
and gas accumulation. If only the cecum
is distended the abdomen may show an
asymmetrical enlargement in the right
sublumbar fossa. Maximum distension
of stomach or small intestines does
not cause appreciable distension of the
abdomen.

Vomiting

Projectile vomiting or regurgitation of
intestinal contents through the nose is
very unusual in the horse and is a serious
sign suggesting severe gastric distension
and impending rupture.

Defecation and feces
Defecation patterns can be misleading. It
is often mistakenly assumed that there is
no complete obstruction because feces
are still being passed. But in the very early
stages of acute intestinal obstruction
there may be normal feces in the rectum,
and the animal may defecate several
times before the more usual sign of an
empty rectum with a sticky mucosa is
observed.

Physical examination

Heart and respiratory rates
The heart rate is a useful indicator of the
severity of the disease and its progression
but has little diagnostic usefulness.
Horses with heart rates less than 40/min
usually have mild disease whereas horses
with heart rates above 120/min are
usually in the terminal stages of severe
disease. Horses with obstructive, non-
strangulating disease often have heart
rates between 40 and 60/min, whereas
horses with strangulating disease or
necrotic bowel will usually have heart
rates over 80/min. However, heart rate is
not an infallible indicator of disease
severity, as horses with torsion of the
colon can have heart rates of 40-50/min.
j The respiratory rate is variable and
i may be as high as 80/min during periods
j of severe pain.

i Mucous membranes and extremities
j Mucous membranes of normal horses
i and of horses without significantly
j impaired cardiovascular function are
j pink, moist and regain their normal color
! within 2 seconds after firm digital
i pressure is removed. Dehydrated horses
j have dry mucous membranes, although
; the capillary refill time and color are

normal. Horses with impaired cardio-
vascular function have pale, dry mucous
membranes with delayed capillary refill
(> 2 s). Endotoxemic horses will often
have bright red mucous membranes with
normal or delayed capillary refill. As the
disease becomes more severe the mucous
membranes develop a bluish tint and
capillary refill is longer than 3 seconds.
Terminal stages of disease are associated
with cold, purple, dry mucous membranes
with a capillary refill time of more than
3 seconds; necrosis of the mucosa of the
gingival margins of the gums, the so-
called 'toxic line', is often seen.

Cool extremities may be indicative of
compromised cardiovascular function but
should be interpreted with caution and
only in the context of the rest of the
clinical examination. Sweating is com-
mon in horses with severe abdominal
pain and, when present in a horse with
cool extremities and signs of cardio-
vascular collapse, is indicative of a poor
prognosis.

Auscultation; percussion
Auscultation of the abdomen can pro-
vide useful diagnostic and prognostic
information and should be performed
thoroughly and without haste. All four
quadrants (dorsal and ventral, left and
right sides) of the abdomen should be
examined for at least 1 minute at each
site. Attention should be paid to the
intensity, frequency and characteristics of
the spontaneous gut sounds (borboiygmi).
Repeated observations are often necess-
ary to detect intermittent or rapid changes
in the character of the borborygmi.

Continuous, loud borborygmi dis-
tributed in all or most quadrants are
indicative of intestinal hypermotility and
consistent with spasmodic colic, impend-
ing diarrhea or the very early stages of a
small-intestinal obstructive/strangulating
lesion. The absence of sounds, or the
presence of occasional high-pitched, brief
sounds, sometimes with a splashing
character, is consistent with ileus. These
sounds should not be mistaken for the
rolling, prolonged sounds of normal
peristalsis.

Combined percussion and auscul-
tation is a valuable procedure for defining
the presence of extensive gas caps, a flick
or abrupt tap with a finger while
auscultating with a stethoscope will elicit
I a'pinging' sound similar to that made by
j flicking an inflated balloon. The detection
] of such sounds indicates the presence of
) tightly gas-distended bowel near the
i body wall. Such bowel is almost always
I large colon or cecum and is consistent
j with gas distension secondary to ileus,
! small 'or large colon impaction, gas colic
; or colon displacement, including torsion-

Diseases of the nonruminant stomach and intestines

221

Rectal examination

A careful rectal examination is probably
the most important part of the clinical
examination in colic and should not be
neglected. The examiner must know the
anatomy of the posterior abdomen in
order to make reasonably accurate deci-
sions about the location of various
organs. Recognition that an important
abnormality exists is a critical factor in the
decision to refer the horse for specialized
evaluation and care.

Normal anatomy

The horse should be restrained so that the
examination can be performed with
minimal risk to both the examiner and
patient. Fractious or painful horses should
be tranquilized. A twitch should be
applied to all but the most cooperative
horses to minimize straining and the
chance of kicking. Rectal examination
in small or unruly horses should be
approached with caution.

Only approximately 40% of the abdo-
men can be examined in a mature horse,
the cranial and ventral structures being

outside the reach of the examiner. In the
normal 425 kg (10001b) horse there
should not be any distended intestine nor
should the small intestine be palpable.
The cecum is readily palpable in the right
caudal abdomen, with its ventral band
running from the dorsal right quadrant
ventrally and slightly to the left. The base
of the cecum may be palpable as a soft,
compressible structure containing fluid
and gas. The caudal border of the spleen
is readily palpable as it lies on the left side
of the abdomen against the body wall.
There should be no bowel between the
spleen and the body wall although
| occasionally small colon can be detected
| dorsal to the spleen. Dorsal and medial to
| the spleen the left kidney should be
| readily palpable, as should the nephro-
j splenic ligament and space. There should
I be no bowel in the nephrosplenic space,
I although some horses have portions of
! small colon in the region of the
I nephrosplenic space. Portions of large
I colon, especially the pelvic flexure, can be
j palpated in the caudal ventral abdomen if
i they contain ingesta. The inguinal rings

may be palpated in males. The ovaries and
uterus can be palpated in mares. The
bladder can be palpated if it contains urine.

Abnormal findings

Abnormalities associated with specific
diseases are discussed under those
headings (Table 5.5). One should be able
to recognize gas and fluid distension of
the cecum and colon, fluid distension of
the small intestine, impaction of the large
and small colon, and displacement of the
large colon.

Small intestinal distension is evi-
dent as loops of tubular structures of up
to 10-15 cm diameter that may extend as
far caudally as the pelvic canal. The
structure is often compressible, akin to
squeezing a fluid-filled tubular balloon,
and slightly moveable. The presence of
distended small intestine is an important
sign suggestive of a small-intestinal
obstructive lesion or anterior enteritis.

Colonic distension, impaction and
displacement. Gas and fluid distension
of the large colon is evident as large
(> 20 cm) taut structures often extending

v'-y • lii j i i’y n io ft;

Rectal abnormality

mtoi:; 'jiiftci! ;;V;%TTuc;^V:!>idi (crs

Disease

Clinical characteristics

Treatment

Distended small

Anterior enteritis

Small intestine mildly to moderately distended. Voluminous

Supportive. Repetitive

intestine

gastric reflux. Marked pain relief on gastric decompression.
Normal peritoneal fluid in most cases

decompression of stomach

Strangulating intestinal
lesion. Small intestinal
volvulus or entrapment

Severe, tight distension of small intestinal. Gastric reflux.
Severe pain not relieved by gastric decompression. Abnormal
peritoneal fluid

Surgery

Ileal impaction

Mild and progressive pain. Gastric reflux only late in disease.
Impaction occasionally palpable per rectum

Medical initially, then surgery if
no resolution

Ileal hypertrophy

Mild to moderate chronic pain occurring after feeding.
Hypertrophy may be palpable

Surgical resection

Ileocecal intussusception

Moderate to severe pain. Gastric reflux later in disease.
Usually young horse

Surgical correction

Large colon distension

Colon torsion

Tenia dorsal in some cases. Cecum displaced medially.
Severe pain. Abdominal distension. No gastric reflux.
Short disease course

Surgical correction

Left dorsal colon

Mild to moderate pain. Bands on rectal examination leading

Replacement by rolling horse.

displacement
(renospleriic entrapment

to renosplenic space. Ultrasonographic confirmation

Surgery

Right dorsal displacement
of colon

Moderate to severe pain. Bands leading ventral to right
dorsal quadrant. Colon lateral to base of cecum

Surgical correction

Impaction of large colon

Impaction palpable per rectum

Fecal softeners and lubricants,
oral and intravenous fluids.
Surgery in refractory cases

Enterolith

Obstruction usually of right dorsal or transverse colon.
Not palpable rectally. Refractory pain. Radiography

Surgical removal

Gas colic

Gas distension of large colon. Pain readily relieved with
analgesics. Short course with rapid recovery. Major
differential is colon torsion

Analgesics, mineral oil

Sand colic

Mild to moderate pain. Sand auscultable in ventral
abdomen. Sand in feces. Occasional watery feces

Analgesics, psyllium orally

Cecal distension

Cecal impaction

Mild to moderate pain, course of several days with
sudden deterioration when cecum ruptures

Analgesics, lubricants, fecal
softeners. Surgical correction

Cecal torsion

Acute, severe pain. Rare

Surgical removal or correction

Displaced spleen

Renosplenic entrapment
of large colon

See above

Large colon displacement.

Mild to moderate pain. Ultrasonographic diagnosis

Analgesics. Surgery

Intra-abdominal masses

Mesenteric abscess

Fever, mild chronic or intermittent abdominal pain.
Increased leukocyte numbers in blood and peritpneal fluid

Long term antibiotics

Neoplasia

Neoplastic cells in peritoneal fluid. Exploratory laparotomy

None

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

into the pelvic canal. Tenial bands are
often not palpable because of the dis-
tension. The distended bowel may extend
into the pelvic canal, preventing exam-
ination of the caudal abdomen. Impaction
is evident as columns of firm ingesta
in the large or small colon. The most
common site is the pelvic flexure in the
caudoventral abdomen and the inlet to
the pelvic canal. The impacted material
remains indented when pressed with the
finger tips.

Distension of the small colon is

detectable as loops of tubular structures
in the caudal abdomen. The loops of
intestine have a prominent antimesenteric
band, a feature not present on small
intestine.

Displacement of the large colon is
evident rectally as tight bands extending
from the ventral abdomen cranially, dorsally
and to the left or cranially, dorsally and to
the right in left and right displacements
of the colon, respectively. Displacement of
the colon, if it obstructs aboral flow
of ingesta and gas, may cause distension.

Nasogastric intubation
Passage of a nasogastric tube is an essen-
tial part of the examination of a horse
with colic because of the diagnostic
information it provides and because relief
of gastric distension may be life-saving.

The nasogastric tube must be passed
into the stomach. This is usually evident
by the release of a small amount of sweet-
smelling gas as the stomach is entered.
The tube should then be advanced further
into the stomach and, if reflux of material
does not occur spontaneously, a siphon
should be established by filling the tube
with approximately 500 mL of water and
rapidly dropping the end of the tube
below the level of the horse's stomach.
This procedure should be repeated at
least three or four times if reflux is not
obtained. If reflux is obtained, its volume
and character should be noted. The
volume should be measured - anything
more than 2L of net reflux is likely
important. If reflux is obtained, the
nasogastric tube should be left in place or
replaced frequently (1 h intervals) until
the colic resolves. If there is no reflux but
the horse remains colicky, then repeated
attempts should be made to obtain reflux.
Oral medications, such as mineral oil,
should not be given to horses with naso-
gastric reflux.

Ancillary diagnostic techniques

Ultrasonography

Ultrasonographic examination of the
abdomen of adult horses is useful in
identifying a number of abnormalities,
including small-intestinal distension,
ileocecal intussusception, gastric disten-

sion, gastric squamous cell carcinoma,
diaphragmatic hernia, peritoneal effusion
and other conditions. 23 The abdomen
should be examined in a systematic
fashion with a 2. 0-3.5 mHz transducer.
Ultrasonographic examination is useful to
detect small-intestinal distension (such as
occurs with anterior enteritis or small
intestinal accidents), reduced motility
(anterior enteritis, enteritis, obstruction),
thickening of intestinal wall (> 4 mm,
enteritis, right dorsal colitis), volume
and characteristics of peritoneal fluid
(peritonitis, hemoperitoneum), abnor-
malities in intestinal contents (such as
presence of sand or excessively fluid
ingesta), presence of sacculations of the
ventral colon (absence indicates, disten-
sion), abnormalities in intestinal architec-
ture (intussusceptions) and presence of
abnormal structures (neoplasia, abscess).
Ultrasonographic detection of small-
intestinal distension is more sensitive
than rectal examination. 24 Ultrasonographic
examination reveals colon with a mural
thickness of 9 mm or greater in horses
with colon torsion. The test has a sensi-
tivity of approximately 67% (i.e. correctly
predicts the presence of colon torsion in
two- thirds of horses that have the
disease) and specificity of 100% (correctly
rules out the diagnosis in 100% of horses
that do not have the disease). 25

Radiology

The large size of the adult horse precludes
detailed radiographic examination of
intra-abdominal structures. However,
enteroliths and sand accumulation can be
detected with reasonable certainty pro-
vided suitable radiographic equipment is
available. 18 Diaphragmatic hernias can be
detected on radiographic examination of
the thorax.

Arterial blood pressure
Arterial blood pressure is a very good
indicator of the degree of shock in colic,
and the availability of a simple technique
makes it a practical aid in assessing
prognosis in a clinical case. If normal
j systolic pressure is about 100 mmHg
| (13.3 kPa), a pressure below 80 mmHg
! (10.6 kPa) indicates a critical situation (it
can be as low as 50 mmHg, 6.6 kPa). In
horses with very severe pain but not
shock, the systolic pressure is likely to be
very high, up to 250 mmHg (33.3 kPa) .

Course of the disease

The course of the disease depends upon
its cause and the severity of the associated
lesions. Spasmodic and gas colic usually
resolves within hours of onset. Horses
with strangulating lesions have severe
clinical signs and usually die within
24 hours of the onset of signs. Horses
with nonstrangulating obstructive lesions

have longer courses, often 48 hours to
1 week, and die when distension causes
bowel to become devitalized and rupture.

When intestinal rupture does occur,
there is a sudden onset ^of shock and
toxemia, the acute pain that preceded it
disappears and the horse becomes quiet
and immobile. The terminal stages after
rupture of the intestine or stomach, or
due to profound endotoxemia, are very
distressing. The horse may be recumbent
but most continue to stand until the
last few minutes, when they literally
drop dead. The respiration is sobbing
and there is gross muscle tremor and
profuse sweating, and there is often a
delirious, staggering wandering. Euthanasia
should be performed before this stage is
reached.

CLINICAL PATHOLOGY

Examination of various clinical pathology
variables is useful in assessing the severity
of the changes occurring as a consequence
of the disease rather than in providing a
definitive diagnosis. Therefore, some
of these variables have prognostic signifi-
cance (Prognostication) and should be
monitored repeatedly in severe cases.

Hematology and serum biochemistry

Measurement of hematocrit and plasma
total protein concentration is useful in
assessing hydration status (see Chapter 2).
Hematocrit increases as a consequence of
splenic contraction or dehydration, making
the use of this variable as a sole indicator
of hydration status unreliable. However,
increases in both hematocrit and total
protein concentration indicate dehydration,
and these variables can be used as crude
estimates of response to fluid therapy.
Plasma total protein concentrations may
decline if there is significant loss of
protein into the gut lumen or peritoneal
space.

Measurement of the blood leukocyte
count has little diagnostic significance,
with the exception that the combination
of leukopenia and a left shift are con-
sistent with the endotoxemia that
accompanies devitalized bowel, enteritis
j or peritonitis.

Horses with severe colic often have
abnormalities in coagulation, with non-
surviving horses and horses with strangu-
lating lesions having the most severe
changes, characterized by low anti-
thrombin activity and prolonged
prothrombin and activated partial
thromboplastin times. 18,26

Measures of serum electrolyte concen-
tration are important in providing an
assessment of the horse's electrolyte
status and in tailoring fluid therapy (see
i Chapter 2). The nature of the abnor-
j malities depends to some extent on the

Diseases of the nonruminant stomach and intestines

cause of fhe disease, but is more markedly
affected by the severity of the disease. Mild
hyponatremia is not uncommon but is
clinically insignificant. Hyperkalemia is
common in horses with severe acidosis and
large sections of devitalized intestine.
Hypokalemia is common in horses with
more long-standing colic, for instance
impaction of the large colon, that have
not eaten for several days. Hypocalcemia
and hypomagnesemia are common in
horses with colic, especially horses with
severe colic. Measurement of total
concentrations (ionized plus non-
ionized) can be misleading in that
reductions in concentration of the
physiologically important ionized
component can be present in horses with
normal concentrations of the total ion. 27,28
Hospitalized horses with colic or diarrhea
are more likely to have hypomagnesemia
than are horses with other diagnoses. 29

Serum enzyme activities are rarely
useful in aiding diagnosis or treatment of
horses with colic, with the exception that
serum gamma glutamyl transferase
(GGT) activity is elevated in approxi-
mately 50% of horses with right dorsal
displacement of the colon, whereas such
elevations are rare in horses with left
dorsal displacement. 30 The elevated GGT,
and less commonly serum bilirubin
concentration, in horses with right dorsal
displacement is attributable to compression
of the common bile duct in the hepato-
duodenal ligament by the displaced
colon. 30 Serum and peritoneal alkaline
phosphatase activities are higher in
horses with ischemic or inflammatory
bowel disease than in horses with other
forms of colic, although the differences
are not sufficiently large as to be useful
diagnostically. 31 Serum creatine kinase
activity above the normal range (385 U/L)
is associated with a fourfold increase in
the likelihood that a horse with colic has
small intestinal ischemia. 32

Serum urea nitrogen and creatinine
concentrations are useful indicators of
hydration status and renal function.
Prerenal azotemia is common in horses
with colic, and may progress to acute renal
failure in severe cases of colic.

High plasma concentrations of intestinal
fatty acid binding protein (> 100 pg/mL)
are associated with increased need for
surgery in horses with colic. 32

Horses that die of colic have higher
circulating concentrations of epinephrine,
cortisol and lactate than do horses that
survive, indicating the greater degree of
sympathetic and adrenal cortical acti-
vation in these horses. 33

Acid-base status

Most horses with severe colic have
metabolic acidosis, although respiratory

acidosis and metabolic alkalosis also
occur. Horses with less severe disease,
such as simple obstructive disease or
spasmodic colic, might not have abnor-
malities in acid-base status. Metabolic
acidosis, when severe, is attributable to
L-lactic acidosis. 34 An estimate of the
plasma lactate concentration can be
obtained by calculating the anion gap:

Anion gap = (sodium + potassium) -
(bicarbonate + chloride).

If bicarbonate concentrations are not
available, total serum carbon dio>«de can
be substituted. Anion gaps of less than
20 mEq/L (mmol/L) are associated with
81% survival, 20-24.9 mEq/L (mmol/L)
with 47% survival, and 25 mEq/L (mmol/L)
or more with 0% survival. 35

Abdominocentesis

Analysis of peritoneal fluid is an import-
ant component of the complete examin-
ation of a horse with colic. 36 Details of the
technique and interpretation of the
results were discussed previously but,
briefly, if there is an increase in the total
protein concentration, a change in the
color to red or blood-tinged, and an
increase in the leukocyte count in
peritoneal fluid, it is likely that there is
some insult to intra-abdominal struc-
tures. 32,36 Total protein concentration
increases when there is an insult to the
gastrointestinal tract that compromises
the serosal surface of the bowel, for
instance strangulating lesions of the small
intestine or in the terminal stages of an
impaction colic in which the bowel wall is
devitalized. 32,36 The presence of intra-
cellular bacteria, plant material and
degenerate neutrophils is indicative of
gastrointestinal rupture provided that one
is certain that the sample came from the
peritoneal space and not from the bowel
lumen (by inadvertent enterocentesis).

PROTOCOL FOR EVALUATING A
COLIC PATIENT

When evaluating a horse with colic the
aims are:

° Determine the nature and cause of
the lesion

° Establish a prognosis
® Determine the most appropriate
therapy, including consideration of
euthanasia

° Determine the need for referral for
specialized care, including surgery.

The suggested protocol for evaluating a
horse with colic is set down below. The
time intervals between repeated examin-
ations depend on a number of factors,
including severity of the disease and the
accessibility of the horse. For a horse with
a possible intestinal obstruction this
should be every hour; for a horse with

probable colonic impaction examinations
every 4 hours are adequate; for a chronic
colic with ileal hypertrophy an examin-
ation every day is usual. The following
observations should be made.

Behavior

The following should be assessed:
severity of pain, frequency and duration
of attacks, whether food is taken, amount
and character of feces, and frequency of
urination.

Clinical and dinicopathological
observations

o Elevated pulse rate with a fall in
pulse amplitude are among'the most
reliable indicators of the state of
dehydration or shock. They can be
temporarily misleading in a horse that
is excited because it is in strange
surroundings, or separated from its
dam, foal or close companion. They
may also be marginally influenced by
a bout of pain. A rate of more than
60/min and a steady climb in heart
rate of about 20 beats/min at each
hour in a series of monitoring
examinations signal a deterioration in
prognosis. A high rate that continues
to worsen during a period of
analgesia as a result of medication
also indicates a bad outcome. A
small-amplitude, 'thready' pulse
characterizes severe shock
° Mucous membrane color and
capillary refill time are assessed.
Deep congestion (dark red) or
cyanosis (purple) and capillary refill
times much longer than 2 seconds are
indicators of peripheral circulatory
failure

° Temperature is infrequently taken
unless there is some positive
indication, such as suspicion of
peritonitis, to do so
0 Respiratory rate, also of minor
importance except as an indicator of
severity of pain, or in terminal stages
of endotoxic shock or dehydration,
when it becomes gasping
° Intestinal sounds. The disappearance
of intestinal sounds indicates ileus.
Hypermotility is usually a sign of less
serious disease, except in the very
early stages of a small intestinal
accident. The development of a 'ping'
on auscultation-percussion indicates
accumulation of gas under some
pressure

f Rectal findings. The development of
palpable abnormalities is an ominous
finding. A decision to intervene
surgically is often made at this point.
The inherent inadequacy of the rectal
examination is that only the caudal
half of the abdominal cavity can be

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

reached. Therefore large bowel and
terminal ileal problems are more
easily detected. With anterior
abdomen small-intestinal lesions,
distended loops do not usually come
into reach until 6 hours after colic
commences. They may reach back as
far as the pelvis by 18 hours

° Amount and nature of feces is
important. Failure to defecate within
12 hours of treatment is a bad sign.
The empty rectum with a dry, tacky
feel, or with a smear of mucus and
degenerated blood some hours after
the last defecation, presages a
completely blocked intestine. The
passage of oil but no feces suggests a
partial blockage of large bowel that
will permit the passage of oil but not
fecal balls

° Reflux through a nasogastric tube.
Acute gastric dilatation or small
intestinal regurgitation of fluid
sufficient to cause reflux of fluid via
the stomach tube is a grim
development. Large-bowel distension
is also associated with fluid
accumulations in the stomach. A
negative test in a case suggestive of
small intestinal obstruction should be
followed by repeated tests; reflux from
a lesion well down in the small
intestine may take some hours to
reach the stomach. In ileocecal valve
impaction gastric reflux may not
develop until 24 hours after the
commencement of the colic

2 Abdominal paracentesis. Repeated
examinations are without serious risk
and can herald the development of
infarction and necrosis of gut wall,
leakage and the development of
peritonitis, or rupture and death due
to endotoxic shock
Visible distension of the abdomen

"> PCV and plasma protein. A rise in
PCV of 5% (i.e. from 55 to 60%) in an
hour is a serious sign. A rise in PCV
with a. stable or declining serum
protein concentration is often indicative
of loss of capillary integrity and leakage
of vascular proteins into extravascular
spaces, such as the intestinal lumen.
This is a sign of a poor prognosis
Skin tenting on its own can be a very
misleading indicator of the state of a
horse's dehydration, but significant
changes from one examination to
another are likely to confirm
deductions made on the basis of heart
rate and mucosal color
Arterial blood pressure is one of the
most reliable prognostic indicators in
cases of colic

Response to analgesics. Diminution
in the relief of pain after
administration of detomidine.

xylazine, butorphanol or flunixin
meglumine can be interpreted as a
serious decline in the status of the
affected intestine.

When to refer the patient

The decision to refer a horse for specialist
care and evaluation is often difficult. Most
referrals occur because of the need for
specialized medical or surgical treatment
and therefore involve considerable expense
and inconvenience to the owner. How-
ever, early referral is critical because of the
improved chances of survival associated
with early medical and surgical therapy of
horses with severe colic.

The criteria for referral include:

0 Severe persistent pain without
identifiable cause for more than
24 hours. Referral should be sooner if
there is evidence of compromised
cardiovascular function, or any of the
signs described below
° Recurrent attacks of colic over a
period as long as several months
0 Failure of an efficient analgesic to
provide analgesia or relief for at least
20 minutes

0 A rectally palpable lesion including
distended small intestine, large colon,
or small colon, or impaction of the
large colon that does not resolve in
24 hours

0 Reflux of more than 4 L of fluid
through a nasogastric tube
Abdominal distension
‘ Blood-tinged, high-protein peritoneal
fluid with a high white cell count
0 A rapid worsening of the pain and
vital signs during a period of
2-4 hours.

Not all of these criteria need to be fulfilled
to warrant a decision to refer and in most
cases the presence of one of these find-
ings is sufficient to justify a recommen-
dation to the owner to refer the horse for
further evaluation and specialized care.

Important in the decision to refer, or to j
perform a laparotomy, is the client's
understanding of the costs involved and
the likely outcomes. Because decisions
to refer are often complicated by the emo-
tional pressures on the owner and the
need to make a decision quickly, it is
important to take the time to fully inform
the owner of the likely costs and out-
comes before a final commitment is made
to refer.

If there is doubt - refer it!

Surgery

The decision to perform surgery is best
made by trained specialists and is usually j
based on a variety of clinical and
clinicopathological findings with most
weight given to the presence of severe
unrelenting or intermittent pain, severe

abdominal distension, large quantities of
reflux through a nasogastric tube, intes-
tinal distension palpable per rectum,
serosanguinous peritoneal fluid, evidence
of cardiovascular compromise including a
high (> 60/min) and increasing heart rate,
poor capillary refill, discolored mucous
membranes and the absence of
borborygmi. 37,38 Presence of abnormal
abdominal fluid (turbid or serosanguinous)
and peritoneal fluid with an elevated total
protein concentration has good sensitivity
(92%) and moderate specificity (74%) for
the need for surgery. 36 Formal modeling
of the need for surgery in horses with
colic at referral institutions provides a
numerical estimate of the need for surgery;
but is seldom used in most referral
practices. 39,40

Prognosis

Given the enormous emotional and
financial costs of having a severely ill
horse with colic, there is an obvious need
for accurate prognostication. Overall best
predictors of survival are those clinical
and clinicopathological factors that assess
cardiovascular and metabolic status. The
important factors include arterial blood
pressure or its clinical correlates, pulse
pressure and/or capillary refill time, pulse
rate, mucous membrane color, indicators
of hydration status (hematocrit, serum
urea nitrogen concentration), blood lactate
concentration and anion gap. 33,41 ' 44

Arterial systolic blood pressure is
one of the best predictors of survival,
with horses with systolic pressures of
90 mmHg (12 kPa) having a 50% chance
of survival while fewer than 20% of
horses with a pressure below 80 mmHg
(10.6 kPa) survive.

Capillary refill time, the clinical
manifestation of arterial blood pressure, is
also a good predictor of the probability of
survival. Capillary refill times of 3 seconds
or more are associated with a survival rate
of 30%. Similarly, increasing heart rate
is associated with diminishing chances
of survival - a horse with a heart rate of
80/min has a 50% chance of survival
whereas one with a heart rate of 50/min
has a 90% chance of surviving. Increasing
blood lactate concentration and anion
gap (see under Clinical pathology, above)
are associated with increased chance of
death. Measures of hydration status are
also good indicators of prognosis. A
hematocrit of 50% (0.50 L/L) is associ-
ated with a 50% chance of survival, while
the chance of surviving drops to 15%
when the hematocrit is 60% (0.60 L/L).
Horses with high circulating epinephrine,
cortisol or lactate concentrations are at
greater risk of death. 33

While' individual variables may be
good prognostic indicators, their predictive

Diseases of the nonruminant stomach and intestines

utility Improves when they are
combined 40,43,44 although this introduces
the need for either remembering models
or keeping the model close at hand,
something often not easily accomplished
in the field. Furthermore, these models
have been developed from cases at
specific referral institutions and may not
be applicable to field cases or even cases
at other referral sites. However, the
general principles probably apply in
all circumstances even if the precise
weighting appropriate for each variable
does not.

NECROPSY FINDINGS

The nature of the necropsy findings
depends on the underlying disease.

DIFFERENTIAL DIAGNOSIS

The following diseases may be mistaken
for colic:

• Laminitis

• Pleuritis

• Enterocolitis

• Rhabdomyolysis

• Obstructive urolithiasis

• Uroperitoneum

• Foaling and dystocia

• Uterine torsion

• Peritonitis

• Cholelithiasis

• Ovulation and ovarian pain

• Esophageal obstruction

• Anterior enteritis

• Gastric ulceration

• Anthrax

• Testicular torsion

• Lactation tetany

• Tetanus

• Rabies

• Botulism

• Grass sickness

• Purpura hemorrhagica

• Clostridial myonecrosis (gas gangrene)

• Psychogenic colic

The clinical characteristics of common
causes of equine colic are summarized in
Table 5.6.

TREATMENT
Medical treatment

The specific treatment of each case of
colic varies and depends on the nature of
the lesion and the severity of the disease.
However several principles are common
to the treatment of most colic:

Provision of analgesia
Correction of fluid, electrolyte and
acid-base abnormalities
Gastrointestinal lubrication or
administration of fecal softeners
Treatment of underlying disease.

Analgesia

Analgesia is important in that it relieves
the horse's discomfort, minimizes the
physiological consequences of pain,

including the pain-induced reduction
in gastrointestinal motility, permits a
thorough clinical examination and reduces
the likelihood of the horse injuring itself
while rolling or thrashing. Analgesics can
be divided into NSAIDs, sedating anal-
gesics and spasmolytics. The doses of
these drugs are provided in Table 5.7.

The analgesic and its dose rate should
be chosen such that the horse's pain is
relieved but signs of progressive cardio-
vascular compromise indicative of the
need for more aggressive therapy or
surgery are not masked. Acupuncture
does not provide effective analgesia in
horses with colic and should not be used
in these animals. 45

Nonsteroidal anti-inflammatory drugs
Flunixin meglumine is a potent, long-
acting analgesic with the ability to mask
signs of surgical disease, with the
consequence that surgery may be delayed
and the chance of recovery diminished.

; Flunixin meglumine should only be used
to control pain when the diagnosis is clear
or when surgical intervention is not an
; option. It should not be used routinely in
horses being monitored for progression
; of disease unless such monitoring is
; frequent and thorough, which may not be
i the situation in field colics. A horse that
remains painful 30 minutes after the
administration of flunixin meglumine is
likely to have severe gastrointestinal
1 disease and should be further evaluated.

Comments similar to flunixin
: meglumine apply to ketoprofen but not
to phenylbutazone, which has relatively
weak analgesic effects in colic patients (as
opposed to its potent analgesic effects in
. musculoskeletal disease). Dipyrone is a
weak analgesic that is useful in treatment
of mild cases of colic.

Flunixin meglumine and etodolac
retard recovery of equine jejunum and
barrier function and flunixin inhibits
electrical activity in the ventral colon. 46,47
However, these effects detected in vitro
have not been demonstrated to have
' practical relevance to treatment of horses
with colic with NSAIDs. Horses in pain
should not, based on current information,

; be deprived of these drugs.

; Alpha-2 agonists

The alpha-2 agonists (xylazine, deto-
midine, romifidine) provide potent
analgesia, especially when combined with
1 the opiate butorphanol. Duration is
: relatively short (up to 90 min for
: detomidine), which means that signs of
j progressive disease are readily detectable,
i The effect of alpha-2 agonists in reducing
! gastrointestinal motility is not clinically
' important in most colic cases and should
: not discourage use of these very useful
| drugs.

j Opiates

j Opiates, including butorphanol,
j meperidine (pethidine), morphine and
I pentazocine, are potent analgesics useful
i in the management of abdominal pain in
j the horse. These drugs are often combined
j with an alpha-2 agonist. Morphine arid
j meperidine can cause excitement or
j urticaria in some horses. All are drugs
! with the potential for human abuse
j and the consequent limitation on their
j availability limits their use in horses,
j

l Other agents

; Acetylpromazine has almost no anal-
| gesic properties, although it is a potent
! sedative, and should not be used in the
j routine treatment of colic. Acetylpromazine
j is a potent hypotensive agent and should
i not be administered to any horse that is
I dehydrated or has compromised cardio-
[ vascular function.

Hyoscine butylbromide, a para-
i sympatholytic drug, is widely used in
j certain parts of the world as the drug of
: choice in the initial treatment of field
i cases of colic. It is often combined with
; dipyrone and is effective in the field treat-
ment of mild, uncomplicated colic.

Atropine causes gastrointestinal stasis
in horses and should not be used in the
routine treatment of colic 48

Lidocaine (Table 5.7) is a potent
analgesic when administered systemically,
but must be given by constant intra-
venous infusion. Overdosing results in
central nervous system excitement.

Prophylaxis and treatment of
.: endotoxemia

Treatment of endolemma has been
recently reviewed. 49 Administration of
plasma from horses hyperimmunized
with Salmonella typhimurium or E. coli
reduces the severity of clinical signs and
shortens the duration of disease in horses
with endotoxemia secondary to entero-
colitis or colic. 50 Polymyxin (5000 IU/kg
intravenously every 8-12 h) attenuates the
effect of endotoxin in experimental
disease and is used for the prevention and
treatment of endotoxemia in hospitalized
horses. 51 Its efficacy in clinical settings has
not been determined. Aspirin (10 mg/kg
orally every 48 h) is administered to
diminish platelet aggregation around
intravenous catheters. Flunixin
I meglumine (1 mg/kg intravenously every
8-12 h) or phenylbutazone (2.2 mg/kg
intravenously every 12 h) is given for
analgesia and to prevent endotoxin-
: induced increases in plasma prosta-
glandins. Pentoxifylline (8 mg/kg orally
every 8 h) is administered for its putative
; effective in attenuating the effects of
endotoxemia. The efficacy of these treat-
ments in a clinical setting and their effect
I on measures of outcome of disease, such

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

The clinical picture varies with time: descriptions relate to clinical signs at 12-24 h of illness.

*Chronic intussusception, terminal ileal hypertrophy, constructive adhesions, Meckel's diverticulum, fibroma at the root of the mesentery.

Diseases of the nonruminant stomach and intestines

227

iJab1e : 5;7:Aha1g‘esic:

and spasmolytics -for use in equinexolic;^ ^ N

H

Drug class

Drug

Dose

Comments

NSAIDs

Flunixin meglumine

0.25-1 .0 mg/kg, IV or IM every 8-24 h

Potent analgesic for up to 12 h.
May masksignsof surgical disease

Ketoprofen

2.2 mg/kg, IV every 12 h

Potent analgesic for up to 12 h

Phenylbutazone

2. 2-4.4 mg/kg, IV or PO every 12 h

Weak analgesic for gastrointestinal pain. -
Minimal effect on motility

Dipyrone

1 0 mg/kg, IV or IM every 4-6 h

Weak analgesic. Often combined with
hyoscine in commercial preparations
(Buscopan compositum)

Opiates

Butorphanol

0.025-0.1 mg/kg, IV or IM as required

Potent analgesia for 30-90 min. Safe.
Often combined with an alpha-2 agonist.
May cause ataxia

Meperidine (pethidine)

0.2-2. 0 mg/kg, slowly IV or IM as required

Moderate analgesia for 0.5-4 h. Can
cause excitement and/or ataxia

Pentazocine

0.5-1 .0 mg/kg, IV or IM as required

Moderate analgesia. May cause ataxia

Morphine sulfate

0.05-0.01 mg/kg slowly IV or IM as required

Potent analgesia. Can cause excitement

Alpha-2 agonists

Xylazine

0. 1-1.0 mg/kg, IV or IM, as needed

Potent analgesia and sedation for up to
30 min. Decreases intestinal motility.
Often combined with butorphanol

Detomidine

10-40 pg/kg, IV or IM as needed

Potent analgesia and sedation for up to
1 20 min

Romifidine

0.04-0.08 mg/kg, IV or IM

Potent analgesia and sedation

Medetomidine

0.01-0.02 mg/kg, IV or IM.

Potent analgesia for up to 120 min.
Sedation

Spasmolytics

Atropine

0.01-0.04 mg/kg IV or IM

Do not use because of induction of ileus

Hyoscine butylbromide

0.1-0. 4 mg/kg, IV or IM every 6-1 2 h

Reduces gastrointestinal motility. Mild
analgesic. Often combined with dipyrone

Other

Acetylpromazine

0.02-0.04 mg/kg, IV or IM every 6-24 h

No analgesia but marked sedation. Potent
hypotensive agent. Do not use

Lidocaine

1 .5 mg/kg IV loading dose followed by
0.05 (mg/kg)/min IV infusion

Substance P inhibitor. Analgesic, anti-
inflammatory, promotility agent

11 W, intramuscularly; IV, intravenously; NSAIDs, nonsteroidal anti-inflammatory drugs; PO, orally

as duration of illness, case fatality rate or
incidence of complications, has not been
determined, with the exception of hyper-
immune plasma or serum. 50

Antibiotics are often administered to
horses with severe colic and evidence of
toxemia because of presumed bacteremia.
The antibiotics of choice should have a
broad spectrum including Gram-negative
and positive and anaerobic bacteria. A
suitable regimen includes an amino-
glycoside and a penicillin, possibly
combined with metronidazole. NSAIDs
are administered to prevent the increased
production of prostaglandins induced by
endotoxin and the associated clinical
abnormalities including fever, malaise
and tachycardia. However, the effect of
NSAIDs in improving survival or shorten-
ing the duration of treatment has not
been demonstrated.

Fluid and electrolyte therapy
Horses with evidence of dehydration,
compromised cardiovascular function
or electrolyte imbalances should be
administered fluids intravenously, prefer-
ably a balanced, isotonic, polyionic fluid
such as lactated Ringer's solution. Horses
with severe colic and signs of cardio-
vascular collapse may require urgent
resuscitation by intravenous administration
of large quantities of fluids or adminis-
tration of hypertonic saline followed by

administration of isotonic fluids. Horses
with hypoproteinemia may benefit from
administration of plasma or colloidal
fluids such as hetastarch. (See Chapter 2
for details on fluid therapy and the
section on Shock for a discussion of the
treatment of this syndrome.)

Intestinal lubricants and fecal softeners
The intestinal lubricant of choice is
mineral oil (Table 5.8). It should be given
only through a nasogastric tube as its
aspiration is associated with severe and
usually fatal pneumonia. Mineral oil is
useful in cases of mild impaction colic and
is often administered when the cause
of the colic is not known, provided that
there is no reflux of gastric contents
through the nasogastric tube.

Dioctyl sodium sulfosuccinate (DSS)
is a fecal softener with the potential to be
toxic at therapeutic doses and its use is
now not generally recommended. 32
Magnesium sulfate is an effective fecal
softener useful in the treatment of
impaction colic. 52 However, it can cause
hypermagnesemia and toxicity character-
ized by depression and signs of central
nervous system dysfunction. 53 Sodium
sulfate is a safe and effective fecal
softener, although it may induce mild
hypernatremia and hypokalemia 54

Other treatments

Promotility agents (Table 5.8) may be

used in cases of ileus or large colon
impaction. Postoperative ileus is a common
complication of surgical colic and should
be treated by maintenance of hydration
and electrolyte status and administration
of promotility agents. 35 Cisapride is
apparently effective in reducing the
incidence of postoperative ileus and may
be useful in the treatment of ileus of other
cause. 36 The clinical efficacy of other
putative promotility agents has not been
demonstrated.

Heparin and low-molecular-weight
heparins have been recommended for the
treatment and prevention of coagulopathies
associated with severe colic. 21 The use of
heparin or low-molecular-weight heparin
is associated with increased risk of
hemorrhage and heparin use causes a
decrease in hematocrit. 21 The efficacy of
this treatment in improving survival has
not been demonstrated.

Trocarization

Occasionally in severe cases of flatulent
(gas) colic or in cases of colon torsion in
which the abdominal distension is
impairing respiration, it may be necessary
to relieve the gas distension of the colon
or cecum by trocarization. Trocarization is
usually performed through the right
paralumbar fossa immediately caudal to
the last rib.The exact place for trocarization
can be located by simultaneous flicking

228

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

AAV :

Drug group

Drug

Dose

Comments

Lubricants

Mineral oil

10-1 5 mL/kg, via nasogastric tube, every 12-24 h

Safe. Lubricant only, does not soften feces. Usually
passed in 12-36 h*

Fecal softeners

Dioctyl sodium
sulfosuccinate (DSS)

12-25 mg/kg, via nasogastric tube, every 24 h

No more than 2 doses. Toxic at higher doses*

Magnesium sulfate

0. 5-1.0 g/kg, via nasogastric tube, in water

Osmotic cathartic. Toxic (CNS signs due to
hypermagnesemia) with repeated dosing*

Sodium sulfate

1.0 g/kg, via nasogastric tube, in water, every 12 h

Osmotic cathartic. Mild hypernatremia. Safe*

Psyllium

1 g/kg, orally, every 24 h

Bulk laxative. Used for treatment of sand
accumulation. Efficacy uncertain but widely used*

Promotility agents

Lidocaine

1.5 mg/kg slow IV, then 0.05 mg/kg infusion

Analgesic, anti-inflammatory, promotility. Used to
treat ileus. Toxicity evident as CNS signs

Metoclopramide

0.25 mg/kg IV slowly over 30 min every 12 h

Toxic. Minimally effective

Erythromycin

0.1 (mg/kg)/h IV

Questionable efficacy. May induce colitis

Cisapride

0.1 mg/kg, IV every 8 h

Effective in prevention and treatment of
postoperative ileus. May prolong cardiac
Q-T interval (importance unknown)

Neostigmine

0.02 mg/kg, IM or SC, every 8-12 h

Increases large-colon motility, decreases small-
intestine motility. May cause colon rupture around
hard impaction

*None of these agents should be given if there is reflux through the nasogastric tube.
CNS, central nervous system; IM, intramuscularly; IV, intravenously; SC subcutaneously.

the body wall with a finger and listening
with a stethoscope. The area of loudest
ping will indicate the point of insertion of
the trocar. A suitable trocar is a 12.5-15 cm
14-16-gauge needle. The needle is
inserted through the skin and advanced
into the abdomen until there is an audible
expulsion of gas through the trocar. The
trocar should be kept in position as long
as gas is escaping. It may need to be
replaced as the bowel is decompressed
and moves away from the trocar. The
procedure is reasonably safe but will
cause inflammatory changes in the
peritoneal fluid. The major danger is
laceration of the colon or cecum and
leakage of ingesta. It is advisable to
administer systemic antibiotics to horses
that have been trocarized.

Management of field colic

Initial treatment of field cases of colic that
do not have signs indicative of the need
for referral or surgery usually includes
administration of an analgesic and an
intestinal lubricant. Analgesics suitable
for the initial treatment of colic in the field
are an alpha-2 agonist, such as xylazine,
hyoscine butylbromide, dipyrone,
butorphanol or phenylbutazone. If there
is no reflux through the nasogastric tube,
then mineral oil should be administered.
Fluids should be administered intra-
venously if there are signs of dehydration,
cardiovascular compromise or electrolyte
imbalance. The response to this therapy
should be monitored as described under
Protocol for evaluating a colic patient.
Further doses of analgesic can be given as
required and the horse should be
monitored for any evidence of deterio-
ration. If referral is contemplated, the

referral institution should be contacted for
advice on analgesia during transportation.
Horses should be transported with a
nasogastric tube in place.

Surgery

The only definitive treatment for many
causes of equine colic is surgical
correction or removal of the lesion. The
availability of surgical facilities staffed by
appropriately trained personnel has
increased over the past two decades and
there is often the opportunity to refer
horses for examination by personnel with
specialist training. Gastrointestinal surgery
should not be attempted by those
untrained or inexperienced in the necess-
ary techniques or without the facilities to
provide postoperative care.

The decision to perform an exploratory
laparotomy on a horse with colic is based
on a number of factors, including the
provisional diagnosis, findings on physical
and laboratory examination and degree of
pain. Horses with severe pain refractory
to treatment with analgesics should have
an exploratory laparotomy even if no
other significant abnormalities can be
detected. Algorithms for the decision to
perform surgery have been developed,
but are not perfect and do not replace the
opinion of an appropriately trained and
experienced examiner. 40 Examination of
peritoneal fluid contributes to the deci-
sion to perform surgery. 3 *’ The survival
rate for horses undergoing surgical
correction of lesions depends on the
nature and location of the underlying
disease and its duration. 57 However,
survival rates range from 50-75%, with
approximately two thirds of horses
returning to their intended use 58-60 The

survival rate of horses with small-
intestinal lesions is less than that of
horses with large-intestinal disease, and
the survival rate for horses with strangu-
lating disease is much less than that of
horses with nonstrangulating disease. 58

Prevention

Minimization of colic episodes depends
on management factors, including
ensuring adequate parasite control, feed-
ing large quantities of forage and
minimizing the amount of concentrate
fed, and providing dental care. However,
most cases of colic not attributable to
parasites or dietary factors cannot be
prevented.

REVIEW LITERATURE

Johnston M. Equine colic - to refer or not to refer. In
Pract 1992; 14:134-141.

Hay WP, Moore JN. Management of pain in horses
with colic. Compend Contin Educ Pract Vet 1997;
19:987-990.

Singer ER, Smith MA. Examination of the horse with
colic: is it medical or surgical? Equine Vet Educ
2002; 14:87.

Cohen ND. Colic by the numbers. EquineVet J 2003;
35:343.

REFERENCES

1. Traub-Dargatz JL et al. J Am Vet Med Assoc 1991;
198:1745.

2. Tinker MK et al. EquineVet J 1997; 29:448.

3. Traub-Dargatz JL et al. J Am Vet Med Assoc 2001;
219:67.

4. Kaneene JB et al. PrevVet Med 1997; 30:23.

5. Proudman CJ. EquineVet J 1991; 24:90.

6. Cohen ND et al. J Am Vet Med Assoc 1999;
215:53.

7. Uhlinger C. EquineVet J 1990; 22:251.

8. Hillyer MH et al. EquineVet J 2001; 33:380.

9. Goncalves S et al. Vet Res 2002; 33:641.

10. Cohen ND. EquineVet J 2003; 35:343.

11. Tinker MK et al. EquineVet J 1997; 29:454.

12. Freeman DE et al. J Am Vet Med Assoc 2001;
219:87.

Diseases of the nonruminant stomach and intestines

229

13. Hudson JM et al. J Am Vet Med Assoc 2001;
219:1419.

14. Reeves MJ et al. J Prevent Med 1996; 26:285.

15. Cohen ND et al. J Am Vet Med Assoc 1995;
206:667.

16. Proudman CJ et al. Equine Vet J 1998; 30:194.

17. Barton MH et al. J Vet Intern Med 1999; 13:457.

18. Prasse KW et al. J Am Vet Med Assoc 1993;
203:685.

19. Monreal L et al. Equine Vet J Suppl 2000; 32:19.

20. Fiege K et al. J Vet Med A 2003; 50:30.

21. Fiege K et al. Equine Vet J 2003; 35:506.

22. Blikslager AT, Roberts MC. J Am Vet Med Assoc
1995; 207:1444.

23. Freeman S. In Pract 2002; May:262.

24. Klohnen A et al. J Am Vet Med Assoc 1996;
209:1597.

25. Ffease AP et al. Vet Radiol Ultrasound 2004;
45:220.

26. Collatos C et al. J Vet Intern Med 1995; 9:18.

27. Garcia -Lopez JM et al. Am JVet Res 2001; 62:7.

28. \fan der Kolk JH et al. Equine Vet J 2002; 34:528.

29. Johansson AM etal.JVetlntemMed 2003; 17:860.

30. Gardner RB et al. JVet Intern Med 2005; 19:761.

31. Saulez M et al. JVet Intern Med 2004; 18:564.

32. Nieta JE et al. Am JVet Res 2005; 66:223.

33. Hinchcliff KW et al. J Am Vet Med Assoc 2005;
227:276.

34. Nappert G, Johnson PJ. CanVet J 2001; 42:703.

35. Bristol DG. J Am Vet Med Assoc 1982; 181:63.

36. Matthews S et al. AustVet J 2002; 80:132.

37. Edwards GB. Equine Vet Educ 1991; 3:19.

38. Baxter GM. Vet Med 1992; 87:1012.

39. Reeves MJ et al. Am JVet Res 1991; 52:1903.

40. Thoefner MB et al. CanVet J 2003; 67:20.

41. P^rry BW et al. Equine Vet J 1983; 15:211.

42. Puotunen-Reinert A. EquineVet J 1986; 18:275.

43. Furr MO et al. Vet Surg 1995; 24:97.

44. Reeves MJ et al.PrevVetMed 1990; 9:241.

45. Merritt AM et al. Am J Vet Res 2002; 63:1006.

46. Tomlinson JE et al. Am JVet Res 2004; 65:761.

47. Freeman DE et al. Am JVet Res 1997; 58:915.

48. Sykes BW, Furr MO. AustVet J 2005; 83:45.

49. Ducharme NG, Fubini SL. J Am Vet Med Assoc
1983; 182:229.

50. Spier SJ et al. Circ Shock 1989; 28:235.

51. Barton MH et al. EquineVet J 2004; 36:397.

52. Freeman DE et al. Am JVet Res 1992; 53:1347.

53. Henninger RW, Horst J. J Am Vet Med Assoc 1997;
211:82.

54. Lopes MAF. Am JVet Res 2004; 65:695.

55. Hoogmoed LM. Vet Clin North Am Equine Pract
2003; 19:729.

56. Velden MA, Klein WR. Vet Q 1993; 15:175.

57. Van der Linden MA et al. JVet Intern Med 2003;
17:343.

58. PhillipsTJ, Y\klmsley JP. EquineVet J 1993; 25:427.

59. Hunt JM et al. EquineVet J 1986; 18:264.

60. Blikslager AT et al. J Am Vet Med Assoc 1994;
205:1748.

COLIC IN THE PREGNANT AND
POSTPARTURIENT MARE

Diagnosis and management of colic in
pregnant and immediately postparturient
mares is challenging because of the
variety of conditions that can cause the
disease, the difficulty in examination of
intra-abdominal organs in late term
mares and concern about the viability of
the fetus. There are also substantial
technical challenges in surgical correction
of abnormalities of either the gastro-
intestinal tract or reproductive tract in the

presence of a gravid uterus. Colic in late
term mare can be caused by any of the
causes of colic in adult horses (Table 5.4)
but some disorders occur more commonly
in late term mares and in addition
abnormalities of the reproductive tract
can cause signs of colic. Causes of colic in
the late term mare include: 1-3

° Idiopathic, chronic or recurrent, low-
grade colic

0 Large colon torsion
° Large colon impaction
a Incarceration of small intestine
through a mesenteric rent
° Rupture of the cecum or colon
0 Uterine torsion
° Uterine rupture

° Middle uterine or utero- ovarian artery
rupture

0 Abdominal wall hernia
° Diaphragmatic hernia
° Dystocia
• Hydrops
° Imminent foaling.

A common presentation of colic in late
term mares is chronic or recurrent, low-
grade abdominal pain that is not associ-
ated with any signs of compromised
cardiovascular or gastrointestinal function.
It is assumed that the large gravid uterus
interferes with normal motility or position-
ing of bowel, with subsequent pain. Severe
colic in late term mares is rarely associ-
ated with the uterus, with the exception
of uterine torsion.

Colic in immediately post-parturient
mares (< 24 h after foaling) include: 1-3

® Cramping associated with uterine
contractions and involution, often
coincident with nursing or
administration of oxytocin
- Rupture of the cecum or colon
Incarceration of the small intestine
through a mesenteric rent
Rupture of the mesocolon with
segmental ischemia of the small colon
Rectal prolapse

Uterine tear, with or without prolapse

of intestine

Uterine prolapse

Inversion of uterine horn

Bladder prolapse through urethra

Hemorrhage from uterine or utero-

ovarian artery

Retained fetal membranes

Uroperitoneum, usually secondary to

rupture of the bladder.

Colic in postparturient mares that is any-
thing more than transient and associated
with passage of placenta or nursing of the
foal should be considered important and
the mare should be examined closely and,
if the colic does not resolve, repeatedly.

Survival rates for colic associated
with anatomical abnormalities in late

term or postparturient mares is 50% and
30%, respectively. 3

Clinical examination of late-term or
postparturient mares with colic uses the
same principles as apply to examination
of nonpregnant adult horses with colic.
Monitoring of vital signs, passage qf a
nasogastric tube, rectal examination and
collection of peritoneal fluid should all be
performed as indicated. However, the
presence of a gravid uterus in late-term
mares impairs rectal examination of the
abdomen and often makes collection of
peritoneal fluid impossible. Manual and
visual, through a speculum, examination
of the vagina and cervix should be
performed.

Rectal examination should be per-
formed and careful attention should be
paid to examination of the uterus,
including position and viability of the fetus,
and broad ligaments. Uterine torsion can
be detected by examination of the broad
ligaments, which in mares with uterine
torsion will be taut and spiral in the
direction of the torsion. Hemorrhage into
the broad ligament, which can extend into
the uterus and perivaginal regions, is
detectable as swelling in these structures.
Additionally, affected mares will have signs
of hemorrhagic shock, including tachy-
cardia, sweating and pallor of mucous
membranes. Palpation of gastrointestinal
structures per rectum is limited in the late-
term mare, although the cecum and small
colon should be palpable. The spleen and
left kidney can be palpated in almost all
normal late-term mares.

The reduced uterine size in post-
parturient mares permits more thorough
per rectum examination of the caudal
abdomen. Again, careful attention should
be given to palpation of the uterus and
associated structures for evidence of
hemorrhage, prolapse or rupture. Rectal
prolapse and eversion of the small colon
in a postparturient mare is an ominous
finding as it is usually associated with
rupture of the mesocolon and ischemic
necrosis of the small colon, a condition
that is almost always fatal. Prolapse of
j small amounts of anal or perirectal tissue
i is not a serious concern.

! The abdominal silhouette should be
i examined for evidence of abdominal
i distension, such as can occur with colon
] torsion or uterine hydrops, and abnor-
malities in contour caused by rupture of
the prepubic tendon and herniation of
: abdominal contents. 4
i Vaginal and cervical examination
! can reveal discharge associated with
I impending abortion or parturition. Vaginal
examination for uterine torsion is of
i limited value as the torsion almost always
i' occurs cranial to the cervix so that, unlike
the cow, the torsion is not apparent as

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

deformation of the'cervix. Manual exam-
ination of the vagina, cervix and uterus of
postparturient mares with colic is import-
ant to detected uterine, cervical and
vaginal trauma, uterine inversion and
retained fetal membranes.

Ultrasonographic examination of
the abdomen in the late-term mare, both
per rectum and percutaneously, allows
examination of structures not palpable
per rectum. The presence and any abnor-
malities in structure, location and motility
of bowel should be noted. For example,
small-intestinal distension caused by
entrapment through a mesenteric rent
may not be palpable per rectum but can
be imaged. Peritoneal fluid should be
examined for quantity and echogenicity.
Intra-abdominal hemorrhage caused by
uterine artery rupture is evident as large
quantities of echogenic fluid that has a
characteristic swirling pattern similar to
turbulent blood flow imaged ultra-
sonographically in the cardiac ventricles
of some horses. The position, number and
viability of the fetus or fetuses should be
ascertained. The nature of allantoic fluid
should be noted.

Collection of peritoneal fluid from
late- term mares can be difficult because
of contact between the gravid uterus and
the ventral abdominal wall. Ultra-
sonographic examination can by useful in
locating pockets of fluid for collection.
Collection of peritoneal fluid is more
readily accomplished in the postpartum
mare. Peritoneal fluid from late- term and
postpartum mares, even those with
assisted vaginal delivery, should have
protein and cell concentrations within
the reference range of nonnal horses. 5,6
Abnormalities in peritoneal fluid in late-
term or postparturient mares should be
considered to be indicative of intra-
abdominal disease. 6

The differential diagnosis of colic is
similar to that of nonpregnant horses
except as indicated above.

Treatment of colic depends on its
cause. Horses with low-grade to moderate,
recurrent colic respond to administration
of low doses of NSAIDs, mineral oil or
fecal softeners.

The risk of abortion in mares with
colic is partially dependent on the severity
of colic and especially the presence of
toxemia. 1,2,7 Severely ill mares with signs
of toxemia have abortion rates of almost
70% 7 while mares with less severe disease
have abortion rates of 12-18%, which is
not markedly different from the rate in
mares without colic. 3 Approximately 40%
of mares with uterine torsion abort. 1

REVIEW LITERATURE

Slcel CM, Gibson KT. Colic in the pregnant and

periparturient mare. Equine Vet Educ 2001; 13:94.

REFERENCES

1. Boening KJ, Leendertse IP. Equine Vet J 1993;
25:518.

2. Santschi EM et al. J Am Vet Med Assoc 1991;
199:374.

3. Steel CM, Gibson KT. Equine Vet Educ 2001;
13:94.

4. Hanson RR, Todhunter RJ. J Am Vet Med Assoc
1986; 189:790.

5. \fan Hoogmoed L et al. J Am Vet Med Assoc 1996;
209:1280.

6. Frazer GS et al. Theriogenology 1997; 48:919.

7. Slone DE. CompendContin Educ PractVet 1993;
15:117.

COLIC IN FOALS

Synopsis gg|

Etiology See Table 5.9
Epidemiology Sporadic. Some are
congenital, others heritable. Inguinal and
scrotal hernias occur only in males
Clinical signs Abdominal pain evidenced
by kicking at the abdomen, flank-
watching, repeated tail movements as if
chasing flies, repeated aborted attempts to
suck, frequent lying down and standing
within a short period, rolling and lying in
dorsal recumbency. Abdominal distension
in some diseases and straining to defecate
with meconium impaction. Radiography
and ultrasonography are useful in
identifying affected bowel
Clinical pathology None diagnostic
Lesions Of the causative disease
Diagnostic confirmation Physical
examination, radiography, ultrasonography,
laparotomy, necropsy
Treatment Pain control, fluid therapy,
treatment of causative disease

ETIOLOGY

Diseases that cause colic in horses less
than 1 year of age include both congenital
and acquired conditions and are listed in
Table 5.9.

EPIDEMIOLOGY

The congenital conditions are discussed
under those headings in Chapter 34,
but it is notable that some, such as ileo-
colonic aganglionosis in white progeny
of Overo spotted horses, are clearly
heritable. Other conditions occur
sporadically, although meconium impac-
tion is more common in colt foals and
occurs only in the newborn foal, intus-
susceptions are most common in foals of
3-5 weeks of age and particularly those
with diarrhea or extraintestinal illness,
and impaction of the small colon by
fecaliths is common in miniature horse
foals. 3,4 Inguinal and scrotal hernias
occur only in male foals. 5

Among neonatal Thoroughbred foals
50% of foals subjected to exploratory
laparotomy had nonstrangulating lesions
and 30% had enteritis. 6 Among foals
2 weeks to 6 months of age, 30 of foals

subjected to exploratory laparotomy had
gastric ulcer disease, 27% strangulating
lesions, 21% nonstrangulating lesions
and 17% enteritis. 6

PATHOPHYSIOLOGY

The pathophysiology of colic in foals does
not differ qualitatively from that of adult
horses (see Equine colic, above). The
importance of pain, gastrointestinal dis-
tension, motility and absorptive disturb-
ances and loss of barrier function are all
similar in foals and adults. Additionally, in
young foals gastrointestinal disease may
prevent nursing and ingestion of col-
ostrum, causing failure of transfer
of passive immunity to the foal. Failure to
nurse also results in hypoglycemia and
dehydration, which may exacerbate
the abnormalities induced directly by the
disease causing colic.

CLINICAL FINDINGS

Pain is the cardinal feature of gastro-
intestinal disease of foals. Foals with mild
abdominal pain are apprehensive and
walk continuously with frequent but brief
(< 1 min) periods of sternal or lateral
recumbency. Affected foals make frequent
attempts to nurse but do not continue to
suckle and may butt the mare's udder even
though there is let-down of milk. The foal
vigorously moves its tail as if chasing flies,
looks at the abdomen and may nip at its
flanks. There are often frequent attempts to
urinate or defecate but without passage of
significant quantities of urine or feces.
Severely affected foals will roll, often
violently, and may spend considerable
periods of time in dorsal recumbency, often
propped up against walls or fences.

Severely affected foals are tachycardic
(> 100/min) and tachypneic (< 40/min)
(recall that young foals have higher heart
and respiratory rates and rectal tempera-
ture than do older foals and adults.
Mucous membrane color and capillary
refill time are similar to that of adult
horses, and changes can be interpreted in
the same manner as for adults.

The external abdomen should be
examined closely for the presence of
inguinal, scrotal or umbilical hernias.
Abdominal distension in foals can be the
result of large-colon or small-intestinal
distension (or uroperitoneum), although
the abdominal distension is greater with
large-colon distension. Abdominal cir-
cumference should be monitored frequently
by direct measurement to detect changes
in the degree of abdominal distension.

Auscultation of the abdomen may
reveal increased or decreased borborygmi
and, if there is gas distension of the large
colon or cecum, pinging sounds on
simultaneous flicking and auscultation of
the abdomen.

Diseases of the nonruminant stomach and intestines

231

le\5;9. Diseases causing^pliain’foafel

Congenital anomalies

Gastrointestinal obstruction
with or without infarction

Other

Anal atresia
Colonic atresia
Rectal atresia
Ileocolonic agangliosis
Myenteric hypogangliosis
Inguinal hernia
Diaphragmatic hernia
Umbilical hernia
Scrotal hernia
Meconium impaction

Ileus, secondary to extraintestinal disease including neonatal
hypoxia

Small-intestinal volvulus
Large-intestinal volvulus
Intussusception
Jejuno-jejunal
Ileocecal

Small colon obstruction
Fecalith
Impaction
Meconium

Entrapment in hernia, mesenteric rents
Large colon obstruction
Impaction
Intussusception
Torsion

Necrotizing enterocolitis

Adhesions

Colonic stricture

Ileal impaction - foreign body

Ascarid impaction - small intestine

Phytobezoar

Gastric ulcer

Duodenal ulcer

Abdominal abscess

Umbilical abscess

Peritonitis

Tyzzer's disease ( Clostridium piliforme )'

Uroperitoneum

Enteritis

Ovarian torsion 2

Rectal examination in foals is limited
to exploration of the rectum with one or
two fingers. The presence or absence of
feces should be noted. Lack of fecal
staining of the rectum suggests a complete
obstruction such as intestinal agenesis.

Nasogastric intubation should be
performed. The presence of more than
300 mL of reflux in a foal is significant and
suggestive of gastric dilatation secondary
to an outflow obstruction or regurgitation
of small intestinal fluid into the stomach
because of a small intestinal obstruction.

Meconium is usually passed within the
first 10-12 hours (usually 3 hours) after
birth. Retention of meconium is evident
as signs of colic and the presence of firm
meconium in the rectum. Palpation of the
caudal abdomen may reveal firm material
in the small colon. Enemas (see under
Treatment, below) usually provide rapid
relief and confirmation of the diagnosis.

Ancillary diagnostic tests

Diagnostic imaging 7

Radiography is useful in the evaluation
of foals with colic although it seldom

provides a definitive diagnosis, with the
possible exception of meconium impaction
and contrast studies of foals with lesions
of the small or large colon, or gastric
outflow obstructions. 8,9 Retrograde con-
trast radiography of the lower gastro-
intestinal tract of foals less than 30 days
old is a sensitive technique for detection
of anatomic anomalies such as atresia
coli and obstruction of the small colon . 9
The technique is performed by the
intrarectal infusion of up to 20 mL/kg of
barium sulfate (30% w/v) in sedated,
laterally recumbent foals. Meconium
impaction may be evident as a mass of
radio-opaque material in the caudal
abdomen with accumulation of fluid and
gas oral to the obstruction. Upper gastro-
intestinal contrast radiography is useful to
detect abnormalities of the stomach and
small intestine, in particular gastric
outflow obstructions. 10

Ultrasonographic examination of
the foal abdomen can demonstrate
intussusceptions, 11 the presence of
excessive peritoneal fluid (such as urine
or blood), edematous intestine, hernias

:

I

j

and colonic impaction. The presence of
atonic, distended small intestine'suggests
the presence of ileus, possibly secondary
to a small intestinal strangulating lesion.
However, ultrasonographic differentiation
of ileus secondary to enteritis from that
accompanying a strangulating lesion is
difficult. 12

Endoscopy

Endoscopic examination of the stomach
is indicated in any foal with recurrent or
continuous mild to moderate colic,
bruxism or ptyalism suggestive of gastric
or duodenal ulceration. Gastroscopy reveals
the presence of any ulcers and their extent
and severity. 12

CLINICAL PATHOLOGY

There are few changes detected by routine
hematological or serum biochemical exam-
ination of foals with colic that provide a
definitive diagnosis. However, changes in
the hemogram and serum biochemical
profile are useful in evaluating the physio-
logical state of the foal and the severity of
the disease. Principles used in the evalu-
ation of these variables in adult horses
apply to foals. It should be appreciated
that the normal range of values for many
clinical pathology variables in foals is age-
dependent and markedly different from
that of adult horses (see Tables 3.5, 3.6).

Profound leukopenia is more likely to
be indicative of enteritis and colic second-
ary to ileus than of small-intestinal
strangulating obstructions. Similarly,
hyponatremia is uncommon with strangu-
lating obstructions but is a common
finding in foals with enteritis.

Newborn foals with colic should have
the adequacy of transfer of passive
immunity examined by measurement of
serum immunoglobulin G concentration,
or an equivalent test.

Examination of abdominal fluid is
useful in the assessment of colic in foals,
as it is in adults. The normal values for
abdominal fluid in foals differs from that
of adult horses 13 and white cell counts
greater than 1500 cells/pL (1.5 x 10 9 cells/L)
should be considered abnormal.

NECROPSY FINDINGS

The findings on necropsy examination
depend on the nature of the disease.

TREATMENT

The principles of treatment of foals with
colic are the same as those for adult
horses: relief of pain, correction of fluid
and electrolyte abnormalities, and treat-
ment of the underlying disease. In
addition, foals with failure of transfer
of passive immunity should receive
plasma.

Foals with gastrointestinal disease
that cannot eat may require parenteral

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

DIFFERENTIAL DIAGNOSIS

Diagnostic features of common causes of
colic in foals are listed in Table 5.10. The
principal differential diagnoses for
gastrointestinal disease of foals with
abdominal pain are:

• Enteritis due to rotavirus infection,
salmonellosis intestinal clostridiosis
{Clostridium perfringens or Clostridium
difficile or other causes

• Uroperitoneum

• Peritonitis

• Gastroduodenal ulcer disease

nutrition to insure adequate caloric
intake.

Meconium impaction can be treated
by administration of an enema of soap
and warm water, commercial enema
preparations or acetylcysteine. Soap and

water enemas can be administered at a
rate of 5mL/kg through a soft Foley
catheter inserted into the rectum.
Acetylcysteine (8 g in 200 mL of water
with 20 g sodium bicarbonate) has the
advantage of actually dissolving part of
the meconium, thereby enhancing
passage of the meconium. Affected foals
may require analgesics to control pain,
intravenous fluids to correct or prevent
dehydration, oral laxatives such as
mineral oil (300 mL via nasogastric tube)
j and plasma to correct failure of transfer of
passive immunity. Surgical correction of
the impaction is rarely required.

Surgical treatment

The proportion of foals surviving varies
j with the disease and age of the foal,
j Younger foals (< 6 months of age) appear
i to have a worse prognosis after surgical
i correction of intestinal lesions than do
} older foals. 6-14 Fewer foals having surgery

for colic live to race than do their normal
cohorts, although affected foals that do
race have similar racing careers. 6 Foals
with nonstrangulating lesions and
enteritis are more likely to survive
than foals with gastric ulcer disease or
strangulating lesions. 6 Suckling foals are
at greatest risk of development of post-
operative adhesions and need for repeated
celiotomy. 6

PREVENTION

Although not proven, the suspected
association between diarrhea and small-
intestinal surgical lesions in foals suggests
that measures to reduce the incidence of
enteritis in foals may reduce the incidence
of colic. Adequate deworming programs
| that reduce or eliminate infestation with
parasites should be implemented. Care
should be taken when deworming foals
with heavy infestations of Parascaris
equorum, as rapid killing of the ascarids

V-;'irX' -lin! 8 1 !>'i H r if, 1 ' ip. sV o ]j GVo^j! i ;cVcJfYi(iWvc s ir:

Disease

History

Clinical findings

Clinical pathology

Treatment

Intestinal atresia
or hypoganglionosis

White progeny of Overo
horses. Otherwise sporadic.
Newborn foals < 4 days old

Failure to pass feces.
Abdominal distension pain

None specific

None

Small-intestinal

volvulus

Any age but more
common at 3-6 months.
Abrupt-onset abdominal pain.
Diarrhea

Severe pain. Nasogastric
reflux. Abdominal distension.
Ultrasonography - distended,
atonic intestine. Radiography -
gas and fluid distension of
small bowel

Increased protein and
leukocytes in abdominal
fluid

Surgical. Low survival rate

Small-intestinal

intussusception

Any age, but usually
3-6 weeks. Diarrhea

Severe pain, abrupt onset.
Nasogastric reflux.
Ultrasonography -
intussusception. Radiography -
gas and fluid distension of
small bowel

Increased protein and
leukocytes in abdominal
fluid

Surgery. 40% survival rate

Ascarid impaction

More than 3 months of age.
Recent history (< 3 d) of
anthelmintic administration

Severe pain. Nasogastric reflux.
Ultrasonography - distended,
atonic bowel, ascarids

None specific

Medical therapy. Lubricants
and analgesics. Surgery

Meconium impaction

Newborn. No passage of
meconium. More common
in males

Mild pain initially, becoming more
severe. Abdominal distension.
Ultrasonography - distended
large colon, may see impaction.
Radiography - contrast may
outline impaction

None specific

Warm soapy enemas
Acetylcysteine. Mineral oil
orally. Surgery for refractory
cases

Large-colon torsion

Sporadic

Severe pain and abdominal
distension. Ultrasonography -
gas distended colon.
Radiography - gas
distended colon

None specific

Surgery. 20% recovery rate

Large-colon

impaction

Sporadic. Poor diet, eating
sand-polluted feed

Mild to moderate pain initially.
Progressive abdominal distension.
Ultrasonography - distended colon
with impacted material

None specific

Medical treatment of
lubricants, fecal softeners
and analgesics. Surgery

Small-colon

impaction

Common in Miniature horses

Moderate to marked pain.
Lack of feces. Abdominal
distension. Ultrasonography -
gas distended colon.
Radiography - impaction of
small colon

None specific

Medical as above. Surgery

Gastroduodenal ulcer

Common in foals with
other disease or stress

Usually clinically inapparent.
Colic, inappetence, teeth
grinding, excessive salivation,
diarrhea. Gastroscopy diagnostic

None diagnostic

Antacids and antiulcer
compounds (Table 5.11).
Rarely surgery to correct
gastric outflow obstruction

may lead to impaction and obstruction of
the small intestine. 14

review literature

Neal, HN- Foal colic: practical imaging of the
abdomen. Equine Vet Educ 2003; 15:263-270.
Bernard W. Colic in the foal. Equine Vet Educ 2004;
16:319-323.

EPIDEMIOLOGY

The incidence of gastric rupture, the most
severe sequela to gastric dilatation, in
horses with colic is approximately 5%,
although in horses subjected to exploratory
laparotomy the rate may be as high as
11%. 3 ' 4 There is no detectable effect of

REFERENCES

1 . St Denis KA et al. Can Vet J 2000; 41:491-492.

2. Valk N et al. J Am Vet Med Assoc 1998;
213:1454-1456.

3 . Chaffin MK, Cohen ND.Vet Med 1995; 90:765.

4. McClure JT et al. J Am Vet Med Assoc 1992;
200:205-

5. Spurlock GH, Robertson JT. J Am Vet Med Assoc
1988; 193:1087.

6. Santschi EM et al. Equine Vet J 2000; 32:32-36.

7. Neal HN. Equine Vet Educ 2003; 15:263-270.

8. Fischer AT et al. Vet Radiol 1987; 28:42.

9. Fischer AT et al. J Am Vet Med Assoc 1995; 207:734.

10. Campbell ML et al. Vet Radiol 1987; 25:194.

11. Bernard WV et al. J Am Vet Med Assoc 1989;
194:395.

12. Chaffin MK, Cohen ND.Vet Med 1995, 90:770.

13. Grindem CB et al. Equine Vet J 1990; 22:359.

14. Vatistas NJ et al. Equine Vet J 1996; 28:139.

GASTRIC DILATATION IN THE
HORSE

age, breed or season on the risk of gastric
rupture. Risk factors for gastric dilatation
include consumption of excess grain,
although horses routinely fed grain are at
lower risk; 3 ingestion of palatable fluids
such as whey has been implicated. Acute
idiopathic dilatation of the stomach
occurs sporadically and is a common
cause of gastric rupture, representing
between 16% and 60% of cases of gastric
rupture. 3,4 Chronic dilatation secondary
to pyloric obstruction due to a tumor is a
sporadic occurrence in older horses, 4
whereas cicatricial obstruction secondary
to gastroduodenal ulceration is more
common in younger horses and those
at risk of developing gastroduodenal
ulcers.

Acute dilatation occurs secondarily to
acute obstruction of the small intestine.

Etiology Gastric outflow obstruction.
Idiopathic. Ingestion of excess fluid or
feedstuffs

Epidemiology Sporadic. No age, breed
or sex predilection
Clinical signs Colic. Reflux from
nasogastric tube. Gastric rupture, acute
severe peritonitis and death
Clinical pathology None diagnostic.
Inflammatory cells and ingesta in peritoneal
fluid of horses with gastric rupture
Diagnostic confirmation Nasogastric
reflux without other identifiable cause
Lesions Gastric dilatation. Gastric rupture
with hemorrhage at margins of rupture
Treatment Gastric decompression. Treat
underlying disease

Control Prevent overeating. Control
inciting diseases

ETIOLOGY

Chronic gastric dilatation can be caused

by:

• Outflow obstruction, such as
cicatricial constriction of the pylorus
secondary to gastroduodenal
ulceration or pressure by a tumor 1,2

* Gastric atony in older horses or wind-
sucking (aerophagic) horses.

Acute gastric dilatation is associated with:

* Reflux of intestinal contents
secondary to acute intestinal
obstruction, e.g. anterior enteritis,
small intestinal strangulation or ileus

• Ingestion of excess fluid or feedstuffs
such as whey or grain

ute idiopathic dilatation after racing.

PATHOGENESIS

Acute obstruction results in gastric
dilatation associated with severe pain and
signs of shock, including elevated heart
rate, sweating and delayed mucosal
capillary refill time. Gastric rupture can
occur within hours and death shortly
thereafter. Chronic dilatation results from
partial obstruction and delayed gastric
emptying. The disease is more prolonged
and clinical signs may be related to the
primary disease.

The obstruction may be as aboral as
the ileocecal valve. Gastric distension
with fluid also occurs late in the course of
impaction of the large or small colon, and
in cases of large intestinal volvulus. The
accumulation of fluid in these cases
appears to be in response to tension on
the duodenocolic fold. 5

Gastric distension causes severe pain
and there is often dehydration and hypo-
chloremia as a result of sequestration of
gastric secretions. Ingestion of material
that putrefies and damages gastric mucosa
may result in toxemia and development of
associated signs of shock.

Engorgement of a readily fermentable
carbohydrate, such as wheat, glucose
or calf feeds, results in a syndrome
characterized by shock, ileus and laminitis.
Gastric dilatation can occur secondary to
grain engorgement but the clinical signs
of the gastric dilatation are often masked
by the more severe signs secondary to
endotoxemia.

CLINICAL FINDINGS

The clinical findings in gastric distension
depend i. large j rrt on the underlying

disease. However, horses with primary
gastric distension have abdominal pain,
often of 12-36 hours duration, that
progressively worsens. The heart and
respiratory rates increase progressively as
the distension worsens, and the horse
may sweat and exhibit signs of increasingly
severe abdominal pain. Paradoxically,
some horses with gastric distension,
especially that which develops over
several days or in horses recovering from
intestinal surgery and being treated with
analgesics, may not exhibit any but the
most subtle signs until rupture of the
stomach occurs.

Vomition in horses is very rare, is
always associated with gastric distension
and is usually a terminal event.

In grain engorgement dilatation
abdominal pain is usually severe. Dehy-
dration and shock develop rapidly, often
within 6-8 hours of ingestion of the grain,
and may be severe. Death from gastric
rupture can occur within 18 hours.

Passage of a nasogastric tube usually
results in the evacuation of large
quantities of foul-smelling fluid, except in
cases of grain engorgement, where the
fluid is absorbed by the grain. However,
significant and life-threatening gastric
dilatation can be present even though
there is no reflux through a nasogastric
tube. If gastric dilatation is suspected then
repeated, persistent efforts should be
made to obtain reflux. The nasogastric
tube should be left in situ until the disease
has resolved.

Acute post-race dilatation occurring
immediately after racing is accompanied
by more serious and acute signs. There is
abdominal distension, coughing and
dyspnea. Tympany is also detectable on
percussion of the anterior abdomen and
large amounts of foul-smelling gas, and
usually fluid, are passed via the stomach
tube. This immediately relieves the
animal's distress.

In chronic dilatation there is anorexia,
mild pain, which is either continuous or
recurrent, scanty feces and gradual loss of
body weight persisting for a period of
months. Vomiting and bouts of pain may
occur after feeding but they are not usually
severe. Dehydration may be present but is
usually only of moderate degree.

The distended stomach cannot be
palpated on rectal examination, but the
presence of distended loops of small
intestine should alert the clinician to the
probability of gastric distension. Rupture
of the stomach, or other viscus, is
characterized during rectal examination
by a negative pressure in the abdomen
and the presence of particulate matter on
the serosal surface of intestine.

Ultrasonographic examination will
reveal a distended stomach containing

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

large quantities of fluid or ingesta and can
reveal evidence of the predisposing
lesion, such as presence of distended
small intestine. 6 Radiographic examin-
ation, with or without a barium meal,
may be of diagnostic value in young
animals with chronic outflow obstruction.
Gastroscopy performed after the stomach
has been emptied can reveal lesions
consistent with obstructed outflow, such
as gastric squamous cell carcinoma or
pyloric abnormalities secondary to gastric
ulcer disease in foals.

CLINICAL PATHOLOGY

Horses with severe gastric dilatation
often, but not always, have slightly low
serum chloride concentrations . 4 Meta-
bolic alkalosis, metabolic acidosis or
mixed disturbances can be present. 4
Other abnormalities depend on the
underlying disease.

Abdominal fluid of horses with
gastric dilatation is normal whereas that
of horses with gastric rupture is charac-
terized by an elevated total protein
concentration (> 2.5g/dL, 25g/L) and
leukocyte count (> 10000 cells/pL,
10 x 10 9 cells/L) which is predominantly
composed of degenerate neutrophils.
Microscopic examination of the fluid
reveals intra- and extracellular bacteria
and plant material.

NECROPSY FINDINGS

After grain engorgement in horses, the
stomach is distended with a doughy, mal-
odorous mass of ingesta. In acute gastric
dilatation due to other causes, the stomach
is grossly distended with fluid and the
wall shows patchy hemorrhages. Rupture,
when it occurs, is usually along the
greater curvature and results in gross
contamination of the abdominal cavity
with ingesta.

DIFFERENTIAL DIAGNOSIS

See Table 5.6.

TREATMENT

Relief of the gastric distension should
be considered an emergency as gastric
rupture invariably causes death. Passage
of a nasogastric tube, important in diag-
nosing the accumulation of fluid within
the stomach, also provides a means for
relieving the distension. Repetition and
persistence may be needed to relieve the
gastric distension. Passage of the naso-
gastric tube through the cardia may be
difficult in horses with gastric distension.
Blowing into the tube to dilate the
esophagus or instillation of lidocaine
(20 mL of 2% solution) may facilitate
passage of the tube. If there is no sponta-
neous reflux of material, a siphon should

be formed by filling the tube with 500 mL
of water and rapidly lowering the end of
the tube below the level of the horse's
stomach. The nasogastric tube should be
left in place until there is no longer
clinically significant quantities of reflux
(1-2 L every 3 h for an adult 425 kg
horse).

Gastric dilatation caused by overeating
of grain, bread or similar material may be
impossible to resolve through a nasogastric
tube because of the consistency of the
material. Gastric lavage using water or
isotonic saline administered through a
large bore nasogastric tube may aid in
removal of inspissated ingesta. Surgical
decompression may be attempted in
refractory cases, but is technically demand-
ing because of the position of the stomach
in the adult horse.

The underlying disease should be
treated to restore normal gastric emptying
or stop reflux from the small intestine.
Supportive therapy, including restoration
of hydration and normal electrolyte and
acid-base status, should be provided
(see Chapter 2). Horses at risk of inha-
lation pneumonia should be treated with
broad-spectrum antibiotics for at least
3 days.

REFERENCES

1. Boy MG. J Am Vet Med Assoc 1992; 200:1363.

2. Laing JA, Hutchins DR. AustVet J 1992; 69:68.

3. Kiper ML et al. J AmVet Med Assoc 1990; 196:333.

4. Todhunter RJ et al. Equine Vet J 1986; 18:288.

5. Harrison IW.\fet Surg 1988; 17:77.

6. Freeman S. In Pract2002; May: 262.

GASTRIC IMPACTION |N HORSES

Primary gastric impaction is characterized
by enlargement of the stomach, subacute
pain, which may exacerbate if fluid is
administered by nasogastric tube, minor
fluid reflux if a tube is passed, and
regurgitation of fluid and ingesta from the
nostrils in some cases. At exploratory
laparotomy the stomach is enlarged with
dry, fibrous feed material but is not
grossly nor acutely distended, and the
intestines are relatively empty. 1 Gastric
impaction occurs secondary to hepatic
fibrosis and insufficiency associated with
poisoning with Senecio jacobea 2 Persimmon
(Diospyros virginiana ) causes gastric
impaction, ulceration and rupture in
horses. 3,4 There is usually a history of a
diet of mature grass, alfalfa hay, com,
sorghum fodder or ensilage. 5 Other causes
include insufficient access to water, poor
teeth causing poor digestion, or the atony
of old age. Long-term signs include
weight loss, intermittent colic, anorexia,
dullness and small amounts of hard, dry
feces. 4 Treatment with an oral adminis-
tration of normal saline or mineral oil is
commonly applied but is not usually
satisfactory because the oil does not

moisten the impacted mass and is likely
to bypass it. The patient may require
exploratory laparotomy because of the
absence of satisfactory diagnostic tests. 6
Rupture of the stomach is a potential
sequel.

REFERENCES

1. Owen RR et al. Vet Rec 1987; 121:102.

2. Milne EM et al.Vet Rec 1990; 126:502.

3. Cummings CA et al. J Vet Diagn Invest 1997;
9:311.

4. Kellman LL et al. J Am Vet Med Assoc 2000;
216:1279.

5. Kiper ML etal.J AmVet Med Assoc 1990; 196:333.

6. Barclay WP et al. J Am Vet Med Assoc 1982;
181:682.

GASTRIC ULCERS

Gastric ulcers occur in cattle (Abomasal
ulceration), swine (Esophagogastric ulcer-
ation), foals and horses. The etiology varies
among the species but the condition is
characterized by the development of
ulcers in the nonglandular and, less
frequently, glandular sections of the
stomach or abomasum. Common factors
in the development of gastric ulcers in all
species are the presence of gastric fluid of
low pH and mechanical disruption or
dysfunction of the mechanism protecting
gastric mucosa from damage by acid and
pepsin. The clinical manifestations vary
with the species affected but include
hemorrhage, anemia and the presence of
melena or occult blood in the feces in
pigs, cattle and, rarely, foals.

GASTRIC (GASTRODUODENAL)
ULCER IN FOALS

Synopsis

. •' 1 - •' . !■*-* // ; •; . y, ; ! •’ 1 jy ’ ^ :

Etiology Unknown in most cases. NSAID
intoxication

Epidemiology Foals from 1 day of age.
50% of normal foals have gastric mucosal
ulceration. Clinical disease in 0.5% of
foals. More severe ulceration in stressed
foals or foals with other diseases
Clinical signs None in most foals. Teeth
grinding, excessive salivation, colic,
diarrhea, inappetence and weight loss.
Sudden death with perforation. Ulcers
present on gastroduodenoscopy
Clinical pathology None diagnostic
Lesions Gastric mucosal ulceration,
duodenal ulceration and stenosis,
esophagitis. Peracute septic peritonitis
Diagnostic confirmation Gastroscopic
demonstration of ulcers in foals with
appropriate clinical signs
Treatment Ranitidine 6.6 mg/kg, orally
every 8-12 hours, or cimetidine
6.6-20 mg/kg orally or intravenously every
6 hours, or omeprazole 2-4 mg/kg orally
or intravenously every 24 hours
Control Minimize occurrence of inciting
or exacerbating diseases

ETIOLOGY

There is no established etiology, although
there is an association with stress (see
below). There is no evidence of an infec-
tious etiology, for instance Helicobacter sp.

epidemiology

Occurrence

Gastric ulcers are reported in foals in
North America, Europe and Australia and
probably occur worldwide. The prevalence
of erosion and ulcers of the gastric
glandular and nonglandular mucosa,
detected by gastroscopic examination,
averages 50% in foals less than 2 months
of age that do not have signs of gastric
ulcer disease. 1,2 Lesions of the squamous
mucosa are present in 45% of foals, while
lesions in the glandular mucosa occur
in fewer than 10% of foals less than
4 months of age.

Disease attributable to gastric or duo-
denal ulcers occurs in approximately 0.5%
of foals 3 although the prevalence is
greater in foals with other diseases such
as pneumonia and septicemia. 4 Duodenal
ulceration was present in 4.5% of foals
examined post mortem 5 but This is
probably a gross overestimation of the
prevalence in normal foals.

Estimates of case fatality rate are not
available.

Risk factors

Age and sex

Age is an important risk factor for
ulceration of the squamous epithelium,
with 88% of foals less than 9 days of age
affected compared to 30% of foals more
than 70 days of age. 1,2 Gastric lesions
occur in fewer than 10% of foals over 90
days of age. 4 There does not appear to be
an effect of age on prevalence of ulcer-
ation of the gastric glandular mucosa, a
much more clinically significant lesion.
There is no effect of sex on the prevalence
of ulcers. 6

Stress/disease

Stress and disease are important risk
factors for development of ulcers of the
glandular mucosa. 1-2 Lesions of the gastric
glandular mucosa occur in 27% of foals
with another disease but in 3% of other-
wise healthy foals. 4

blood flow and the presence of an intact,
bicarbonate-rich layer of mucus over the
epithelium are essential to maintaining
the resistance of the epithelium to
digestion by gastric acid and pepsin.
Mucosal blood flow and bicarbonate
secretion into the protective mucus layer
are dependent in part on normal
prostaglandin E concentrations in the
mucosa. Factors that inhibit prostaglandin
E production, such as NSAIDs and
ischemia, contribute to the development
of ulcers.Trauma to the gastric epithelium
may disrupt the protective layer and allow
an ulcer to develop, as may the presence
of compounds in duodenal fluid, such as
bile salts, that intermittently reflux into
the stomach of normal foals.

Normal foals develop the capacity for
secretion of gastric acid and ability to
achieve gastric pH less than 4 within
1-2 days of birth. 8 Ingestion of milk
increases gastric pH and it is a generally
held belief that frequent ingestion of milk
provides a protective effect against the
adverse effects of low pH on gastric
mucosa. 8 However, development of gastric
lesions in foals is not solely a result of
prolonged exposure to low pH, although
this might be a necessary factor, as ill
neonatal foals that are at high risk of
gastric erosion or ulceration have gastric
pH that is often greater than 5-6. 9 The
elevated pH, which may be alkaline in
severely ill foals at greatest risk of death, 9
is not consistent with development of
gastric lesions.

Most ulcers do not produce clinical
signs. Severe ulceration is associated
with delayed gastric emptying, gastric
distension, gastroesophageal reflux and
subsequent reflux esophagitis and pain.
Ulcers may perforate the stomach wall
and cause a peracute, septic peritonitis or
erode into a large blood vessel with
subsequent hemorrhage and occasional
exsanguination. Ulcers and the attendant
inflammation and pain might cause
gastroparesis and delay gastric emptying
and chronic lesions can result in both
functional and physical obstructions to
gastric emptying with subsequent gastric
dilatation and reflux esophagitis.

PATHOGENESIS

The pathogenesis of gastric ulceration in
foals has not been definitively determined
and much is extrapolated from the
disease in humans and other animals. It is
assumed that ulcers occur because of an
imbalance between the erosive capability
of the low gastric pH and the protective
mechanisms of the gastric mucosa. 7 Low
gastric pH is essential for the develop-
ment of a gastric ulcer and foals as young
as 2 days of age have a gastric pH of less
^-I’re sei vation^

CLINICAL FINDINGS

There are six syndromes associated with

gastroduodenal ulcers in foals:

• Ulceration or epithelial desquamation
of the squamous mucosa of the
greater curvature and area adjacent to
the margo plicatus. These lesions are
very common in foals less than

60 days of age and usually do not
cause clinical signs. The lesions heal
without treatment

• Ulceration of the squamous
epithelium rf the less r curvature and

fundus. This is more common in older
foals (> 60 days) and is usually
associated with clinical signs
including diarrhea, inappetence and
colic

• Ulceration of the glandular mucosa,
sometimes extending into the pylorus.
This lesion occurs in foals of any age
and is most common in foals with
another disease. Clinical signs due to
the ulcer can be severe and include
teeth grinding, excessive salivation,
inappetence, colic, and diarrhea. There
is often reflux esophagitis

• Gastric outflow obstruction due to
pyloric or duodenal stricture secondary
to pyloric or duodenal ulceration. This
occurs in 2-5-month-old foals and is
evident as colic, inappetence, weight
loss, gastric dilatation,
gastroesophageal reflux, excessive
salivation and teeth grinding

• Peracute peritonitis secondary to
gastric perforation. This usually occurs
in foals that do not have a history of
signs of gastric ulceration. Clinical
signs include unexpected death,
shock, dehydration, sweating and an
increased respiratory rate

• Hemorrhagic shock secondary to
blood loss into the gastrointestinal
tract from a bleeding gastric ulcer. 10
This is an unusual presentation.

The typical signs of gastric ulcers in foals
include depression, teeth grinding,
excessive salivation and abdominal pain
that can range in intensity from very mild
to acute and severe, similar to that of a
foal with an acute intestinal accident.
Diarrhea, with or without mild to moderate
abdominal pain, is often associated with
gastric ulcer disease in foals. Treatment
with antiulcer drugs is sometimes associ-
ated with resolution of diarrhea and signs
of gastric ulcer disease. There may be pain
evinced by deep palpation of the cranial
abdomen but this is not a reliable diag-
nostic sign. 11

Definitive diagnosis is provided by
gastroscopic examination. The endoscope
should be 2 m in length, although aim
endoscope may allow partial examination
of the stomach of young or small foals.
Diameter of the endoscope should be less
than 1 cm. Foals can usually be examined
without sedation, although sedation may
facilitate examination in larger or
fractious foals. Ideally, older foals should
have food withheld for 12 hours before
the examination but this may be neither
necessary nor advisable in sick foals.
Young foals (those relying on milk intake
for their caloric needs) should have food
withheld for 1-2 hours. Adequate exam-
ination of the nonglandular stomach can
usually be achieved without fasting.

16

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

especially in younger foals, but thorough
examination of the glandular mucosa and
pylorus requires fasting.

Nasogastric intubation may cause
pain and cause affected foals to gag. Foals
with gastric outflow obstruction, due
either to pyloric or duodenal stricture or
to gastroparesis, will have reflux of material
through a nasogastric tube.

Contrast radiographic examination is
useful in defining gastric outflow obstruc-
tion and may demonstrate filling defects
in the gastric wall that are consistent with
ulcers. The principal use of radiography is
to establish delays in gastric emptying.
Normal foals have complete emptying
of barium sulfate (10-20 mL/kg BW
administered through a nasoesophageal
or nasogastric tube) from the stomach
within 2 hours of administration. Gastric
ulcers are occasionally apparent as filling
defects, but contrast radiography is not
sufficiently sensitive to justify its routine
use for diagnosis of gastric ulceration.

CLINICAL PATHOLOGY

There are no diagnostic changes in the
hemogram or serum biochemical profile.
Serum pepsinogen values are of no use in
diagnosing gastric ulcers in foals. 12 Testing
for fecal occult blood is neither sensitive
nor specific for gastric ulceration in foals.
Foals with perforation of the stomach
have changes consistent with septic
peritonitis.

NECROPSY FINDINGS

Gastric ulcers and erosions are common
findings in foals dying of unrelated
disease and their presence should not be
overinterpreted. The gross characteristics
of the gastric lesions are described above.
Foals dying of gastric ulcer disease do
so from peracute diffuse peritonitis,
exsanguination or starvation secondary to
the gastric outflow obstruction.

DIAGNOSTIC CONFIRMATION

The combination of compatible clinical
signs, endoscopic demonstration of gastric
ulcers, a favorable response to antacid
therapy and the elimination of other
diseases permits a diagnosis of gastric
ulcer disease.

pit [; jsUyua , .

The combination of teeth grinding,
excessive salivation, depression,
inappetence and colic in foals is virtually
diagnostic of gastric ulcer disease. Other
causes of colic in foals are listed in
Table 5.9.

0 Promotion of healing by reducing
gastric acidity and enhancing mucosal
protection

° Enhancement of gastric emptying
° Provision of nutritional and metabolic
support

° Treatment of other disease.

Reduction of gastric acidity is achieved
by administration of one of several drugs
that reduce secretion of gastric acid and
increase gastric pH (Table 5. 11). 13 These
drugs are either histamine type 2 (H 2 )
receptor antagonists or inhibitors of the
proton pump in the gastric parietal cells.
Administration of ranitidine (6.6 mg/kg
orally every 8 h) effectively increases
gastric pH in normal neonatal foals but
does not affect gastric pH in hospitalized
neonates. 8,9 Omeprazole (4 mg/kg orally
every 24 h), a proton pump inhibitor,
increases gastric pH within 2 hours of
administration and for 24 hours in
clinically normal neonatal foals. 14 How-
ever, similarly to ranitidine, the efficacy of
omeprazole in ill neonatal foals has not
been determined. Omeprazole does
enhance healing of spontaneous ulcers in
foals older than 28 days and does not

have important or frequent adverse
effects. 15,16 Sucralfate is used to provide
protection of denuded gastric epithelium,
although its efficacy in preventing lesions
or enhancing healing of existing lesions
in foals with spontaneous disease is
doubted.

A common treatment protocol involves
administration of a H 2 antagonist or
omeprazole. Treatment should begin as
soon as the presence of a clinically sig-
nificant ulcer is suspected and should
continue for at least 1 week after the
resolution of clinical signs or until there is
endoscopic confirmation of healing. Foals
are often treated for 2-6 weeks.

Foals with gastroparesis secondary to
severe gastroduodenal ulceration or
gastritis may benefit from the adminis-
tration of bethanechol (Table 5.11) to
increase gastric motility and enhance
gastric emptying. Surgical bypass of
pyloric or duodenal strictures may be
necessary in foals with physical obstruc-
tions to gastric emptying. 17

Nonsteroidal anti-inflammatory
drugs such as phenylbutazone or flunixin
meglumine are ulcerogenic and should be
used sparingly in sick foals, and should not

TREATMENT

The principles of treatment of gastro-
duodenal ulcer disease in foals are:

>\ ■f'": iD/fSuib!
ihlTo;-fy

Drug class

Drug

! r'-'-' : i!i i| ii R P): 1 (o) : i .b j « : f:ji if?<p>'9 ? u faXgSlaf

Dose, route and
frequency

n-srl '.ql! fc-iV (SfosM&Tr (o)if

Comments

H 2 antagonists

Cimetidine

6.6-20 mg/kg PO
every 6 h

Potent acid suppression. Short
elimination half-life necessitates
frequent administration.
Preferably use at the higher dose
rate

Cimetidine

6.6 mg/kg IV every 6 h

Rapid and potent acid
suppression. Use when oral
administration is not feasible or
rapid effect is required

Ranitidine

6. 6-8.8 mg/kg IV or PO
every 8-1 2 h

Potent acid suppression and rapid
resolution of clinical signs

Proton pump

Omeprazole

4 mg/kg PO as paste every

Potent, rapid onset and long-

inhibitor

24 h

lasting acid suppression

Pantoprazole

1.5 mg/kg ivq 12-24 h

Potent acid suppression in foals

Protectants

Sucralfate

40 mg/kg PO every 6 h

Can be given at the same time as
inhibitors of acid secretion

Prostaglandin

analogues

Misoprostol

5 pg/kg PO every 1 2 h

Causes diarrhea and mild colic.
Effective as a prophylactic for
NSAID-induced ulcers in humans
but minimal efficacy in enhancing
healing of existing ulcers

Antacids

Aluminum

hydroxide

1-2 g PO every 4-6 h

Ineffective. Do not use

Magnesium

hydroxide

1-2 g PO every 4-6 h

Ineffective. Do not use

Calcium

carbonate

1-2 g PO every 4-6 h

Ineffective. Do not use

Promotility agents

Bethanechol

0.025 mg/kg SC every 6 h

Enhances gastric motility with
minimal increased gastric acid
secretion. Used to treat
gastroparesis. Contraindicated if
physical outflow obstruction
exists

H 3 , histamine type 2 receptor; IV, intravenously; NSAID, nonsteroidal antiinflammatory drug; PO, orally;
SC, subcutaneously.

Diseases of the nonruminant stomach and intestines

be given*to foals with gastric or duodenal
ulcers unless absolutely necessary. 18

Nutritional and metabolic support
should be provided as necessary to foals
that are unable to eat or drink or that have
abnormalities of fluid and electrolyte
status.

CONTROL

Control of diseases that predispose foals
to gastroduodenal ulcer may reduce the
incidence or severity of ulcer disease.
Prophylactic treatment of sick or stressed
foals with H 2 antagonists, sucralfate or
omeprazole is widely practiced. However,
the efficacy of pharmacological prophylaxis
in prevention of disease or death due to
gastric ulceration has not been demon-
strated. Indeed, suppression of gastric
acidity (increasing gastric pH) in either
sick or normal foals may be unwise
because of the protective effect of low
gastric pH on gastric colonization of
bacteria.

REVIEW LITERATURE

Murray MJ. Gastroduodenal ulceration in foals.
Equine Vet Educ 1999; 11:199-207.

REFERENCES

1. Murray MJ et al. J Am Vet Med Assoc 1990;
196:1623.

2. Murray MJ et al. Equine V?t J 1990; 22:6.

3. Sweeney HJ. Equine V?t Educ 1991; 3:80.

4. Murray MJ. J Am Vet Med Assoc 1989; 195:1135.

5. Wilson JH. In: Proceedings of the 2nd Equine
Colic Research Symposium 1986:126.

6. SandinA et al. ActaVet Scand 1999; 40:109-120.

7. Murray MJ. Equine Vet J Suppl 1992; 13:63.

8. Sanchez LC et al. J Am Vet Med Assoc 1998;
212:1407.

9. Sanchez LC et al. J Am V?t Med Assoc 2001;
218:907-911.

10. Tiaub-Dagartz J et al. J Am \bt Med Assoc 1985;
186:280.

11. Becht JL, Byars TD. Equine Vet J 1986; 18:307.

12. Wilson JH, Ptarson MM. In Proceedings of the
31st Annual Convention of the American
Association of Equine Practitioners, Toronto,
Canada, 1985:149.

13. Geor RJ, Fhpich MG. Compend Contin Educ
PractVet 1990; 12:403.

14. Sanchez LC et al. Am J Vet Res 2004;
65:1039-1041.

15. Murray MJ ct al. Equine Vet J Suppl 1999;
29:67-70.

16. MacAllister CG et al. Equine Vet J Suppl 1999;
29:77-80.

17. Campbell-Thompson ML ct al. J Am Vet Med
Assoc 1986; 188:840.

18. Carrick JB et al. Can J Vet Res 1989; 53:195.

GASTRIC ULCER IN ADULT
HORSES

ETIOLOGY

The etiology of the most common occur-
rence of gastric ulcers in the horse is
unknown but several risk factors have
been identified, which are described
under epidemiology. The disease is
common in horses undertaking regular
exercise and might be related to decreased

Etiology Unknown in most cases. NS AID
intoxication

Epidemiology Common in
Thoroughbred, Standardbred and Quarter
horses in racing or training, and horses
used for endurance racing. Occasionally
associated with colic

Clinical signs None in most horses. Poor
appetite, failure to bloom, mild colic in
some horses. Ulcers or erosions present on
gastroduodenoscopy

Clinical pathology None diagnostic
Necropsy lesions Gastric ulceration.
Rarely a cause of death
Diagnostic confirmation Gastroscopic
demonstration of ulcers
Treatment Omeprazole 1-4 mg/kg orally
once daily. Ranitidine and cimetidine are
used but are less efficacious and
convenient

Control Minimize risk factors, including
confinement and intermittent feeding.
Prolonged administration of omeprazole to
symptomatic horses

stomach volume and subsequent exposure
of the squamous mucosa of the proximal
parts of the stomach to acid during
exercise (see Pathogenesis, below).

Individual cases of gastric ulcers are
associated with parasitic gastritis, such as
in horses infested with Gasterophilus spp.,
and Habronema megastoma larvae. Tumors
of the stomach, such as gastric squamous
cell carcinoma or lymphosarcoma, may
cause ulceration of the gastric mucosa.
Gastric phytobezoars and persimmon
seeds (D. virginiana) have been associated
with gastric impaction, ulceration and
perforation of the glandular portion of the
stomach of a horse. 1 There is no evidence
that infection by Helicobacter sp. or similar
organisms is associated with gastric ulcer
disease in horses.

EPIDEMIOLOGY

Occurrence

The occurrence of gastric ulceration is
detected by either postmortem examin-
ation or gastroscopic examination. The
frequency with which gastric ulcers are
detected depends the method of examin-
ation, the group of horses examined and
the reasons for examining them. Studies
reporting on incidence of gastric ulcer-
ation in horses with clinical abnormalities
or at necropsy examination revealed a
high frequency of gastric lesions in horses
with colic and in race horses. 2 ' 5 More
recent studies have examined large num-
bers of horses without clinical signs of
gastric ulcer disease but from populations
at risk and have demonstrated a high
prevalence in horses undertaking strenuous
exercise on a regular basis. 6 " 10

Gastric ulcer disease in horses is a
recently recognized disease, with most

reports originating after 199£) and
coinciding with the widespread availability
of endoscopes of sufficient length to
permit examination of the stomach of
adult horses. However, a longitudinal
study of horses submitted for postmortem
examination in Sweden demonstrated
that horses have been affected with
gastric ulcers since 1924. 3

The condition is common in race
horses and other breeds of horse used for
athletic events and this population
represents the most important occurrence
of the disease. 6 " 10

Thoroughbred and Standardbred

horses in training or racing have a high
prevalence of gastric lesions. Gastroscopic
studies of convenience samples of
clinically normal Thoroughbred race
horses in training reveal a prevalence of
lesions of the gastric mucosa of
82-93%. 8,9 Gastric lesions are detected in
63-87% of Standardbred horses in train-
ing and actively racing. 6,7 Postmortem
examination ofThoroughbred race horses
in Hong Kong, where many horses that
retire from racing are examined post
mortem, reveals a prevalence of gastric
lesions of 66%, with the prevalence
increasing to 80% when only horses that
had raced recently were considered. 5
Among race horses selected for gastro-
scopic examination because of clinical
abnormalities, including inappetence,
failure to race to expectation, poor hair
coat or poor body condition, lesions of
the gastric mucosa were detected in
86-90%. 2,11

There were lesions of the gastric
mucosa in approximately 20 of 30
endurance horses examined immediately
after racing 50-80 km. 10 Eight horses had
lesions of the gastric glandular mucosa.
Gastric lesions were present in 58% of
show horses that had competed in the
30 days prior to gastroscopic examination. 12

Risk factors

Risk factors for gastric lesions in horses
include being in training for an athletic
event, exercise and the amount of time
exercising, and colic. Suspected risk
factors include the disposition of the
horse (nervous horses are at greater risk),
diet, feeding practices, housing (pasture
vs stall), stress (although the definition of
stress is often not clear) and adminis-
tration of NSAIDs such as phenyl-
butazone. 13 While each of these risk
factors can be considered separately,
it is likely that many are related and
act in concert to increase the risk of
development of lesions of the gastric
mucosa. For instance, being in training
often coincides with confined housing,
intermittent feeding, daily bouts of
| strenuous exercise and administration of

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

NSAIDs. The combination of these factors,
even without NSAID administration,
reliably induces ulcers in Thoroughbred
race horses. 14 Young horses (2 years old)
that had arrived at the track within the
month before first gastroscopic examin-
ation had a marked increase in severity of
lesions at the time of a second gastro-
scopic examination 1 month later. 10

Animal risk factors

Among adult horses, age and sex are only
weak risk factors, if at all, for presence of
gastric lesions. 6-8 Gastric lesions tend to
be more severe in older horses. 6,7,9 Among
Standardbred race horses, trotters are
twice as likely as pacers to have gastric
lesions. 7 Horses with a nervous dis-
position are considered to be at greater
risk of developing gastric lesions but
objective evidence is not available to
support this observation. 8 NSAIDs are
ulcerogenic and often administered to
horses in training. However, among
Thoroughbred race horses there is no
clear association between administration
of these drugs and risk of having gastric
lesions. 8

Colic is associated with presence of
gastric lesions, although a cause and
effect relationship is often not clear in
individual cases. In a series of 111 horses
with clinical evidence of abdominal
discomfort of varying duration and
severity, 91 had endoscopic evidence of
gastric ulceration. 4 Other abnormalities of
the gastrointestinal tract or abdominal
viscera were not found in 57 of the
91 horses with gastric ulcers. Thus gastric
ulceration was the primary cause of colic,
based on lack of concurrent abnor-
malities, clinical response to treatment
with H 2 antagonists, and confirmation of
improvement or resolution of gastric
ulceration by endoscopy. 4 However, 34 of
the 91 horses with gastric ulceration had
concurrent abnormalities of the gastro-
intestinal tract, demonstrating that gastric
lesions can develop in horses with colic.
Thus, colic can cause gastric lesions and
gastric ulcers can cause colic.

Management and environmental risk
factors

Race horses in training have a higher
prevalence of ulcers than do race horses
that are spelling (not in active training) 5,7,9
and horses that are racing regularly have
a higher prevalence than resting horses or
horses in training but not racing. 7
Standardbred race horses in training are

2.2 times more likely to have gastric
lesions, and those racing regularly are

9.3 times more likely to have gastric
lesions, than are horses not training or
racing. 7 Although, as discussed above,
many factors can contribute to the likeli-
hood of a horse having gastric lesions.

exercise is strongly associated with
development of gastric lesions in horses.
This is probably through the increase in
intragastric pressure and decrease in pH
in the proximal (nonglandular) stomach
that occurs during exercise. 14

Feed withholding causes gastric
ulcers in horses, probably because of the
lack of buffering of acid produced during
periods when the stomach is empty. 15 It is
likely that the intermittent access to feed
that occurs in many stables results in
periods of time during each day when
horses do not have feed within the
stomach. The loss of buffering is due to
lack of feed material in the stomach and
to decreased production of saliva, which
normally buffers gastric acid. Horses
grazing at pasture eat frequently and have
food in the stomach almost all the time.
Diet is suggested to be a risk factor for
development of gastric ulcers, but defini-
tive studies are lacking. Horses in training
for racing are usually fed diets high in
concentrated rations and this is suspected
to predispose these horses to gastric
ulcers. Feeding of alfalfa hay and grain
was associated with fewer gastric lesions
in six research horses than was feeding
brome grass hay. 16

Confinement to stalls is associated
with an increased prevalence of gastric
lesions, whereas gastric lesions are
uncommon to rare in horses at pasture.
Horses with gastric lesions during con-
finement have healing of these lesions
when they are pastured. Again, there is
considerable confounding among the
various risk factors, as housing at pasture
is associated with constant access to feed,
and therefore no periods of feed with-
holding, changes in diet from that rich in
concentrates to that predominated by
grasses, and, often, cessation of forced
exercise.

PATHOGENESIS

The equine stomach is comparatively
small relative to the size of the gastro-
intestinal tract. The stomach mucosa is
divided into two parts. The proventricular
part is glistening white in color, is
composed of thick stratified squamous
epithelium and contains no glands. It
covers approximately one-third of the
mucosal area and ends abruptly at the
margo plicatus, a slightly raised irregular
serrated border with the glandular mucosa.
Most gastric lesions in horses occur in
squamous mucosa.

The glandular mucosa has a velvet-
like structure and is usually covered by a
thick layer of viscous mucus. The mucosa
contains three main gland types: mucus-
secreting cardiac glands; fundic glands,
which contain mucus-secreting cells,
hydrochloric-acid -producing parietal cells

and pepsinogen-secreting chief cells; and
pyloric glands, which consist largely of
mucus-secreting cells. The stratified
squamous epithelial mucosa has minimal
resistance to gastric acid. The glandular
epithelium has elaborate mechanisms,
including the mucus-bicarbonate barrier,
prostaglandins, mucosal blood flow and
cellular restitution, to protect itself from
peptic injury. Hydrochloric acid and
pepsinogens, which are converted to the
proteolytic enzyme pepsin in an acidic
environment, are secreted in the glandular
mucosa by parietal cells and chief cells,
respectively. The horse is a continuous,
variable hydrochloric acid secretor, and the
pH of equine gastric contents in the pylorus
and antrum is often less than 2.0. Gastric
pH is lowest, and acidity highest, when
horses have been deprived of feed or have
voluntarily stopped eating, often for as
little as 2 hours. Thus there are periods
during the day when gastric acidity is
high. Periods of prolonged high gastric
acidity (pH < 2.0) can be induced in horses
by intermittent deprivation of feed, which
often results in severe ulceration in the
gastric squamous epithelial mucosa. Con-
current administration of the H 2 antagonist
ranitidine during feed deprivation sub-
stantially reduces the area of lesion in the
gastric squamous epithelial mucosa. 17

The pathogenesis of gastric ulcer is
uncertain. Exposure of squamous mucosa
to acid is probably involved in the
development of ulcers in most horses.
During exercise intragastric pressure
increases from approximately 14 mmHg
at rest to as high as 50 mmHg, stomach
volume decreases and the acidity of fluid
within the proximal part of the stomach
declines from 5-7 to 2^4. 14 The combi-
nation of reduced blood flow and exposure
to low pH increases the likelihood of
mucosal damage, loss of protective
mechanisms and development of gastric
mucosal lesions.

Other factors, including physical injury
to gastric mucosa, reflux of bile acids from
the duodenum 18 and presence of volatile
fatty acids in the stomach all may
contribute to the development of gastric
lesions, 19 but the definitive roles, if any, of
each of these factors have not been
determined.

CLINICAL FINDINGS

The vast majority of horses with lesions of
the gastric mucosa, including ulceration,
do not have clinical signs. Among race
horses, signs of poor performance, feed
refusal, fussy eating (not consuming all of
the meal at a constant rate) and poor
body condition have been associated with
presence of gastric ulcers. Of these signs
only poor hair coat and poor body
condition have been proved to be

Diseases of the nonruminant stomach and intestines

associated' with gastric ulcers. 7,8 The high
prevalence of both some of the clinical
signs, for instance failure to perform to
expectation, and gastric ulcers means that
there is a high likelihood that horses with
a given clinical sign will have an ulcer by
chance. However, clinical experience
indicates that horses with more extensive
or severe lesions will have more severe
clinical signs, including colic.

Colic is associated with presence of
lesions of the gastric mucosa, including
ulceration. Ulceration can result from
lesions elsewhere in the gastrointestinal
tract, probably because of feed with-
holding or feed refusal by horses with
colic. Alternatively, gastric ulceration can
cause colic. The four criteria to determine
whether gastric ulceration is the primary
cause of colic in horses are:

o Endoscopic confirmation of gastric
ulceration

o Absence of another alimentary tract
abnormality

o Clinical response to treatment that
effectively suppresses or neutralizes
gastric acidity

® Confirmation of improvement or
complete healing of gastric lesions. 4

Most gastric ulcers in horses are not
associated with hemorrhage and so signs
of anemia or melena are unusual in
horses. Horses with severe gastric ulcer-
ation and reflux esophagitis often have
bruxism and retching. Rupture of gastric
ulcers, perforation and subsequent
peritonitis, and exsanguination from a
bleeding ulcer are rare in adult horses.

Involvement of the spleen in the horse
with a perforating gastric ulcer, a rare
event, results in fever, anorexia, toxemia,
pain on deep palpation over the left flank
and leukocytosis with a left shift.

Gastroscopic examination is the only
means of demonstrating gastric lesions
and assessing their extent and severity.
Gastroscopic examination of the adult
horse requires an endoscope of at least
2.5 m in length, although 3 m is prefer-
able. Presence of feed material within the
stomach prevents complete examination
of the gastric mucosa, and in particular of
the pylorus and antrum. The horse should
be prepared by having feed withheld for
at least 12 hours and water withheld for
4 hours before examination. If the horse is
stabled on edible material such as straw
or shavings, it should be muzzled to
prevent it eating this material. The horse
may need to be sedated before examin-
ation (xylazine hydrochloride 01-0.3 mg/kg
intravenously) and a twitch applied.
The gastric mucosa is examined in a
systematic fashion. As the end of the
endoscope passes through the cardia. the
greater curvature and margo plicatus are

examined.The endoscope is then advanced
and rotated so that the lesser curvature
and cardia are examined. The stomach
should be inflated with air during the
procedure. Excess fluid in the pylorus and
antrum can be aspirated to allow better
visualization of these regions. Careful
attention should be paid to the margo
plicatus as this is the most common site
for lesions. The gastric glandular mucosa
should be examined carefully for lesions
as they are easily missed in this region. 20
Material adherent to the mucosa should
be washed away by flushing water
through the endoscope. The endoscope
can be passed into the duodenum to
permit complete examination of the
antrum. Endoscopic examination usually
underestimates the number of gastric
ulcers, compared to necropsy examin-
ation, and does not accurately predict the
severity or depth of ulcers. 20

Grading systems for description of
gastric lesions in horses are: 20

Score

Number of lesions

0

No lesions

1

1-2 localized lesions

2

3-5 localized lesions

3

6-10 lesions

4

> 10 lesions

Score

Description

0

No lesions

1

Appears superficial

2

Deeper structures involved
(deeper than #1)

3

Multiple lesions and variable
severity

4

Same as #2 and in addition
presence of hyperemia or
darkened lesion crater

5

Same as #4 but hemorrhage or
blood clot adherent to ulcer

A simplified scoring system recommended
for use in practice is: 21

Score Description

0 Intact mucosal epithelium

1 Intact mucosal epithelium with
reddening or hyperkeratosis

2 Small single or small multifocal
lesions

3 Large single or large multifocal
lesions or extensive superficial
lesions

4 Extensive often coalescing
lesions with areas of apparent
deep ulceration

Most lesions in race horses are in the
gastric squamous mucosa with less than
20% of lesions being in the glandular
mucosa. The situation is different in
hospitalized adult horses, in which
lesions in the squamous and glandular
mucosa occur with about the same
frequency (58%). 22 Most lesions in the
glandular mucosa of hospitalized horses
occur in the antrum or pylorus, as
opposed to the glandular mucosa of the
body of the stomach. 22

Idiopathic gastroesophageal reflux
disease occurs sporadically and rarely in
adult horses. 23 Affected horses have
bruxism and ptyalism that can be severe.
Endoscopic examination reveals ulceration
and erosion of the esophagus that is more
severe in the distal esophagus. Often
there is no evidence of impaired gastric
outflow, as is common in foals with this
disease.

CLINICAL PATHOLOGY

There are no specific laboratory tests for
gastric ulceration. Horses with gastric
ulcers have higher concentrations of
creatinine and activity of alkaline
phosphatase in serum than do unaffected
horses, but these differences are not
sufficient to be clinically useful. 8 Horses
with gastric ulcer disease are typically not
anemic. A test using concentrations of
sucrose greater than 0.7 mg/dL in urine
after intragastric administration of 10%
sucrose (1 g/kg orally after feeding) solu-
tion has a sensitivity and specificity of
83% and 90%, respectively, for detection
of gastric ulceration 24 Sucrose is absorbed
intact across the damaged gastric mucosa
and excreted in urine, whereas that
entering the small intestine is degraded to
fructose and glucose.

NECROPSY FINDINGS

Ulcers may be singular or multiple and
are most commonly located in the
squamous epithelial mucosa adjacent to
the margo plicatus along the lesser
curvature of the stomach. They may be
linear or irregular in shape; with the
exception of those in the glandular
mucosa, they are rarely circular in appear-
ance. Ulcers in the squamous mucosa
often have slightly raised brown -stained
keratinized borders and contain small
amounts of necrotic material at their base;
frank blood is uncommon. Ulcers in the
glandular zone are less common and
are usually circular or oval depressions
surrounded by an intense zone of
inflammation.

When perforation has occurred, there
is an area of local peritonitis, the stomach
wall is adherent to the tip of the spleen
and an extensive suppurative splenitis
may be present. In some cases, especially
when the stomach is full at the time of

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

perforation, a long “tear develops in the
wall and large quantities of ingesta spill
into the peritoneal cavity. Tumor masses
may be present and accompanied by
several glandular ulcers.

DIFFERENTIAL DIAGNOSIS

Gastric ulceration of adult horses must be
differentiated from the common causes of
recurrent colic.

TREATMENT

The goals of treatment of horses with
gastric ulcer disease are: healing of the
ulcer, suppression of pain and prevention
of ulcer recurrence. The principle under-
lying treatment of gastric ulcers in horses
is suppression of gastric acidity (increase
intragastric pH). This can be achieved by
inhibiting acid production or increasing
buffering of acid. Mucosal protectants are
administered with the aim of preventing
exposure of damaged mucosa to acid.
Management changes may reduce the
risk of horses developing disease.

Acid suppression

The agents available to suppress acid
production are compounds including
omeprazole and lansoprazole that block
the proton pump on the luminal surface
of gastric parietal cells, and H 2 receptor
antagonists including cimetidine, ranitidine
and famotidine.

Omeprazole

Omeprazole is currently the favored
treatment for gastric ulcer disease in
horses. The pharmacokinetics, pharma-
codynamics, safety, and efficacy of the
drug have been extensively investigated
in horses under a variety of conditions
and management systems. Omeprazole
(4 mg/kg body weight orally every 24 h) as
a commercial suspension (Gastrogard®) is
very effective in promoting healing of
ulcers in horses that continue to train or
race, a situation in which ulcers will not
heal spontaneously. 21,23 ' 26 Omeprazole is
safe and no adverse effects from its
administration have been reported.
Original studies were conducted using
omeprazole at a high dose (4 mg/kg),
whereas more recent evidence suggests
that it may be effective at lower doses
(1 mg/kg orally every 24 h), especially
when administered as acid-resistant
enteric-coated granules. 27 A frequently
used treatment regimen is omeprazole
4 mg/kg once daily for 14 days followed
by maintenance therapy of 1-2 mg/kg
once daily for as long as the horse is
at risk of developing gastric ulcers.
Omeprazole paste administered at
1 mg/kg orally once daily is effective in
both preventing development of ulcers in

horses entering race training and pre-
venting recurrence of ulcers in horses in
which ulcers have healed during treat-
ment with a higher dose of omeprazole 28,29
The composition of the excipients and
form of omeprazole is important in
determining efficacy. Forms of omeprazole
other than that in the commercial
preparation are associated with reduced
or nil efficacy. 30,31 Omeprazole is more
effective than cimetidine (20 mg/kg orally
every 8 h) for treatment of gastric ulcers in
race horses. 32,33

Cimetidine

Cimetidine is the prototypical H 2 receptor
antagonist. It acts by blocking action of
histamine on the basilar membrane of the
gastric parietal cells. It is used for treat-
ment of gastric ulcer disease in horses, for
which is must be administered frequently
and in high doses (20-25 mg/kg orally
every 6-8 h). The drug has variable
absorption after oral administration to
horses. 34 It is usually cheaper than
omeprazole, but is less effective. 32,33
Cimetidine can be administered intra-
venously (7 mg/kg every 6 h) if rapid
action is needed or the animal cannot
take medication orally (e.g. a horse with
colic) .

Ranitidine and famotidine
Ranitidine (6.6 mg/kg orally every 8 h)
effectively suppresses gastric acidity and
prevents development of ulcers in horses
deprived of feed. 35 Commercial prep-
arations for use in horses are marketed in
some countries. It is effective in prevent-
ing ulcers induced in experimental
horses, but its efficacy in field situations is
not reported.

Famotidine is an H 2 receptor antagonist
marketed for use in humans. It is effective
in suppressing gastric acidity in horses
(3 mg/kg orally every 12 h or 0.3 mg/kg
intravenously every 12 hours) but is
expensive.

Gastric antacids

Gastric antacids given orally neutralize
| stomach acid to form water and a neutral
salt. They are not absorbed and decrease
pepsin activity, binding to bile salts in the
stomach, and stimulate local prostaglandin.
One oral dose of 30 g of aluminum
| hydroxide and 15 g magnesium hydroxide
| can result in a significant increase in
gastric pH for up to 4 hours 36 The short
| duration of action, minimal and transient
effect on gastric pH and need for
! administration of large volumes orally
| render these products less than optimal.
! Moreover, there is evidence that antacids
; are not effective in treatment of gastric
i ulcers in race horses. 32

I

j Protectants

I Sucralfate is an antiulcer drug with

cytoprotective effect on the gastric
mucosa. Sucralfate dissociates in gastric
acid to sucrose octasulfate and aluminum
hydroxide. The aluminum hydroxide acts
as an antacid and the sucrose octasulfate
polymerizes to a viscous, sticky substance
that creates a protective effect by binding
to ulcerated mucosa. This prevents back
diffusion of hydrogen ions, inactivates
pepsin and absorbs bile acid. Sucralfate is
administered to horses (22 mg/kg orally
every 8 h) but is not effective in promoting
healing in induced disease nor associated
with a lower risk of gastric ulcers in race
horses administered the compound. 32

Pectin-lecithin complexes are not
effective in treatment of gastric ulcer
disease in horses. 37

Management changes

Horses with gastric ulcers experience
spontaneous healing when removed from
training and kept at pasture. These
management changes are not appropriate
in most instances, and emphasis should
be place on feeding diets that have a low
ulcerogenic potential (such as alfalfa hay)
and using feeding practices that minimize
or eliminate periods when the horse does
not have access to feed. Hay should be
constantly available to horses, if at all
possible.

Overview of treatment

The usual approach to treatment is to
promote healing of the ulcer by adminis-
tration of effective agents (omeprazole or
possibly ranitidine) at high dose until the
ulcer has healed, as demonstrated by
gastroscopy. The horse is then administered
omeprazole at a lower dose (1-2 mg/kg
orally every 24 h) for the duration of time
that it is at risk of developing gastric
ulcers. Changes in management, including
importantly feeding practices and diet,
should be instituted at the start of
treatment. While not statistically associated
with risk of gastric ulceration, use of
phenylbutazone or other NSATD should be
minimized in horses at high risk of disease.

CONTROL

Prevention of gastric ulcer disease in
athletic horses centers upon minimizing
the effect of factors that promote ulcer
development. This may involve the
chronic administration of omeprazole
(1 mg/kg orally once daily), 29 but should
include attention to dietary and feeding
practices (discussed above) that minimize
the time that horses have no feed in their
j stomach. Ideally, horses at risk would be
j kept at pasture, but this is not feasible
| under many management or husbandry
| systems. All horses in athletic training
j and confined to stalls should be con-
j sidered at high risk of development of
| gastric ulcers and should be managed

Diseases of the nonruminant stomach and intestines

241

accordingly. Horses at pasture, such as
brood mares, are at minimal risk of
development of gastric ulcer disease and
no specific control measures are indicated.

REVIEW LITERATURE

Equine Gastric Ulcer Council. Recommendations for
the diagnosis and treatment of equine gastric
ulcer syndrome. Equine Vet Educ 1999; 11:262.
\&rious authors. Equine gastric ulceration. Equine Vet
J Suppl 1999; 29:1.

Buchanan BR, Andrews FM. Treatment and
prevention of equine gastric ulcer syndrome. Vet
Clin North Am Equine Pract 2003; 19:575.

REFERENCES

1. Cummings CA et al. J Vet Diagn Invest 1997;
9:311.

2. Johnson JH et al. Equine Vet Educ 2001; 13:221.

3. Sandin A et al. EquineVet J 2000; 32:36.

4. Murray MJ. J Am Vet Med Assoc 1992; 201:117.

5. Hammond CJ et al. EquineVet J 1986; 18:284.

6. Rabuffo RS et al. J Am Vet Med Assoc 2002;
221:1156.

7. Dionne RM et al. J Vet Intern Med 2003; 17:218.

8. Vatistas NJ et al. EquineVet J Suppl 1999; 29:34.

9. Murray MJ et al. EquineVet J 1996; 28:368.

10. Nieto JEetal. Vet J 2004; 167:33.

11. BeggLM, O'Sullivan CBAustVet J 2003; 81:199.

12. McClure SR et al. J Am Vet Med Assoc 1999;
215:1130.

13. Meschter CL et al.Vet Pathol 1990; 27:244.

14. Lorenzo-Figueras M, Merritt AM. Am J Vet Res
2002; 63:1481.

15. Murray MJ. Dig Dis Sci 1994; 12:2530.

16. Nadeau JA et al. Am J Vet Res 2000; 61:784. ;

17. Murray MJ, Eichom ES. Am J Vet Res 1996;

57:1599. j

18. Berschneider HM et al. EquineVet J Suppl 1999; j

29:24. I

19. Nadeau JA et al. Am J Vet Res 2003; 64:413. I

20. Andrews FM et al. EquineVet J 2002; 34:475.

21. Equine Gastric Ulcer Council. Equine Vet Educ

1999; 11:262. I

22. Murray MJ et al. JVet Intern Med 2001; 15:401. '

23. Baker SJ et al. J Am Vet Med Assoc 2004; 224:1967. i

24. Hewetson M et al. J Vet Int Med 2006; 20:388.

25. Buchanan BR, Andrews FM. Vet Clin North Am
Equine Pract 2003; 19:575.

26. Murray MJ et al. EquineVet J 1997; 29:425.

27. Andrews FM et al. Am J Vet Res 1999; 60:929. i

28. McClure SR et al. J Am Vet Med Assoc 2005;
226:1681.

29. McClure SR et al. J Am Vet Med Assoc 2005;
226:1685.

30. Merrritt AM et al. EquineVet J 2003; 35:691.

31. Nieto JEetal.J Am Vet Med Assoc 2002; 221:1139. j

32. Orsini J A etal.J Am Vet Med Assoc 2003; 223:336. ■

33. Nieto JE et al. Equine \fct Educ 2001; 13:260.

34. Smyth GB et al. EquineVet J 1990; 22:48.

35. Murray MJ, Schusser GF. Equine Vet J 1993; f
25:417.

36. Vatistas NJ et al. EquineVet J Suppl 1999; 29:44.

37. Murray MJ, Grady TC. EquineVet J 2002; 34:195.

INTESTINAL OBSTRUCTION IN
HORSES

Intestinal obstruction is an important
cause of colic in horses, and can involve
the small intestine, cecum, large (ascend- [
ing) colon, or small (descending) colon, j
Because the clinical characteristics of
obstruction of the various bowel seg- I
ments are quite different, intestinal |
obstruction is discussed based on the site j

affected (small intestine, cecum, large or
small colon).

SMALL-INTESTINAL
OBSTRUCTION IN HORSES

Synopsis •

Etiology Volvulus; intussusception;
incarceration and strangulation in epiploic
foramen, Meckel's diverticulum, mesenteric
rents, or umbilical, inguinal or
diaphragmatic hernia, or by pedunculated
lipoma; obstruction due to foreign bodies,
intramural tumors including hematomas,
neoplasms and abscesses; ileal
hypertrophy; ileal impaction
Epidemiology Mostly sporadic diseases,
although the age affected can vary with
the disease

Clinical signs Strangulating lesions cause
acute, severe disease with intense pain,
tachycardia, dehydration and
hemoconcentration, and usually distended
loops of small intestine palpable rectally.
Death occurs in untreated horses within
48 hours. Obstructive, nonstrangulating
lesions cause less severe pain and clinical
abnormalities and have a longer course
until death

Clinical pathology None diagnostic.
Hemoconcentration and azotemia are
indicative of dehydration. Leukopenia and
left shift are consistent with endotoxemia
and peritonitis. Peritoneal fluid may be
serosanguinous with infarcted intestine
Lesions Consistent with the disease
Diagnostic confirmation Surgical
exploration or necropsy
Treatment Surgical correction of lesion.
Analgesia. Correction of fluid, electrolyte
and acid-base abnormalities

ETIOLOGY

A working classification is outlined below.

Obstruction with infarction

Volvulus or torsion of the mesentery
Incarceration in or strangulation by:
Mesenteric rents 1
Epiploic foramen 2
Meckel's diverticulum 3
Pedunculated lipoma 4
Adhesions
Inguinal hernia 5
Umbilical hernia 6
Diaphragmatic hernia 7
Rents in mesentery or intra-
abdominal ligaments (e.g.
gastrosplenic) or spleen 8
" Spermatic cord in geldings 9
Developmental defects in
mesentery 10

Obstruction without infarction

Intussusception:

Jejunojejunal, ileoileal, and other
small intestinal 11,12
Acute and chronic ileocecal 13,14
Foreign body:

Wood chip or fencing material

impaction of duodenum or
jejunum 15
° Phytobezoars
° Linear foreign bodies such as
string or baling twine
■ Impaction of the duodenum or
jejunum by molasses-containing
feedblocks 16

° Impaction of Parascaris equorum 17
0 Impaction of the terminal ileum 18
° Muscular hypertrophy of the terminal
ileum 19

o Intramural masses such as neoplasms
(intestinal adenocarcinoma, focal
lymphosarcoma, leiomyoma), 20
hematomas, 21 abscesses and fungal
infections (intestinal pythiosis), focal
eosinophilic enteritis 22 and Lawsonia
intracellularis proliferative enteropathy

• Compression of intestine by intra-
abdominal masses including
abscesses and neoplastic tumors.

Functional obstruction

• Anterior enteritis

• Postoperative ileus

• Myenteric ganglioneuritis 23

• Intestinal ischemia of any cause
(thromboembolic colic, mesenteric
accidents, post-exertional ileus. 24

The classification used above should be
used only as a guide, as the actual clinical
presentation may vary. For instance,
intussusceptions usually result in infarc-
; tion of the intussuscepted segment but,
because this segment is effectively
isolated from the body, the clinical signs
are often not characteristic of a horse with
an infarctive lesion. Similarly, horses with
small intestine entrapped in the epiploic
foramen often have less severe clinical
signs than anticipated for the severity of
the lesion.

EPIDEMIOLOGY

The epidemiology of colic is covered in a
previous section. There are no recognized
risk factors for small-intestinal volvulus
and for many small-intestinal accidents.

: Epidemiological information is available
’ for some small-intestinal obstructive
diseases and is presented below. Obstruc-
tive diseases of the small intestine
compromise approximately 20% of colic

■ cases referred for further evaluation and
treatment. 25 For small-intestinal diseases

■ requiring surgical correction, the case
fatality rate is 100% if surgery is not
performed. Short-term survival of horses

; undergoing surgical correction of small
intestinal obstruction is 34-74%. 26,27
Mortality rate is greatest in the peri-
[ operative period. 27 Survival rates vary
I depending on the nature and severity of
the lesion, with long-term survival rates
being lower for horses that require

\2

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

resection of intestine, especially for
resections of more than 2 m or more than
one surgery. 28 ' 29

Intestinal herniation through the
epiploic foramen

This occurs in approximately 5% of horses
with small intestinal disease requiring
surgery. 2 Geldings are four times more
likely than mares to be affected. Thorough-
breds were over-represented in two studies,
suggesting a breed predisposition, and
there was no effect of age on incidence. 2,30
There appears to be an increased in
incidence of the disease between October
and March in Britain. 30 The case fatality
rate for horses subjected to surgery was
between 30% and 40%, 2,24,30 although
older reports of the disease had a much
higher case fatality rate. Horses with colic
that crib (a behavioral abnormality in
which horses grasp a fixed object such as
a fence rail or post with the incisors, flex
the neck and draw air into the esophagus)
are 8-34 times more likely to have
herniation of the small intestine through
the epiploic foramen than are horses that
do not crib. 30,31 The reason for this
association is not known but may be
related to factors that predispose horses
to both cribbing and intestinal herniation
through the epiploic foramen, such as
diet, exercise or housing. Alternatively,
cribbing might cause changes in intra-
abdominal pressure that favor herniation. 31
There is no age predisposition to develop-
ment of this disorder 26

Pedunculated lipomas

The prevalence of colic caused by
pedunculated lipoma is 1-2.6% of horses
with colic and 1-17% of all horses that
have a celiotomy because of small
intestinal disease. 4,26 The prevalence
varies depending on the population of
horses studied. The proportion of horses
with colic due to pedunculated lipomas
increases with age, with the median age
of affected horses being 19 years. 26
Pedunculated lipomas cause small
intestinal obstruction in older horses
(> 8 years) with geldings (2 x) and ponies
(4 x) being at increased risk. 4 Pedunculated
lipomas occasionally (5 of 75 cases) cause
strangulating obstructive lesions of the
small colon. 4 The case fatality rate for
horses subjected to surgery is over 60%.

Inguinal hernias

Inguinal hernias occur only in males.
Congenital inguinal hernias are usually
self-limiting, do not require medical or
surgical therapy and resolve by the time
foals are 3-6 months of age. Congenital
inguinal hernias rarely cause a strangu-
lating lesion of the small intestine (see
Colic in foals). Acquired inguinal hernias
occur almost exclusively in stallions, the

disease being rare in geldings. 5 There is
no apparent breed or age predilection.
The case fatality rate for horses subjected
to surgery is 25%.

Intussusception

Small-intestinal intussusception occurs
more commonly in young horses and
foals but also occurs in adult horses. 11,12
Approximately 50% of intussusceptions
in adult horses are associated with a
luminal or mural mass, whereas this is not
the case in younger horses and foals. 11,12
The case fatality rate of horses subjected
to surgery is 25-60%.

Both acute and chronic ileocecal
intussusceptions occur more commonly
in young (6-30 months) horses, although
they are rare in foals. 13,14 There is no breed
or sex predilection. The disease is acute in
approximately 70% of cases and chronic
in the remainder. 13 Ileocecal intus-
susceptions constitute approximately
75% of all intussusceptions involving the
small intestine, and 60% of all intus-
susceptions. 13 The case fatality rate
for horses with acute ileocecal intus-
susception when surgery is available is
approximately 70%, whereas that for
chronic intussusception is less than
10%. 13,14 There is strong evidence of
an association between tapeworm
(. Anoplocephala perfoliata) infestation
and ileocecal disease causing colic in
horses. 3233

Foreign body

Foreign body obstructions occur most
frequently in foals and yearlings, possibly
because of their tendency to explore and
eat unusual items. Impaction by Parascaris
equorum occurs in foals between 3 and
18 months of age and is often associated
with the administration of anthelmintics
to previously untreated foals. 17 Small-
intestinal obstruction by feedblocks
containing molasses is associated with
ingestion of large quantities of the
material. 26

Impaction

Ileal impaction occurs more commonly
in mares and only in animals over 1 year
of age. 18 The disease represented 7% of
surgical colic cases in one series. 34 The
case fatality rate of animals treated at a
referral institution was 64%. 20 The disease
is attributed to the feeding of finely
ground, high-fiber feed such as Bermuda
hay. 35 Horses with colic that have been
fed coastal Bermuda hay are approxi-
mately three times more likely to have
ileal impaction than are horses with colic
that have not been fed this feedstuff. 35
Similarly, lack of administration of a
compound effective against tapeworms is
associated with a three-times greater risk
of ileal impaction among horses with

colic, 35 and tapeworm infestation is associ-
ated with an increased incidence of
spasmodic colic and ileocecal impaction
in Thoroughbred race horses. 36

Mesenteric rents

Incarceration of small intestine through
mesenteric rents is a cause of colic in
approximately 2% of colic patients under-
going exploratory celiotomy. 1 The long-
term survival rate is approximately 40%.
There are no identified age, breed or sex
predilections.

PATHOGENESIS

The effects of intestinal obstruction and
the particular influence of the related
endotoxemia in horses have been detailed
earlier. The type of lesion is important,
depending on whether the blood supply
to a large section of intestine is occluded
or whether effective circulation is
maintained. Obstructions that do not
cause widespread intestinal ischemia,
such those caused by focal external
pressure, such as occurs with some forms
of disease caused by pedunculated
lipomas, or caused by internal foreign
bodies such as phytobezoars, are less
acutely lethal and do not cause as severe
signs as do volvulus and forms of intus-
susception that result in ischemia of large
sections of intestine. In the latter case,
endotoxins from the gut lumen pass
through the devitalized tissues of the gut
wall into the circulation, resulting in signs
of toxemia and cardiovascular collapse.

CLINICAL FINDINGS

Acute disease - infarctive lesions

In acute, complete obstructions of the
small intestine, with intestinal ischemia
due to volvulus, intussusception or
strangulation, there is usually an almost
immediate onset of severe abdominal
pain. The pain may be minimally or only
transiently responsive to administration
of analgesics. During this early stage
intestinal sounds may still be present and
feces still passed. The pulse rate increases
to 60-80/min, the respiratory rate may be
as high as 80/min, and sweating begins in
many horses. It may be 8-12 hours before
distended loops of intestine are palpable
on rectal examination and it is about the
same time that clinical and laboratory
evidence of hypovolemia is first apparent.
Depending on the site of the obstruction
there may be reflux of fluid on passage of
a nasogastric tube. More proximal lesions
result in distension of the stomach earlier
in the course of the disease. Small-
intestinal distension is readily detected by
percutaneous or rectal ultrasonographic
examination. The sensitivity and specificity
of ultrasonographic examination for
detecting small-intestinal distension
(98% and 84%, respectively) is greater

Diseases of the nonruminant stomach and intestines

2 .

than that" of rectal examination (50% and
98%, respectively). 37

In the period 12-24 hours after
obstruction commences, the pulse rate
rises to 80-100/min, loops of distended
intestine can be palpated per rectum, gut
sounds and defecation cease, and the
rectum is empty and sticky to the touch.
Abdominal paracentesis yields blood-
stained fluid. From 24 hours onwards,
signs of hypovolemia and toxic shock
become marked but the pain may not
worsen. The horse will often appear
depressed and poorly responsive to
external stimuli. Sweating may persist.
The heart rate increases to 100-120/min,
intestinal loops are easily palpable, and
reflux filling of the stomach occurs, with
much fluid being evacuated via the
stomach tube; the horse may vomit.
Death due to endotoxemia or rupture
of the intestine usually occurs within
48 hours. The terminal stage is one of
severe endotoxic shock, with or without
intestinal rupture and peracute diffuse
peritonitis.

Subacute cases - noninfarctive
lesions

If there is no vascular involvement in the
small -intestinal obstruction, the pain is
less severe than for horses with infarctive
lesions, it is usually responsive to
analgesics and the heart rate is only
mildly elevated (50-60 bpm). The pain
may be low-level continuous or inter-
mittent with moderate attacks of pain
alternating with periods of uneasiness
without signs of overt pain. Fhin is usually
responsive to administration of analgesics.
The duration of colic in these cases may
be several days to several weeks. Palpable
intestinal distension and clinical and
laboratory evidence of hypovolemia may
be evident. Surgical intervention becomes
an option because of the failure of the
patient to improve.

Intussusception of the small
intestine

This may cause a syndrome of acute,
subacute or chronic colic, depending on
the degree of involvement of the blood
supply. Horses with acute ileocecal
intussusception have an abrupt onset of
moderate to severe abdominal pain,
tachycardia, reflux through a nasogastric
tube, complete absence of borborygmi,
and tightly distended small intestine
evident on rectal palpation. The course of
the disease is usually less than 24 hours.
Horses with chronic ileocecal intus-
susception have a history of chronic,
intermittent colic occurring after feeding,
weight loss and reduced fecal volume. 13,14
The abdominal pain is mild and inter-
mittent and the horses are not dehydrated
or tachycardic. Rectal examination may

reveal the presence of mildly distended
small intestine, especially after a meal,
and in approximately 25% of cases the
intussusception can be palpated per
rectum. Mild abdominal pain may be
present for weeks without an abdominal
crisis occurring. Ultrasonographic exam-
ination may reveal the intussusception in
the right flank.

Volvulus of the small intestine

This presents a typical syndrome of acute
intestinal obstruction and infarction. The
onset of signs is abrupt and there is severe
pain, tachycardia, sweating and a rapid
deterioration in the horse's clinical
condition.

Strangulated inguinal hernia

This entity is often missed in the early
stages because the distension of the
scrotum is easily missed unless a specific
examination of that area is performed.
Severe pain in an entire male, even when
distended loops of small intestine arc not
palpable, should prompt a thorough
examination of the scrotum and, per
rectum, the internal inguinal rings.

Strangulated diaphragmatic hernia

When acquired after birth, this lesion may
have no distinguishing characteristics and
may be identified only on thoracic radio-
graphy or exploratory laparotomy. There
is often a history of trauma, such as
dystocia or, in adults, a fall or being hit by
a car. The clinical course is characteristic
of any acute, strangulating intestinal
lesion. Small intestine or large colon may
herniate into the thoracic cavity and
be evident on radiographic or ultra-
sonographic examination of the thorax. 7

Epiploic foramen entrapment

Entrapment of small intestine in the
epiploic foramen is associated with an
array of clinical signs, some of which are
subtle. Strangulation of small intestine
through the epiploic foramen typically
causes signs of acute abdominal pain with
reflux of material through a nasogastric
tube. 2,38 However, approximately 40% of
affected horses do not have signs of
abdominal pain when examined at a
referral center and 52% do not have
nasogastric reflux. 2 Horses with less
severe clinical signs presumably have
shorter lengths of incarcerated small
intestine or incomplete obstructions to
passage of luminal material or blood flow.
Herniation of the parietal (antimesenteric)
margin of the small intestine is sometimes
associated with incomplete obstruction of
the small intestine and signs of mild
disease 39 Because of the anterior location
of the lesion, distended small intestine
cannot usually be palpated per rectum
and is not identifiable without ultra-
sonographic examination or surgical

intervention. A fatal complication of
epiploic foraminal herniation is rupture of
the portal vein, leading to sudden death
from internal hemorrhage. Tension by the
incarcerated section of gut on the portal
vein causes tearing of its wall and sub-
sequent hemorrhage. 34 Hemoperitoneum
in a horse with colic should prompt
consideration of entrapment of small
intestine in the epiploic foramen as a cause
of the disease. The outcome of this combi-
nation of diseases is almost always fatal.

Functional obstruction

Functional obstructions due to anterior
enteritis, intestinal ischemia or post-
operative ileus can be difficult to dis-
criminate from obstructive lesions of the
small intestine that require surgical
correction. Postoperative ileus is charac-
terized by continued pain and reflux
through a nasogastric tube after surgical
correction of an intestinal lesion. The ileus
is probably a result of the diffuse
peritonitis and inflammation of the intes-
tine that results from surgical exploration
of the abdomen. If sufficient doubt exists
over the cause of a horse's signs of
intestinal obstruction, then laparotomy or
repeat laparotomy should be performed.

Foreign body

Foreign body impaction of the duodenum
by agglomerations of chewed wood or
cracked corn kernels cause signs of acute
obstruction but without the endotoxemia
caused by infarction. 15

Ileocecal valve impaction

Impaction of the ileocecal valve is mani-
fest as an initial period of 8-12 hours of
subacute abdominal pain with mild
increases in heart rate. Intestinal sounds
are increased in frequency and intensity.
Rectal examination may reveal the
enlarged, impacted ileum in the upper
right flank at the base of the cecum in
approximately 10% of cases 35 It is easily
confused with an impaction of the small
colon. Reflux on nasogastric intubation
occurs in approximately 50% of cases.
After 24-36 hours the pain increases in
severity. There is severe depression,
patchy sweating and coldness of the
extremities and the animal stands with its
head hung down, sits on its haunches and
rolls and struggles violently. The abdomi-
nal pain becomes severe and continuous,
the pulse rate rises to between
80-120/min and the pulse is weak. The
abdominal sounds are absent and there is
reflux of sanguineous fluid through a
nasogastric tube. On rectal examination
the small intestine is tightly distended
with gas and fluid. Death usually occurs
within 36-48 hours after the onset of
illness without surgical or effective medical
intervention.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Idiopathic muscular hypertrophy
(terminal ileal hypertrophy)

This causes a long-term chronic or mild
intermittent colic, with reduced appetite
and weight loss, which persists over a
period of weeks, sometimes months, in
horses more than 5 years and up to
18 years old. 19 Colic pain is associated with
feeding. On rectal examination the greatly
thickened ileum can be palpated at the
base of the cecum, and there may also be
distended loops of thick-walled ileum.

Difficulty can be experienced in differ-
entiating ileal hypertrophy from chronic
intussusception, especially of the terminal
ileum into the cecum. Fluid ingesta can
pass the much constricted lumen of an
intussusception so that mural hypertrophy
occurs orally. A similar clinical picture
results from stenosis of the small intestine
by adhesions, usually resulting from
verminous migration. In all three diseases
there is increased motility of the small
intestine and there is no interference with
the blood supply.

Caudal abdominal obstructions

Obstructive lesions of small intestine in
the caudal abdomen, and therefore more
likely to be palpable, include strangu-
lation through tears in the mesentery,
through a defect in the gastrosplenic liga-
ment, entrapment behind the ventral
ligament of the bladder or through a tear
in the broad ligament of the uterus.

Radiography is not useful in diag-
nosing the cause of small-intestinal
obstruction in adult horses, but ultra-
sonographic examination of the abdomen
is rewarding and has greater sensitivity
for detection of distended loops of small
intestine than does rectal examination. 2,37
If available, ultrasonographic examination
is indicated in the initial or second exam-
ination of all horses with colic. Ultra-
sonographic examination can detect, in
addition to distended small intestine,
reductions in or absence of motility \
associated with ileus, thickening of the |
intestinal wall, intussusceptions, increased |
volume of peritoneal fluid and abnor- :
malities in the echogenicity of peritoneal ;
fluid. 40 I

CLINICAL PATHOLOGY j

While laboratory examinations of animals i
with intestinal obstruction may not be j
used in the diagnosis of the obstruction, !
they are useful in assessing its severity. In j
general, the laboratory findings in acute i
intestinal obstruction include the following:

° Hemoconcentration (the PCV usually
exceeds 50%)

0 Increase in serum creatinine

concentration (depending on severity
of the decrease in circulating blood
volume)

° Decreases in plasma bicarbonate and
pH, with increases in lactate
concentration and anion gap
0 Leukopenia and neutropenia. This is
due to devitalization of infarcted
intestine and the development of
endotoxemia and, in some cases,
peritonitis

0 An increase in the total number of
leukocytes, erythrocytes and the
protein concentration in the
peritoneal fluid obtained by
paracentesis. In acute intestinal
obstruction with infarction, the
peritoneal fluid will be bloodstained.
As necrosis and gangrene develop
there is an increase in the total
number of leukocytes with an
increase in the number of immature
neutrophils. As devitalization
proceeds, but prior to perforation of
the gut wall, intra- and extracellular
bacteria may be seen in the fluid.
Peritoneal fluid from horses with
intestinal infarctive lesions has a
higher alkaline phosphatase
activity than fluid from horses
with nonstrangulating
obstructions. 41

NECROPSY FINDINGS

The physical lesions are characteristic of
the disease.

DIFFERENTIAL DIAGNOSIS

Other diseases that may mimic pain
caused by gastrointestinal disease are
listed under Differential diagnosis in equine
colic. Gastrointestinal causes of colic that
must be differentiated from
small intestinal obstructive disease
include:

• Enteritis and acute diarrhea

• Equine monocytic ehrlichiosis

• Anterior enteritis

• Gastric ulcer in foals and adults

• Disorders of the large or small colon

• Intestinal tympany (gas colic)

• Thromboembolic cole.

See also Table 5.6.

TREATMENT

The principles of treatment of horses with
small intestinal obstructive lesions are
similar to those of any colic and are set
out in detail under Equine colic, above.

Every attempt should be made to
relieve the horse's pain using appro-
priate doses of effective analgesics (see
Table 5.7). Care should be taken when
using flunixin meglumine that signs of a
lesion requiring surgical correction are
not masked until the severity of the
disease makes successful treatment
unlikely.

Almost all obstructive lesions of the
small intestine require surgical correc-
tion. In addition to surgery, attention
should be paid to maintaining the horse's
fluid, acid-base and electrolyte status, as
discussed under Equine colic and in
Chapter 2. Treatment of postoperative
ileus should be aggressive and include
correction of acid-base, fluid and electrolyte
abnormalities, continued gastric decom-
pression through a nasogastric tube and
administration of promotility drugs such
as cisapride, lidocaine, erythromycin and
metoclopramide (Table 5.8).

Ileal impactions can be treated
medically by the administration of intra-
venous fluids, gastric decompression and
administration of mineral oil. 42 Horses
treated medically should be closely
monitored as prompt surgical intervention
may be necessary if the horse's condition
deteriorates.

REFERENCES

1. Gayle JM et al. J Am Vet Med Assoc 2000;
216:1446.

2. Vachon AM, Fischer AT. Equine Vet J 1995; 27:373.

3. Hooper RN. J Am Vet Med Assoc 1989; 194:943.

4. Edwards GB, Proudman CJ. Equine Vet J 1994;
26:18.

5. Schneider RKet al. Am J Vet Resl982; 180:317.

6. Rijkenhuijen ABM et al. Equine Vet Educ 1997;
9:3.

7. Santschi EM et al.Vet Surg 1997; 26:242.

8. Helie P et al. Can Vet J 1999; 40:657.

9. Moll HD et al. J Am Vet Med Assoc 1999; 215:824.

10. Steenhaut M et al.Vet Rec 1992; 129:54.

11. Gift LJ et al. J Am Vet Med Assoc 1993; 202:110.

12. Greet TRC. Equine Vet J 1992; 24:81.

13. FordTS et al. J Am Vet Med Assoc 1990; 196:121.

14. Hackett MS, Hackett RP. ComellVet 1989; 79:353.

15. Green P, Tong JMJ. Vet Rec 1988; 123:196.

16. MairTS. Equine Vet J 2002; 34:532.

17. Southwood L et al. Compend Contin Educ Pract
Vet 1998; 20:100.

18. RarksAH et al. ComellVet J 1989; 79:83.

19. Chaffin MK et al. Equine Vet J 1992; 24:372.

20. Kasper C, Doran R. J Am Vet Med Assoc 1993;
202:769.

21. Van Hoogmoed L, Snyder JR. J Am Vet Med Assoc
1996; 209:1453.

22. Southwood LL et al.Vet Surg 2000; 29:415.

23. Burns GA et al. Cornell Vet 1990; 80:53.

24. Schott HC, Charlton MR. Compend Contin Educ
Pract Vet 1996; 18:559.

25. Van der Linden MA et al. JVet Intern Med 2003;
17:343.

26. Freeman DE, Schaeffer DJ. J Am Vet Med Assoc
2001; 219:87.

27. Van den Boom R,van derVelden MA. Vet Q 2001;
23:109.

28. Freeman DE et al. Equine Vet J Suppl 2000; 32:42.

29. Morton AJ, Blikslager AT. Equine Vet J 2002;
34:450.

30. Archer DC et al.Vet Rec 2004; 155:793.

31. Archer DC et al. J Am Vet Med Assoc 2004;
224:562.

32. Proudman CJ et al. Equine Vet J 1998; 30:194.

33. Pearson GR et al.Vet Rec 1993; 132:179.

34. Emberston RM et al. J Am Vet Med Assoc 1985;
186:570.

35. Little D, Blikslager AT. EquineVet J 2002; 34:464.

36. Proudman CJ, Hodlstock NB. EquineVet J 2000;
32:37.

37. Klohnen A et al. J Am Vet Med Assoc 1996;
209:1597.

38. Engelbert TA et al.Vet Surgl993; 22:57.

39. Hammock PD et al. J Am Vet Med Assoc 1999;
214:1354.

40. Freeman S. In Pract 2002; May:262.

41. Saulez MN et al. J Vet Intern Med 2004; 18:564.

42. Hanson RR et al. J Am Vet Med Assoc 1996;
208:898.

ANTERIOR ENTERITIS
(DUODENITIS - PROXIMAL
JEJUNITIS, PROXIMAL ENTERITIS)

Synopsis

Etiology Unknown
Epidemiology Sporadic disease. Case
fatality rate of 6-75%

Clinical signs Colic, voluminous reflux
on nasogastric intubation, mild fever,
resolution of pain on gastric
decompression

Clinical pathology None diagnostic
Lesions Duodenitis, proximal jejunitis.
Gastric and small intestinal distension
Diagnostic confirmation None.
Resolution of disease
Treatment Gastric decompression.
Correction of fluid and electrolyte
abnormalities

ETIOLOGY

The etiology of anterior enteritis is
unknown. C. difficile might be involved 1
Experimental intoxication with culture
media of Fusarium moniliforme produces
histological, but not clinical, signs con-
sistent with the disease. 2

EPIDEMIOLOGY

The disease is reported from the USA and
Europe. 2,3 There is no apparent effect of
age, with the exception that the disease is
not reported in horses less than 1 year of
age and is uncommon in horses less than
2 years of age. 4 There is no breed or sex
predilection for the disease. There are
anecdotal reports of farms with a high
incidence of the disease, especially among
brood mares. Similarly, some consider
feeding of large amounts of concentrated
feeds to horses to be a risk factor for
the disease. Anterior enteritis occurs
more commonly in the warmer months. 4
There are no reports of the incidence,
morbidity/mortality of anterior enteritis.
The case fatality rate varies from 6%
to 75%. 4,5

PATHOGENESIS

The primary lesion is inflammation and
edema of the duodenum and jejunum
with sloughing of villus epithelium and
villus atrophy. 5 These lesions are probably
associated with ileus and failure of small
intestinal absorptive function. Fluid
accumulation in the atonic small intestine
causes distension and pain and reflux of

Diseases of the nonruminant stomach and intestines

249

alkaline small-intestinal contents into the
stomach. Sequestration of fluid, electrolytes
and bicarbonate in the stomach and small
intestine causes a reduction in blood
j volume, shock and metabolic acidosis.
Gastric and small intestinal distension
and hypovolemia cause tachycardia.
Disruption of the small intestinal mucosal
barrier allows absorption of toxins,
including endotoxins, that further compro-
mise cardiovascular and metabolic function.

I Death in untreated cases results from
acute, diffuse peritonitis secondary to
gastric rupture, or shock and metabolic
disturbances secondary to hypovolemia
j and endotoxemia.

CLINICAL FINDINGS

The onset of clinical signs is usually
abrupt and characterized by mild to
severe colic. Affected horses are depressed,
j dehydrated and have prolonged capillary
j refill time and heart rates between 50 and
| 80/min. The respiratory rate is variable.

| The horse may sweat profusely and there
; are muscle fasciculations in severely
: affected cases. Borborygmi are absent
| although there may be tinkling sounds
i of gas bubbling in fluid-filled atonic
intestine. Rectal examination usually
reveals the presence of multiple loops of
: moderately to severely distended small
intestine. Reflux of fluid through a
nasogastric tube is a consistent finding,
and usually results in marked relief of
pain and resolution of tachycardia. The
fluid is often sanguineous, malodorous,
alkaline and of large (10-12 L) volume. 4

Gastric decompression and adminis-
tration of intravenous fluids results in
marked improvement of clinical signs,
although affected horses may continue to
have nasogastric reflux for 24 hours to
10 days. Most cases resolve within 5 days.

. If untreated, horses develop severe gastric
distension with subsequent rupture and
death from peracute, diffuse peritonitis, or
die as a result of hypovolemia and toxemia.
A common sequela is the development of
laminitis. Approximately 10% of horses
with anterior enteritis have cardiac
arrhythmias, including ventricular depolar-
izations and atrio-ventricular conduction
disturbances. 6 Arrhythmia resolves with
resolution of the anterior enteritis.

CLINICAL PATHOLOGY

There is hemoconcentration with
; hematocrits as high as 0.70 L/L (70%) and
; total serum protein as high as 96g/L
(9.6 g/dL) in severely affected horses. The
; leukogram is variable and not diagnostic
- leukocytosis and left shift are common. 5
; Serum potassium concentration may be
mildly low and blood bicarbonate con-
; centration and pH are low in most cases.
I Horses with anterior enteritis have serum
; bilirubin concentrations and serum

gamma-glutamyl transpeptidase, aspartate
aminotransferase and alkaline phosphatase
activities higher than horses with small
intestinal infarctive lesions. 7 However, the
differences are not sufficiently large for
these variables to be useful in the differ-
i entiation of horses with anterior enteritis
from horses with small-intestinal infarc-
tive lesions.

Peritoneal fluid has a normal nucleated
cell count in 65% of cases; in the remain-
| ing cases it is increased. 4 Peritoneal fluid
j protein concentration is often normal in
cases sampled early in the disease but
may be increased in more severe or
prolonged disease and is a useful prog-
nostic indicator. 8

NECROPSY FINDINGS

\ Gross lesions are restricted to the
j stomach, duodenum and jejunum in most
! cases. The affected stomach and small
! intestine are distended and the serosal
j surface has numerous petechial and
j ecchymotic hemorrhages. 5 The mucosa is
1 deep red and contains petechial hemor-
rhages and occasional foci of necrosis and
! ulceration. Histological changes include
neutrophilic inflammation, edema, hyper-
emia, epithelial sloughing and villus
atrophy. There is necrosis of mucosa,
fibrin-rich edema and heavy neutrophil
infiltration of the submucosa, and exten-
sive hemorrhage in the tunica muscularis
and serosa. 5 A proportion of horses with
anterior enteritis have biochemical and
histological evidence of liver disease,
including hepatocellular vacuolization
and neutrophilic inflammation. 7 Some
horses with anterior enteritis have
myocarditis. 6

The most important differential diagnosis is
a small intestinal obstructive lesion.

DIAGNOSTIC CONFIRMATION

Horses with small-intestinal obstructive
lesions require urgent surgical correction,
while horses with anterior enteritis
respond well to medical therapy. The
differentiation of anterior enteritis and a
small- intestinal obstructive lesion on
clinical grounds is difficult and there is no
one variable that allows the distinction to
be made reliably. Horses with anterior
enteritis have a lower heart rate, higher
rectal temperature (fever), lower volume
of gastric reflux and less turgid small
intestine on rectal examination than do
horses with obstructive lesions, 4 although
others report that horses with anterior
enteritis have a higher volume of reflux at
first examination and during the first

246

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

24 hours of disease. 7 However, these
differences are not sufficiently great to be
conclusive. Horses with anterior enteritis
more often have normal peritoneal fluid
than do horses with small-intestinal
obstructive lesions. The response to gastric
decompression and intravenous fluid
therapy is useful in discriminating between
diseases as horses with anterior enteritis
have marked resolution of abdominal
pain and tachycardia within minutes of
gastric decompression, whereas horses
with small-intestinal obstruction have
minimal or no resolution of these signs.
In general, horses with a heart rate below
60/min after gastric decompression,
mildly to moderately distended loops of
small intestine, resolution of abdominal
pain after gastric decompression and
normal peritoneal fluid probably have
anterior enteritis. However, horses should
be examined frequently for changes in
clinical condition. Worsening pain and
cardiovascular status in the face of ade-
quate fluid therapy warrant reconsideration
of a diagnosis of anterior enteritis.

TREATMENT

The principles of treatment of anterior
enteritis are gastric decompression, cor-
rection of fluid, acid-base and electrolyte
abnormalities and provision of main-
tenance fluid and electrolytes, relief of
pain, and prophylaxis of laminitis.

Gastric decompression is an urgent
need in affected horses and can be
accomplished by nasogastric intubation.
The nasogastric tube should be left in
place, or replaced frequently, for as long
as there is reflux of clinically significant
quantities of fluid (more than 2-4 L/4 h in
a 425 kg horse) . Discontinuation of gastric
siphonage should be approached
cautiously and the should be patient
monitored for any increase in heart rate or
development of abdominal pain that may
indicate recurrence of gastric distension.
After the nasogastric tube is removed, the
horse should be reintroduced cautiously to
oral fluids and food. Small amounts (1-2 L)
of water should be offered frequently (every
1-2 h) during the first 12-24 hours. Horses
should not be given immediate access to ad
libitum water as some horses in the early
convalescent period from anterior enteritis
will consume a large quantity of water and
develop gastric dilatation and colic. Feed
should be reintroduced gradually over
24-48 hours.

Complications of prolonged or repeated
gastric siphonage through a nasogastric
tube are pharyngitis, esophagitis, eso-
phageal stricture and esophageal perfor-
ation with subsequent cellulitis.

Fluid, electrolyte and acid-base
abnormalities should be corrected by
the administration of intravenous fluid.

Isotonic, polyionic fluids such as lactated
Ringer's solution are suitable. Affected
horses may loss considerable chloride and
potassium in reflux fluid necessitating
supplementation of fluids with potassium
(up to 20 mEq/L) .

Analgesia can be provided by adminis-
tration of any of a number of drugs,
including flunixin meglumine or ketoprofen
(Table 5.7). If the diagnosis of anterior
enteritis is uncertain, potent analgesics
such as flunixin meglumine should not be
used until there is no possibility that a
lesion requiring surgical correction exists.

Promotility agents such as lidocaine
and cisapride (Table 5.8) and antacids
such as cimetidine (Table 5.11) are
sometimes administered, although their
efficacy has not been determined. 9

Antibiotics, such as penicillin and an
aminoglycoside, are often administered to
affected horses because of the presumed
bacteremia associated with the disease.

Surgical treatment of the disease is j
described 3,5 but most cases resolve with-
out surgical intervention. 4

REVIEW LITERATURE

Riradis MR. Prokinetic drugs in the treatment of
proximal enteritis. Compend Contin Educ Pract
Vet 1999; 21:1147-1149.

Freeman DE. Duodenitis - proximal jejunitis. Equine
Vet Educ 2000; 12:322-332.

REFERENCES j

1. Arroyo LG et al. Proc Am Assoc Equine Pract j
| 2005; 51:38.

! 2. Schumacher J et al.Vfet Hum Toxicol 1995; 37:39.

3. Huskamp B. Equine Vet J 1985; 17:314.

4. Johnson JK, Morris DD. J Am Vet Med Assoc 1987; I

| 191:849.

j 5. White NA et al. J Am\fet Med Assoc 1987; 190:311. !
j 6. Cornick JL, SeahornTL. J Am Vet Med Assoc 1990; j
j 197:1054.

| 7. Davis JL et al. JVet Intern Med 2003; 896.

• 8. SeahornTL et al. JVet Intern Med 1992; 6:307.

I 9. Riradis MR. Compend Contin Educ Pract Vet
1999; 21:1147.

| DISEASES OF THE CECUM

; ETIOLOGY

“ Cecal impaction
1 Cecal rupture

J Cecocecal and cecocolic
intussusceptions
; Cecal torsion

I Cecal tympany

Cecal infarction.

■ There is strong support for a role of
i Anoplocephala perfoliata infestation in
! cecal disease of horses. 1-3 Infestation with
j A. perfoliata results in edema, hyperemia
j and hemorrhagic foci in the ileocecal
] valve mucosa with light parasitism through
i regional necrotizing enteritis, with exten-
j sion of lesions to the muscularis mucosa
| and eosinophilic inflammation around
| arterioles and submucosal neural plexus
| with heavy parasitism. 3

Etiology Cecal impaction, perforation,
cecocecal and cecocolic intussusceptions,
cecal torsion and cecal tympany
Epidemiology Sporadic diseases. Cecal
impaction and cecal perforation are
reported in horses hospitalized for
unrelated conditions. Cecal rupture occurs
in mares during parturition
Clinical signs Cecal impaction is evident
as mild, intermittent colic that may not be
noticed by a casual observer. Cecal
perforation or rupture is evident as acute
shock, sweating and tachycardia secondary
to diffuse peritonitis. Cecocolic
intussusception causes acute severe colic
while cecocecal intussusception causes
mild, intermittent colic
Clinical pathology None diagnostic
Lesions Gross lesions consistent with the
disease

Diagnostic confirmation Physical
examination, exploratory laparotomy, or
necropsy examination
Treatment Cecal impaction treated
medically with overhydration, fecai
softeners and analgesics. No treatment for
cecal rupture or perforation. Surgical
correction of some cecal impactions and all
cecocecal and cecocolic intussusceptions

Larval cyathostomiasis is also associated
with cecocolic and cecocecal intus-
susception in young horses. 4 Other
causes include intramural and extramural
masses, including cecal abscesses, and
alterations in cecal and colonic motility.

Disturbed cecal motility or dehydration
! of cecal contents secondary to dietary
! changes are thought to be the cause of
I most cases of cecal impaction and rupture. 5
Horses with recurrent cecal impaction
have lower neurone densities in muscle
layers of the base of the cecum and cecal
body than do normal horses, supporting
j the hypothesis that disturbed motility
| secondary to neuronal abnormalities is a
j cause of the disease/’ Administration of
I drugs that interfere with cecal motility or
I secretory function has the potential to
j increase the risk of cecal disease.

j EPIDEMIOLOGY

| Cecal disease accounts for approximately
| 4-10% of colic in horses examined for
| abdominal pain at referral centers. 7,8

| Cecal impaction

j Cecal impaction is the cause of colic in
1 approximately 5% of horses treated for
! colic in referral institutions. This estimate

S

| probably reflects a selection bias, with
j horses with less severe disease not being
j referred for further examination. Cecal
| impaction is therefore probably much less
| common as a cause of colic in field cases.
| Cecal impaction is the most common
> cause of cecal disease. 7 There is no sex
! predisposition to the disease but Arabians,

Diseases of the nonruminant stomach and intestines

247

Morgan?- and Appaloosa breeds might
be at greater risk of developing cecal
impactions. 9 Older horses are dis-
proportionately affected, with horses over
15 years at increased risk compared to
horses less than 7 years of age. 9,10 The
disease occurs sporadically but is reported
in horses hospitalized for unrelated
disease, and it is speculated that anes-
thesia, surgeiy and/or administration of
NSAIDs are risk factors for the disease. 10
Fasting, poor dentition, poor-quality feed
and restricted water intake might also be
risk factors for the disease. The case
fatality rate is approximately 50%. 10

Cecal rupture

Cecal rupture at parturition occurs in
0.1% of mares. 11 Cecal rupture represents
approximately 27% of cecal disease in
horses, that associated with concurrent
but apparently unrelated disease being
the most common (13%). 7 Cecal rupture
or perforation is otherwise a sporadic
disease that is often, but not always, a
sequela to cecal impaction. 12 The case
fatality rate is 100% , 12 Cecal rupture, often
without recognized pre-existing disease,
is recognized as a complication of
anesthesia and phenylbutazone adminis-
tration 9,12 ' 13 As with other cecal diseases,
infestation with A. perfoliata has been
implicated as a cause of cecal rupture,
although not all horses with cecal rupture
have tapeworms. 9

Cecocecal or cecocolic
intussusceptions

Cecocolic and cecocecal intussusceptions
are the cause of 1% of colic cases treated
surgically and approximately 3-7% of
cecal disease. 7,14 The case fatality rate is
approximately 50-70%. 14,15 There are no
recognized epidemiological patterns to
the occurrence of cecal or cecocolic
intussusceptions, with the exception
that younger horses (<3 years) and
Standardbreds are disproportionately
affected. 14,15 Infestation with tapeworm
(A. perfoliata ) is suspected to increase the
risk of cecal intussusceptions, although
this suspicion is not universal. 15,16

Cecal torsion

Cecal torsion occurs rarely and is associ-
ated with hypoplasia of the cecocolic fold
in some but not all cases. 7,17

Primary cecal tympany is rare. Cecal
infarction is caused by thromboembolic
disease secondary to Strongylus vulgaris
arteritis or necrotizing enterocolitis. 18

PATHOGENESIS

Cecal impaction is probably a result of
impaired or altered cecal motility, with
resultant reduced cecal emptying into the
right ventral colon. 5 Accumulation of feed
material causes cecal distension and
excessive tension in the wall of the cecum

with ischemia, necrosis and rupture.
Infestation by tapeworms, including A.
perfoliata, cause disruption of the cecal
mucosa and submucosa, necrosis and
inflammation, changes that could contri-
bute to cecal dysfunction. 3 Death results
from peracute diffuse peritonitis.

Cecal rupture at parturition is probably
the result of high intra -abdominal press-
ures associated with expulsion of the
fetus. The pathogenesis of cecal rupture
without cecal impaction is unknown.

CLINICAL FINDINGS
Cecal distension and impaction
Cecal distension occurs as two clinical
syndromes. Cases in which the cecum is
impacted and distended with inspissated
feed material usually have signs of mild to
moderate abdominal pain that is often
intermittent over a 1-4-day period. The
signs of pain may be sufficiently mild as to
be missed by a casual observer. Affected
horses are usually mildly depressed and
have a diminished appetite. The heart rate
is 40-60/min, borborygmi are reduced
and there may be mild dehydration.
Nasogastric intubation yields reflux fluid
only late in the course of the disease.
Rectal examination reveals a doughy
mass in the right caudal abdomen. The
ventral, and occasionally the medial, tenia
of the cecum are palpable, as is firm feed
materia] in the base and body of the
cecum. The mass extends cranially,
ventrally and across the midline of the
abdomen. If not treated, the cecum
ruptures, causing an acute onset of tachy-
cardia, sweating, delayed capillary refill
and shock, with death occurring in hours.
It is not unusual for the initial signs of the
disease to be missed and the problem to
be recognized only after the cecum
aiptures.

Horses with chronic, recurrent cecal
impaction have a mild disease charac-
terized by recurrent subtle to moderate
signs of colic, reduced food intake, weight
loss and loose feces. 19

Cecal distension also occurs as a
syndrome in which fluid accumulates in
the cecum. This disease has a much more
acute course and is characterized by
severe abdominal pain, tachycardia and
signs consistent with toxemia. Rectal
examination demonstrates a cecum tightly
distended with fluid ingesta. Without
surgical intervention the outcome is cecal
rupture and death.

Perforation

Cecal perforation may occur secondary
to cecal distension or as a primary entity.
There are usually only very mild pre-
monitory signs and the disease becomes
apparent when the cecum ruptures and
acute diffuse peritonitis develops. Detec-
tion of serosa with a gritty feel and free

gas in the abdomen on rectal examination
is diagnostic of a ruptured viscus and
diffuse peritonitis.

Intussusception

Cecocecal intussusception may present
as an acute severe colic or as a mild inter-
mittent colic, depending on the degree of
involvement of the apex of the cecum.
Small intussusceptions that cause little
obstruction and no infarction of the
invaginated section cause only mild pain.
Cecocolic intussusception causes acute
and severe pain and has a short course.
Rectal examination may reveal a mass in
the right dorsal quadrant, lack of a cecum
and pain on palpation of the right dorsal
quadrant. Ultrasonographic examination
of the right flank reveals the presence of
the cecum in the colon, apparent in cross-
section as a'target-like'pattern or taurus 20

CLINICAL PATHOLOGY

Cecal impaction with feed material is
usually associated with mild hemo-
concentration. Cecal perforation results in
severe leukopenia and left shift, hemo-
concentration (hematocrit > 50%, 0.50 L/L)
and azotemia.

Peritoneal fluid from horses with
cecal impaction is usually normal. How-
ever, if the cecum becomes ischemic, then
the fluid is sanguineous with an elevated
white blood cell count (> 8000 cells/pL,
8 x 10 9 cells/L) and protein concentration
(> 2.5 g/dL, 25 g/L). 10 Cecal perforation is
evident as a high proportion of degenerate
neutrophils, intra- and extracellular
bacteria and plant material.

NECROPSY FINDINGS

The distended cecum and diffuse perito-
nitis are readily apparent. Cases of cecal
perforation without distension will have
diffuse peritonitis but the cause is only
apparent on close examination of the
intestinal tract. There is usually no
underlying disease apparent on histologic
examination.

DIFFERENTIAL DIAGNOSIS

Causes of colic are set out in Table 5.6.

TREATMENT

Treatment of cecal impaction involves
control of pain (Table 5.7), restoration of
normal fluid, acid-base and electrolyte
status (see Ch. 2), and administration of
fecal softeners such as sodium sulfate
(Table 5.8). Mineral oil, although fre-
quently used, may not be sufficient alone
to facilitate passage of the impaction
because it does not cause fecal softening.

Intravenous administration of fluid
at 2-3 times maintenance needs is often

248

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

used in an attempt to'-hasten fecal soften-
ing by increasing secretion of water into
the impaction. Oral administration of
large quantities of water (4 L every 2 h for
24 h) may soften the impaction.

Horses with cecal impaction should be
closely monitored for signs of deterio-
ration, and especially of cecal ischemia, by
frequent physical examinations and
repeated abdominocentesis. Lack of reso-
lution within 24 hours or signs of deterio-
ration should prompt surgical exploration
with typhlotomy and evacuation of
the cecum and possible partial cecal
bypass. 12,21

Horses with cecal perforation always
die and should be euthanized without
delay.

Cecocecal and cecocolic intus-
susceptions must be corrected surgically.

REVIEW LITERATURE

Dabareiner RM, White NA. Diseases and surgery of
the cecum. Vet Clin North Am Equine Pract 1997;
13:303-315.

Dart AJ et al. Caecal disease. Equine \fet Educ 1999;
11:182-188.

REFERENCES

1. Proudman CJ et al. Equine Vet J 1998; 30:194.

2. Pearson GR et al.Vet Rec 1993; 132:179.

3. Rodriguez -Bertos A et al. J Vet Med A 1999; 46:261.

4. MairTS et al. Equine Vet J Suppl 2000; 32:77.

5. Gerard MP et al. J Am Vet Med Assoc 1996;
209:1287.

6. Schusser GF et al. Equine Vet J Suppl 2000; 32:69.

7. Dart AJ et al. Equine Vet Educ 1999; 11:182.

8. Van der Linden MA et al. J Vet Intern Med 2003;
17:343.

9. Dart AJ et al. AustVet J 1997; 75:552.

10. Collatos C, Romano S. Compend Contin Educ
Pract Vet 1993; 15:976.

11. Littlejohn A, Ritchie JD. J S Afr \fet Med Assoc
1975; 46:87.

12. Ross MW et al. J Am Vet Med Assoc 1985;
187:249.

13. Edwards JF, Ruoff WW. J Am Vet Med Assoc 1991;
198:1421.

14. Gaughan EM, Hackett RP. J Am Vet Med Assoc
1990; 197:1373.

15. Martin BB et al. J Am Vet Med Assoc 1999;
214:80-84.

16. Owen RR et al.Vet Rec 1989; 124:34-37.

17. Harrison IW. CornellVet 1989; 79:315.

18. Saville WA et al. JVet Intern Med 1996; 10:265.

19. Huskamp B, Scheidemann W. Equine Vet J Suppl
2000; 32:65-68.

20. Taintor J et al. J Am Vet Med Assoc 2004;
225:1829-1830.

21. Roberts CT, Slone DE. Equine Vet J Suppl 2000;
32:74-76.

DISPLACEMENT AND VOLVULUS
OF THE LARGE (ASCENDING)
COLON

Syndromes: nephrosplenic entrapment,
renosplenic entrapment, left dorsal dis-
placement of the large colon, right dorsal
displacement of the large colon.

ETIOLOGY

Left dorsal displacement of the large
colon (renosplenic or nephrosplenic

Synopsis L V

Etiology Unknown, probably involves
disturbance of colonic motility
Epidemiology Volvulus is more common
in mares during late gestation or after
parturition. Left dorsal displacement
(renosplenic entrapment) may be more
common in large male horses
Clinical signs Left displacement of the
large colon causes signs of mild to
moderate colic. Rectal examination reveals
large colon in the renosplenic space and
ultrasonographic examination confirms the
diagnosis. Right dorsal colon displacement
causes mild to moderate colic. Rectal
examination reveals colon lateral to the
base of the cecum. Volvulus of the large
colon causes mild to extremely severe
abdominal pain, tachycardia, shock and
abdominal distension. Rectal examination
reveals the distended, displaced colon
Clinical pathology None diagnostic
Lesions Displaced large colon
Diagnostic confirmation Physical
examination, laparotomy, necropsy
examination

Treatment Volvulus and right dorsal
displacement should be treated by surgical
correction. Left dorsal displacement can be
corrected by rolling the anesthetized horse
or jogging the horse after administration
of phenylephrine

entrapment and entrapment of the
large colon lateral to the spleen)

0 Right dorsal displacement of the large
colon

Volvulus (both strangulating and
nonstrangulating) .

The etiology of these conditions is
unknown but presumably involves some
disturbance to normal colonic motility.
Other causes of obstruction of the large
colon include congenital abnormalities of
the right ventral colon, 1 cystic duplication
of the ascending colon, 2 defects in the
mesocolon 3 and incarceration in epiploic
I foramen or gastrosplenic ligament. 4,5
! Intussusception of the large colon causes
; infarction and severe colic. 5
j The term volvulus refers to rotation of
the segment of bowel about the long axis j
i of its mesentery, while torsion refers to j
rotation about the long axis of the bowel.

I Because of the anatomical arrangement of
the mesocolon, either term may be ’
i correctly used to describe displacements j
= of the large intestine. 5

| EPIDEMIOLOGY

| Left dorsal displacement of the large
| colon (Fig. 5.1) is the cause of 2-10%
i of colic cases referred for specialist
S treatment. 6 There is no breed, age or sex
j predisposition, although some authors
j suggest that males and large horses are
| more likely to be affected. The case fatality

rate is approximately 5% for horses
treated correctly. 7 ' 10

Right dorsal displacement of the
large colon (Fig. 5.2) occurs sporadically
and without recognized risk factors. The
case fatality rate is reported to be as high
as 43%. 10

Risk factors for noninfarctive displace-
ment of the large colon include cribbing
or wind sucking (odds ratio (OR) = 90),
number of hours stabled per day (OR for
24 h stabling = 35), lack of regular exercise
(OR = 3.3), change in exercise program
(OR = 9), lack of anthelmintic adminis-
tration (OR = 13) and history of transport
in the previous 24 hours (OR = 17). 11

Volvulus of the large colon is the
cause of colic in 11-17% of colic cases in
which abdominal surgery is performed. 12
The disease occurs commonly in mares,
especially those late in gestation or
having recently foaled. 13,14 The disease
has a recurrence rate of up to 15% in
brood mares. 15 The disease occurs in
horses from 2 days of age and there does
not appear to be an effect of breed on
occurrence of the disease. 16 The case
fatality rate varies depending on the
extent of the volvulus, with lesser degrees
of volvulus (< 270°) having a 30% fatality
rate and volvulus of 360° or more having
a 65% fatality rate. 13

Ingestion of large quantities of grain,
such as might be fed to horses in heavy
work, is associated with changes in
plasma electrolyte concentrations, presence
of dehydrated, foamy and homogeneous
right dorsal colon contents, and fetid, less
formed feces. 17 These effects of a high-
grain diet may be associated with colonic
disease in horses. 17

PATHOGENESIS

Proximate factors leading to volvulus
or displacement are unknown, although
risk factors have been identified (see
above). A plausible scenario is that altered
colonic motility and subsequent dis-
tension with gas or ingesta predisposes
the colon to displacement, either spon-
taneously or as a result of the horse
rolling or lying down in response to
abdominal pain.

Left dorsal and right dorsal displace-
ments of the colon rarely compromise
colon blood flow and represent non-
strangulating obstructive lesions. Patho-
genesis in equine colic section). The
displacement of the large colon (Figs 5.1 &
5.2) impedes aboral movement of ingesta
and gas and may result in colonic
distension. Should the distension become
sufficiently severe, colon blood flow will be
impaired and cause ischemia and necrosis
of the colon. The obstruction to blood flow
is predominantly in venous drainage,
resulting in hemorrhagic strangulating

Diseases of the nonruminant stomach and intestines

Fig. 5.1 A Left lateral view of abdomen of a normal horse. B Left dorsal
displacement of the left colon, left lateral view. The left ventral and dorsal
colon is displaced lateral and dorsal to the spleen and occupies the renosplenic
space. 1 = liver, 2 = stomach, 3 = left dorsal colon, 4 = left ventral colon,

5 = spleen, 6 = left kidney and renosplenic ligament, 7 = pelvic flexure. (With
permission from Johnston JK, Freeman DE. Vet Clin North Am Equine Pract

1997; 13:317.)

obstruction with progressive development
of intramural edema, extravasation of red
blood cells, microvascular thrombosis,
mesothelial cell loss from the serosal
surface, and mucosal necrosis with loss of
colonic epithelium. 18

Volvulus of the large colon of less
than 270° does not compromise blood
supply but does impede aboral move-
ment of ingesta and gas. 13 Volvulus of
360° or more causes ischemia through
occlusion of both arterial and venous
circulation of the involved large colon

with rapid loss of colonic mucosal
integrity and colon viability. Irreversible
mucosal damage occurs after 3^1 hours of
ischemia. Loss of mucosal integrity
impairs normal barrier function and j
permits toxins and substances normally ’
confined to the colonic lumen to enter the ;
systemic circulation. Additionally, loss of i
barrier function allows leakage of vascular j
proteins and in severe cases red blood '
cells into the colonic lumen. Subsequent ;
signs are typical of strangulating obstruc- '
tion (see Equine colic) with development 1

of toxemia, cardiovascular collapse and
death within 12-18 hours.

The most common displacement is
medial and dorsal movement of the
ventral colon to complete a 360° volvulus
of the large intestine (Fig. 5. 3). 16 Lateral
and dorsal displacement of the ventral
colon is much less common. The volvulus
is usually at the level of the cecocolic fold,
although volvulus involving the cecum or
at the diaphragmatic and sternal flexures
does occur.

CLINICAL FINDINGS

Left dorsal displacement (renosplenic
entrapment)

The disease usually has an acute onset
and a duration of up to 4 days, although it
can be a cause of chronic, recurrent
colic. 6-9 Abdominal pain in the initial
| stages is mild to moderate and becomes
j progressively more severe as distension of
| the large colon develops. The heart rate is
usually between 50 and 70/min, but may
be as low as 30/min. Rectal temperature is
within normal limits. Mucous membrane
color and refill time are usually normal
provided that there is no ischemia of the
colon. Abdominal distension is appreci-
able in some affected horses. 6 There is
more than 2 L of reflux from a nasogastric
| tube in approximately 28% of cases,

| although rarely is there profuse reflux. 9
| Rectal examination reveals the presence
j of bowel in the renosplenic space in
| approximately 70% of cases with the
j typical finding of taenia of the ventral colon
j being traced into that space. Distension of
| the large colon may impair detection of
j bowel in the nephrosplenic space. The
spleen is usually displaced caudally,
medially and ventrally from its normal
position against the left body wall (Fig. 5.1) .

Ultrasonographic demonstration of
colon in the renosplenic space confirms
j the diagnosis with an accuracy of 88%. 19
I Gas in the displaced colon obscures the
j left kidney and dorsal border of the spleen
normally visible on ultrasonographic
examination of the left paralumbar region. 19

Approximately 8% of horses with
nephrosplenic entrapment have an
i additional lesion. 9 Entrapment in which
the sternal and diaphragmatic flexures are
displaced cranial to the stomach and liver
occurs in less than 3% of cases. 9

Right dorsal displacement

Severity of colic varies from mild to severe
in horses with right dorsal displacement
of the colon. Tachycardia (50-80/min) and
mild abdominal distension are character-
istic provided that the entrapped bowel is
not ischemic. There is usually no reflux
from a nasogastric tube, although as the
disease progresses gastric distension may
occur. Rectal examination reveals the
presence of large colon lateral to the base

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

DEF

Fig. 5.2 Right dorsal displacement of the colon, right lateral view. The colon
has passed lateral to the cecum, the pelvic flexure is displaced cranially and the
sternal and diaphragmatic flexures are displaced caudally. 1 = right dorsal
colon, 2 = base of cecum, 3 = right ventral colon, 4 = liver, 5 = cecum, 6 = left
ventral colon, 7 = pelvic flexure. (With permission from Johnston JK,

Freeman DE. Vet Clin North Am Equine Pract 1997; 13:317.)

Fig. 5.3 A 360° clockwise volvulus of the colon viewed from the right side. The
volvulus has occurred in the direction of the arrow. 1 = cecum, 2 = right dorsal
colon, 3 = right ventral colon. (With permission from Johnston JK, Freeman DE.
Vet Clin North Am Equine Pract 1997; 13:317.)

of the cecum, although colonic distension
may make detection of the displaced
bowel difficult. Right dorsal displacement
is a not uncommon sequel to impaction of
the pelvic flexure.

Volvulus

The onset of pain is abrupt and the dura-
tion of the disease ranges from hours, in
horses with strangulating lesions, to days
in horses with torsion of less than 270°.

The pain ranges from mild to severe and
intractable, with the horse violently
throwing itself to the ground. Pain in
horses with volvulus of 360° or greater is
often unresponsive to any analgesics.
Heartrate is variable and maybe less than
40/min in horses with severe disease,
although usually it is more than 60/min
and increases with severity of the disease.
Rectal temperature is within the normal
range. The mucous membranes are dark

red to blue and capillary refill time is more
than 3 seconds in severely affected
horses. Abdominal distension is marked,
usually severe, and may impair respir-
ation in horses with 360° or greater
volvulus. Auscultation of the abdomen
reveals a lack of borborygmi and the
presence of high-pitched, tympanitic
'pings' on simultaneous percussion and
auscultation. The pings are due to the
presence of gas in tightly distended large
colon or cecum. There is usually no reflux
through a nasogastric tube. Rectal exam-
ination may be limited by the distended,
gas-filled colon occupying the caudal
abdomen. In untreated cases death occurs
within 12-24 hours from cardiovascular
collapse. Ultrasonographic examination
reveals colon with a mural thickness of 9
mm or greater in horses with colon
torsion. The test has a sensitivity of
approximately 67% (i.e. correctly predicts
presence of colon torsion in two -thirds of
horses that have the disease) and
specificity of 100% (correctly rules out the
diagnosis in 100% of horses that do not
have the disease) . 20

CLINICAL PATHOLOGY

Changes in the hemogram, serum
biochemical profile and peritoneal fluid
are non-existent to mild in horses with
uncomplicated left dorsal displacement,
right dorsal displacement and volvulus of
less than 270°. Horses with ischemic
colon as a result of strangulation usually
have a leukopenia with left shift, hemo-
concentration and increased anion gap. 16

Serum gamma glutamyl transferase
(GGT) activity is elevated in approxi-
mately 50% of horses with right dorsal
displacement of the colon, whereas such
elevations are rare in horses with left
dorsal displacement. 21 The elevated GGT,
and less commonly serum bilirubin
concentration, in horses with right dorsal
displacement is attributable to compression
of the common bile duct in the hepato-
duodenal ligament by the displaced
colon. 21

Horses with large -colon volvulus have
a high prevalence of abnormalities in
hemostatic variables, including thrombin-
antithrombin concentration, D-dimer
concentration, antithrombin activity,
prothrombin time and platelet count.
Nonsurviving horses have lower platelet
counts, increased prothrombin time and
reduced antithrombin activity. 22

Peritoneal fluid often has an increased
total protein concentration (> 25 g/L,
2.5 g/dL) and white blood cell count
(> 8000 cells/pL, 8 x 10 9 cells/L) in horses
with compromised bowel. Examination of
peritoneal fluid is often not necessary to
achieve a diagnosis in horses with colon
torsion, although it does have prognostic
value in that horses with blood-tinged

Diseases of the nonruminant stomach and intestines

25

peritoneal fluid have a poor prognosis.
The risk of inadvertent enterocentesis is
increased in horses with severe distension
of the colon and abdominocentesis
should be attempted with caution in such
cases. Use of a bovine teat cannula or
similar blunt instrument is preferred to
the use of a needle.

NECROPSY FINDINGS

The colon is displaced as described above
for each of the diseases. Death usually
results from ischemic necrosis of the
colon and the associated peritonitis,
endotoxemia and shock. Histological
lesions in horses dying of colon volvulus
are more severe than of those that survive
and are characterized by hemorrhage into
the lamina propria, edema and loss of the
mucosal cells and crypt architecture. 13

TREATMENT

Treatment should consist of pain control,
correction of fluid, acid-base and electro-
lyte abnormalities, support of cardio-
vascular function and correction of the
underlying disease (Equine colic). Decom-
pression by trocarization of gas-distended

colon or cecum maybe beneficial. Correc-
tion of colon volvulus or right dorsal dis-
placement of the colon requires surgical
exploration of the abdomen and manual
correction of the displacement.

Left displacement

Correction of left dorsal displacement can
be achieved by either nonsurgical or
surgical means. Nonsurgical correction
is achieved by rolling the anesthetized
horse in a particular sequence that causes
the displaced colon to return to its normal
position in the abdomen. Nonsurgical
correction is successful in approximately
80% of cases, 7,27 although complications
are reported, 28 and is recommended as
the initial definitive treatment for horses
with uncomplicated left dorsal dis-
placement. 27 The sequence of events
following diagnosis of the condition is
depicted in Figure 5. 4. 29 Phenylephrine
(0.02-0.04 mg/kg, intravenously as a
10 min infusion) causes splenic contraction
and is thought to increase the chances of
the colon returning to its normal position.
The horse is anesthetized within
10 minutes of phenylephrine adminis-
tration and placed in right lateral recum-
bency. The horse is then slowly rolled into
dorsal recumbency and the abdomen is
vigorously massaged in an attempt to cause
the colon to move ventrally and medially. If
a hoist is available the horse can be lifted
into dorsal recumbency. The sequence ends
with the horse being rolled into left lateral
recumbency and a rectal or ultrasound j

DIFFERENTIAL DIAGNOSIS

See Table 5.6. Less common conditions of
the large colon include:

• Entrapment of the pelvic flexure in the
epiploic foramen 23

• Colocolic intussusceptions 24

• Colonic adenocarcinoma 25,26

E

F

G

examination being performed to determine
the position of the colon.

An alternative means of nonsurgical
correction involves administration of
phenylephrine (0.01 mg/kg, intravenously,
slowly) and then jogging the horse. 30,31
This technique was successful in correct-
ing the displacement in 11 of 12 horses. 31
It may be advantageous to relieve large-
colon distension by percutaneous
trocarization before jogging. 9

Cases that are refractory to nonsurgical
treatment require laparotomy (ventral
midline or left flank) and manual correc-
tion of the displacement. Recurrence of
the displacement occurs in 3-7% of
cases. 7 Horses with recurrent disease may
benefit from surgical ablation of the
nephrosplenic space. 32

Right dorsal displacement and colon
volvulus

These diseases require surgical correction
of the anatomical abnormality.

REVIEW LITERATURE

Burba DJ, Moore RM. Renosplenic entrapment: a
review of clinical presentation and treat-
ment. Compend Contin Educ Pract Vet 1997;
9:180-184.

Johnston JK, Freeman DE. Diseases and surgery of the
large colon. Vet Clin North Am Equine Pract 1997;
13:317-340.

Gibson KT, Steel CM. Strangulating obstructions of
the large colon in mature horses. Equine Vet Educ
1999; 11:234-242.

Lopes MA, Pfeiffer CJ. Functional morphology of the
equine pelvic flexure and its role in disease. A
review. Histol Histopathol 2000; 15:983-91.

D

Fig. 5.4 Steps in correction of left dorsal displacement of the colon (renosplenic entrapment). A Caudal view of
abdomen of horse with left dorsal displacement of the colon. Entrapped colon is shown in black; K = left kidney,

S = spleen. B Injection of phenylephrine and contraction of spleen. C Horse anesthetized and placed in right lateral
recumbency. D-H'Horse rolled through dorsal recumbency to left lateral recumbency. Entrapped colon moves ventrally
and then medially to the contracted spleen. (Modified with permission from Kalsbeek HC. Equine Vet J 1989; 21:442.)

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

REFERENCES ~

1. MairTS.Vet Rec 2002; 151:152.

2. Bassage LH et al. Equine Vet J 2000; 32:565.

3. Latimer FG et al. Equine Vet Educ 1999; 11:229.

4. Segura D et al. EquineVet Educ 1999; 11;227.

5.. Gibson KT, Steel CM. Equine Vet Educ 1999;
11:234.

6. Livesey MA et al. Can Vet J 1988; 29:135.

7. Baird AN et al. J Am Vet Med Assoc 1991;
198:1423.

8. Knottenbelt DC, Hill FWG. Vet Annu 1989;
29:161.

9. Hardy J et al. EquineVet J Suppl 2000; 32:95.

10. Van der Linden MA et al. J Vet Intern Med 2003;
17:343.

11. Hillyer MH et al. EquineVet J 2002; 34:455.

12. Fisher AT, Meagher DM. Compend Contin Educ
Pract Vet 1985; 8:S25.

13. Snyder JR et al. J Am Vet Med Assoc 1989;
195:757.

14. Moore JN, Dreesen DW. Proc Am Assoc Equine
Pract 1993; 38:99.

15. Hance SR, Emberstson RM. J AmVet Med Assoc
1992; 201:782:787.

16. Harrison IW. Vet Surg 1988; 17:77.

17. Lopes M A. F et al. Am JVet Res 2004; 65:687.

18. Snyder JR et al. Am J Vet Res 1988; 49:801.

19. Santshi EM et al.Vet Surg 1993; 22:281.

20. Pease AP et al. Vet Radiol Ultrasound 2004;
45:220.

21. Gardner RB et al. JVet Intern Med 2005; 19:761.

22. Dallap BL et al. J Vet Emerg Crit Care 2003;
13:215.

23. Steenhaut M et al. EquineVet J 1993; 25:550.

24. Dyson S, Orsini JA. J Am \fet Med Assoc 1983;
182:720.

25. RoyMF et al. EquineVet J 2002; 34:102.

26. Harvey-Micay J. Can\fet J 1999; 40:729-730.

27. Abutarbush SM, Naylor JM. J Am Vet Med Assoc
2005; 227:603.

28. Markel MD et al. J Am Vet Med Assoc 1985;
187:1379.

29. Kalsbeek HC. EquineVet J 1989; 21:442.

30. Johnston JK.Vet Surg 1996; 25:13.

31. Van Harreveld PD et al. NZ Vet J 1999;
47:109-111.

32. Zekas LJ et al. J Am Vet Med Assoc 1999;
214:1361-1363.

IMPACTION OF THE LARGE
INTESTINE OF THE HORSE

Synopsis

Etiology Idiopathic, often associated with
restricted exercise, poor-quality diet or
restricted access to water
Epidemiology Sporadic, more common
in mares. Accounts for approximately
10-1 5% of colics at referral institutions.
Case fatality rate of 20%

Clinical signs Mild to moderate colic
often of several days duration. Rectal
examination reveals impacted, distended
large colon

Clinical pathology No diagnostic
changes

Lesions Impaction of large colon, usually
pelvic flexure or right dorsal colon

Diagnostic confirmation Physical
examination

Treatment Pain control. Administration
of fecal softeners (sodium sulfate).
Overhydration by oral or intravenous
administration of isotonic fluids at
3-5 times maintenance needs

ETIOLOGY

i The cause of most impactions of the large
! colon is unknown. Known or speculated i
| causes include:

j c Poor dentition, such as occurs in older
horses

° Poor feeding regimens, such as
infrequent feeding of stalled horses
Horses not fed, in preparation for
surgery or racing, and then given
unrestricted access to feed or allowed
to eat bedding materials
’ Horses fed diets too high in fiber, e.g.
mature sorghum or maize plants, or
even mature Bermuda grass ( Cynodon
spp.) meadow hay, especially if their
water intake is limited; 1 ingestion of
large volumes of indigestible seeds,
e.g. Crataegus crusgalli (cockspur
hawthorn), may cause outbreaks
of impaction of the right dorsal
colon 2

Horses that come into loose boxes
and are offered hard feed after being
on soft grass on pasture are also likely
to develop impaction colic
American miniature horses develop
impaction of the colon 3
General debility

Enteroliths and fiber balls may also
cause obstruction of the large
intestine and usually result in
recurrent attacks of colic
Amitraz, a formamidine acaricide for
cattle, causes impaction colic in
horses 4

Retention of the meconium in foals
(see Colic in foals)

Administration of NSAIDs, which
alter colonic motility and might
predispose to impaction, 5 although
epidemiological support of this
etiology is not available
Restricted water intake, such as
during winter when watering points
freeze or water is unpalatable.

EPIDEMIOLOGY

The disease occurs in horses of any age
and is more common in females. 6 There
does not appear to be a breed pre-
disposition. The disease represented 13%
of colics treated at a referral facility. 6,7 An
important risk factor is a change in
management, especially one that involves
a reduction in exercise and change in
diet. 6 Risk factors for nonstrangulating
disease of the large colon, including pelvic
flexure impaction, include cribbing or
wind sucking, stabling with the risk
increasing with the number of hours
stabled per day, change in regular exercise
program, travel within the previous
24 hours and lack of anthelmintic
administration. 8 The case fatality rate is
approximately 1-20% 6,7

PATHOGENESIS

Development of impaction of the large
colon is frequently attributed to abnormal
colonic motility. 9 Other factors, including
mild dehydration as a result of limited
water intake or ingestion of poorly
digestible material, cause impaction in
many instances. Ingestion of large quan-
tities of grain, such as might be fed to
horses in heavy work, is associated with
changes in plasma electrolyte concen-
trations, presence of dehydrated, foamy
and homogenous right dorsal colon
contents, and fetid, less formed feces. 10
These effects of a high grain diet may be
associated with colonic disease in
; horses. 10 The end result is accumulation
i of a large mass of inspissated feed
i material in the large colon. Material
| usually accumulates first at the pelvic
flexure or right dorsal colon, presumably
because of the reduction in lumen
diameter at those points. Accumulation
of inspissated material causes disten-
sion of the colon and prevents aboral
passage of ingesta. Distension causes
pain and changes in colonic motility that
exacerbate or perpetuate the impaction. If
the distension is sufficiently severe or
prolonged the colon may become
ischemic and necrotic with subsequent
rupture, peracute diffuse peritonitis and
death.

CLINICAL FINDINGS

Moderate abdominal pain is the typical
sign in affected horses and pulse rate and
respiration are relatively normal. This
often continues for 3-4 days and some-
times for as long as 2 weeks. The horse is
not violent, the principal manifestation of
pain being stretching out and lying down
and the bouts of pain are of moderate
severity occurring at intervals of up to a
half-hour. There is anorexia and the feces
are passed in small amounts and are hard
and covered with thick, sticky mucus.
Intestinal sounds are absent or much
decreased in intensity. The pulse rate is
usually less than 50/min.

On rectal examination impaction of
the pelvic flexure of the large colon is the
commonest site and the distended, solid
loop of the intestine often extends to the
pelvic brim or even to the right of the mid-
line. Lying on the floor of the abdomen, it
is easily palpated, the fecal mass can be
indented with the fingers and the
curvature and groove between the dorsal
and ventral loops of the left colon can be
easily discerned. Impaction of the right
dorsal colon cannot usually be palpated
per rectum and the only abnormality may
be distension of the colon with soft
ingesta that has accumulated behind the
obstruction.

Diseases of the nonruminant stomach and intestines

CLINIC ALfATHOLOGY

Hemogram, blood chemistry and
peritoneal fluid are normal until the colon
becomes ischemic at which time there is a
leukopenia with left shift, and an increase
in the white blood cell count and protein
concentration in peritoneal fluid.

NECROPSY FINDINGS

The large intestine is packed full of firm,
dry fecal material and rupture may have
occurred.

DIFFERENTIAL DIAGNOSIS

See Table 5.6.

• Impaction of the pelvic flexure is readily
diagnosed on rectal examination

• A clinical similar syndrome is produced
by strictures of the large colon"

TREATMENT

The principles of treatment are pain
control, correction of fluid and electrolyte
abnormalities and softening of ingesta to
facilitate its passage. Fhin control is dis-
cussed in Table 5.7. Fluid therapy is
discussed in Chapter 2.

Softening of ingesta is achieved by
rehydrating the inspissated material and
providing lubrication to hasten its passage.
Fecal softeners (Table 5.8) such as
magnesium sulfate or sodium sulfate can
be given to increase the fecal water con-
tent and soften the impacted, inspissated
ingesta. Magnesium sulfate is associated
with a small risk of hypermagnesemia
and neurologic signs 12 whereas sodium
sulfate causes a mild hypernatremia and
hypokalemia. 13 Oral administration of a
balanced, polyionic electrolyte solution is
associated with the greatest increase in
colonic water content and no change in
serum electrolyte concentrations. 13 Enteral
administration of 10 L/h (to a 500 kg
horse) of a balanced, isotonic, polyionic
electrolyte solution is more effective than
intravenous administration of the same
quantity of fluid in combination with oral
administration of Mg0 4 in hydrating
colonic contents in normal horses. 14
Mineral oil (Table 5.8) is a lubricant and
may not penetrate the impacted ingesta
sufficiently to soften the material
although it is frequently given to horses
with colon impaction.

Overhydration by oral administration
of polyionic, isotonic fluids at 3-5 times
maintenance needs (approximately 10 L/h)
is the treatment of choice for colon
impaction. 6,13 Water can be given by
nasogastric tube at a rate of 4-10 L for a
450 kg horse every 1-2 hours until the
impaction softens. However, some horses
develop decreased small intestinal motility
or ileus with the disease, have delayed

gastric emptying and have reflux of fluid
through the nasogastric tube. Such horses
should not be administered any medi-
cation or water through the nasogastric
tube until reflux has resolved. Alter-
natively, isotonic fluids can be given
intravenously at 10 mL/kg/h until the
impaction is passed.

Promotility agents such as neo-
stigmine are usually contraindicated
because of the risk of rupture of the
distended colon when vigorous contrac-
tions are induced pharmacologically.

Horses may need to be treated for
1-6 days until the impaction resolves and
should not be fed during this time. When
feed is again provided it should be easily
digestible and initially be of limited
volume. Horses recovered from impaction
of the large intestine have a higher than
expected rate of recurrence of colic
(30 %). 6

Surgical treatment may be needed for
refractory cases (about 15%) but is associ-
ated with a poor prognosis because of the
risk of iatrogenic rupture of the colon
during attempts to exteriorize it from the
abdomen during surgery. 6 Impaction of
the right dorsal colon is more likely to
require surgical treatment. 15

REVIEW LITERATURE

White NA, Dabareiner RM. Treatment of impaction
colics. Vet Clin North Am Equine Pract 1997;
13:243-259.

REFERENCES

1. Pugh DG, Thompson JT. Equine Pract 1992; 14:9.

2. Rook JS et al. Equine Pract 1991; 13:28.

3. Ragle CL et al. J Am Vet Med Assoc 1992; 201:329.

4. Roberts MC, Seawright Al I. Aust Vet J 1979;
55:553.

5. Van Hoogmoed LM et al. Am J Vet Res 2000;
61:1259-1263.

6. Dabrareiner RM, White NA. J Am Vet Med Assoc
1995; 206:679.

7. Van der Linden MA et al. J Vet Intern Med 2003;
17:343.

8. I Iillyer MI I et al. Equine Vet J 2002; 34:155.

9. Sellers AF, Lowe JE. Equine Vet J 1986; 18:261.

10. Lopes MAF et al. Am J Vet Res 2004; 65:687.

11. Rose PL et al.Vet Surg 1991; 20:260.

12. Henninger RW, Horst J. J Am Vet Med Assoc
1997; 211:82.

13. Lopes MAF et al. Am JVet Res 2004; 65:695.

14. Lopes MAF et al. Equine \fct J 2002; 34:505.

15. Mezerova J et al.Vet Med Czech 2001; 46:293.

ENTEROLITHS AND FECALITHS

ETIOLOGY

Enteroliths are rock -like concretions,
which are either spherical or tetrahedral,
that form in the large colon of horses,
usually around a foreign body. 1 Most
enteroliths in the large colon of horses
are of two major types: magnesium
phosphates/struvite and magnesium
vivianite. 1,2 There is wide variability in
macrotexture and ionic concentrations
between and within enteroliths of am-

monium magnesium phosphate (struvite). 1
Affected horses often have more than one
enterolith and the enteroliths can weigh
up to 12 kg.

Fecaliths are aggregations of indigest-
ible material, such as fencing, plastic or
rope, that often have an irregular shape. ,

EPIDEMIOLOGY

Enteroliths occur sporadically in horses
in most regions of the world but there is a
greater than expected incidence in certain
areas, such as California. 3 Equids with
enterolithiasis represented 15.1% of
patients admitted for treatment colic, and
27.5% of patients undergoing celiotomy
for treatment of colic in a study from
California but less than 2% of horses with
colic examined at a referral center in
Texas. 4,5 Arabians and Arabian crosses,
Morgans, American Saddlebreds and
donkeys are over-represented, and
Thoroughbreds, Standardbreds, warm-
bloods and stallions are under-repre-
sented in some studies, suggesting a
predilection of these breeds for the
disease. 3-5 Enteroliths rarely occur in horses
less than 4 years of age and are more
common in older horses (> 11 years) . 4,6 The
disease is reported in American Miniature
Horses. 7 Feeding alfalfa hay and stabling
for more than 12 hours a day are associ-
ated with increased risk of enterolithiasis. 5,8
The mean pH of colonic contents from
horses with enterolithiasis is significantly
higher than for control horses and horses
with enterolithiasis have a significantly
lower percentage of dry matter in colonic
fecal samples and higher mean mineral
concentrations than controls. 8 About 15%
of cases examined at referral institutions
that see large numbers of cases develop a
ruptured viscus caused by the enterolith
and die. The long-term survival rate of
horses treated surgically is approximately
90%. 4

Fecaliths occur sporadically and
appear to be more common in younger
horses, perhaps because of their propensity
to dietary exploration and ingestion of
foreign materials.

PATHOGENESIS

The mechanism underlying enterolith
formation is not known. Enteroliths are
formed in the large colon and, rarely, the
cecum. They are clinically inapparent,
even if quite large, until they cause
obstruction of aboral passage of ingesta,
usually by occluding the right dorsal or
transverse colon. Occasional enteroliths
pass into the small colon. Obstruction of
the colon causes mild to moderate, often
intermittent, colic, presumably when the
j enterolith or fecalith obstructs the colon,
j with the pain resolving when the
i enterolith moves and the obstruction

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

clears. Complete Sbstruction results in
obstruction of aboral movement of ingesta,
accumulation of gas and ingesta proximal
to the obstruction and distension of the
large colon. There is no loss of integrity of
the colon early in the disease but with
time and distension there is ischemia and
necrosis of the colon, with subsequent
perforation, development of acute peri-
tonitis, and death.

CLINICAL FINDINGS

The most common historic manifestation
of enterolithiasis in horses is recurrent,
intermittent colic (about one- third of
cases), often with passage of enteroliths
in feces (about 10% of cases). 4,9 Horses
with acute obstruction have signs typical
of obstructive, nonstrangulating disease
of the large colon, including mild to
moderate colic with failure to pass feces.
The heart rate is 50-70/min, borborygmi
are decreased but not absent, and there is
mild abdominal distension. Rectal exam-
ination may reveal mildly distended large
colon but the offending enterolith is never
palpable, except on the rare occasion that
the enterolith or fecalith is lodged in the
small colon. Over a period of 6-12 hours
the severity of pain increases and there is
readily apparent distension of the large
colon. There is usually no reflux through a
nasogastric tube. The terminal phase,
which may take 72 hours to occur and is
due to rupture of a viscus, is marked by
moderate to severe pain, abdominal dis-
tension, tachycardia (> 80/min), decreased
capillary refill time and discolored
mucous membranes, sweating, muscle
fasciculations and death. Rupture of a
viscus and acute peritonitis occurs in
approximately 15% of cases. 4

Radiography of the abdomen is use-
ful in identifying enteroliths in horses
with colic. 10,11 The accuracy of the diag-
nosis is approximately 80% for enteroliths
in the large colon and 40% for those in
the small colon. 11 The most common |
reason for not detecting an enterolith is j
poor imaging of the abdomen because of j
inadequate penetration by the X-ray !
beam, 11 emphasizing the need for appro-
priate radiographic equipment.

CLINICAL PATHOLOGY

There are no diagnostic changes in the
hemogram, serum biochemical profile or
examination of peritoneal fluid. Horses
with enteroliths have higher serum
bilirubin concentrations on examination
at referral centers, but this change is not
sufficiently large to be useful as a diag-
nostic aid. 5 Similarly, horses with
enteroliths have higher protein and white
cell counts in peritoneal fluid than do
horses with other forms of colic but again
these differences are too small to be of
diagnostic significance. 5 Changes in

hematological and biochemical variables
during the terminal phases of the disease
are characteristic of acute, diffuse perito-
nitis and include leukopenia with left
shift, hemoconcentration and azotemia.

NECROPSY FINDINGS

Enteroliths are frequent incidental find-
ings at necropsy examination of mature
horses and their presence should not be
overinterpreted. Obstructive disease
caused by an enterolith is characterized
by colon distension, presence of an
enterolith in the right dorsal, transverse or
small colon and, in cases dying of the
disease, acute diffuse peritonitis resulting
from colon rupture or perforation at
the site of the enterolith. Tetrahedral
enteroliths with sharp points are believed
to be more dangerous than are spherical
enteroliths. 6

DIFFERENTIAL DIAGNOSIS

See Table 5.6.

The main differential diagnosis is colon
impaction, which may be difficult to
differentiate from enterolith obstruction in
the absence of radiographic examination
of the abdomen.

TREATMENT

The definitive treatment is surgical removal
of the enterolith. Supportive care including
analgesia and fluid therapy should be
provided as described under Equine colic.

CONTROL

Prevention of ingestion of foreign bodies,
such as small pieces of metal, may
decrease the incidence of the disease. 3
Strategies that decrease fecal pH and
mineral content of feces might also
decrease the incidence of the disease. 8

REFERENCES

1. Blue MG, Wittkopp RW. J Am \fet Med Assoc
1981; 179:79.

2. Hassel DM et al. Am J Vet Res 2001; 62:350.

3. Lloyd K et al. Cornell \^t 1987; 77:172.

4. Hassel DM et al. J Am Vet Med Assoc 1999;
214:233.

5. Cohen ND et al. J Am Vet Med Assoc 2000;
216:1787.

6. Evans DR et al. Compend Contin Educ Pract Vet
1981; 3:S383.

7. Ragle CA et al. J Am Vet Med Assoc 1992; 201:329.

8. Hassel DM et al. JVet Intern Med 2004; 18:346.

9. Colgan SA et al. AustVet J 1997; 75:100.

10. Rose JA, Rose EM. Proc Am Assoc Equine Pract
1987; 33:95.

11. Yarbrough TB et al. J Am Vet Med Assoc 1994;
205:592.

SAND COLIC

Sand colic is a disease of horses grazing
sandy fields with short pasture, fed on
sandy ground or provided with feed con-
taminated with sand. It is often associated
with underfeeding. Horses of all ages are

affected, including foals, which acquire
the sand while eating dirt. The case
fatality rate for horses treated by surgical
removal of sand is 20-40%. 1,2 The disease
is attributable to sand accumulation in the
right dorsal or transverse colon, or pelvic
flexure, causing obstruction. Sand in the
ventral colon does not cause obstruction
but is associated with colon volvulus and
displacement.

Clinical signs are of mild to moderate,
chronic colic with diarrhea and anorexia.
The colic is often very mild unless there is
colon torsion or volvulus, in which case
the signs are typical of that disease. The
diarrhea is watery but not profuse or
malodorous. Auscultation over the
cranial ventral abdomen just caudal to the
xiphoid reveals sounds similar to those
made when a paper bag is partially filled
with sand and rotated. 3 This sound is
diagnostic of sand accumulation in the
ventral colon. Rectal palpation may
reveal sand impaction in the ventral
colon, but more frequently colon dis-
tension with gas is present. 1,2 Rectal pal-
pation will not detect sand accumulation
in the transverse colon. Radiography
will demonstrate sand in the ventral
and dorsal colons and can be used to
monitor the efficacy of treatment. 4-6
Ultrasonography has good sensitivity
(88%) and specificity (88%) compared to
radiography for detection of sand in the
ventral colon. 7 Ultrasonography is not as
effective at detecting sand in the right
dorsal or transverse colon. 7 Abdominal
fluid is normal except when there is
ischemia or necrosis of the colon or when
peritonitis is present. 4 Sand will settle out
when feces is mixed with water in a
clear plastic rectal sleeve and hung for
30 minutes.

Treatment consists of pain relief,
correction of fluid and electrolyte abnor-
malities, prevention of continued inges-
tion of sand and removal of the sand. In
horses with acute obstruction of the right
dorsal or transverse colon by sand,
surgical removal is indicated. Medical
treatment to effect sand removal is
indicated in less acute cases. A widely
used medical treatment is administration
of psyllium mucilloid (0.5-1 g/kg orally
every 12 h for 4-8 weeks) administered
via a nasogastric tube or as a dressing on
feed. However, in an experimental model
of the disease this treatment was no more
effective than no specific treatment in
removal of sand from the cecum and
colons. 8 Mineral oil (1 mL/kg) or MgS0 4
(1 g/kg) orally may hasten sand removal. 6
Pasturing of horses with sand accumu-
lation housed in stables aids removal of
the sand. 6 Control of the disease is by
preventing ingestion of sand by feeding
horses hay and grain from clean feeding

Diseases of the nonruminant stomach and intestines

bins, providing adequate roughage in the
diet, pasturing horses in fields with
adequate grass cover, and perhaps, in
areas where sand ingestion is unavoid-
able, daily administration of psyllium
mucilloid.

FURTHER READING

Walesby HA et al. Equine sand colic. Compend
Contin Educ PractVet 2004; 26:712.

REFERENCES

1 . Specht TE, Colahan PT . J A m Vet Med Assoc 1988;
193:1560.

2. Ragle CA et al. Vet Surg 1989; 18:48.

3. Ragle CA et al. J Vet Intern Med 1989; 3:12.

4. Bertone JJ et al. J Am Vet Med Assoc 1988;
193:1409.

5. Rose JA, Rose EM. Proc Am Assoc Equine Pract
1987; 33:95.

6. Ruohoniem M et al. Equine Vet J 2001; 33:59.

7. Korolainen R, Ruohoniemi M. Equine Vet J 2002;
34:499.

8. Hammock PD et al. Vet Surg 1998; 27:547.

RIG HT DORSAL COLITIS

This is a chronic disease caused by ulcer-
ative colitis of the right dorsal colon. The
disease is associated with prolonged
administration of NSAIDs, such as phenyl-
butazone, in most, but not all, cases. 1 The
case fatality rate is greater than 50%,
although descriptions of large numbers of
affected horses are not available.

The pathogenesis involves inhibition
of mucosal prostaglandin synthesis and
consequent decreases in water, chloride
and bicarbonate secretion by mucosa of
the right dorsal colon and apoptosis
(programmed cell death) of mucosal
cells. 2 Loss of secretion of bicarbonate
might be associated with failure of
alkalinization of right dorsal colon con-
tents and subsequent development of
mucosal lesions. The right dorsal colon is
the only section of the colon with net
water secretion, and this unique activity
may predispose this section of colon to
disease. Exposure of mucosal cells to
phenylbutazone can occur both from the
lumen and from blood. Luminal exposure
may be related to release of phenyl-
butazone from ingesta in the right dorsal
colon. 3 Ulceration of the colonic mucosa
allows leakage of plasma constituents
into the colonic lumen, resulting in hypo-
albuminemia and loss of electrolytes, and
entry of colonic substances such as
endotoxin into the systemic circulation,
with consequent signs of endotoxemia
and systemic inflammatory response
(leukopenia, hyperfibrinogenemia, fever).
Chronic and extensive mucosal ulceration
causes growth of granulation tissue and
fibrosis of the right dorsal colon with
subsequent loss of secretory function,
stricture and partial obstruction. 4

Clinical signs include depression,
anorexia, mild fever (38.6-39.5°C,

101.5-103°F), mild intermittent colic,
ventral edema, weight loss and occasion-
ally mild diarrhea. There is almost always
a history of administration of a NSAID.
The disease can persist for weeks and
often prompts inappropriate administration
of nonsteroidal anti-inflammatory drugs.
Rectal examination is unremarkable.
Ultrasonography is useful in the diag-
nosis of right dorsal colitis by detecting
the presence of a hypoechogenic sub-
mucosal layer and permitting measure-
ment of the wall thickness of the right
dorsal colon. 5 The hypoechogenic layer
in the wall of the right dorsal colon
corresponds with edema and cellular
infiltrates observed histologically. The
right dorsal colon in adult horses has a
maximal thickness of 6 mm while that in
horses with right dorsal colitis is greater
than 8 mm and can be as great as 16 mm. 5
Additionally, the ratio of right dorsal
colon to right ventral colon wall thickness
is up to 1.6 in normal horses and greater
than 2.0 in affected horses 5 Scintigraphic
detection of right dorsal colitis is achieved
by administration of technicium-"m
hexamethylpropyleneamine -oxime -
labeled white blood cells. 6 Images
obtained 20 hours after administration of
labeled white cells demonstrate uptake of
cells into the right dorsal colon (right
cranioventral abdomen).

There is often mild peritonitis
(neutrophilia in peritoneal fluid).
Leukopenia with left shift and hypo-
proteinemia are characteristic. Serum
biochemical abnormalities include hypo-
albuminemia, hyponatremia (< 135 mEq/L),
hypochloremia (< 90 mEq/L) and azotemia
(serum creatinine > 2mg/dL, 170 pmol/L). 1,7

Necropsy examination reveals ulcer-
ative colitis of the right dorsal colon. In
chronic cases there may be stricture of the
right colon with subsequent impaction of
ingesta and colon rupture. 1

Treatment is often unrewarding
although successful treatment by feeding
of a low residue diet, such as a complete
pelleted ration fed 4-6 times daily, is
reported. 8 Psyllium (120 g once daily) for
3-6 weeks might enhance healing of the
colon. Administration of misoprostol
(Table 5.11) has been suggested but has
no demonstrated efficacy. Surgical exci-
sion of the lesion is difficult because of its
location in the abdomen but bypass of the
right dorsal colon may be beneficial.
Control involves minimizing the amount
of NSAIDs administered to horses.

FURTHER READING

Bueno AC et al. Diagnosis and treatment of right

dorsal colitis in horses. Compend Contin Educ

Pract Vet 2000; 22:173.

REFERENCES

1. Karcher LF et al. J Vet Intern Med 1990; 4:247.

2. Richter R et al. Am J Vet Res 2002; 63:934.

3. Lees P et al. Res Vet Sci 1988; 44:50. "

4. Hough ME et al. Aust Vet J 1999; 77:785.

5. Jones SL et al. J AmVet Med Assoc 2003; 222:1248.

6. East LM et al. Vet Radiol Ultrasound 2000; 41:360.

7. Cohen ND et al. \fet Med 1995; 90:687.

8. Cohen ND et al. J Vet Intern Med 1995; 9:272.

SMA LL COLON OBSTR U CTION

ETIOLOGY

° Small colon impaction 1,2
° Obstruction by enterolith or fecalith 1
° Meconium retention (see Foal colic)

° Atresia coli (see Foal colic)

0 Strangulation by pedunculated
lipoma, 3 volvulus, intussusception, 4
herniation through mesenteric rents
including the mesocolon or
gastrosplenic ligament 5,6 or enlarged
ovary 7

• Neoplasia (intramural)

° Hematoma

° Rectal prolapse
° Rupture of mesocolon 8

• Colonic lipomatosis 9
° Perirectal abscess.

EPIDEMIOLOGY

Small colon disease is present in approxi-
mately 2.5-5% of horses treated for colic
at referral institutions and small colon
impaction represents approximately 2%
of horses with colic. 1,2,10 Aged female
horses are most commonly affected
although the conditions can occur in
horses of any age. 3 Arabians, ponies and
Miniature horses are reported to be at
increased risk of small colon disease
although others have not detected this
apparent predilection. 3,10 Rupture of the
mesocolon occurs during parturition. 4
The case fatality rate depends on the
condition and is 30-40% for impaction of
the small colon. 2,10 Small colon impaction
can occur as limited outbreaks in a
number of horses on a single farm over a
period of days to weeks, without obvious
predisposing causes or inciting events.

PATHOGENESIS

Obstruction of the small colon causes
accumulation of ingesta and gas in the
small colon aboral to the obstruction and
in the large colon, with subsequent
distension, pain and reduced motility.
Distension of the small colon may impair
blood flow with subsequent ischemia,
necrosis and rupture or perforation of the
small colon. Incarceration of the small
colon results in ischemia of the entrapped
segment and restriction of flow of ingesta.
Subsequent signs are characteristic of
toxemia and intestinal obstruction. The
high proportion of affected horses from
which Salmonella spp. are isolated sug-
gests a role for colitis in the pathogenesis
of small colon impaction. 2,10

;6

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

CLINICAL FINDINGS
Nonstrangulating lesions
Nonstrangulating lesions manifest as
mild to moderate colic that may persist
without a change in severity for up to
36 hours. The heart rate depends on the
severity of the colic but averages 60/min
with a range of 30-110/min. 2 There is mild
dehydration. Abdominal distension is
usually mild initially but increases as
the disease progresses. Borborygmi are
reduced and tympanitic sounds may
develop as the large colon and cecum
become distended. Rectal examination
reveals the presence of distended
large colon but no evidence of colon
displacement.

Small colon impaction is palpable as
a tubular column of material in the small
colon although it may be missed if the
impaction is in the cranial section of the
small colon. Approximately 30% of cases
have diarrhea and 13% strain to defecate. 10
Complete examination per rectum may
be difficult because of large colon
distension and accumulation of feces in
the distal small colon. There is reflux
through the nasogastric tube in approxi-
mately 30% of cases. 2

Strangulating lesions
Strangulating lesions that interfere with
small colon blood supply usually present
as acute colic of moderate to severe
intensity. There is tachycardia and
evidence of toxemia. Abdominal disten-
sion is usually marked and there is an
absence of borborygmi. Rectal examin-
ation reveals distension of the large colon
and occasionally soft, compressible
distension of the small colon.

Avulsion of the mesocolon occurs
during parturition and is often evident as
a rectal prolapse in the mare. Avulsion
results in ischemia of the distal colon.
Initially the mare does not display signs
of pain but, as the section of the colon
from which the mesocolon has avulsed
becomes necrotic, signs of toxemia
develop.

CLINICAL PATHOLOGY

There are no characteristic changes in the
hemogram or serum biochemical profile.
Peritoneal fluid is normal until the
viability of the small colon is compro-
mised, at which time the protein concen-
tration and white blood cell count
increase. Salmonella spp. are isolated from
approximately 20% of cases of small colon
impaction, suggesting a role for colitis in
the pathogenesis of the disease. 10

NECROPSY FINDINGS

Small colon impaction is evident as a
tubular column of firm ingesta in the
small colon with large colon distension.
Small colon accidents, such as rupture of

the mesocolon at parturition and intus-
susception, are readily apparent. 4,8

DIFFERENTIAL DIAGNOSIS

See Table 5.6.

TREATMENT
Small-colon impaction

The principles of treatment of small-colon i
! impaction are relief of pain and of the j
j impaction. Horses with signs of mild to j
j moderate colic easily controlled with j
j analgesics should be treated medically. ;
| Horses with intractable pain or pro- ;
| gressively worsening pain, abdominal i
' distension or abnormal peritoneal fluid j
| should be treated surgically. Horses ]
\ treated surgically have a worse prognosis i
than do horses treated medically, prob- ■
ably because the former group has more )
severe disease. 2,10

Medical treatment of small-colon
impaction involves administration of
! analgesics (see Table 5.7), correction of :
; fluid, electrolyte and acid-base abnor-
malities, and administration of fecal
: softeners (Table 5.8). Treatments to hasten '
softening and passage of the impaction
include overhydration, administration of
sodium or magnesium sulfate and a lubri-
cant such as mineral oil, and occasionally
administration of an enema to the
standing horse. Overhydration should be
achieved by either intravenous or oral
administration of polyionic fluids at
3-5 times maintenance (10 mL/kg/h).
Administration of enemas to standing
horses is controversial and should be
done with care so as not to rupture the
small colon. Trocarization of the large
colon or cecum may be necessary in
horses with severe abdominal distension.

Small-colon accidents including
strangulation and intussusception require
surgical correction. Surgical correction of
rupture of the mesocolon is not available
because of limited surgical access to the
site of the lesion.

REVIEW LITERATURE

Edwards GB. A review of 32 cases of small colon
obstruction in the horse. Equine Vet J Suppl 1992;
13:42-47.

Edwards GB. Diseases and surgery of the small colon.
Vet Clin North Am Equine Pract 1997;
13:359-375.

Schumacher J, Mair TS. Small colon obstructions in
the mature horse. Equine Vet Educ 2002; 14:19.

REFERENCES

1. White NA, Lessard P. Proc Am Assoc Equine
Pract 1986; 23:637.

2. Ruggles AJ, Ross MW. J Am Med Assoc 1991;
199:1762.

3. Dart AJ et al. J Am\fet Med Assoc 1992; 200:971.

4. Ross MW et al. J Am Vet Med Assoc 1988;
192:372.

5. Booth TM et al. AustVet J 2000; 78:603.

6. Rhoads WS, Parks AH. J Am Vet Med Assoc 1999;
214:226.

7. MairTS. EquineVet Educ 2002; 14:17.

8. Dart A J et al. J Am Vet Med Assoc 1991; 199:1612.

9. Henry GA, Yamini B. J Vet Diagn Invest 1995;
7:578.

10. Rhoads WS et al. J Am Vet Med Assoc 1999;
214:1042.

SPASMODIC COLIC

ETIOLOGY

Spasmodic colic occurs sporadically and
causative factors are not usually identified.
Suggested causes include excitement,
such as occurs during thunderstorms,
preparations for showing or racing, and
drinks of cold water when hot and
sweating after work, although epi-
demiologic evidence of these associations
is lacking. Presence of a heavy burden of
tapeworms is associated with a high
incidence of spasmodic (undiagnosed)
colic. 1 Mucosal penetration and submucosal
migration of Strongylus vulgaris larvae are
known to cause changes in ileal myo-
electrical activity that could lead to the
development of colic in horses. 2 Psycho-
genic colic occurs rarely in horses. 3

EPIDEMIOLOGY

The condition is sporadic. It affects horses
of all ages but is not recognized in young
foals. No apparent breed or sex pre-
disposition is noted.

PATHOGENESIS

The hypermotility of spasmodic colic in
horses is thought to arise by an increase
in parasympathetic tone under the
influence of the causative factors mentioned
above.

CLINICAL FINDINGS

Spasmodic colic of horses is characterized
by brief attacks of abdominal pain. Tire
pain is intermittent, the horse rolling,
pawing and kicking for a few minutes,
then shaking itself and standing normally
for a few minutes until the next bout of
pain occurs. Intestinal sounds are often
audible some distance from the horse and
loud, rumbling borborygmi are heard on
auscultation. The pulse is elevated
moderately to about 60/min and there
may be some patchy sweating, but rectal
findings are negative and there is no
diarrhea. Rectal examination is usually
unremarkable. The signs usually disappear
spontaneously within a few hours.

CLINICAL PATHOLOGY AND
NECROPSY fiNDINGS

Laboratory examinations are not used in
diagnosis and the disease is not fatal.

See Table 5.6.

TREATMENT

Acute hypermotility as manifested by
spasmodic colic is usually transient
and the use of specific spasmolytics is
not necessary. Detomidine, xylazine or
butorphanol are effective analgesics.
Administration of hyoscine is effective.
Affected horses are often administered
mineral oil (1 mL/kg) by nasogastric
intubation.

REFERENCES

1. Proudman CJ, Holdstock NB. Equine Vet J 2000;
32:37.

2. Berry CR et al. Am JVet Res 1986; 47:27.

3. Murray MJ, Crowell Davis SL. J Am \fet Med
Assoc 1985; 186:381.

INTESTINAL TYMPANY IN
HORSES

ETIOLOGY

The cause of most cases of idiopathic
intestinal tympany is unknown, although
the ingestion of highly fermentable green
feed is considered to be a risk factor.
Feeding of rations rich in grains is associ-
ated with changes in colonic contents
that might predispose to tympany. * 1
Intestinal tympany occurs secondary to
obstructive diseases that prevent aboral
passage of ingesta and gas.

PATHOGENESIS

The excessive production of gas or its
retention in a segment of bowel causes
distension and acute abdominal pain.
Intestinal distension reduces intestinal
motility and may contribute to the course
of the disease. Severe tympany may
interfere with normal respiration and
cardiovascular function (see Pathogenesis
of equine colic).

CLINICAL FINDINGS

Abdominal distension is evident and pain
is acute and severe. Peristaltic sounds are
reduced but fluid may be heard moving in
gas-filled intestinal loops, producing a
tinkling, metallic sound. Pinging sounds
consistent with tightly distended viscus
may be heard on simultaneous flicking
and auscultation of the abdomen. On
rectal examination, gas-filled loops of
intestine fill the abdominal cavity and
make proper examination of its contents
impossible. In primary tympany much
flatus is passed. It is important to differ-
entiate primary tympany from that occur-
ring secondary to obstructive diseases such
as enterolithiasis and displacement of the
colon.

CLINICAL PATHOLOGY

Laboratory examinations are of no value
in diagnosis.

NECROPSY FINDINGS

In cases of secondary tympany, the causa-
tive obstruction is evident. In primary

Diseases of the nonruminant stomach and intestines

cases, the intestines are filled with gas
and the feces are usually pasty and loose.

DIFFERENTIAL DIAGNOSIS

See Table 5.6.

TREATMENT

The principles of treatment are the relief
of pain and distension, maintenance
of hydration and reduction of gas pro-
duction. In secondary tympany the
primary disease should be identified and
treated.

Pain should be relieved by adminis-
tration of xylazine, detomidine or
butorphanol, or similar agents (Table 5.7).
Distension of the bowel should be
relieved by trocarization but trocarization
should only be performed if there is no or
minimal response to analgesic medi-
cation and no return of normal peristaltic
activity. Normal hydration should be
restored by intravenous administration of
polyionic fluids. Intestinal gas production
should be minimized by the adminis-
tration of mineral oil or a similar laxative
(Table 5.8).

REFERENCE

1. Lopes MAF et al. Am JVet Res 2004; 65:687.

VERMINOUS MESENTERIC
ARTERITIS (VERMINOUS
ANEURYSM, THROMBOEMBOLIC
COLIC)

ETIOLOGY

Unknown, although it is presumed to
result from thromboemboli originating at
sites of verminous arteritis in the cranial
mesenteric artery.

EPIDEMIOLOGY

The disease is assumed to be more
prevalent among horses on poor parasite
control programs; however, except
in extreme cases that die and have a
necropsy examination or exploratory
laparotomy, the diagnosis is not con-
firmed. Therefore accurate measures of its
incidence are not available. Cases may
occur in foals as young as 3-6 months. 1
The incidence of the disease has
decreased remarkably with the advent of
effective broad-spectrum anthelmintics
and almost complete prevention of
Strongylus spp. infection in horses in
developed countries.

PATHOGENESIS

Migration of the larvae of Strongylus
vulgaris into the wall of the cranial
mesenteric artery and its branches
occurs commonly in horses and may
cause thromboemboli that restrict blood
supply to the intestines, with subsequent
ischemia and dysfunction. 2 The recurrent

colic of verminous arteritis is possibly jdue
to impairment of the vascular and nerve
supply to the intestine. The disease is
basically an infarction of bowel wall
without displacement of the bowel. The
small intestine, colon and cecum can be
affected. The disease has been associated
with larval cyathostomiasis. 3

CLINICAL FINDINGS

Signs vary depending on the severity of
the disease. It is assumed that mild,
intermittent colics that respond to anal-
gesics in the short term and anthelmintics
in the long term are due to verminous
arteritis. Affected horses are often
depressed and spend long periods
recumbent. Weight loss and inappetence
are features of the disease in some horses.
The disease can have a course of weeks to
months.

Acute, severe cases of the disease are
due to infarction of parts or all of the
small intestine, cecum or colon. Affected
horses have an acute onset of severe
abdominal pain, tachycardia (> 100/min)
and sweating. Auscultation reveals
decreased borborygmi. There is mild
distension of small intestine or large
colon, depending on the segment of
bowel affected, on rectal examination.
There are rarely signs of intestinal
obstruction. Palpation of the cranial
mesenteric artery may reveal thickening
and pain but is not a useful diagnostic
sign for the acute disease. Death is due to
peritonitis secondary to devitalization of
the intestine, usually within 24 hours of
the onset of signs.

CLINICAL PATHOLOGY

There are no diagnostic changes in the
hemogram or serum biochemical profile.
Peritoneal fluid in mild cases may have
mild elevations in protein concentration
and white blood cell count. In severe
cases, peritoneal fluid protein concen-
tration is increased (> 25 g/L, 2.5 g/dL) as
is white blood cell count (9000-100 000
cells/pL, 9-100 x 10 9 cells/L). 4

NECROPSY FINDINGS

Infarction of the colon and cecum is most
common and evident as either gangrene
of large sections of the organ or multifocal
mottled lesions that are red and edematous.
Histological examination rarely reveals
the presence of thrombi. There may be
venninous arteritis of the cranial mesenteric
I artery, evident as thickening of the intima
j and narrowing of the lumen.

DIFFERENTIAL DIAGNOSIS

1 See Table 5.6.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

TREATMENT

Mild, recurrent cases are treated with
analgesics such as flunixin meglumine
(Table 5.7), laxatives such as mineral oil
(Table 5.8), and anthelmintics (ivermectin
200 i.ig/kg orally once; or fenbendazole
50 mg/kg orally every 24 h for 3 d).

Severe cases are treated with analgesics
(Table 5.7), intravenous fluids (Ch. 2) and
supportive care. Usually the severity of
the colic prompts surgical exploration of
the abdomen with resection of small
lesions. Most severe cases do not survive.

REVIEW LITERATURE

White NA. Thromboembolic colic in horses.
CompendContin Educ 1985; 7:S156-S161.

REFERENCES

1. DeLay J et al. Can Vet J 2001; 42:289.

2. Sellers AF et al. Cornell Vet 1982; 72:233.

3. MairTS, Fbarson GR. Equine Vet J 1995; 27:154.

4. White NA. J Am Vet Med Assoc 1981; 178:259.

GASTRITIS (INFLAMMATION OF
THE MONOGASTRIC STOMACH,
ABOMA SITIS)

Inflammation of the stomach is mani-
fested clinically by vomiting and is
commonly associated with enteritis in
gastroenteritis.

ETIOLOGY

Gastritis maybe acute or chronic but both
forms of the disease may be caused by the
same etiological agents acting with vary-
ing degrees of severity and for varying
periods. The inflammation may be associ-
ated with physical, chemical, bacterial,
viral or metazoan agents.

Cattle and sheep

Diseases of the rumen and abomasum are
presented in Chapter 6. For comparative
purposes the causes of abomasitis are j
listed here. For sheep there is no infor-
mation other than about parasites. They
are listed with cattle for convenience sake.

Physical agents

Physical agents such as frosted feeds
affect only the rumen. In calves, gross j
overeating and the ingestion of foreign j
materials may cause abomasitis. In adults,
there is a very low incidence of foreign
bodies in the abomasum, 1 half the cases
being associated with traumatic reticulitis.

Chemical agents

All the irritant and caustic poisons,
including arsenic, mercury, copper,
phosphorus and lead, cause abomasitis.
Fungal toxins cause abomasal irritation,
especially those of Fusarium spp. and
Stachybotris altemans. Acute lactic acidosis
due to engorgement on carbohydrate -
rich food causes rumenitis with some
run-off into the abomasum and the
development of some abomasitis/
enteritis.

Infectious agents

Only the viruses of rinderpest, bovine
virus diarrhea and bovine malignant
catarrh cause abomasal erosions. Bacterial
causes are very rare - sporadic cases
of extension from oral necrobacillosis,
hemorrhagic enterotoxemia due to
C. perfringens types A, B, C, rarely as an
adjunct to colibacillosis and its enteric
lesion in calves. Fungi, e.g. Mucor spp. and
Aspergillus spp. complicate abomasal ulcer
due to other causes.

Metazoan agents

Nematodes - Trichostrongylus axei,
Ostertagia spp., Haemonchus spp. larval
paramphistomes migrating to the rumen.

Pigs

Physical agents

Foreign bodies, bedding, frosted feeds,
moldy and fermented feeds are all
possible causes.

Chemical agents

As listed under cattle, these are also
possible causes of gastritis in pigs.

Infectious agents

Venous hyperemia and infarction of the
gastric mucosa occur in erysipelas,
salmonellosis, swine dysentery and acute
colibacillosis in weaned pigs. Similar
lesions occur in swine fever, African swine
fever and swine influenza. Fungal gastritis
also occurs secondarily.

Metazoan agents

The red stomach worm, Hyostrongylus
rubidus, and the thick stomach worms
Ascarops strongylina and Physocephalus
s exalatus are of low pathogenicity but
cannot be disregarded as causes of
gastritis in pigs.

Horses

Physical and chemical agents as listed
under cattle may cause gastritis rarely.
Infectious causes of gastritis are rare in
the horse but emphysematous gastritis
associated with C. perfringens has been
recorded.

Metazoan agents causing gastritis in
horses include massive infestation with
botfly larvae ( Gasterophilus spp.); Habronema
muscae and Habronema microstoma
infestation; Habronema megastoma causes
granulomatous and ulcerative lesions and
may lead to perforation and peritonitis.

PATHOGENESIS

Gastritis does not often occur in animals
without involvement of other parts of the
alimentary tract. Even in parasitic infes-
tations where the nematodes are rela-
tively selective in their habitat, infestation
with one nematode is usually accompanied
by infestation with others, so that
gastroenteritis is produced. It is dealt with
as a specific entity here because it may

occur as such, and enteritis is common
without gastric involvement. The net
effects of gastroenteritis can be deter-
mined by a summation of the effects of
gastritis and enteritis.

The reactions of the stomach to
inflammation include increased motility
and increased secretion. There is an
increase in the secretion of mucus, which
protects the mucosa to some extent but
also delays digestion and may allow
putrefactive breakdown of the ingesta.
This abnormal digestion may cause
further inflammation and favors spread of
the inflammation to the intestines. In
acute gastritis, the major effect is on
motility; in chronic gastritis, on secretion.
In acute gastritis there is an increase in
motility, causing abdominal pain and
more rapid emptying of the stomach,
either by vomiting or via the pylorus in
animals unable to vomit. In chronic
gastritis, the emptying of the stomach is
prolonged because of the delay in diges-
tion caused by excessive secretion of
mucus. This may result in chronic gastric
dilatation. The motility is not necessarily
diminished and there may be subacute
abdominal pain or a depraved appetite
due to increased stomach contractions
equivalent to hunger pains.

CLINICAL FINDINGS
Acute gastritis

When the inflammation is severe, pigs
and, rarely, horses and ruminants vomit
(or ruminants regurgitate excessive quan-
tities of rumen contents) . In monogastric
animals, such as pigs, the vomitus con-
tains much mucus, sometimes blood, and
is small in amount, and vomiting is
repeated, with forceful retching move-
ments. The appetite is always reduced,
often absent, but thirst is usually excessive
and pigs affected with gastroenteritis may
stand continually lapping water or even
licking cool objects. The breath has an
offensive odor and there may be abdomi-
nal pain. Diarrhea is not marked unless
there is an accompanying enteritis but the
feces are usually pasty and soft. Additional
signs are usually evident when gastritis is
part of a primary disease syndrome.
Dehydration and alkalosis with tetany
and rapid breathing may develop if
vomiting is excessive.

Chronic gastritis

Chronic gastritis is much less severe. The
appetite is depressed or depraved and
vomiting occurs only sporadically, usually
after feeding The vomitus contains much
viscid mucus. Abdominal pain is minor and
dehydration is unlikely to occur, but the
animal becomes emaciated through lack of
food intake and incomplete digestion.

Anorexia, tympanites, gastritis, pyloric
stenosis and gastric ulcers are the clinical

Diseases of the nonruminant stomach and intestines

manifestations of abomasal foreign body
in cattle.

CLINICAL PATHOLOGY

Specimens taken for laboratory examin-
ation are usually for the purpose of
identifying the causative agent in specific
diseases. Estimations of gastric acidity are
not usually undertaken but samples of
vomitus should be collected if a chemical
poison is suspected.

NECROPSY FINDINGS

The signs of inflammation vary in severity
from a diffuse catarrhal gastritis to severe
hemorrhagic and ulcerative erosion of the
mucosa. In the mucosal diseases there are
discrete erosive lesions. In parasitic gastritis
there is usually marked thickening and
edema of the wall if the process has been
in existence for some time. Chemical
inflammation is usually most marked on
the tips of the rugae and in the pyloric
region. In severe cases the stomach
contents may be hemorrhagic; in chronic
cases the wall is thickened and the con-
tents contain much mucus and have a
rancid odor suggestive of a prolonged
sojourn and putrefaction of the food.

It is important to differentiate between
gastritis and the erythematous flush of
normal gastric mucosa in animals that
have died suddenly. Venous infarction in
the stomach wall occurs in a number of
bacterial and viral septicemias of pigs and
causes extensive submucosal hemorrhages,
which may easily be mistaken for
hemorrhagic gastritis.

) D| FFERENTIAL DIAGNOSIS

• Gastritis and gastric dilatation have many
similarities but in the latter the vomitus is
more profuse and vomiting is of a more
projectile nature, although this difference
is not so marked in the horse, in which
any form of vomiting is severe

• Gastritis in the horse is not usually
accompanied by vomiting but it may
occur in gastric dilatation

• In esophageal obstruction, the vomitus
is neutral in reaction and does not have
the rancid odor of stomach contents

• Intestinal obstruction may be
accompanied by vomiting and, although
the vomitus is alkaline and may contain
bile or even fecal material, this may also
be the case in gastritis when intestinal
contents are regurgitated into the
stomach

• Vomiting of central origin is extremely
rare in farm animals

• Determination of the cause of gastritis
may be difficult but th e presence of
signs of the specific diseases and history
of access to poisons or physical agents
listed under etiology above may provide
the necessary clues

• Analysis of vomitus or food materials
may have diagnostic value if chemical
poisoning is suspected

TREATMENT

Treatment of the primary disease is the
first principle and requires a specific
diagnosis. Ancillary treatment includes
the withholding of feed, the use of gastric
sedatives, the administration of electro-
lyte solutions to replace fluids and
electrolytes lost by vomiting, and stimu-
lation of normal stomach motility in the
convalescent period.

In horses and pigs, gastric lavage may
be attempted to remove irritant chemicals.
Gastric sedatives usually contain insoluble
magnesium hydroxide or carbonate, kaolin,
pectin or charcoal. Frequent dosing at
intervals of 2-3 hours is advisable. If
purgatives are used to empty the ali-
mentary tract, they should be bland
preparations such as mineral oil to avoid
further irritation to the mucosa.

If vomiting is severe, large quantities of
electrolyte solution should be administered
parenterally. Details of the available
solutions are given under the heading of
disturbances of body water. If the liquids
can be given orally without vomiting
occurring, this route of administration is
satisfactory.

During convalescence, the animal
should be offered only soft, palatable,
highly nutritious foods. Bran mashes for
cattle and horses and gruels for calves
and pigs are most suitable and are
relished by the animal.

REFERENCE

1. Weldon ADetal. Cornell Vet 1991; 81:51.

ACUTE GASTRIC DILATATION IN
PIGS

j In the pig, simple gastric distension is
I usually readily relieved by vomiting.

ACUTE GASTRIC TORSION IN
SOWS

This is a much more serious problem. 1
Torsion is thought to occur because the
sow eats a large, sloppy meal very quickly.
i The occurrence is specifically related to
intense excitement and activity occurring
; at feeding time. Death occurs 6-24 hours
; after the pig's last meal. At necropsy the
: stomach is enormous (50-60 cm diameter),

: with engorgement of vessels and hemor-
rhagic effusion into the stomach, which
contains much gas and usually a lot of
food. Rotation varies in degree from
90-360° and is usually to the right. The
spleen is markedly displaced, the liver is
bloodless and the diaphragm encroaches
deeply into the chest. 2

INTESTINAL REFLUX

Acute dilatation also occurs in pigs
secondarily to acute obstruction of the
small intestine. The obstruction may be as

far down as the ileocecal valve. The oral
segment of intestine dilates and fills with
fluid, and refluxes into the stomach, filling
it. In the pig vomiting follows. The out-
come depends on whether sufficient
gastric motility returns to evacuate the
stomach.

DIAGNOSIS

The vomiting in gastric dilatation is more
profuse and projectile than that of
gastritis or enteritis but may be simulated
by that of obstruction of the upper part of
the small intestine.

REFERENCES

1. Blackburn PW et al.\fet Rec 1974; 94:578.

2. Senk L. Vet Glasnik 1977; 31:513.

INTESTINAL OBSTRUCTION IN
PIGS

ETIOLOGY

Some causes of intestinal obstruction are:

° Torsion of the coiled colon about its
mesentery occurs in adult pigs
° Obstruction of the terminal small colon
in young piglets causes very hard fecal
balls, or barley chaff used as bedding
may be implicated in obstruction
° Heavy feeding on lactose 1 causes a
dilatation and atony of the intestine in
the same way as grain feeding does in
ruminants.

CLINICAL FINDINGS

In pigs, distension of the abdomen,
absence of feces and complete anorexia
are evident. The distension may be
extreme in young pigs when the terminal
I colon is obstructed. Death usually occurs
in 3-6 days.

IMPACTION OF THE LARGE
INTESTINE OF PIGS

ETIOLOGY

r In pigs impaction of the colon and
rectum occurs sporadically, usually in
adult sows that get little exercise and
are fed wholly on grain. The disease
also occurs in pigs that are
overcrowded in sandy or gravelly
outdoor yards

A special occurrence in young weaned
pigs causes obstruction of the coiled
colon

A presumed inherited megacolon of
fattening pigs is reported as a cause of
abdominal distension, constipation
and wasting. There is no anal
stricture. 1

CLINICAL FINDINGS

In impaction of the large intestine the
effects appear to be due largely to auto-
intoxication, although the commonly
occurring posterior paresis seems more
likely to be due to pressure from
inspissated fecal material.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Retention of the meconium has no
specific signs. There is anorexia and
dullness and the pig is recumbent much
of the time. Feces passed are scanty, very
hard and covered with mucus. Weakness
to the point of inability to rise occurs in
some cases. Hard balls of feces in the
rectum are usually detected when a
thermometer is inserted.

In paralysis of the rectum there is
inability to defecate and usually some
straining. The anus and rectum are
ballooned and manual removal of the
feces does not result in contraction of the
rectum. Spontaneous recovery usually
occurs 3-4 days after parturition.

REFERENCE

1. Shearer IJ, Dunkin AC. NZ J Agric Res 1968;
11:923.

INTESTINAL TYMPANY IN PIGS

ETIOLOGY

° Primary tvmpany occurs with

ingestion of excess whey. Recorded in
adult dry sows. Distension of proximal
colon causes rupture with death from
endotoxic shock 1

- Secondary large bowel tympany -
usually secondary to acute intestinal
obstruction.

REFERENCE

1. McCausland IP, Southgate W. Aust Vet J 1980;

56:190.

ENTERITIS (INCLUDING
MALABSORPTION, ENTEROPATHY
AND DIARRHEA)

The term enteritis is used to describe
inflammation of the intestinal mucosa
resulting in diarrhea and sometimes
dysentery, abdominal pain occasionally,
and varying degrees of dehydration and
acid-base imbalance, depending on the
cause of the lesion, its severity and
location. In many cases, gastritis also
occurs together with enteritis.

There are several diseases of the
intestines of farm animals in which
diarrhea and dehydration are major
clinical findings, but classical inflam-
mation of the mucosa may not be present.
The best example of this is the diarrhea
associated with enterotoxigenic E. coli,
which elaborate an enterotoxin that
causes a large net increase of secretion of
fluids into the lumen of the gut, with very
minor, if any, structural changes in
the intestinal mucosa. This suggests that j
a word other than enteritis may be j
necessary to describe alterations in the j
intestinal secretory and absorptive j

j mechanisms that result in diarrhea but in
I which pathological lesions are not
j present. However, with the above qualifi-
cations, we have chosen, for convenience,
I to continue to use the term enteritis to
describe those diseases in which diarrhea
! is a major clinical finding due to mal-
s absorption in the intestinal tract.

ETIOLOGY AND EPIDEMIOLOGY

There are many causes of enteritis or
! malabsorption in farm animals and the
disease varies considerably in its severity
j depending upon the causative agent.

Enteropathogens include bacteria, vimses,
: fungi, protozoa and helminths. Many
chemicals and toxins can also cause
enteritis (Tables 5.12-5.15). In addition to
the primary etiological agents of enteritis,
there are many epidemiological charac-
teristics of the animal and the environ-
ment that are important in facilitating or
suppressing the ability of the causative
agent to cause enteritis. Thus newborn
calves and piglets that are deficient in
colostral immunoglobulins are much
more susceptible to diarrhea, and with a
high mortality rate from diarrhea, than
animals with adequate levels. Enteric
salmonellosis is commonly precipitated
by the stressors of transportation or
deprivation of feed and water. The stress

nc?tei«yr t^iud) u« ifett uTs lia . i i #«= un i is

Etiological agent or
disease

Age and class of animal affected and important
epidemiological factors

Major clinical findings and diagnostic criteria

Bacteria

Enterotoxigenic E. coli

Newborn calves < 3-5 days of age, colostral immune

Acute profuse watery diarrhea, dehydration and acidosis.

status determines survival. Outbreaks common

Culture feces for enteropathogenic type

Salmonella spp.

All ages. Outbreaks occur. Stress-induced

Acute diarrhea, dysentery, fever and high mortality possible.

Clostridium perfringens

Young well nourished calves < 1 0 days of age

Culture feces

Severe hemorrhagic enterotoxemia, rapid death. Fecal smear

types B and C

Mycobacterium avium subsp.

Mature cattle, sporadic, single animal

Chronic diarrhea with loss of weight, long course.

paratuberculosis

No response to therapy. Special tests

Proteus spp. and

Calves treated for diarrhea with prolonged course

Chronic to subacute diarrhea, poor response to treatment,

Pseudomonas spp.

of antibiotics

progressive loss of weight. Culture feces

Fungi

Candida spp.

Young calves following prolonged use of oral

Chronic diarrhea, no response to treatment. Fecal smears

Viruses

Rotavirus and coronavirus

antibacterials

Newborn calves, 5-21 days old, explosive outbreaks

Acute profuse watery diarrhea. Demonstrate virus in feces

Winter dysentery

Mature housed cows, explosive outbreaks

Acute epizootic of transient diarrhea and dysentery lasting

( Coronavirus )

24 hours. Definitive diagnosis not possible currently

Bovine virus diarrhea

Young cattle 8 months to 2 years. Usually

Erosive gastroenteritis and stomatitis. Usually fatal. Virus

(mucosal disease)

sporadic but epidemics occur

isolation

Rinderpest

Highly contagious, occurs in plague form

Erosive stomatitis and gastroenteritis. High morbidity and

Bovine malignant catarrh

Usually mature cattle, sporadic but small outbreaks

mortality

Erosive stomatitis and gastroenteritis, enlarged lymph nodes,

occur

ocular lesions, hematuria and terminal encephalitis.

Helminths

Ostertagiasis

Young cattle on pasture

Transmission with whole blood

Acute or chronic diarrhea, dehydration and hypoproteinemia.

Protozoa

Fecal examination. Plasma pepsinogen

Eimeria spp.

Calves over 3 weeks old and cattle up to 12 months

Dysentery, tenesmus, nervous signs. Fecal examination

of age. Outbreaks common

diagnostic

Cryptosporidium spp.

Calves 5-35 days of age

Diarrhea. Fecal smear and special stain

Diseases of the nonruminant stomach and intestines

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Etiological agent or disease

»

Age and class of animal affected and important
epidemiological factors

Major clinical findings and diagnostic criteria

Viruses

Classical and African

Hemorrhagic diarrhea at any age

Many other signs(pyrexia) variety of lab tests (isolation, ELISA,

swine fever

PCR etc.)

Transmissible gastroenteritis

Explosive outbreaks in newborn piglets. High

Acute diarrhea, vomition, dehydration and death. No response

(TGE)

morbidity and mortality

to treatment (lab tests include virus isolation, ELISA, EM, FATs)

Rotavirus and coronavirus

Outbreaks in newborn piglets and weaned piglets.

Acute diarrhea and dehydration. May continue to suck the

(Epidemic diarrhea)

May occur in well-managed herds

sow. Death in 2-4 days. Virus isolation and pathology of gut,

EM, FATs (PED), PAGE for rotavirus

Bacteria

Enterotoxigenic E. coli

Common disease of newborn, 3-week-old and

Acute diarrhea, dehydration. Responds to early treatment.

weaned piglets. Outbreaks. Colostral immune status

Fecal culture and serotype. Virulence factor determination

important

Salmonella spp.

All ages. Most common in feeder pigs

Acute septicemia or chronic diarrhea. Responds to early

treatment. Culture and serotyping

Clostridium perfringens type C

Newborn piglets. High mortality

Acute and peracute hemorrhagic enterotoxemia. Toxin

demonstration and culture

Clostridium perfringens type A

Slightly oider pigs, first week of life, lower mortality

As above

Clostridium difficile

Diarrhea in preweaned pigs

Smears of colon wall, culture, FAT, PCR

Brachyspira hyodysenteriae

Usually feeder pigs. Outbreaks common

Dysentery, acute to subacute, fever. Responds to treatment.

(swine dysentery)

Culture, FATs, PCR on mucosal smears

Lawsonia intracellularis

Growing and mature pigs. Outbreaks common

Acute dysentery and death. MZN on mucosal smears, PCR,

(PIA, PHE)

silver-stained sections

Brachyspira pilosicoli

Usually weaned pigs

PCR

Protozoa

Isospora spp.

Newborn piglets 5-14 days of age. High morbidity,

Acute diarrhea. Poor response to therapy with amprolium.

low mortality

Fecal examination for oocysts

Other species ( Eimeria )

In older pigs

Histology of gut sections

Parasites

Ascaris suum and

Young pigs

A. lumbricoides

All ages, usually older pigs

Mild diarrhea for few days. Worm egg count

Trichuris suis

Diarrhea, dysentery and loss of weight. Fecal examination and

gross pathology

Nutritional deficiency

Iron deficiency

Young piglets 6-8 weeks. Not common in well

Mild diarrhea and anemia

managed swine herds

EU5A, enzyme-linked immunoassay; EM, electron micrograph ; FATs, fluorescence antibody transfer; MZN, Modified ziehl-neilson; PAGE, Poly acrylamide get

electrophoresis; PCR, polymerase chain reaction; PED, Porcine epidemic diarrhea.

of weaning in pigs is a risk factor for
postweaning diarrhea. The prolonged use
of antimicrobials orally in all species may
alter the intestinal microflora and allow
the development of a superinfection by
organisms that would not normally cause
disease.

The salient epidemiological character-
istics and clinical findings of the diseases
in which diarrhea, due to enteritis or
malabsorption, is a principal clinical
finding in each species are summarized
by species in Tables 5.12-5.15. There are
many other diseases in which diarrhea
may be present but in which it is only of
minor importance.

PATHOGENESIS

Normal intestinal absorption

Under normal conditions, a large quantity
of fluid enters the small intestine from the
saliva, stomach, pancreas, liver and
intestinal mucosa. This fluid and its
electrolytes and other nutrients must be
absorbed, mainly by the small intestines,
although large quantities move into the
large intestine for digestion' and absorp-
tion, especially in the horse. The brush

border membrane of the villous epithelial
cells is of paramount importance for the
absorption of water, electrolytes and
nutrients.

Details of the physiology and patho-
physiology of epithelial secretion in the
gastrointestinal tract are becoming clear,
leading to new models of the mechanisms
underlying diarrhea. 1 The enteric nervous
system is a critical component of the
mechanism regulating fluid secretion in
the normal intestine and a key element in
the pathophysiology of diarrhea. Neural
reflex pathways increase epithelial fluid
secretion in response to several enteric
pathogens of veterinary importance such
as Salmonella spp., Cryptosporidium parvum,
rotavirus and C. difficile. The enteric
nervous system also has an important
role in epithelial secretion triggered by
products of activated leukocytes during
inflammation.

Mechanisms of diarrhea

Any dysfunction of the intestines will
result in failure of adequate absorption
and diarrhea. Depending on the causative
agent, intestinal malabsorption may be

the result of at least four different
mechanisms:

Osmotic diarrhea
Exudative diarrhea
Secretory diarrhea
Abnormal intestinal motility.

Osmotic diarrhea

There may be an osmotic effect when
substances within the lumen of the intes-
tine increase the osmotic pressure over a
greater than normal length of intestine,
resulting in an osmotic movement of an
excessive amount of fluid into the lumen
of the intestine. The fluid is not
reabsorbed and accumulates in the lumen.
Examples include saline purgatives,
overfeeding, indigestible feeds and
disaccharidase deficiencies. A deficiency
of a disaccharidase leads to incomplete
digestion and the accumulation of large
quantities of undigested material, which
acts as a hypertonic solution.

Malabsorption is associated with several
epitheliotropic viruses that affect the
villous absorptive cells, causing a
disaccharidase deficiency. Examples include
the TGE (transmissible gastroenteritis)

Diseases of the nonruminant stomach and intestines

Etiological agent or disease

Age and class of animal affected and important
epidemiological factors

Major clinical findings and diagnostic criteria

Bacteria

Enterotoxigenic Escherichia

Newborn lambs in crowded lambing sheds. Cold

Acute diarrhea (yellow feces), septicemia and rapid death.

coli (colibacillosis)

chilling weather. Outbreaks. Inadequate colostrum.
Mismothering problems. Poor udder development

Culture feces for enterotoxigenic E. coli

Clostridium perfringens

Newborn lambs up to 10 days of age. Overcrowded

Sudden death, diarrhea, dysentery, toxemia. Fecal smear

type B (lamb dysentery)

lambing sheds

Clostridium perfringens

Adult lactating does

Peracute, acute and chronic forms occur. Enterocolitis. Watery

type D (enterotoxemia)

diarrhea with feces containing blood and mucus, weakness,
abdominal colic

Salmonella spp.

Newborn lambs. Adult sheep in pregnancy

Acute diarrhea and dysentery in lambs. Acute toxemia,
diarrhea in ewes followed by abortion. Fecal culture and
pathology

Mycobacterium

Mature sheep and goats; several animals may

Loss of weight, chronic diarrhea, long course, no response to

paratuberculosis

Viruses

be affected

therapy. Serological tests

Rotavirus and coronavirus

Newborn lambs. Many lambs affected

Acute profuse watery diarrhea. No toxemia. Usually recover
spontaneously if no secondary complications. Virus isolation

Parasites
Nematodirus spp.

Lambs 4-10 weeks of age on pasture.

Anorexia, diarrhea, thirsty, 10-20% of lambs may die if not

Sudden onset. Outbreaks. Ideal environmental
conditions for parasite are necessary

treated. Fecal examination

Ostertagia spp.

Lambs 10 weeks of age and older lambs and young
ewes on grass. Types 1 and II

Many lambs develop diarrhea, weight loss. Abomasitis

Trichostrongylus spp.

Older lambs 4-9 months of age

Dull, anorexic, loss of weight and chronic diarrhea. Fecal
examination

Protozoa

Eimeria spp.

Overstocking on pasture and overcrowding indoors.

Acute and subacute diarrhea and dysentery. Loss of weight.

poor sanitation and hygiene. Commonly occurs
following weaning and introduction into feedlot

Mortality may be high. Fecal examination

Cryptosporidium

Lambs 7-10 days of age

Dullness, anorexia, afebrile, diarrhea, may die in 2-3 days,
survivors may be unthrifty. Examination of feces and intestinal
mucosa. No specific treatment

virus in newborn piglets, and rotavirus
and coronavirus infections in newborn
calves and other species. The usual patho-
genetic sequence of events is selective
destruction of villous absorptive cells,
villous atrophy, loss of digestive and
absorptive capacities (malabsorption),
diarrhea, crypt hyperplasia and recovery.
Recovery depends on the severity of the
lesion, the relative injury done to the
villous cells and crypt epithelium, and the
age of the animal. Newborn piglets
affected with TGE commonly die of
dehydration and starvation before there is
sufficient time for regeneration of the
villous cells from the crypt epithelium. In
contrast, older pigs have greater capacity
for regeneration of the villous cells and
the diarrhea may be only transient.

Exudative diarrhea

Acute or chronic inflammation or necrosis
of the intestinal mucosa results in a net
increase in fluid production, inflam-
matory products, including loss of serum
proteins, and a reduction in absorption of
fluids and electrolytes. Examples include
many of the diseases associated with
bacteria, viruses, fungi, protozoa, chemical
agents and tumors that are summarized
in Tables 5.12-5.15. The classic example is
enteric salmonellosis, in which there is

severe inflammation with the production i
i of fibrinous, hemorrhagic enteritis. Other i
i notable examples include swine dysentery, |
j bovine virus diarrhea and inorganic |
arsenic poisoning.

' Secretory diarrhea j

A secretory-absorptive imbalance i

: results in a large net increase in fluid
secretion with little if any structural j
change in the mucosal cells. The entero- i
; toxin elaborated by enterotoxigenic E. coli !
results in intestinal hypersecretion. The ■
villi, along with their digestive and j
1 absorptive capabilities, remain intact. The ‘
crypts also remain intact; however, their j
secretion is increased beyond the absorp-
tive capacity of the intestines, resulting in
j diarrhea. The increased secretion is due to
an increase in cyclic adenosine mono-
l phosphate, which in turn may be stimu- j
i lated by prostaglandins. The integrity of j
the mucosal structure is maintained and
the secreted fluid is isotonic, electrolyte- ■
rich, alkaline and free of exudates. This .
; is useful diagnostically in enterotoxic ;
j colibacillosis.

An important therapeutic principle can j
be applied in secretory diarrhea disease, j
j Whenever possible, because of the cost of j
parenteral fluid therapy, fluids and '
electrolytes should be given orally. The i

mucosa remains relatively intact and
retains normal absorptive capacity. Fluid
replacement solutions containing water,
glucose and amino acids can be given
orally and are absorbed efficiently.
Glucose and amino acids enhance the
absorption of sodium and water, thus
replacing or diminishing fluid and
electrolyte losses.

There is also evidence that active electro-
lyte secretion occurs in enterocolitis due to
salmonellosis in several species of animal.
In diseases such as swine dysentery, the
permeability of the colon may remain
normal or even decrease, but the absorption
of water and electrolytes is decreased. This
suggests that the primary cause of fluid and
electrolyte loss in some diseases of the
colon may be failure of the affected
epithelium to absorb fluids and electrolytes.

Abnormal intestinal motility
Hyperexcitability, convulsions and the
stress of unexpected sudden confinement
may result in diarrhea, which may be due
to increased peristalsis, resulting in
'intestinal hurry' and reduced intestinal
absorption due to rapid passage of intes-
tinal fluids in an otherwise normal
intestine. This can occur in animals that
are being assembled for transportation
and during transportation.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Location of lesioft

The location of the lesion in the intestinal
tract may also influence the severity of
the enteritis or malabsorption. Lesions
involving the small intestine are con-
sidered to be more acute and severe than
those in the large intestine because
approximately 75-80% of the intestinal
fluids are absorbed by the small intestine
and much lesser quantities by the large
intestine. Thus, in general, when lesions
of the large intestine predominate, the
fluid and electrolyte losses are not as
acute nor as severe as when the lesions of
the small intestine predominate. How-
ever, the horse is an exception. The total
amount of fluid entering the large
intestine from the small intestine, plus the
amount entering from the mucosa of the
large intestine, is equal to the animal's
total extracellular fluid volume, and 95%
of this is reabsorbed by the large intestine.
This illustrates the major importance of
the large intestine of the horse in absorb-
ing a large quantity of fluid originating
from saliva, the stomach, liver, pancreas,
small intestine and large intestine. Any
significant dysfunction of the absorptive
mechanism of the large intestine of the
horse results in large losses of fluids and
electrolytes. This may explain the rapid
dehydration and circulatory collapse that
occurs in horses with colitis-X. Moderate
to severe ulcerative colitis of the right
dorsal colon in horses treated with
phenylbutazone results in marked dehy-
dration, endotoxic shock and death. 2

Dehydration, electrolyte and
acid-base imbalance

The net effect of an increase in the total
amount of fluid in the intestinal lumen
and a reduction in intestinal absorption is
a loss of fluids and electrolytes at the
expense of body fluids and electrolytes
and the normal intestinal juices. The fluid
that is lost consists primarily of water, the
electrolytes sodium, chloride, potassium
and bicarbonate, and varying quantities of
protein. Protein is lost (protein -losing
enteropathy) in both acute and chronic
inflammation, leading to hypoproteinemia
in some cases. The loss of bicarbonate
results in metabolic acidosis, which is of
major importance in acute diarrhea. The
loss of sodium, chloride and potassium
results in serum electrolyte imbalances.
In the horse with enteric salmonellosis,
there is severe dehydration and marked
hyponatremia. In the calf with neonatal
diarrhea there are varying degrees of
dehydration and a moderate loss of all
electrolytes. With acute severe diarrhea,
there is severe acidosis and reduced
circulating blood volume, resulting in
reduced perfusion of the liver and kidney
and of peripheral tissues. This results in

uremia, anaerobic oxidation and lactic
acidosis, which accentuates the metabolic
acidosis. Hyperventilation occurs in some
animals in an attempt to compensate for
the acidosis.

In acute diarrhea, large quantities of
intestinal fluid are lost in the feces and
large quantities are present in the
intestinal lumen (intraluminal dehy-
dration), which accounts for the
remarkable clinical dehydration in some
affected animals. The fluid moves out of
the intravascular compartment first, then
out of the extravascular compartment
(interstitial spaces), followed lastly by
fluid from the intracellular space. Thus in
acute diarrhea of sudden onset the actual
degree of dehydration present initially
may be much more severe than is
recognizable clinically; as the diarrhea
continues, the degree of clinical dehy-
dration becomes much more evident.

Chronic enteritis

In chronic enteritis, as a sequel to acute
enteritis or developing insidiously, the
intestinal wall becomes thickened and
mucus secretion is stimulated, the
absorption of intestinal fluids is also
decreased but not of the same magnitude
as in acute enteritis. In chronic enteritis
there is a negative nutrient balance
because of decreased digestion of nutrients
and decreased absorption, resulting in
body wasting. The animal may continue
to drink and maintain almost normal
hydration. In some cases of chronic
enteritis, depending on the cause, there is
continuous loss of protein, leading to
clinical hypoproteinemia. Intestinal
helminthiasis of all species, Johne's
disease of ruminants, and chronic diarrheas
of the horse are examples. Lymphocytic
plasmacytic enteritis causing chronic
weight loss occurs in the horse. 3

Regional ileitis is a functional
obstruction of the lower ileum associated
with granulation tissue proliferation in
the lamina propria and submucosa, with
or without ulceration of the mucosa, and
a massive muscular hypertrophy of the
wall of affected areas of the intestine. It
has been recognized with increased
frequency in recent years in pigs, horses
and lambs. The lesion undoubtedly inter-
feres with normal digestion and absorp-
tion but diarrhea is not a common clinical
finding.

Replacement of villous epithelial
cells

The villous absorptive epithelial cells of
the small intestine are involved in almost
every type of enteritis or malabsorptive
syndrome. These cells that line the villi
and face the lumen of the intestine con-
tain important digestive enzymes such as
the disaccharidases. They are also involved

in absorption of fluids, electrolytes,
monosaccharides such as glucose, and
amino acids, and in the transport of fat
micelles. Their replacement time is up to
several days in the newborn calf and
piglet, and only a few days when these
animals are older (at 3 weeks). This may
explain the relatively greater susceptibility
of the newborn to the viral enteritides,
such as TGE in piglets and rotavirus
infection in all newborn farm animal
species. Almost any noxious influence can
increase the rate of extrusion of these
cells, which are then replaced by cells that
are immature and not fully functional. The
villi become shortened (villous atrophy)
and chronic malabsorption similar to the
'sprue gut' of humans may be the result.
The destruction of villous epithelial cells
explains the long recovery period of
several days in some animals with acute
enteritis and the chronic diarrhea in
others with chronic villous atrophy.

The literature on the mechanisms
of intestinal mucosal repair has been
reviewed. 4

Role of neutrophils in intestinal
mucosal injury

Neutrophils are critical elements of the
cascade of events that culminates in
mucosal injury in many inflammatory
diseases of the gastrointestinal tract,
including ischemia and reperfusion injury. 5
Neutrophils mediate their detrimental
actions by several mechanisms, especially
physical disruption of the epithelium.
These findings have resulted in consider-
ation of strategies to attenuate neutrophil-
mediated mucosal injury by preventing
neutrophil trans endothelial migration
into the intestinal mucosa and sub-
sequent activation during inflammation.
Newer pharmacological drugs that inhibit
beta-2-integrin activation, and therefore
beta 2-integrin function, may be useful
clinically to inhibit neutrophil-mediated
injury during inflammation. 5

Intestinal motility in enteritis

The motility of the intestinal tract in
animals with enteritis has not been
sufficiently examined and little infor-
mation is available. It was thought for
many years that intestinal hypermotility,
and increased frequency and amplitude of
peristalsis, was present in most enteritides
as a response to the enteritis and that the
hypermotility accounted for the reduced
absorption. However, when the patho-
genesis of the infectious enteritides is
considered, for example the unique
secretory effect of enterotoxin, it seems
more likely that, if hypermotility is
present, it is a response to the distension
of the intestinal lumen with fluid rather
than a response to irritation. With a fluid-
filled intestinal lumen, very little intestinal

Diseases of the nonruminant stomach and intestines

265

peristalsis would be necessary to move
large quantities of fluid down the
intestinal tract. This may explain the fluid-
rushing sounds that are audible on
auscultation of the abdomen in animals
with enteritis. It is possible that the
intestines may be in a state of relative
hypomotility rather than hypermotility,
which makes the use of antimotility drugs
for the treatment of enteritis questionable.

Concurrent gastritis

Gastritis commonly accompanies enteritis
but does not cause vomition except
perhaps in the pig. Gastritis (or abomasitis)
may also be the primary lesion, resulting
in a profuse diarrhea without lesions of
the intestines. Examples are ostertagiasis
and abomasal ulceration in cattle. Pre-
sumably the excessive amount of fluid
secreted into the affected abomasum
cannot be reabsorbed by the intestines.

Effects of enteritis on
pharmacodynamics of drugs

Enteritis may alter the pharmaco-
dynamics of orally administered drugs. In
acute diarrheal states there is delayed or
impaired absorption, resulting in sub-
therapeutic plasma concentration. In
chronic malabsorption states, decreased,
increased or delayed absorption may
occur, depending on the drug. Also,
gastric antacids, anticholinergic drugs and
opiates, administered orally for the treat-
ment of diarrhea, may impair absorption
of other drugs by altering solubility or
delaying gastric emptying time.

CLINICAL FINDINGS

The major clinical finding in enteritis or
malabsorption is diarrhea Dehydration,
abdominal pain, septicemia and toxemia
with fever occur commonly and their
degree of severity depends on the causa-
tive agent, the age and species of the
animal and the stage of the disease.

In acute enteritis, the feces are soft or
fluid in consistency and may have an
unpleasant odor. They may contain blood
(dysentery), fibrinous casts and mucus or
obvious foreign material such as sand.
The color of the feces will vary con-
siderably: they are usually pale yellow
because of the dilution of the brown bile
pigments but almost any color other than
the normal is possible and, with the
exception of frank blood (hematochezia)
or melena (black tarry feces), the color
of the feces is usually not representative
of a particular disease. When the feces are
watery, they may escape notice on clinical
examination. Some indication of the
nature of the enteritis may be obtained
from the distribution of the feces on the
animal's perineum. Thus, in calves, the
smudge pattern may suggest coccidiosis
when both the staining that accompanies

it and the feces are smeared horizontally
across the ischial tuberosities and the
adjoining tail, or helminth infestation
when there is little smearing on the
pinbones but the tail and insides of the
hocks are liberally coated with feces.
Straining may occur, especially in calves,
and be followed by rectal prolapse,
particularly when the lesions are present
in the colon and rectum. Intussusception
may occur when the enteritis involves the
small intestine.

There are a number of diseases in
which dysentery with or without toxemia
occurs and death may occur rapidly. These
include lamb dysentery, hemorrhagic
enterotoxemia of calves, acute swine
dysentery and hemorrhagic bowel syn-
drome of pigs.

Acute intraluminal hemorrhage due

to ulceration of unknown etiology in the
small intestine has been recorded in adult
cows. 6 Duodenal ulceration may also
occur in cattle in association with left-side
displacement of the abomasum. 7

Systemic effects

The systemic effects in enteritis vary
considerably. Septicemia, toxemia and
fever are common in the infectious
enteritides. An increased body tempera-
ture may return to normal following the
onset of diarrhea or if circulatory collapse
and shock are imminent. Dehydration
will vary from being just barely detectable
at 4-6% of body weight up to 10-12% of
body weight, when it is clinically very
evident. The degree of dehydration can be
best assessed by tenting the skin of the
upper eyelid or neck and determining the
time taken for the skin fold to return to
normal. The degree of recession of the
eyeball is also a useful aid. In the early
stages of acute enteritis, the degree of
clinical dehydration may be under-
estimated because of the time required for
fluid to shift from the interstitial and
intracellular spaces to the intravascular
space to replace fluids already lost. Dehy-
dration is usually evident by 10-12 hours
following the onset of acute enteritis and
clinically obvious by 18-24 hours.
Peripheral circulatory collapse (shock)
occurs commonly in acute and peracute
cases. There may be tachycardia or
bradycardia and arrhythmia depending
on the degree of acidosis and electrolyte
imbalance. In acute enteritis, there may
be severe abdominal pain, which is most
severe in the horse and is often sufficient
in this species to cause rolling and kicking
at the abdomen. Abdominal pain in
enteritis is unusual in the other species
although it does occur in heavy inorganic
metal poisonings, such as arsenic and
lead, and in acute salmonellosis in cattle.
Some severe cases of enteric colibacillosis

in calves are characterized by abdominal
pain evidenced by intermittent' bouts of
stretching and kicking at the abdomen.
The passage of intestinal gas also occurs
commonly in horses with acute and
chronic diarrhea.

Intestinal sounds in enteritis

Auscultation of the abdomen usually
reveals sounds of increased peristalsis
and fluid-rushing sounds in the early
stages of acute enteritis. Later there may
be paralytic ileus and an absence of
peristaltic sounds with only fluid and gas
tinkling sounds. The abdomen may be
distended in the early stages because of
distension of intestines and gaunt in the
later stages when the fluid has been
passed out in the feces. Pain may be
evidenced on palpation of the abdomen
in young animals.

Chronic enteritis

In chronic enteritis, the feces are usually
soft and homogeneous in consistency,
contain considerable mucus and usually
do not have a grossly abnormal odor.
Progressive weight loss and emaciation or
'ranting' are common and there are
usually no systemic abnormalities. Animals
with chronic enteritis will often drink and
absorb sufficient water to maintain clinical
hydration but there may be laboratory
evidence of dehydration and electrolyte
loss. In parasitic enteritis and abomasitis
there may be hypoproteinemia and sub-
cutaneous edema. In terminal ileitis, there
is usually chronic progressive weight loss
and occasionally some mild diarrhea. The
lesion is usually recognized only at
necropsy. Intestinal adenomatosis of pigs,
rectal strictures in pigs, granulomatous
enteritis of horses and lymphosarcoma of
the intestine of horses are examples of
enteric disease causing chronic anorexia
and progressive weight loss, usually with-
out clinical evidence of diarrhea. These
are commonly referred to as mal-
absorption syndromes.

CLINICAL PATHOLOGY

The laboratory testing of animals to
obtain an etiological diagnosis of enteritis
can be a complex and expensive pro-
cedure, which requires careful consider-
ation of the history, the clinical findings
and the number of animals affected. In
outbreaks of enteric syndromes, it may be
important to submit samples from both
affected and normal animals. The details
of the sampling techniques and the
tissues required for the diagnosis of
diseases of the digestive tract caused by
feeding mismanagement, infections,
toxins and other agents have been
outlined and this is recommended as a
reference. 8

i6

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Fecal examination

Examination of the feces to determine the
presence of causative bacteria, helminths,
protozoa, viruses and chemical agents
is described under specific diseases
throughout this book. It is important that
fecal specimens be taken as the differ-
entiation of the etiological groups
depends on laboratory examinations. In
outbreaks of diarrhea, fecal samples
should also be taken from a represen-
tative number of normal animals in the
same group as the affected animals.
Comparison of the fecal examination
results between affected and normal
animals will improve the accuracy of
interpretation.

Fecal samples can be examined for the
presence of leukocytes and epithelial
cells, which occur in exudative enteritis.

Intestinal tissue samples

In outbreaks of diarrhea, especially in
neonates, it may be useful to do necropsies
on selected early untreated cases of acute
diarrhea. The lesions associated with the
enteropathogens are well known and a
provisional etiological diagnosis may be
possible by gross and histopathological
examination of the intestinal mucosa.

Hematology and serum biochemistry

With increasing sophistication in diag-
nostic laboratories and in large-animal
practice, it is becoming common to do
considerable laboratory evaluation to
determine the actual changes that are
present, for purposes of a more rational
approach to therapy. For each specific
enteritis there are changes in the
hemogram and serum biochemistry that
aid in the diagnosis and differential
diagnosis. In bacterial enteritis, such as
acute enteric salmonellosis in the horse,
there may be marked changes in the total
and differential leukocyte count, which is
a useful diagnostic aid. In most cases of
acute enteritis there is hemoconcentration,
metabolic acidosis, an increase in total
serum solids concentration, a decrease in
plasma bicarbonate, hyponatremia, hypo-
chloremia and hypokalemia. However,
abnormalities in body fluid compart-
ments caused by diarrhea depend on the
pathogenetic mechanisms involved and
the duration of the diarrhea. In horses
with diarrhea of less than 6 days'
duration, the most common abnormality
may be a combined anion gap, metabolic
acidosis and metabolic alkalosis charac-
terized by hyponatremia, hypochloremia
and hyperkalemia. The acid-base
imbalances may vary considerably from
case to case and it is suggested that
optimal fluid therapy should be based on
laboratory evaluation of the animal's
blood gas and electrolytes. Hyperkalemia
may occur in severe acidosis. An increase

in serum creatinine may be due to
inadequate renal perfusion associated
with the dehydration and circulatory
failure.

Digestion/absorption tests
Digestion and absorption tests are

available for the investigation of chronic
malabsorptive conditions, particularly in
the horse. Intestinal biopsy may be
necessary for a definitive diagnosis of
chronic intestinal lesions that cannot be
determined by the usual diagnostic tests.
Examples include intestinal lympho-
sarcoma, granulomatous enteritis and
perhaps Johne's disease. Serum electro-
phoresis and the administration of
radioactively labeled albumin may be
necessary to determine the presence of a
protein -losing enteropathy.

NECROPSY FINDINGS

The pathology of enteritis or malabsorption
varies considerably depending on the
cause. There may be an absence of grossly j
visible changes of the mucosa but the j
intestinal lumen will be fluid-filled or |
| relatively empty, depending on the stage j
| of examination in enterotoxigenic coli- j
bacillosis. When there is gross evidence of j
inflammation of the mucosa there will be j
1 varying degrees of edema, hyperemia, j
| hemorrhage, foul-smelling intestinal |
j contents, fibrinous inflammation, ulcer- j
j ation and necrosis of the mucosa. With j
; acute necrosis there is evidence of frank ;
I blood, fibrinous casts and epithelial I
j shreds. The mesenteric lymph nodes j
j show varying degrees of enlargement, i
i edema and congestion, and secondary
I involvement of spleen and liver is not i
| unusual. In chronic enteritis, the epi- I
; thelium may appear relatively normal but :
the wall is usually thickened and may be j
| edematous. In some specific diseases j
■ there are lesions typical of the particular I
i disease. j

! Approach

• The approach to the diagnosis of
diarrhea requires a consideration of the
epidemiological history and the nature
and severity of the clinical findings,
i With the exception of the acute

enteritides in newborn farm animals,
most of the other common enteritides
have reasonably distinct epidemiological
j and clinical features

| • In some cases, a necropsy on an

| untreated case of diarrhea in the early
stages of the disease can be very useful
| • If possible, a hemogram should be

j obtained to assist in determining the

presence or absence of infection

Appearance of feces

• The gross appearance of the feces may
provide some clues about the cause of
the diarrhea. In general, the diarrheas
caused by lesions of the small intestine
are profuse and the feces are liquid and
sometimes as clear as water. The
diarrheas associated with lesions of the
large intestine are characterized by small
volumes of soft feces, often containing
excess quantities of mucus

• The presence of toxemia and fever-
marked changes in the total and
differential leukocyte count suggest
bacterial enteritis, possibly with
septicemia. This is of particular
importance in horses and cattle with
salmonellosis

• The presence of frank blood and/or
fibrinous casts in the feces usually
indicates a severe inflammatory lesion of
the intestines. In sand-induced diarrhea
in horses the feces may contain sand

Weight loss

• A chronic diarrhea with a history of
chronic weight loss in a mature cow
suggests Johne's disease

• Chronic weight loss and chronic
diarrhea, or even the absence of
diarrhea, in the horse may indicate the
presence of granulomatous enteritis,
chronic eosinophilic gastroenteritis,
alimentary lymphosarcoma, tuberculosis
and histoplasmosis

Dietary diarrhea and toxicities

• In dietary diarrhea the feces are usually
voluminous, soft and odoriferous, the
animal is usually bright and alert and
there are minimal systemic effects. An
examination of the diet will usually
reveal if the composition of the diet or
irregular feeding practices are
responsible for the diarrhea. Analysis of
samples of new feed may be necessary
to determine the presence of toxic
chemical agents

• Arsenic poisoning is characterized by
dysentery, toxemia, normal temperature
and nervous signs

• Copper deficiency conditioned by an
excess of molybdenum causes a
moderately profuse diarrhea with soft
feces, moderate weight loss and there is
usually normal hydration and possibly
depigmentation of hair

Parasitism

• Intestinal helminthiasis such as
ostertagiasis causes a profuse diarrhea and
marked loss of weight; the temperature is
normal and there is no toxemia

Miscellaneous causes

• In cattle, the oral cavity must be
examined for evidence of lesions
characteristic of viral diseases

• Many diseases of the stomach,
including ulceration, parasitism, gastritis
and tumors, may result in diarrhea and
must be considered in the differential
diagnosis of chronic diarrhea

• The soft scant feces associated with
some cases of incomplete obstruction of
the digestive tract of cattle affected
with the complications of traumatic
reticuloperitonitis must not be confused
with diarrhea

Diseases of the nonruminant stomach and intestines

2 S3

TREATMENT

The principles of treatment of enteritis
are:

0 Removal of the causative agent
o Alteration of the diet
° Fluids and electrolytes
0 Intestinal protectants and adsorbents
c Antidiarrheal drugs.

Removal of causative agent

Specific treatment is usually directed at
intestinal helminthiasis with anthelmintics,
antiprotozoan agents against diseases
such as coccidiosis and antimicrobial
agents against the bacterial enteritides.
There are no specific treatments available
for the viral enteritides in farm animals.

While considerable investigations have
been done on the enteritides on fanu
animals, the emphasis has been on the
immunology, pathology, microbiology and
body fluid dynamics, each with different
emphasis in different species. For example,
there is considerable infonnation on the
microbiology and immunology of the
common enteritides in calves and piglets in
addition to the extensive knowledge of the
body fluid dynamics in calves. In the horse
there is some information on body fluid
dynamics but the microbiology of the
diarrheas is not well understood. In none
of the species is there sufficient infor-
mation on the effects of antibiotics on the
intestinal microflora.

Antimicrobials

The use of antimicrobials, either orally or
parenterally, or by both routes simulta-
neously, for the treatment of bacterial
enteritides is a controversial subject in
both human and veterinary medicine.
Those who support their use in acute
bacterial enteritis claim that they are
necessary to help reduce the overgrowth
of pathogenic bacteria responsible for the
enteritis and to prevent or treat bacteremia
or septicemia that may occur secondary to
an enteritis. Those who suggest that they
are contraindicated or unnecessary in
bacterial enteritis suggest that the drugs
may eliminate a significant proportion of
the intestinal flora in addition to the
pathogenic flora. This may reduce the
effect of competitive antagonism in the
intestine, which in turn may permit the
development of a superinfection (the
appearance of bacteriological and clinical
evidence of a new infection during the
chemotherapy of a primary one). Also, the
use of antimicrobials in infectious enteric
disease allows the development of
multiple drug resistance, which is a
major public health concern. The use of
antimicrobials may also increase the
length of time over which affected animals
excrete the organisms which, for example,
may occur in enteric salmonellosis.

Many different antimicrobial prep-
arations for both oral and parenteral
administration are available. The choice
will depend on previous experience,
the disease suspected and the results of
culture and drug sensitivity tests.
Parenteral preparations are indicated in
animals with acute diarrhea, toxemia and
fever. Many antimicrobials, when given
parenterally, are excreted by the liver into
the lumen of the intestine and oral
preparations may not be necessary. In
cases of subacute diarrhea with minimal
systemic effects, the use of an oral
preparation may be sufficient. Flowever,
oral preparations should not be used for
more than 3 days to avoid a super-
infection. The preparations and doses of
the antimicrobials commonly used in
bacterial enteritides are described under
each disease.

Mass medication of feed and water
supplies

Mass medication of the drinking water
supply with antimicrobials for the treat-
ment of outbreaks of specific infectious
enteritides in animals is used commonly
and with success. One of the best
examples is the use of antimicrobials in
the drinking water of pigs affected with
swine dysentery. However, not all affected
animals will drink a sufficient quantity of
the medicated water and daily intake
must be monitored carefully. Severely
affected animals in an outbreak need
individual treatment.

Alteration of the diet

If the cause of the diarrhea is dietary in
origin the feed should be removed until
the animal has fully recovered; feed
should then be replaced by another
source or reintroduced gradually. The
question of whether or not a normally
digestible diet should be removed
temporarily or the total daily intake
reduced in animals with acute enteritis is
a difficult one. The rationale is that in
acute enteritis the digestibility of nutrients
is reduced considerably and undigested
feed provides a substrate for fermentation
and putrefaction to occur, the products of
which may accentuate the malabsorptive
state. However, temporary withdrawal of
feed presents practical problems, especially
in the young. For example, the temporary
removal from the sow of newborn piglets
affected with acute enteritis presents
practical problems and is of doubtful
value; similarly with beef calves nursing
cows on pasture. With foals it is relatively
easy to muzzle them for 24 hours. With
weaned piglets affected with weanling
diarrhea and feeder pigs with swine
dysentery, it is common practice to reduce
the normal daily intake by half for a few
days until recovery is apparent. Mature

horses affected with diarrhea should not
have access to any feed for at least
24 hours. During the period of temporary
starvation, the oral intake of fluids
containing glucose and electrolytes is
desirable and necessary to assist in
maintaining hydration. In newborn calves
with diarrhea, if oral fluid intake is
maintained, the total loss of water from
feces and through the kidney is not
significantly greater than in normal calves
because in diarrheic calves the kidney will
effectively compensate for fecal losses.
When recovery is apparent, the animal's
usual diet may be reintroduced gradually
over a period of a few days.

Fluids and electrolytes

The initial goals of fluid and electrolyte
therapy for the effects of enteritis are: the
restoration of the body fluids to normal
volume, effective osmolality, composition
and acid-base balance. The quality and
quantity of fluids required to achieve
these goals depend on the characteristics
of the dehydration and acid-base electro-
lyte imbalance. Under ideal conditions
when a laboratory is available, the deter-
mination of packed cell volume, total
serum proteins, plasma bicarbonate,
blood pH, serum electrolytes and a
hemogram would provide the clinician
with a laboratory evaluation initially and
throughout the course of therapy, to
assess the effectiveness of the treatment.
However, such laboratory service is
expensive and usually not readily avail-
able. The clinician must therefore assess
the degree of clinical dehydration and,
based on the history and clinical findings,
estimate the degree of acidosis and
electrolyte deficits that are likely to be
present. A practical approach to fluid
therapy in the horse has been described.
Fluids should be given orally whenever
possible to save time and expense and to
avoid the complications that can arise
from long-term parenteral fluid therapy.
Also, fluids should be given as early as
possible to minimize the degree of
dehydration. With good kidney function
there is a wider safe latitude in the
solution used.

The three major abnormalities of
dehydration, acidosis and electrolyte
deficit are usually corrected simultaneously
with fluid therapy. When severe acidosis
is suspected, this should be corrected
immediately with a hypertonic (5%)
solution of bicarbonate given intra-
venously at the rate of 5-7 mL/kg BW at a
speed of about 100 mL/min. This is
followed by the administration of electro-
lyte solutions in quantities necessary to
correct the dehydration. With severe
dehydration, equivalent to 10% of BW,
large amounts of fluids are necessary.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Animal Dehydration

(%)

500 kg horse 10

75 kg foal 10

45 kg calf 10

The initial hydration therapy should be
given over the first 4-6 hours by continuous
intravenous infusion, followed by main-
tenance therapy for the next 20-24 hours,
or for the duration of the diarrhea if severe,
at a rate of 100-150 mL/kg BW/24h.
Horses with acute enteritis have severe
hyponatremia and following fluid therapy
may become severely hypokalemic, as
evidenced by weakness and muscular
tremors. The hypertonic solution of sodium
bicarbonate will assist in correcting the
hyponatremia but potassium chloride
may need to be added to the large
quantity of fluids given for dehydration;

1 g of potassium chloride added to each
liter of fluid will provide an additional
14 mosmol/L (14 mmol/L) of potassium.
In preruminant calves with diarrhea, the
fluids and electrolytes required for main-
tenance may be given orally in divided
doses every few hours. In the early stage
of acute diarrhea and for animals that are
not severely dehydrated, the oral route
can also be used successfully to correct
dehydration and prevent it from
becoming worse. The formulae of oral
glucose-electrolyte solutions are given in
the section under colibacillosis. Piglets
and lambs affected with dehydration are
most effectively treated using balanced
electrolyte solutions given subcutaneously
at the dose rates of 20 mL/kg BW every
4 hours and orally at 20 mL/kg BW every

2 hours. Details of the treatment of fluid
and electrolyte disturbances are given
under that heading in Chapter 2.

Intestinal protectants and
adsorbents

Kaolin and pectin mixtures are used
widely to coat the intestinal mucosa,
inhibit secretions and increase the bulk of
the feces in animals with enteritis. In
children with diarrhea, kaolin and pectin
will result in formed rather than watery
feces, but the water content of the feces is
unchanged. It is not possible at this time
to make a recommendation on their use
in animals.

Antidiarrheal drugs

Antimotility drugs

Anticholinergic drugs and opiates are
available to decrease intestinal motility.
The anticholinergic drugs block the action
of acetylcholine on smooth muscle and
glands. This results in decreased gastric
secretion and emptying and a reduction
on both segmental and propulsive
movements of the intestines. Dosages of
anticholinergics necessary to produce

effectiveness may also cause side effects
such as xerostomia, photophobia, tachy-
cardia, urinary retention and neuro-
muscular paralysis. The opiates function
by producing an increase in segmentation
while reducing propulsive movements in
the intestine. The net effect is an increase
in resistance to passage of intestinal
contents and more complete absorption
of both water and nutrients occurs with a
subsequent decrease in the frequency of
defecation.There are no published reports
of clinical trials using antimotility drugs
for the treatment of diarrhea in farm
animals and at the present time, there-
fore, they cannot be recommended with
any assurance of effectiveness.

Antisecretory drugs

Antisecretory drugs are also available for
the treatment of diarrhea due to the
hypersecretory activity of enterotoxin
produced by bacteria such as entero-
toxigenic £. coli. Loperamide hydrochloride
given orally to calves with experimentally
induced diarrhea can delay the onset
of diarrhea by its inhibition of fluid
secretion. Antisecretory drugs include
chlorpromazine, opiates, atropine and
prostaglandin inhibitors. These have not
yet been adequately evaluated and the
provision of balanced fluids and electro-
lytes, containing sodium chloride, sodium
bicarbonate, potassium chloride and
glucose, given both parenterally and orally,
are considered to be adequate and
effective for treating the effects of the
hypersecretion.

Because prostaglandins have an
important reparative role in the intestine,
NSAIDs may retard recovery of ischemic-
injured intestine and are contraindicated. 9

CONTROL

The control and prevention of enteritis in
farm animals is a major topic and activity
of large-animal practice. The control of
each specific enteritis is presented under
each specific disease in Part II of this
book. The principles of control include the
following:

° Reduce infection pressure by
controlling population density
3 Ensure adequate nonspecific
resistance by adequate colostrum
intake of neonatal farm animals and
maintaining adequate nutritional
status

0 Vaccinate for those diseases for which
there is an effective vaccine
0 Minimize managemental and
environmental stressors
® Monitor morbidity and mortality and
ensure that a diagnosis is obtained so
that control measures for newly
introduced diseases into a herd can be
instituted.

REVIEW LITERATURE

Blikslager AT, Roberts MC. Mechanisms of intestinal
mucosal repair. J Am Vet Med Assoc 1997;
211:1437-1441.

Blanchard PC. Sampling techniques for the diagnosis
of digestive disease. Vet Clin North Am Food
Anim Pract 2000; 16:23-36.

Waters WR. Immunology of inflammatory diseases of
the bowel. Vet Clin North Am Food Anim Pract
2001; 17:517-534.

Jones SL, Blikslager AT. Role of the enteric nervous
system in the pathophysiology of secretory
diarrhea. J Vet Intern Med 2002; 16:222-228.

Tomlinson J, Blikslager A. Role of nonsteroidal anti-
inflammatory drugs in gastrointestinal tract injury
and repair. J Am Vet Med Assoc 2003;
222:946-951.

REFERENCES

1. Jones SL, BlikslagerT. JVet Intern Med 2002; 16:222.

2. Karcher LF et al. JVet Intern Med 1990; 4:247.

3. MacAllister CG et al. J Am Vet Med Assoc 1990;
196:1995.

4. Blikslager AT, Roberts MC. J Am Vet Med Assoc
1997; 211:1437.

5. Gayle JM et al. J AmVet Med Assoc 2000; 217:498.

6. Ruggles A J et al. CornellVet 1992; 82:181.

7. West HJ, Baker JR.Vet Rec 1991; 129:196.

8. Blanchard PC. Vet Clin North Am Food Anim
Pract 2000; 16:23.

9. Tomlinson J, Blikslager A. J Am \fet Med Assoc
2003; 222:946.

ACUTE DIARRHEA OF ADULT
(NONSUCKLING) HORSES

Etiology Salmonella spp., Strongylus
spp., cyathostomes, Neorickettsia
(, Ehrlichia ) risticii, Clostridium spp.,
antibiotic administration, idiopathic
Epidemiology Usually a sporadic disease
of young horses, often temporally
associated with mild respiratory disease or
a stressful event such as transport.
Helminthiasis has a seasonal distribution
and can occur as a herd problem. N. risticii
has a defined geographical distribution
Clinical signs Acute onset of profuse
watery diarrhea. Depression, fever,
dehydration and anorexia are common
Clinical pathology Leukopenia,
hemoconcentration, hyponatremia,
hypokalemia or hyperkalemia, metabolic
acidosis. IFA or PCR for N. risticii, fecal
culture of Salmonella spp. may be positive.
Fecal culture for Clostridium spp. and ELISA
to demonstrate toxin in feces
Lesions Colitis with or without enteritis
Diagnostic confirmation Cause is
frequently not confirmed
Treatment Intense supportive care
including maintenance of hydration and
correction of acid-base and electrolyte
abnormalities. Oxytetracycline for equine
monocytic ehrlichiosis. Metronidazole for
C. difficile- associated diarrhea
Control None

ETIOLOGY

Causes are as follows:

° Salmonellosis: Various Salmonella
spp.

Fluid
deficit (L)

50

7.5

4.5

Diseases otthe nonruminant stomach and intestines

e Helminthiasis: Strongylus sp.,
cyathostomes

o Equine monocytic ehrlichiosis

(Potomac horse fever Equine
neorickettsiasis) : Neorickettsia
risticii

o Antibiotic administration: macrolides
(lincomycin, tylosin, erythromycin),
tetracyclines, ciprofloxacin,
trimethoprim-sulfonamide
combination, penicillin,
aminoglycosides, ceftiofur, and others
g Intestinal clostridiosis: C. perfringens
(types A and C), 1 toxigenic strains of
C. difficile 2 and possibly Clostridium
cadaveris

o Aeromonas spp.: Isolated from
horses with diarrhea, definitive role as
a causative agent has not been
demonstrated 3
o Colitis-X: Idiopathic.

E. coli does not appear to be an important
cause of diarrhea in adult horses. 4

In most cases (65%) of acute diarrhea
in horses the cause is not determined, or
if the cause is determined it is frequently
at necropsy examination or after the horse
•has recovered. 5

EPIDEMIOLOGY

Occurrence

The syndrome of acute diarrhea occurs
worldwide in adult horses of all breeds
and both sexes. The pattern of occurrence
of the syndrome is dependent on the
causative factors, with equine monocytic
ehrlichiosis (equine neorickettsiasis),
associated with N. risticii, having a
geographical distribution and acute
cyathostomiasis having a seasonal
distribution. Salmonellosis can occur
sporadically or as outbreaks in stables,
barns and veterinary hospitals. C. difficile
enterocolitis is associated with hospital-
ization and/or antibiotic administration to
adult horses. 2 The disease also occurs in
foals.

Colitis-X is usually a sporadic disease,
but multiple cases can occur in a barn or
racing stable over a period of weeks and
cause considerable economic hardship.
With the exception of salmonellosis,
equine monocytic ehrlichiosis, strongylosis
and colitis-X, the syndrome is characterized
by a sporadic distribution. Estimates of
incidence, morbidity and mortality are
not available for all diseases.

The case fatality rate for the sponta-
neous disease can be 25-50% even in
intensively treated horses. 5-8 The case
fatality rate is higher for horses with
C. difficile -induced diarrhea than for horses
with acute diarrhea of other causes 2
and for horses with antibiotic-induced
diarrhea. 8 The prognosis is worse in
horses with tachycardia, severe dehy-
dration (PCV > 45% (0.45 L/L)), azotemia.

metabolic acidosis, low serum albumin
concentration or higher immature
neutrophil (band cell) count in peripheral
blood. 6-8

Risk factors

The risk factors for salmonellosis, equine
monocytic ehrlichiosis and strongylosis
are addressed under those topics.

Stress

Stressful episodes, such as shipping or
racing, hospitalization, surgery, adminis-
tration of antibiotics or mild respiratory
disease, frequently precede the onset of
diarrhea. 6

Celiotomy

Celiotomy for colic is associated with an
incidence of severe diarrhea of up to 27%
in surviving horses. 9 The risk of diarrhea is
greatest in horses with large-colon
disease or with enterotomy, but is not
influenced by the type of antibiotic
administered after surgery. 9

Antibiotic administration
Antibiotic administration is associated
with acute diarrhea in horses. The
macrolide antibiotic lincomycin causes
acute, often fatal, disease of horses even
when administered at relatively low
doses, such as that resulting from horses
ingesting medicated pig feed. 10 Tetra-
cyclines have been associated with the
development of acute diarrhea but, when
given intravenously at therapeutic doses
(6.6 mg/kg every 12-24 h) are probably no
more likely to cause diarrhea than other
broad-spectrum antibiotics. Tetracycline
contamination of feed causes outbreaks of
diarrhea on horse farms. 11 Ciprofloxacin
might be a cause of diarrhea in horses. 12
The combination of trimethoprim and
sulfadiazine given orally causes diarrhea
in 7% of hospitalized horses, whereas
pivampicillin, a prodrug of ampicillin,
causes diarrhea in 3%. 13 However, horses
treated with trimethoprim-sulfadiazine
combinations are not at greater risk of
developing diarrhea than horses treated
with penicillin. 14 Almost all adult horses
with diarrhea from which C. difficile or its
toxin can be isolated were administered
antibiotics before onset of diarrhea. 15

PATHOGENESIS

Diarrhea is the result of abnormalities in
colonic water and electrolyte metabolism.
Approximately 90 L of isotonic fluid
enters the colon of an adult (450 kg) horse
every 24 hours, and any disruption to the
normal absorption of this fluid results in
increased fecal water and electrolyte
excretion. Colitis results from physical,
chemical or infectious causes that induce
inflammation in the colon. The proximate
causes vary with the etiology of the disease.
For example, colitis due to infection by

toxigenic strains of C. perfringens type C is
attributable to binding of beta-2- toxin to
colonic mucosa, 16 whereas colitis due to
salmonellosis is associated with invasion
of the organism and loss of colonic
mucosa. Colitis is associated with increased
production of inflammatory cytokines,
including tumor necrosis factor, in the
colon, 17 and with impaired mucosal
absorptive function. Additionally, bacterial
toxins and inflammation result in an
increase in mucosal permeability with
loss of plasma proteins into the colonic
lumen and systemic absorption of toxins,
including endotoxin. Loss of plasma
proteins causes a reduction in plasma
colloidal oncotic pressure with subsequent
extravasation of water and electrolytes and
development of edema and decreased
effective intravascular volume (hypo-
volemia). The effect of the decrease in
oncotic pressure becomes most apparent in
horses that are treated aggressively with
fluids. These horses, which often receive
excessive amounts of sodium, rapidly
develop edema of the ventral body wall
and colon, among other tissues. Loss of
other plasma proteins, including anti-
thrombin IH, and absorption from the gut
of activators of coagulation, fibrinolysis or
inflammation, may contribute to the
disseminated intravascular coagulation
often observed in horses with enterocolitis.

The large volume of diarrhea in horses
causes a reduction in body water and
electrolyte content. Hypovolemia, hypo-
natremia, hypochloremia and hypo-
proteinemia develop. Derangements in
acid-base and electrolyte status impair
gastrointestinal motility. Hypovolemia
impairs perfusion of peripheral tissues,
which, combined with absorption of
endotoxin through the damaged colonic
mucosa, results in toxemia, lactic acidosis
and death.

CLINICAL SIGNS

The onset of clinical signs is usually
abrupt, although in some horses diarrhea
may be presaged for up to several days by
inappetence, mild depression and a mild
fever. The disease varies in severity from
short-lived with mild to moderate
diarrhea and minimal systemic signs of
disease to a fulminant disease with death
in hours. The description here is of the
more severe forms of the disease. Once
diarrhea occurs there is rapid progression,
with some horses dying within 12 hours
of initial clinical signs, although most
survive at least 24 hours. In a peracute
form of the disease horses die, often within
6 hours, before developing diarrhea.

Typically horses are often severely
depressed and stand with their heads
down. They may play in water, but rarely
eat or drink. Horses are usually mildly

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

pyrexic (101.5-103°F, 38.6-39.5°C) but
markedly tachycardic (80-100 bpm),
tachypneic (30-40 bpm) and dehydrated
(8-12%). There is slow capillary refill of
mucous membranes, which are usually
bright red initially and then become
bluish-purple as toxemia and dehydration
become severe. The development of a
purple line at the gingival margins is a
sign of a poor prognosis. Most horses are
oliguric.

The diarrhea is profuse and watery.
Abdominal pain is usually present but
mild; the onset of severe abdominal pain
is often associated with necrosis of the
large colon or cecum and impending
death. Rectal examination reveals large
amounts of fluid feces with minimal
distension of the large colon.

Complications of acute, severe
enterocolitis include laminitis, thrombo-
phlebitis of the jugular veins, thrombosis
of vessels including arteries in the limbs. 18
renal failure, pulmonary aspergillosis 19 ' 21
and necrotizing enterocolitis. 22 Laminitis
develops within 1-3 days of onset of
diarrhea in approximately 10% of cases
and can occur in any horse with
enterocolitis, but is most common in
horses with Potomac horse fever (equine
monocytic ehrlichiosis). Thrombophlebitis,
which may or may not be septic, usually
affects veins, usually jugular, that have or
have had catheters placed or are the site
of frequent intravenous injections.
Thrombosis of the vein can occur several
days to a week after removal of the
catheter, although most occur while
the catheter is in place. Renal failure
occurs as a result of the combined insults
of hypovolemia, endotoxemia and
administration of nephrotoxic drugs,
including aminoglycosides and NSAIDs.
Pulmonary aspergillosis is usually clinically
inapparent. 20 Clinically affected horses
have rapidly progressive toxemia, respir-
atory distress, hypoxemia and blood-
tinged, frothy nasal exudates. Fatal
necrotizing enterocolitis of horses is
characterized by a brief course, most
horses dying within 48 hours of onset of
diarrhea, profound dehydration, electro-
lyte derangements, severe metabolic
acidosis and, terminally, severe abdomi-
nal pain. 22

Most horses that survive have reso-
lution of diarrhea in about 7 days, although
a small but clinically important pro-
portion develop chronic diarrhea.

CLINICAL PATHOLOGY

Hematological examination reveals an
increased hematocrit (45-60%), variable
changes in plasma protein concentration
and neutropenia with a marked left shift.
As the disease progresses and horses are
treated by intravenous administration of

fluids, plasma protein concentrations and
plasma oncotic pressure decline. Plasma
or serum albumin concentration may be
as low as 1.2 g/dL (12 g/L). Changes in
coagulation and fibrinolysis are evident
as increases in one or more of one-stage
prothrombin time, activated partial
thromboplastin time and concentration of
fibrin degradation products, variable
changes in plasma fibrinogen concen-
tration and a reduction in blood platelet
concentration. 23 Approximately one-third
of horses hospitalized for treatment of
severe diarrhea have subclinical evidence
of disseminated intravascular coagulation, 23
which carries a reduced likelihood of
recovery.

Serum biochemical analysis usually
reveals hyponatremia, hypochloremia,
variable changes in serum potassium
concentration, hypocalcemia (both con-
centrations of ionized and total calcium 24 ),
azotemia (increased serum urea nitrogen
and creatinine concentrations), hyper-
phosphatemia and increased activities
of enzymes indicative of muscle
(creatine kinase) or intestinal damage
(aspartate aminotransferase and alkaline
phosphatase).

Blood gas analysis often reveals a
severe metabolic acidosis, and the more
negative the base excess the worse the
prognosis. 7 Interpretation of acid-base
status in horses with severe enterocolitis
is difficult because of the opposing effects
of hypoproteinemia and combination of
lactic acidosis and electrolyte loss on
blood pH. Hypoproteinemia causes a
metabolic alkalosis whereas increases in
plasma lactate concentration and hypo-
natremia cause metabolic acidosis. The
presence of hypoproteinemia therefore
tends to diminish the effect of lactic
acidosis on blood pH, which under-
estimates the severity of the acidosis.
Acid-base status in horses with severe
abnormalities in plasma protein con-
centration should be ascertained by
examination of base excess, strong ion
gap or strong ion difference. 25

Plasma endothelin concentrations are
higher in horses with enterocolitis than in
normal horses, 26 although the clinical
significance of this finding is unclear.

Abdominal fluid is usually normal
initially but becomes bloody and has an
increased white blood cell count and
protein concentration if intestinal necrosis
occurs.

DIAGNOSTIC CONFIRMATION

This depends on the results of fecal
culture for Salmonella sp., fecal examin-
ation for helminth eggs or larvae, and
indirect fluorescent antibody (IFA) or
polymerase chain reaction (PCR) tests for
N. risticii. Demonstration of large numbers

of salmonellae in feces on multiple fecal
samples, or in lymph nodes of horses
dying of the disease, is persuasive
evidence that the horse had salmonellosis.
However, demonstration of low numbers
of salmonellae in a single fecal culture is
not definitive evidence that Salmonella sp.
infection was the cause of the horse's
diarrhea. Fecal examinations for helminth
eggs may be negative in cases of acute
cyathostomiasis, although large numbers
of fourth stage larvae may be present in
the feces. Diagnosis of N. risticii infection
is based on a positive IFA test. Isolation of
Clostridium sp. and demonstration of
clostridial enterotoxin in feces of horses
with acute diarrhea supports a diagnosis of
intestinal clostridiosis, although demon-
stration of toxin alone is usually con-
sidered sufficient evidence for diagnosis. 27
Latex agglutination tests are available
for the detection of C. perfringens type A
and C. difficile toxins. 1,28

NECROPSY

There are extensive lesions at necropsy
examination, the most dramatic being in
the large intestine, especially the cecum
and ventral colon. These include hyperemia,
extensive petechiation, and edema of the
gut wall in the early stages, and later
an intense, greenish black, hemorrhagic
necrosis. The contents are fluid, often
foamy and foul- smelling, and may be
bloodstained.

Histological examination demonstrates
mucosal necrosis with a fibrinohemorrhagic
exudate and extensive inflammation of
the mucosa and submucosa.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis list:

• Salmonellosis

• Equine monocytic ehrlichiosis (equine
neorickettsiasis) (Potomac horse fever)

• Cyathostomiasis

• Antibiotic-induced diarrhea

• Clostridium sp. infection (C. difficile)

• Colitis-X

• Intoxication with inorganic arseni,
cantharidin or purgatives such as castor
oil

• The incipient disease in horses before
onset of diarrhea can resemble colon
torsion or ischemia of the large colon
secondary to verminous arteritis

TREATMENT

Horses with mild disease, those that do
not manifest systemic signs of disease,
usually recover with symptomatic treat-
ment. However, horses with severe
disease require more specific treatment
and supportive care, which is often inten-
sive and expensive.

Diseases of the nonruminant stomach and intestines

2

The principles of treatment for horses
with acute diarrhea are:

o Restoration and maintenance of
normal hydration
o Correction of electrolyte and
acid-base abnormalities
o Provision of analgesia
o Prophylaxis and treatment of the
effects of endotoxemia
o Prevention of absorption of toxins
a Correction and prevention of
disseminated intravascular
coagulation.

Restoration of hydration

Restoration of hydration should be con-
sidered an emergency procedure in
severely affected horses. Fluids should be
administered intravenously until hydration
is restored, after which hydration can be
maintained by either oral (via nasogastric
tube) or intravenous administration of
fluids. Suitable fluids for restoration of
hydration are sodium -rich, isotonic,
preferably polyionic, electrolyte solutions
such as lactated Ringer's or Ringer's
solution. Isotonic sodium chloride is
also suitable. Isotonic dextrose solutions
are not suitable because they do not
contain any electrolytes. After correction
of dehydration, attention should be paid
to sodium balance because adminis-
tration of excessive quantities of sodium,
especially to horses with plasma oncotic
pressure that is lower than normal, may
cause expansion of the extracellular fluid
volume and edema.

Fluid therapy is discussed elsewhere.
Maintenance of hydration in severely
affected horses can be challenging and
is best accomplished by intravenous
administration of fluids. Oral adminis-
tration of fluids to horses with diarrhea,
although not providing ideal rehydration
or maintenance of hydration, may be
effective and less costly than intravenous
administration. 29-31

Horses that become hypoproteinemic
may require transfusions of plasma.
Clinical signs indicating the need for
transfusion include a persistently elevated
heart rate and poor peripheral perfusion
in spite of administration of large quan-
tities of fluids. Ventral edema and edema
of the head and legs may develop in
hypoproteinemic horses. Sufficient plasma
should be administered to restore the
plasma protein concentration to at least
40 g/L.

Electrolyte and acid-base status
Hyponatremia and hypochloremia will
usually be corrected by administration of
isotonic, sodium-rich electrolyte solutions
such as lactated Ringer's solution. If this
does not occur, then sodium chloride or
sodium bicarbonate can be added to the

intravenous fluids, or given orally. Hypo-
calcemia can be corrected by the addition
of calcium gluconate (20 mL of 23%
calcium gluconate per liter of fluids) to
the fluids, provided that the fluids do not
contain sodium bicarbonate. The mixture
of sodium bicarbonate and calcium
gluconate causes calcium to precipitate
out of solution. Affected horses have total
body potassium depletion , 32 even
though serum potassium concentrations
may be normal or elevated, and main-
tenance fluids should contain potassium
at up to 25 mEq/L. Fluids with high pot-
assium concentration should be admin-
istered slowly. Alternatively, potassium
chloride can be given orally (50-100 g per
450 kg every 12 h).

The metabolic acidosis in horses with
acute diarrhea often resolves either
partially or completely when hydration is
restored. However, severe acidosis can
be treated with intravenous sodium
bicarbonate. Oral administration of
sodium bicarbonate (100 g per 450 kg
every 8-12 h) is often adequate in
restoring and maintaining normal acid-
base status. The serum sodium concen-
tration should be monitored if large
quantities of sodium bicarbonate are
administered.

Antimicrobial therapy

Administration of tetracycline to horses
with acute diarrhea associated with
N. risticii is clearly indicated and is often
curative. However, the administration of
antimicrobial drugs to horses with acute
diarrhea other than that associated with
N. risticii is controversial. There is no
evidence that administration of anti-
microbials improves the prognosis of
horses with acute diarrhea. 7,33 The concern
with antimicrobial administration is that
antimicrobials may exacerbate the diarrhea
in some cases. Conversely, withholding
antimicrobials from severely ill horses
with damaged colonic mucosa, and
therefore presumably increased risk of
bacteremia, is problematic. Regardless,
many clinicians chose to treat horses with
acute diarrhea with broad-spectrum anti-
biotics such as the combination of
potassium penicillin (20 000 IU/kg, intra-
venously every 6 h) and gentamicin
i (7 mg/kg intravenously or intramuscularly
I every 24 h) or trimethoprim and
! sulfadiazine (30 mg/kg intravenously or
| orally every 12 h). Metronidazole
j (15-20 mg/kg orally every 6-12 h) or
i vancomycin have been recommended
| for horses with intestinal clostridiosis,

| although the wisdom of veterinary use of
J vancomycin, a drug used for the treat-
! ment of methicillin-resistant staphylococci .
| in humans, could be questioned. 34 In

j areas in which equine monocytic

! I

ehrlichiosis (equine neorickettsiasis) is
endemic, all suspected cases should be
treated with tetracycline (6.6 mg/kg
intravenously every 12 h for 3 d), or another
effective antibiotic, pending confinnation
of the disease. Isolates of toxigenic
C. difficile from horses with diarrhea are
almost always susceptible to metronidazole
(15-29 mg/kg orally every 6-12 h). 15

Prophylaxis and treatment of
endotoxemia

Treatment of endolemma has been
recently reviewed. 35 Administration of
plasma from horses hyperimmunized
with Salmonella typhimurium or E. coli
reduces the severity of clinical signs and
shortens the duration of disease in horses
with endotoxemia secondary to enteroc-
olitis or colic. 36 Polymyxin (5000 IU/kg
intravenously every 12 h) attenuates
the effect of endotoxin in experimental
disease and is used for the prevention and
treatment of endotoxemia in hospitalized
horses. 37 Its efficacy in clinical settings has
not been determined. Aspirin (10 mg/kg
orally every 48 h) is administered to
diminish platelet aggregation around intra-
venous catheters. Flunixin meglumine
(1 mg/kg intravenously every 8-12 h) or
phenylbutazone (2.2 mg/kg intra-
venously every 12 h) is given for analgesia
and to prevent endotoxin-induced
increases in plasma prostaglandins.
Pentoxifylline (8 mg/kg orally every 8 h)
is administered for its putative effective in
attenuating the effects of endotoxemia.
The efficacy of these treatments in a clinical
setting and their effect on measures of
outcome of disease, such as duration of ill-
ness, case fatality rate and incidence of
complications, has not been determined,
with the exception of hyperimmune
plasma or serum. 36

Binding of toxins

Smectite or activated charcoal are some-
times administered to horses with acute
enterocolitis in an attempt to adsorb
toxins, such as those produced by
Clostridium spp., and prevent systemic
absorption. There is in-vitro evidence that
smectite may bind clostridial toxins and
endotoxin, 38 but evidence of efficacy in
vivo is lacking.

Disseminated intravascular
coagulation

Prevention and treatment of disseminated
intravascular coagulation includes monitor-
ing for changes in variables indicative of
| coagulation and fibrinolysis including D-
! dimer concentration, antithrombin III
1 activity, one-stage prothrombin and
activated partial thromboplastin times,
platelet count and fibrinogen concen-
tration. Plasma can be administered to
increase blood antithrombin III activity.

'2

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - 1

often in conjunction with heparin or low-
molecular- weight heparin (dalteparin or
enoxaparin). Doses of 50 U of dalteparin
or 40 U of enoxaparin per kilogram sub-
cutaneously every 24 hours seem to be
adequate for prophylactic anticoagulatory
treatment of horses. For treatment of
coagulation disorders or for ill horses
that are considered to be at high risk of
developing thrombotic disease, dosages
may need to be increased to 100 U of
dalteparin or 80 U of enoxaparin per
kilogram subcutaneously every 24 hours. 39

CONTROL

Specific control measures for Salmonella
spp. infection, equine monocytic ehrli-
chiosis and cyathostomiasis are discussed
under those headings. The incidence of
antibiotic-induced colitis can be reduced
by minimizing the frequency with which
antibiotics are administered to horses.

REVIEW LITERATURE

Divers TJ. Prevention and treatment of thrombosis,
phlebitis, and laminitis in horses with gastro-
intestinal diseases. Vet Clin North Am Equine
Pract 2003; 19:779.

McConnico R. Acute equine colitis. Compend Contin
Educ PractVet 2003; 25:623.

REFERENCES

1. Donaldson MT, Palmer JE. J Am Vet Med Assoc
1999; 215:358.

2. Weese JS et al. Equine Vet J 2001; 33:403.

3. HathcockTL et al. JVet Intern Med 1999; 13:357.

4. Van Duijkeren E et al.Vet Q 2000; 22:162.

5. MairTS et al.Vet Rec 1990; 126:479.

6. Stewart MC et al. AustVet J 1995; 72:41.

7. Staempfli HR et al. Can Vet J 1991; 32:232.

8. CohenND, Woods AM. J Am Vet Med Assoc 1999;
214:382.

9. Cohen ND et al. J Am Vet Med Assoc 1996;
209:810.

10. Raisbeck MF et al. J Am Vet Med Assoc 1981;
179:362.

11. Keir AAM et al. Can Vet J 1999; 40:718.

12. Weese JS et al. Equine Vet Educ 2002; 14:182.

13. Ensink JM et al.Vet Rec 1996; 138:253.

14. Wilson DA et al. JVet Intern Med 1996; 10:258.

15. Baverud V et al. Equine Vet J 2003; 35:465.

16. Bacciarini I.N et al.Vet Pithol 2003; 40:376.

17. Davidson AJ et al. Res Vet Sci 2002; 72:177.

18. Brianceau P, Divers TJ. Equine Vet J 2001; 33:105.

19. Rosenstein DS, Mullaney TP. Equine Vet Educ
1996; 8:200.

20. Sweeney CR, Habecker PL. J Am Vet Med Assoc
1999; 214:808.

21. Slocombe RF, Slauson DO. Vet Pathol 1988;
25:277.

22. Saville WJ et al. J Vet Intern Med 1996; 10:265.

23. Dolente BA et al. J Am Vet Med Assoc 2002;
220:1034.

24. Van der Kolk JH et al. Equine Vet J 2002; 34:528.

25. Constable PD. Vet Clin Pithol 2000; 29:115.

26. Ramaswamy CM et al. Am JVet Res 2002; 63:454.

27. Weese JS et al. Proc Am Assoc Equine Pract 1999;
45:50.

28. Traub-Dargatz JL, Jones RL. Vet Clin North Am
Equine Pract 1993; 9:411.

29. Schott HC. Vet J 1998; 155:119.

30. Ecke P et al.Nfet J 1998; 155:161.

31. McGinniss SG et al. Compend Contin Educ Pract
Vet 1996; 18:942.

32. Muylle E et al. Equine Vet J 1984; 16:450.

33. Van Duijkeren E et al.Vet Q 1997; 18:153.

34. Jang SS et al. Clin Infect Dis 1997; 25(Suppl
2):S266.

35. Sykes BW, Furr MO. AustVet J 2005; 83:45.

36. Spier SJ et al. Circ Shock 1989; 28:235.

37. Barton MH et al Equine Vet J 2004; 36:397.

38. Weese JS et al. EquineVet J 2003; 357:638.

39. Schwarzwald CC et al. Am J \fet Res 2002; 63:769.

CHRONIC UNDIFFERENTIATED
DIARRHEA OF HORSES

Etiology Common sign of many enteric
and non-enteric diseases
Epidemiology Sporadic disease of adult
horses, except for cyathostomiasis and
salmonellosis, which are discussed under
those headings

Clinical signs Passage of unformed or
liquid feces, either in increased or normal
quantities. Weight loss, increased appetite.
Otherwise normal physical examination.
Rectal examination is usually normal
Lesions Colitis in most cases
Diagnostic confirmation Examination
of feces for cyathostome larvae, rectal
biopsy demonstrating lymphoma or
granulomatous enteritis. Salmonella spp. in
rectal mucosal biopsy or feces. Sand in
feces or evident on abdominal radiography
Treatment Supportive: anthelmintics,
corticosteroids, antidiarrheal preparations
Control As for cyathostomiasis and
salmonellosis

ETIOLOGY

Chronic diarrhea is the final common
sign of a number of causes of colonic
dysfunction in horses. Diseases that cause
chronic (more than 2 weeks duration)
diarrhea in horses include: cyathostomiasis,
chronic idiopathic colitis, salmonellosis,
alimentary lymphosarcoma, granulo-
matous colitis, eosinophilic colitis,
ingestion of sand, chronic liver disease,
peritonitis, lymphangiectasia and as a
sequela to acute diarrhea. Immune defi-
ciency, including variable adult onset
B-cell deficiency, may predispose to the
disease. 1 Brachyspira sp. have been impli-
cated as a cause of chronic diarrhea in
horses in Australia and Japan. 2,3

There are many causes and their
relative importance varies between loca-
tions. Even with concerted effort, a defini-
tive antemortem diagnosis is achieved in
fewer than 30% of cases. 4

EPIDEMIOLOGY

The occurrence is sporadic, with only
single cases occurring in a group. Other
horses in contact are not affected. The
case fatality rate is 35-65%. 5 There appears
to be no age-related, sex-related or
breed-related variation in incidence.
Older horses do not appear to be at
increased risk of having chronic diarrhea. 6
The epidemiology of cyathostomiasis

and salmonellosis are discussed under
those headings.

PATHOGENESIS

Diarrhea is attributable to colonic dys-
function, which may result in excessive
loss of electrolytes in feces and diminished
absorption of nutrients from the large
colon. Disease of exclusively the small
intestine does not cause diarrhea in
horses. Protein-losing enteropathy may
be present. Colonic dysfunction may be
associated with inflammatory or infil-
trative lesions of the colon but in many
cases an anatomical lesion is not
detected. However, the colonic contents
of affected horses have a greater fermen-
tative capacity than those of normal
horses, suggesting that in some horses
the disease is essentially one of abnormal
colonic digestion and absorption. 7

CLINICAL FINDINGS

The characteristic finding is chronic
diarrhea. The feces vary in consistency
from thick porridge (oatmeal), through
undigested fibers in liquid, to liquid
without fiber. The consistency of the feces
in an individual horse may vary widely
from one day to the next. The duration of
the diarrhea is variable but may be
lifelong. Death or euthanasia usually
results from progressive weight loss. The
onset of diarrhea is usually abrupt and
may be associated with signs of toxemia
and dehydration, as described under
Acute diarrhea, above. However, often
there is no toxemia or other systemic sign
apart from weight loss, and affected
horses are bright and alert and have a
normal or increased appetite.

Rectal examination usually fails to
reveal any abnormalities, although horses
with granulomatous enteritis or alimentary
lymphosarcoma may have enlarged
mesenteric lymph nodes.

Abdominal radiography may reveal
the presence of excessive amounts of
sand in the large colon.

CLINICAL PATHOLOGY

° Hematological examination may reveal
a mild neutrophilia and anemia, but
these changes are of little use in
determining the etiology of the diarrhea
° Serum biochemical examination
typically demonstrates a mild
hypoalbuminemia,
hypoglobulinemia, hyponatremia
and hypokalemia, but again these
changes are not specific for any
particular disease

c Hypoalbuminemia is consistent with
the presence of protein -losing
enteropathies such as chronic colitis,
alimentary lymphosarcoma,
cyathostomiasis and granulomatous
colitis

Diseases of the nonruminant stomach and intestines

2 S3

° Hyperbilirubinemia and elevated
serum concentrations of serum bile
acids are suggestive of liver disease
° Increases in serum alkaline

phosphatase activity, while common,
are of no diagnostic utility
o Horses with cyathostomiasis may
have increased concentrations of
beta- globulins, although the
sensitivity of this test is low. 5

Peritoneal fluid has a neutrophilic
leukocytosis and increased (>25 g/L)
protein concentration in horses with
peritonitis but is normal in most horses
with chronic diarrhea, including those
with alimentary lymphosarcoma or
granulomatous colitis.

Fecal examination of horses with
cyathostomiasis may reveal strongyle-type
ova or fourth-stage cyathostome larvae. The
presence of sand in feces, demonstrated by
allowing feces to settle in a transparent
rectal glove or similar container, suggests
sand accumulation in the colon as a cause
of the diarrhea. The presence of protozoa in
feces has no diagnostic significance. 8
Giardia spp. are commonly found in feces
of normal horses of all ages and, despite
earlier reports of their presence in feces of
horses with diarrhea, they are not
associated with disease. 9 Coccidiosis is
very uncommon in horses, and Eimeria
leuckarti is probably not pathogenic. 10

Demonstration of Salmonella spp. in
feces or rectal mucosal biopsy, either by
culture or PCR, is suggestive but not diag-
nostic of salmonellosis, given the high
proportion of normal horses that shed
Salmonella spp. in feces. Isolation of
Khodococcus equi from feces of young horses
with diarrhea is suggestive of enteric
disease associated with that organism.

An abnormal D-xylose, glucose or
starch absorption test indicates small-
intestinal disease and is suggestive of
granulomatous enteritis, although most
horses with this disease do not have
diarrhea.

Exploratory laparotomy, either ventral
midline under general anesthesia or
through the left flank under local anes-
thesia, and intestinal biopsy may
demonstrate alimentary lymphosarcoma,
granulomatous enteritis, eosinophilic
enteritis, chronic colitis and other abdomi-
nal disease. Rectal biopsy is less expen-
sive and invasive but has a relatively poor
sensitivity, although good specificity for
granulomatous enteritis, eosinophilic
enteritis and alimentary lymphosarcoma. 11

NECROPSY FINDINGS

Necropsy findings are consistent with
the underlying disease, although in many
cases gross lesions are not evident. The
histological changes in some cases are
restricted to a mild inflammatory response

and may be difficult to correlate with the
severity of clinical disease. In some of
these cases the diarrhea probably reflects
an imbalance in the microflora of the
large bowel, and demonstration of a
specific etiological agent is an unrealistic
goal. Conversely, isolation of Salmonella
spp. from the gastrointestinal tract or
mesenteric lymph nodes should be inter-
preted with caution in the absence of
histological evidence of salmonellosis.

Because of the wide variety of poten-
tial causes of chronic diarrhea of horses it
is not possible to list all the samples
required to 'confirm' a diagnosis. In most
instances, formalin-fixed samples from
the liver, mesenteric lymph nodes and
numerous levels of the gastrointestinal
tract comprise the minimum diagnostic
material required. Regardless of what
other testing is performed, it is prudent to
hold back frozen segments of both large
and small bowel (with content) in case
other tests are deemed necessary.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis list:

• Chronic idiopathic colitis

• Salmonellosis

• Cyathostomiasis

• Granulomatous colitis

• Sand ingestion ’ 2

• Lymphosarcoma

• Peritonitis

• Intestinal lymphangiectasia

• Hyperlipemia

• Liver disease

• Basophilic enteritis

• Eosinophilic gastroenteritis.

TREATMENT

The principles of treatment are to deal
with the underlying disease, correct fluid
and electrolyte disturbances, give symp-
tomatic treatment of diarrhea and provide
supportive care. Except in cases of
cyathostomiasis or sand accumulation,
treatment of horses with chronic diarrhea
is frequently unrewarding.

Specific treatments
Cyathostomiasis should be treated with
larvicidal doses of anthelmintics such as
fenbendazole (50 mg/kg once, or 7.5 mg/kg
daily for 3 d), moxidectin (400 pg/kg) or
ivermectin (200 pg/kg). Treatment may be
unrewarding if there is severe damage to
the large colon.

Diarrhea secondary to sand accumu-
lation in the gastrointestinal tract should
be treated by preventing the horse
from ingesting sand and, although the
efficacy is debatable, with psyllium
mucilloid (1-2 g/kg orally once daily for
4-5 weeks.

Chronic idiopathic colitis may be

treated with corticosteroids (dexa-

methasone 0.2-0.4 mg/kg once^daily) or
prednisolone (0.5-1 .0 mg/kg once daily)
for 3-4 weeks and the dose reduced as
clinical signs permit.

Chronic salmonellosis has been
treated with enrofloxacin (2.5-5 mg/kg
orally every 12 h for 3-4 weeks), some-
times in combination with metronidazole
(15-20 mg/kg orally every 6-12 h), but
one should be aware of the risk of arti-
cular cartilage damage in horses treated
with enrofloxacin.

Many diseases commonly associated
with chronic diarrhea are not treatable.

Symptomatic and supportive
treatments

Symptomatic treatments include metroni-
dazole (7.5-20 mg/kg orally every 6-12 h)
or iodochlorhydroxyquin (10-20 mg/kg
orally once daily). While some horses have
resolution of diarrhea while being treated
with these compounds, there is no clear
demonstration of their efficacy. Antibiotic
administration, other than as described
above, does not usually alter the course of
the disease. Antidiarrheal preparations
such as codeine phosphate, loperamide
and bismuth subsalicylate often provide
temporary improvement in fecal con-
sistency. Some horses with chronic diarrhea
respond to transfaunation, whereby 5-10 L
of colonic fluid collected immediately after
death from a horse without enteric disease
is administered via nasogastric intubation.

Supportive treatment includes provision
of supplemental electrolytes, principally
sodium, potassium and bicarbonate, as a
feed additive. Suitable supplements include
some commercial products designed for
fluid replacement in diarrhetic calves, or a
mixture of potassium chloride (300 g),
sodium chloride (400 g) and sodium bicar-
bonate (300 g). This mixture is isotonic
when dissolved at the rate of 90 g/12 L, or
can be given orally at the rate of 30-90 g per
400 kg horse every 24 hours. Unsupple-
mented water should be supplied without
restriction and serum electrolyte concen-
trations should be monitored. Severely
affected horses may require intravenous
administration of polyionic isotonic
electrolyte solutions or plasma.

Nutritional support should include
provision of a diet of high-quality rough -
age and grain. Some trials may be needed
to determine the diet that is best for
individual horses, but care should be
taken that the diet contains adequate
energy and is nutritionally balanced.
Horses should be fed to attain, and then
maintain, an ideal body weight.

Spontaneous recovery does occur,
particularly in young horses, and this, and
the often lengthy duration (6-12 months)
of the illness, make it difficult to decide
accurately the value of the treatment.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract- I

CONTROL

Control of cyathostomiasis and
salmonellosis is discussed under those
headings. Diarrhea due to sand accumu-
lation in the colon should be prevented by
not feeding horses on the ground and by
avoiding grazing of short pastures on
sandy soil.

REVIEW LITERATURE

Merritt AM. Chronic diarrhea in horses: a summary.
Met Med 1994; 89:363-367.

REFERENCES

1. MacLeay JM et al. Vet Immunol Immunopathol
1997; 57:49.

2. ShibaharaT et al. J Vet Med Sci 2002; 64:633.

3. Lester GD. Proc Am CollVet Int Med Forum 2005;
23:181.

4. Love S et al.Vet Rec 1992; 130:217.

5. MairTS et al. Equine Vet J 1993; 25:324.

6. Brosnahan MM, Paradis MR. ] Am Vet Med Assoc
2003; 223:99.

7. Minder HP et al. Am J Vet Res 1980; 41:564.

8. Ike K et al. Jpn J Vet Sci 1983; 45:157.

9. Xiao L, Herd RP. Equine Vet ) 1994; 26:14.

10. Taylor MA. Equine Vet ] 1994; 26:4.

11. Lindberg R et al. Equine Vet J 1996; 28:275.

12. Bertone JJ et al. J Am Vet Med Assoc 1988;
193:1409.

ACUTE DIARRHEA OF SUCKLING
FOALS

ETIOLOGY

The causes of diarrhea in suckling foals
are listed in Table 5.16. In a large
proportion of foals the cause of diarrhea
is not determined, in part because the

'UilsiK

Etiological agent or disease

Important epidemiological factors

Major clinical findings; diagnostic criteria

Idiopathic

Foal heat diarrhea
Bacterial causes

Foals < 2 weeks of age.

No systemic signs of disease. Diarrhea is mild and pasty.
No specific diagnostic criteria

Septicemia (coliforms,

Newborn foal to < 2 weeks of age. Failure of

Signs of systemic sepsis in addition to diarrhea. Fever,

Actinobacillus sp.,
Salmonella sp.,

Klebsiella sp. and others)

transfer of passive immunity

depression, recumbency, failure to nurse, swollen joints,
pneumonia, omphalitis or omphalophlebitis. Blood culture

Salmonella sp.

Outbreaks in newborn foals, even those with
adequate passive immunity. Mare likely carrier.
Hygiene at parturition may prevent disease

Acute onset diarrhea, depression, fever, toxemia. Culture
of blood and feces

Escherichia coli

Not well documented disease in foals (cf. calves
and piglets)

Nonfetid diarrhea. Culture of feces yields heavy growth of
mucoid E. coli ( circumstantial evidence only)

Enterococcus ( Streptococcus )
durans

Young foals. Disease is rarely reported

Diarrhea. Demonstration of S. durans in feces

Rhodococcus equi

Foals 2-5 months of age, some with history of
respiratory disease

Diarrhea associated with R. equi pneumonia; culture
respiratory tract

Clostridium difficile

< 2 weeks of age.

Colic, fever, ileus, hematochezia, toxemia, depression. Fecal
culture and demonstration of toxin in feces

Clostridium perfringens type c

Neonatal foals. Sporadic disease to annual outbreaks
on breeding farms. Most foals excrete C. perfringens
type A, which rarely causes diseases in foals

Colic, fever, ileus, hematochezia, toxemia, depression.
Culture of C. perfringens type C in feces,
demonstration of toxin in feces

Lawsonia intracellularis

Older suckling foals and weanlings. Sporadic or
outbreaks on farms

Weight loss, mild to moderate diarrhea, ventral edema,
depression, hypoproteinemia. Serology and PCR on feces

Yersinia pseudotuberculosis

Suckling foals. Outbreaks on breeding farms

Watery diarrhea and suppurative pneumonia. Culture of feces
and lesions

Aeromonas hydrophila
Viral causes

Reports of disease are uncommon. Uncertain
importance

Diarrhea. Culture of feces

Rotavirus

< 3 months of age. Occurs as outbreaks or
endemic disease on farm. Highly contagious

Profuse watery diarrhea with variable hypovolemia
and depression. Detection of virus in feces by
electron microscopy, IF A EUSA

Adenovirus

Immunodeficient foals (Arabians with severe
combined immunodeficiency)

Diarrhea, depression. May be associated with other
diseases including pneumonia. Detection of virus
in feces by electron microscopy

Coronavirus

Parasites

Young foals (age range not well defined).
Apparently rare cause of diarrhea in foals

Diarrhea. Detection of virus in feces by electron microscopy

Cryptosporidium sp.

Foals of any age. May be spread from other species,
including calves and cria

Inapparent infection to fulminant disease with diarrhea,
hypovolemia, and collapse. Chronic diarrhea.

Detection of oocysts in feces, IF A

Strongyloides western
Other

Individual foals. Uncertain importance as a cause
of diarrhea

Acute to chronic diarrhea. Patent infections evident by fecal
examination for parasite eggs

Nutritional

Sporadic. Orphan foals fed inappropriate or poor-
quality milk replacers. Nursing foals fed inappropriate
supplements

Mild to moderate chronic diarrhea. Failure to thrive. Feed
diet intended for foals (not plant-protein- or bovine-milk-
based)

Lactose intolerance

Nursing foals

Moderate to profuse diarrhea. Fiistoricai confirmation of
administration of compounds

Overdosing of cathartics

Sporadic. Secondary to viral diarrhea. Occurs only in

Moderate to severe watery, acidic diarrhea. Oral lactose

(DSS, MgS0 4 , NaS0 4 , castor oil)

milk-fed foals

tolerance test or trial administration of lactase with milk
feedings

Enema

History of administration. Diarrhea short-lived

Bright alert and responsive foal with mild to moderate
diarrhea. No specific diagnostic tests

Antibiotic-induced

Administration of antibiotics

Mild to moderate diarrhea. May be associated with Candida
sp. or C. difficile. Culture of feces, examination forC. difficile
toxin

Diseases of the nonruminant stomach and intestines

2

disease is* usually sporadic, mild and
transient. The more common causes of
diarrhea in foals on breeding farms in
Britain include Clostridium perfringens,
rotavirus. Salmonella, Cryptosporidium sp.,
and Strongyloides western, U3 although the
relative importance of various pathogens
varies from year to year, from farm to farm
and from region to region.

C. perfringens causes diarrhea in young
foals. There are five major types of
C. perfringens and, while the organism is
clearly associated with disease, a definitive
role for each of these types in causing
disease has not been established, partly
because toxin production for strains
isolated from foals with diarrhea has not
been routinely documented. However,
there is clear evidence that C. perfringens
type C causes diarrhea in foals. 4
C. perfringens types A, B, D and E might be
associated with disease in foals, but
definitive proof is lacking. E. coli, an
important cause of disease in neonates of
other livestock species, does not appear to
be an important cause of diarrhea in foals,
although some strains are pathogenic. 5,6
Similarly, although there are reports of
coronavirus causing severe disease in foals,
this does not appear to be a common
cause of diarrhea in foals. 7,8 Candida spp.
can cause diarrhea in critically ill foals and
those administered antibiotics. 9 Yersinia
spp. have been associated with diarrhea in
foals but do not appear to be a common
cause of disease. 10 Bacteroides fragilis is an
uncommon cause of diarrheal disease in
foals. The role of Campylobacter spp. in foal
diarrhea, if there is any, is unclear.

EPIDEMIOLOGY

Diarrhea is common in suckling foals
worldwide although studies of its inci-
dence, risk factors and outcome are
exiguous. Diarrhea affects 21% of foals
annually in Texas, being second only to
respiratory disease (22%) as a cause of
disease. 11 The frequency of disease varies
with age: 25% of foals 0-7 days of age
have diarrhea, compared to 40% and 8%
of foals aged 8-31 days and 32-180 days,
respectively. 11 While a common disease
syndrome, diarrhea is not associated with
a high death rate (2. 6%). 11 Results of the
Texas study may not be applicable to foals
in other regions.

Among the common causes of diarrhea
the highest death rates are associated
with diarrhea associated with C. perfringens,
Salmonella sp. and Cryptosporidium sp. 2

Risk factors for development of the
diarrhea vary depending on its etiology,
but in general the disease is less common
in foals born at pasture and at low
stocking density. 11

Rotavirus diarrhea is often endemic on
farms and the disease occurs as outbreaks

on successive years. Affected foals range
in age from less than 7 days to more than
3 months.

Diarrhea due to Rhodococcus equi
occurs in foals with R. equi pneumonia
and the disease is endemic on some farms.
Not all foals with R. equi pneumonia
develop diarrhea. The disease occurs in
foals 2-5 months of age.

Salmonellosis also occurs as outbreaks
of disease among foals less than 8 days of
age on breeding farms and is associated
with a carrier status in mares. 12

Diarrhea associated with C. perfringens
type C occurs in foals less than 10 days of
age with most foals being less than 6 days
old 4 and can occur as a farm problem with
multiple foals affected on each of several
successive years. 13 Farm risk factors
include presence of other livestock, stock-
horse-type foals, foals born on dirt, and
stall or diy lot confinement for the first
few days of life. 14 C. perfringens type A is
i excreted in feces of most normal foals,

; whereas C. perfringens type C is rarely
isolated from feces of normal foals. 15
Clostridium difficile causes diarrhea in
foals not administered antibiotics, 16 in
j contrast to the situation in adult horses,
and usually affects foals less than 14 days
of age, although foals up to 120 days of
age may be affected. 17 Failure of transfer
of passive immunity is not a risk factor for
C. perfringens or C. difficile enteritis in
foals.

Lawsonia intracellularis causes mild
to moderate diarrhea in older suckling or
: weaned foals. The disease occurs as out-
breaks on breeding farms. There are no
recognized foal or farm risk factors.

PATHOGENESIS

The pathogenesis of diarrhea varies some-
what depending on the inciting cause
(see appropriate sections of this text for
discussion of pathogenesis), although if
sufficiently severe all cause excessive loss
of fluid and electrolytes in feces and
subsequent hypovolemia, electrolyte
abnormalities, metabolic acidosis and
weakness. Although not demonstrated in
foals, diarrhea in calves causes metabolic
acidosis through loss of sodium and other
cations in feces, which results in a
decrease in the strong ion difference in
blood, causing acidosis. Bicarbonate loss,
per se, is not a cause of the metabolic
. acidosis, at least in calves. Infectious
agents generally cause enteritis, although
rotavirus infection is associated with loss
of villus cells and subsequent loss of
i enzyme activity derived from the mature
j epithelial cell. The loss of enzyme activity,
including that of disaccharidases, causes
malabsorption of nutrients in milk and
j other feed. Failure to absorb nutrients in
i the small intestine causes them to be

delivered to the cecum and large intestine
where they are fermented. Subsequent
reductions in colonic pH and increases in
osmotic activity of the colon contents
results in excretion of large quantities of
fluid and electrolytes. C. difficile and
C. perfringens produce enterotoxins that
cause damage to intestinal cells and
accumulation of hemorrhagic fluid in the
intestine. 16 L. intracellularis causes an
infiltrative and proliferative enteropathy
with subsequent protein loss and,
possibly, malabsorption.

CLINICAL SIGNS

Clinical signs vary from mild, pasty
diarrhea that adheres to the perineum
and causes no detectable systemic signs
of disease to profuse water diarrhea
with rapid development of loss of suck-
ling, depressed mentation, tachycardia,
increased skin tent, ileus and recumbency.

Signs of systemic disease include failure
to nurse, increased frequency or prolonged
duration of recumbency, foals at pasture
may fail to follow the mare, fatigue, less
frequent urination, production of concen-
trated urine (urine from normal foals is
normally dilute) and weakness. Affected
foals often have depressed mentation,
tachycardia, fever (depending on the cause
of the diarrhea), decreased capillary refill
time, diy mucous membranes, increased
skin tent and eyes that are retracted into
the orbit (consistent with dehydration).
Depending on the cause of the diarrhea,
foals may have colic, which can range from
mild with intermittent flank watching or
biting and restlessness, through profound
agitation, rolling and dorsal recumbency.
Severely affected foals may have seizures as
a result of profound hyponatremia. 18

Chronic diarrhea and that due to nutri-
tional imbalance or lactose intolerance
causes rapid weight loss, failure to thrive,
poor hair coat and lethargy. Chronic fecal
contamination of the perineum and
escutcheon causes excoriation and loss
of hair.

Diarrhea associated with foal heat is
usually mild and transient and not
associated with systemic signs of disease.
However, diarrhea due to infectious
agents is often severe and accompanied
by systemic signs of disease.

Diseases associated with Clostridium
sp. are often severe with rapid onset of
signs of toxemia, colic, hypovolemia and
death. Diarrhea is usually present and is
often bloody, although it may be watery
and profuse. Severely affected foals may
have signs of colic, toxemia and ileus and
not develop diarrhea before dying.
Salmonellosis can present as septicemia,
with subsequent development of diarrhea,
although in older foals diarrhea is a
common presenting sign.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - 1

CLINICAL PATHOLOGY

Diarrhea in foals with systemic signs of
disease cause hyponatremia, hyper-
"kalemia, hypochloremia, metabolic acidosis,
hypoproteinemia and azotemia. The
magnitude of abnormalities varies with
the cause of disease and its severity.
Hyponatremia may be profound
(< 100 mEq/L). Hypoproteinemia may be
a result of loss of protein from the
inflamed intestine or a reflection of failure
of transfer of passive immunity. All young
foals with diarrhea should have serum or
plasma immunoglobin concentrations
measured or some other test for transfer
of passive immunity performed.

Viral causes of diarrhea can be diag-
nosed by examination of feces by electron
microscopy. However, more rapid and
sufficiently sensitive and specific tests
exist for diagnosis of rotaviral disease
(ELISA, IF A). Culture of feces will
demonstrate Salmonella spp in most
cases if they are the cause of disease. Fecal
culture yielding C. perfringens or C. difficile
is insufficient for diagnosis of clostridial
enterocolitis as these organisms can be
recovered from normal foals. Confirmation
of the diagnosis is achieved by demon-
stration of clostridial toxins in feces,
which can be problematic given that the
toxins are very labile.

DIAGNOSTIC CONFIRMATION

For diagnostic criteria for specific diseases,
see the appropriate sections in this text.

LESIONS

Lesions associated with diarrhea in foals
depend on the inciting cause. Charac-
teristically in severe cases there is enteritis
and colitis with ulceration of intestinal
mucosa. Foals with rotavirus diarrhea,
most of which survive, have flattening of
small-intestinal epithelium.

TREATMENT

The principles of treatment are:

■- Correction and maintenance of
hydration, acid-base and electrolyte
status

' Ensuring adequate transfer of passive
immunity

0 Ensuring adequate nutrition

Preventing complications of disease,
including bacteremia.

Correction of hypovolemia and electrolyte
abnormalities should follow the general
guidelines presented elsewhere in this
text. Mildly affected foals, such as those
with no systemic signs of disease, might
not require administration of fluids orally
or parenterally. More severely affected
foals might require oral supplementation
with balanced, isotonic electrolyte
rehydration solutions, such as those
marketed for use in calves. The amount

!

t

I

I

and frequency will depend upon the size
of the foal, severity of disease and
response to treatment. Foals that have
clear signs of hypovolemia should be
administered fluids intravenously. These
fluids should ideally be selected based on
the foal's serum electrolyte concen-
trations, but in most instances a balanced,
polyionic, isotonic fluid such as lactated
Ringer's solution is appropriate. Correc-
tion of hyponatremia in some but not all
foals requires administration of hypertonic
(7%) sodium chloride intravenously.
However, rapid correction of hyponatremia,
especially if it is long-standing (more
than 24 h) might be associated with an
increased risk of cerebral demyelination.
Correction of hyponatremia will resolve
seizure activity.

Correction of acid-base usually occurs
with correction of fluid and electrolyte
abnormalities. Provision of fluids that are
sodium-rich and have a high strong ion
gap, for instance lactated Ringer's solu-
tion, will usually correct the metabolic
acidosis common in foals with diarrhea.
However in some foals the rate of fecal
loss of cations including sodium, and
perhaps bicarbonate, prevents resolution
of metabolic acidosis without adminis-
tration of sodium bicarbonate. Sodium
bicarbonate can be administered intra-
venously or orally. Oral administration
has the advantages that it is convenient
and does not require administration of
large amounts of fluid or of hypertonic
solutions. The dose of sodium bicarbonate
can be calculated from the foal's
body weight and base deficit. As a
guideline, a 40 kg foal that is not hypo-
volemic but has continued profuse watery
diarrhea and metabolic acidosis should
receive 30 g sodium bicarbonate orally
every 6 hours. Serum sodium and bicar-
bonate concentrations should be measured
at least daily and doses of sodium
bicarbonate should be adjusted on the
basis of these values. Overdosing, or
continued dosing when diarrhea has
resolved, results in hypernatremia and
metabolic alkalosis.

Foals with diarrhea should have serum
immunoglobulin concentrations measured.
Hypogammaglobulinemic foals should
be administered plasma intravenously
(20-40 mL/kgBW).

Ensuring that foals affected by
diarrhea continue to ingest sufficient
calories is critical to the foal's survival.
Foals require up to 150 (kcal/kg)/d for
growth but can maintain weight on as
little as 50 (kcal/kg)/d, especially if the
nutrients are provided intravenously.
Foals with mild to moderate diarrhea
should be permitted to nurse at will. If
there is concern that the foal is not
nursing sufficiently, a feeding tube can be

placed and the foal's diet supplemented
with mare's milk, milk substitute lactose-
free milk. Lactase is sometimes added to
the milk on the assumption that enteritis
causes lactase deficiency (for details of
lactose tolerance testing in foals) .

Foals with severe diarrhea benefit from
parenteral administration of nutrition and
gastrointestinal rest. Feed withholding
results in a marked reduction in fecal
volume and the extent of electrolyte and
acid-base abnormalities. However, it is
critical for foal recovery that complete
feed withholding be accompanied by
partial parenteral nutrition.

Antibiotics are usually administered to
foals with severe diarrhea on the pre-
sumption that such foals are more
likely to have bacteremia. Although there
is no evidence that parenteral adminis-
tration of antibiotics reduces morbidity or
case fatality rate, the precaution has
merit, as it does in calves. 19 Oral
administration of antimicrobials to foals
with diarrhea is common but is not
recommended because of the risk of
exacerbating the disease, and unknown
efficacy. Foals with suspected clostridial
enterocolitis should be administered
metronidazole (15-20 mg/kg, intravenously
or orally, every 6-12 h).

Drugs that affect gastrointestinal
motility, such as loperamide, para-
sympatholytics and narcotics, have no
demonstrated efficacy in reducing mor-
bidity or case fatality rate and their use is
not recommended.

CONTROL

Control of foal diarrhea is problematic
because it is very common, many cases
are mild and transient, a definitive diag-
nosis is frequently not available in a
timely fashion, and it can be associated
with a wide variety of infectious and non-
infectious agents. Basic principles include
ensuring adequate transfer of passive
immunity, reducing exposure to pathogens
and minimizing the effect of other risk
factors.

Of the important causes of disease, in
terms of morbidity and case fatality rate,
control of diarrhea associated with
rotavirus and clostridial species is most
important. Control of rotaviral diarrhea is
discussed elsewhere. Control of clostridial
diarrhea on farms with an endemic
problems includes vaccinating of mares,
administration of metronidazole to at-risk
foals and supplementation of passive
immunity with antitoxins to clostridial
toxins. Vaccination of mares with toxoids
(C. perfringens type c and d toxoid)
prepared for use in other species has been
practiced, but there are no reports of safety
or efficacy. Administration of antitoxin
raised against C. perfringens C, D and E

Diseases of the nonruminant stomach and intestines

may provide protection against the alpha,
beta and epsilon toxins that have the
potential to affect foals. The antiserum,
which is intended for use in ruminants, is
administered orally (50-100 mL per foal)
soon after birth. The efficacy of this
practice has not been determined. Foals
at risk may also be administered
metronidazole (10 mg/kg every 12 h) for
the first 4-5 days of life. Again, the
efficacy of this practice has not been
determined.

Administration of a probiotic contain-
ing Lactobacillus pentosus WE7 did not
confer any protection against develop-
ment of diarrhea in foals, and was associ-
ated with an increased risk of clinical
disease, including diarrhea. 20

REVIEW LITERATURE

Jones RL. Clostridial enterocolitis. Vet Clin North Am
Equine Pract 2000; 16:471.

REFERENCES

1. Grinberg A et al. Vet Rec 2003; 153:628.

2. Netherwood T et al. Epidemiol Infect 1996;
117:375.

3. Browning GF et al. Equine \fet J 1991; 23:405.

4. East LM et al. J Am Vet Med Assoc 1998; 212:1751.

5. Holland RE et al.Vbt Microbiol 1996; 52:249.

6. Holland RE et al.Vet Microbiol 1996; 48:243.

7. Guy JS et al. J Clin Microbiol 2000; 38:523.

8. Davis E et al. J Vet Diagn Invest 2000; 12:153.

9. De Bruijn CM, Wijnberg ID. Vet Rec 2004; 155:26.

10. Czernomysy-Furowicz D. Zentralbl Bakteriol
1997; 286:542-546.

11. Cohen ND. J Am Vet Med Assoc 1994; 204:1644.

12. Walker RL et al.Vet Diagn Invest 1991; 3:223.

13. MacKay RJ. Compend Contin Educ Pract Vet
2001; 23:280.

14. East LM et al. PrevVet Med 2000; 46:61.

15. Tilloston K et al. J Am \fet Med Assoc 2002;
220:342.

16. Arroyo LG et al. JVet Intern Med 2004; 18:734.

17. Magdesian KG et al. J Am Vet Med Assoc 2002;
220:67.

18. Lakritz J. J Am\fet Med Assoc 1992; 200:1114.

19. Constable PD. JVet Intern Med 2004; 18:8.

20. Weese JS, Sousseau J. J Am Vet Med Assoc 2005;
226:2031.

INTESTI NAL HY PERMOTILITY

A functional increase in intestinal motility
seems to be the basis of a number of
diseases of animals. Clinically there is
some abdominal pain and, on auscultation,
an increase in alimentary tract sounds
and, in some cases, diarrhea. Affected
animals do not usually die and necropsy
lesions cannot be defined but it is prob-
able that the classification as it is used
here includes many of the diseases often
referred to as catarrhal enteritis or
indigestion.

The major occurrence of intestinal
hypermotility is spasmodic colic of the
horse. Other circumstances in which
hypermotility and diarrhea occur without
evidence of enteritis include allergic and
anaphylactic states and a change of feed
to lush pasture.

| DIETARY DIARRHEA

j Dietary diarrhea occurs in all species and
j all ages but is most common in neonatal
i animals that ingest too much milk or a
diet that is indigestible.

j ETIOLOGY
; Milk replacers

; The use of inferior-quality milk replacers
; in young calves under 3 weeks of age is
; one of the commonest causes of dietary
j diarrhea. The quality of the milk replacer
may be affected by the use of skim-milk
j powder that was heat-denatured during
: processing, resulting in a decrease in the
i concentration of noncasein proteins. This
results in ineffective clotting in the abo-
masum and reduced digestibility. The use
of excessive quantities of nonmilk carbo-
hydrates and proteins in milk replacers
for calves is also associated with a high
incidence of diarrhea, loss of weight,
emaciation and starvation. The use of
large quantities of soybean protein and
fish protein concentration in milk replacers
for calves will result in chronic diarrhea
and poor growth rates.

Most attempts to raise calves on diets
based on large amounts of certain soybean
products, such as heated soybean flour,
have been unsuccessful because the
animals developed diarrhea, loss of appe-
tite and weight or inferior growth rate.
Preruminant calves develop gastrointestinal
hypersensitive responses to certain soy-
bean products because major proteases of
the digestive tract do not denature soluble
antigenic constituents of the soybean
protein. 1

Diarrhea of nutritional origin has
become one of the most important
problems where large numbers of calves
are raised under intensive conditions.
Because of the relatively high cost of
good-quality skim-milk powder, large
quantities of both nonmilk proteins and
carbohydrates are used in formulating
milk replacers. While some calves in these
large units can satisfactorily digest the
nutrients in these milk replacers, many
cannot and this leads to a high incidence
of diarrhea and secondary colibacillosis
and enteric salmonellosis.

Milk replacers made from bovine milk
and milk byproducts used to feed orphan
piglets, lambs and foals may cause
nutritional diarrhea for the same reasons
as given above. In milk-replacer-fed
calves, increasing the total daily fluid
intake as a percentage of body weight
causes a greater incidence of loose feces,
dehydration and dullness than lower
levels of fluid intake and higher dry
matter concentration. This suggests that a
greater amount of fluid intake increases
the passage rate of dry matter and
decreases absorption. The concentration

of solids in the liquid diet should jrange
between 10% and 13% and should be
! offered at 8 % of body weight in calves fed
j milk replacer once daily and allowed free
access to calf starter.

Overfeeding of milk

] The feeding of excessive amounts of
j cows' whole milk to hand-fed calves will
j result in large amounts of abnormal feces
, but usually not a profuse watery diarrhea
' with dehydration and loss of weight. This
; suggests that simple overfeeding of milk
; may not be a cause of acute neonatal
j diarrhea of calves. However, it may pre-
j dispose to secondary colibacillosis. There
j is some limited evidence that dietary
j diarrhea may occur in nursing beef calves
; ingesting milk that does not clot properly,
j Only the milk from cows with diarrheic
calves showed evidence of impaired
clotting in an in-vitro test.

The ingestion of excessive quantities of
sows' milk by piglets at 3 weeks of age is
thought to be a contributory cause of
3-week diarrhea of piglets. This may be
due to the sow reaching peak production
at 3 weeks.

Beef calves sucking high-producing
cows grazing on lush pasture are often
affected with a mild diarrhea at about
3 weeks of age. The cause is thought to be
simple overconsumption of milk. Similarly,
vigorous lambs sucking high-producing
ewes may develop diarrhea.

Foals commonly have diarrhea at
about 9 days of age, which coincides with
the foal heat of the mare. It has been
thought for many years that the cause
was a sudden change in the composition
of the mare's milk but this has not been
supported by analyses of mares' milk at
that time. The fecal composition in foal
heat diarrhea suggests that the diarrhea is
a secretory-type hypersecretion of the
small intestine mucosa, which may not be
controlled by an immature colon. 2

There is considerable interest in the
optimal conditions for feeding liquid diets
to young calves. The temperature of the
liquid when fed, feeding once or twice
daily and the amount of dry matter intake
can affect the performance of calves.
However, there is a range of safety in
which the performance of the calves will
not be significantly affected if manage-
ment is good. •

Change of diet

Dietary diarrhea also occurs in all species
following a sudden change in diet, but
particularly in animals at weaning time.
This is particularly important in the pig
weaned at 3 weeks of age and not
adjusted to the postweaning ration.
Diarrhea occurs commonly when animals
are moved from a dry pasture to a lush
pasture and when first introduced to

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract- I

liberal quantities of concentrates contain-
ing a large percentage of the common
cereal grains.

PATHOGENESIS
Digestion of milk

In calves, the ingestion of excessive
quantities of cows' whole milk after
several hours of no intake causes gross
distension of the abomasum and possibly
of the rumen. Under these conditions, the
milk-clotting capacity of the abomasum
may be limited, resulting in incomplete
clotting. The flow of nutrients from the
abomasum is more uniform in calves fed
twice daily than once daily, which sug-
gests that twice-daily feeding allows for
more effective clotting and digestion.

Under normal conditions, the milk clot
forms in the abomasum within minutes
after feeding, and the whey moves to the
duodenum 5-10 minutes later. The
dilution of cows' whole milk will result in
increased clotting time when treated with
rennin (chymosin). Overfeeding could
result in whole milk or excessive quantities
of whey entering the duodenum, which
cannot digest whole milk or satisfactorily
digest and hydrolyze the substrates in
whey. The presence of excessive quantities
of such substrate, especially lactose, in
the intestinal lumen would serve as a
hydragogue and result in a large increase
in intestinal fluid, failure of complete
absorption and abnormal feces. The speed
of drinking is probably also important.
Prolongation of drinking time results in
dilution of the milk with saliva and the
production of a more easily digested milk
clot. Failure of the esophageal reflex in
pail-fed calves may also be important. The
milk enters the rumen, where it under-
goes putrefaction.

Milk replacers and diarrhea

The pathogenesis of diarrhea in calves fed
inferior-quality milk replacers is well
known. In calves fed low-heat-treated
skim-milk powder milk replacer, curd
formation in the abomasum, compared
with no curd formation, slows down the
passage of total abomasal content (retained
matter from the last feeding, residual
matter from the penultimate feeding,
saliva, and gastric secretions), dry matter,
crude protein and fat from the abomasum
to the intestine. 3 Heat-denatured skim-
milk powder is incompletely clotted in the
abomasum, leading to reduced digestibility.

Nonmilk carbohydrates and nonmilk
proteins are not well digested by
preruminant calves under 3 weeks of age
because their amylase, maltase and
sucrase activities are insignificant, and
their pepsin-HCl activity is not well
developed until at least 3 weeks of age.
Following the ingestion of these nutrients,
there is reduced digestibility, malabsorption

and diarrhea. This results in a negative
nutrient balance, loss of body weight and
gradual starvation, all of which are
reversible by the feeding of cows' whole
milk. The digestion of fat is particularly
affected, resulting in varying degrees of
steatorrhea. Preruminant calves fed milk
replacer containing corn oil will have
diarrhea and not do well because of
inadequate dispersion of the oil. 4

The mechanism for the diarrhea,
which may occur in all species following a
sudden change in diet, is not well under-
stood. However, several days may be
necessary for the necessary qualitative
and quantitative changes to occur in the
digestive enzyme capacity. Not much is
known about the development of
intestinal enzymes in the fetus and new-
born, but this is likely to be of importance
in individual animals. In calves, lactase
activity is fully developed at birth and in
the period between birth and weaning
there are significant changes in enzyme
activity, some of them influenced by the
presence or absence of dietary substances.

In dietary diarrhea, the presence of
undigested substrate in the intestine may
result in marked changes of the bacterial
flora, which may result in excess fermen-
tation of carbohydrates and putrefaction
of protein, the products of which accen-
tuate the malabsorption. If entero-
pathogenic E. coli or Salmonella spp. are
present they may colonize, proliferate
in large numbers and cause enteric
colibacillosis and salmonellosis.

CLINICAL FINDINGS

Nursing beef calves

; Dietary diarrhea of beef calves 3 weeks of
j age on pasture is characterized by the
) passage of light yellow feces that are foul-
smelling and soft. The perineum and tail
i are usually smudged with feces. The
calves are bright and alert and usually
recover spontaneously without treatment
in a few days.

Hand-fed dairy calves

When overfed on cow's whole milk these
animals are usually dull, anorexic and
their feces are voluminous, foul-smelling
and contain considerable mucus. The
abdomen may be distended because of
distension of the abomasum and intestines.
Secondary enteric colibacillosis and
salmonellosis may occur, resulting in
severe dehydration. Most uncomplicated
cases will respond to oral fluid therapy
and withdrawal from or deprivation of
milk.

Milk replacer diarrhea

In calves fed inferior-quality milk replacers,
there will be a chronic diarrhea with
gradual weight loss. The calves are bright
and alert, they usually drink normally.

appear distended after drinking and
spend considerable time in recumbency. -
Not uncommonly, many treatments will
have been tried unsuccessfully. The
diarrhea and weight loss continues and in
2-4 weeks emaciation is evident and
death from starvation may occur. Affected
calves will often have a depraved appetite
and eat bedding and other indigestible
materials, which further accentuates the
condition. When large numbers of calves
are involved, the incidence of enteric
colibacillosis and salmonellosis may
become high and the case mortality very
high. This is a common situation in veal-
calf -rearing units.

Alopecia occurs occasionally in calves
fed a milk replacer, but the cause is
unknown.

CLINICAL PATHOLOGY

Laboratory evaluation of the animals with
dietary diarrhea is usually not necessary
other than for elimination of other poss-
ible causes of the diarrhea. When milk
replacers are being used the determi-
nation of the rennet- clotting time of the
milk replacer compared with whole milk
is a useful aid in assessing the quality of
the skim-milk powder for calves.

NECROPSY FINDINGS

Emaciation, an absence of body fat, dehy-
dration and serous atrophy are present in
calves which have died from diarrhea and
starvation while being fed inferior quality
milk replacers.

differential diagnosis

• Dietary diarrhea occurs following a
change in diet, the consumption of too
much feed at once, or poor quality
feed. There are usually no systemic signs
and recovery occurs spontaneously
when the dietary abnormality is
corrected or the animal adapts to a new
diet

• Dietary diarrhea must be differentiated
from all other common causes of
diarrhea in a particular age group within
each species

• Examination of the recent dietary history
and examination of the diet and its
components will usually provide the
evidence for a dietary diarrhea

TREATMENT

Alter diet of hand-fed calves

In hand-fed calves affected with dietary
diarrhea, milk feeding should be stopped
and oral electrolyte solutions given
for 24 hours. Milk is then gradually
reintroduced. If milk replacers are being
used their nutrient composition and
quality should be examined for evidence
of indigestible nutrients. Occasional cases
of dietary diarrhea in calves will require
intensive fluid therapy and antibacterials

Diseases of the nonruminant stomach and intestines

2 '

orally and parenterally. The feeding prac-
tices should be examined and the necess-
ary adjustments made.

The care and management of hand-
fed calves to minimize the incidence of
dietary diarrhea is an art. Much has been
said about the use of slow-flowing nipple
bottles and pails to reduce dietary
diarrhea but they are not a replacement
for good management. Calves that are
raised for herd replacements should be
fed on whole milk if possible for up to
3 weeks. When large numbers of calves
are reared for veal or for feedlots the milk
replacer used should be formulated using
the highest quality milk and milk by-
products that are economically possible.
The more inferior the milk replacer the
more impeccable must become the
management, which is difficult given
today's labor situation.

Monitor beef calves with dietary
diarrhea

Beef calves affected with dietary diarrhea
while sucking the cow and running on
pasture do not usually require treatment
unless complications develop. They must
be observed daily for evidence of dullness,
anorexia, inactivity and profuse watery
diarrhea, at which point they need some
medical care.

Muzzle foals

Foals with dietary diarrhea should be
muzzled for 12 hours, which may require
hand-stripping of the mare to relieve ten-
sion in the udder and to prevent engorge-
ment when the foal begins to suck again.
Antidiarrheal compounds containing
electrolytes, kaolin and pectin with or
without antibiotics are used commonly
but are probably not any more effective
than oral electrolyte solutions for
24 hours.

REFERENCES

1. Lalles JP, Dreau D. ResVet Sci 1996; 60:111.

2. Masri MD et al. Equine Vet J 1986; 18:301.

3. Cruywagen CW et al. J Dairy Sci 1990; 73:1578.

4. Jenkins KJ. J Dairy Sci 1988; 71:3013.

INTESTINAL OR DUODENAL
ULCERATION

Intestinal ulceration occurs in animals
only as a result of enteritis and clinically
with manifestations of enteritis. As far as
is known there is no counterpart of the
psychosomatic disease that occurs in
humans. Ulceration does occur in many
specific erosive diseases listed elsewhere,
and in salmonellosis and swine fever, but
the lesions are present in the terminal
part of the ileum, and more commonly in
the cecum and colon.

Duodenal ulcers in cattle and horses
have a similar epidemiological distri-
bution to gastric ulcers and also resemble

them clinically. Occasionally they perforate,
causing subacute peritonitis. A perforated
duodenal ulcer in a foal is recorded as
causing acute, fatal peritonitis manifested
by pain, dyspnea and vomiting. Moderate
to severe ulceration of the mucosa of the
cecum and colon is described in phenyl-
butazone toxicity in ponies. The dose rate
of phenylbutazone was 12 mg/kg BW per
day for 8 days. There is significant hypo-
proteinemia due to protein loss from the
gut. A similar hypoproteinemia has been
produced in Thoroughbred horses, but
there was no clinical illness.

DIVERTICULITIS AND ILEITIS OF
PIGS (PROLIFERATIVE ILEITIS)

In this disease there is thickening of
the wall of the ileum, particularly in the
terminal portion, so that the intestine
becomes thick and rigid. There is a close
clinical similarity to Crohn's disease in
humans and the etiology of both con-
ditions is obscure. Familial predisposition
is probable in humans and has been
suggested in pigs.

The signs are those of acute peritonitis
due to ulceration and, sometimes,
perforation of the affected ileum. Illness
occurs suddenly with loss of appetite,
excessive thirst, dullness and disincli-
nation to rise. The temperature is sub-
normal, the respiration is distressed and
there is a bluish discoloration of the skin.
Death occurs in 24-36 hours. Acute cases
occur in young pigs up to 3 months of
age, and chronic cases, due to ulceration
and chronic peritonitis, in the 7-8-month
age group.

At necropsy there may be diffuse
i peritonitis due to leakage of alimentary
; tract contents through perforating ileal
| ulcers. Gross thickening of the ileal wall
\ with nodular proliferation of the ileal
; mucosa and enlargement of the mesenteric
: lymph nodes are common accompani-
ments. Although the macroscopic findings
are similar to those of Crohn's disease in
: man, the histopathological findings differ
: markedly. There is an obvious and
significant protein loss through the intes-
tinal lesion and a marked hypoproteinemia.

RECTAL PROLAPSE

Prolapse of the rectum occurs commonly
in pigs, is an occasional occurrence in
cattle and is rarely seen in the other
species. In a prospective study of rectal
prolapse in a commercial swine herd, 1 %
of the pigs prolapsed between 12 and
28 weeks of age, with a peak incidence
occurring at 14-16 weeks of age. 1
Prolapse rates were highest during the
winter and autumn months. Other risk
factors included:

° Male - relative risk 2.3
® Birth weight less than 1000 g -
relative risk 3.4

o A particular Yorkshire boar - relative
risk 2.8

o Dams of litter number 1 - relative risk
14.9; number 2 - relative risk 8.2;
number 3 - relative risk 9.8.

There was no evidence to support the
hypothesis that diarrhea and coughing
are factors associated with a risk of pro-
lapse. Feeding rations with lysine concen-
trations in excess of the requirements is
considered a risk factor for rectal prolapse
in swine. 2

The common causes include enteritis
with profuse diarrhea, violent straining
such as occurs in coccidiosis in young
cattle, in rabies sometimes, in spinal cord
abscess and also when the pelvic organs
are engorged. The use of estrogens as a
growth stimulant and access to estrogenic
fungal toxins predispose to rectal prolapse
for this reason. It has been suggested that
mycotoxins in swine rations are a cause of
rectal prolapse but there is insufficient
evidence to make such a claim.

Treatment is surgical. 3

REFERENCES

1. Gardner IA et al. Vet Rec 1988; 123:222.

2. Amass SF et al.\fet Rec 1995; 137:519.

3. Douglas RGA.Vet Rec 1985; 117:129.

RECTAL STRICTURE

There are two notable occurrences: as part
of an inherited rectovaginal constriction
in Jersey cattle and a syndrome of acquired
j rectal stricture that occurs in feeder pigs
j at about 2-3 months of age. Although the
j latter is generally classed as a sequel to
I enteric salmonellosis associated with
: Salmonella typhimurium, it has been sug-
gested that there is an inherited
| component in the etiology. The presumed
pathogenesis is that a prolonged entero-
colitis with ulcerative proctitis results in an
! annular cicatrization of the rectal wall
2-5 cm anterior to the anorectal junction.
This results in colonic dilatation and
compression atrophy of the abdominal
and thoracic viscera. Clinically there is
progressive abdominal distension, in-
appetence, emaciation, dehydration and
watery to pasty feces. The stricture of the
rectum can be palpated on digital exam-
ination of the rectum. Most affected pigs
die or are destroyed but a surgical tech-
nique for relief of the condition is
described. Some pigs with incomplete
strictures are unaffected clinically. The
disease can be reproduced experimentally
with S. typhimurium or the surgical
manipulation of the rectal arterial blood
supply, resulting in ischemic ulcerative
proctitis.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

At necropsy there is a low-grade |
peritonitis and dilatation of the colon, and j
sometimes the terminal ileum also. A :
stricture is present 2-5 cm from the anus, j
and may be so severe that it exists as a
scirrhous cord with or without a narrow i
luminal remnant in the center. Histo- ;
logically there is necrotic debris and
granulation tissue at the site of the •
stricture.

Congenital defects of the
alimentary tract

HARELIP AND CLEFT PALATE

Harelip may be unilateral or bilateral and ;
may involve only the lip or extend to the j
nostril. It may be associated with cleft j
palate and cause dysphagia and nasal
regurgitation of milk and food, and a risk
of inhalation pneumonia. It may be
inherited or result from poisoning of
lambs with Veratrum califomicum. Cleft
palate is difficult to correct surgically,
especially in foals, in which it is a com-
mon congenital defect. Cleft palate
(palatoschisis) is a common inherited
defect in calves and is described under
that heading.

ATRESIA OF THE SALIVARY
DUCTS

Congenital atresia of salivary ducts
usually results in distension of the gland
followed by atrophy. Rarely the gland may
continue secreting, resulting in a gross
distension of the duct.

AGNATHIA, MICROGNATHIA AND
BRACHYGNATHIA

These are variations of a developmental
deficiency of the mandible, relatively
common in sheep. The mandible and its
associated structures are partially or
completely absent. Single cases of a
similar defect, combined with cleft palate,
are recorded in calves

Brachygnathia is an abnormal shorten-
ing of the mandible, resulting in mal-
occlusion of the maxillary and mandibular
dental arcades and creating the appearance
of a maxillary overbite. 2 It is considered to
be a congenital abnormality but may be
acquired within the first few months of
life. The incisive malocclusion is of little
consequence to the nursing foal but can
affect the ability to prehend and masticate
as the animal matures. It is not known to
spontaneously regress and surgical
intervention is necessary to correct the
malocclusion.

The cause may be genetic or environ-
mental. Some reports indicate a genetic
influence but the mode of inheritance is

controversial. One report suggests that i
brachygnathia in Angus calves was trans- j
mitted by a single autosomal recessive :
gene but such mode of inheritance has
not been supported in other studies. 2 In a ;
series of 20 horses with brachygnathia the
amount of disparity between the mandible
and premaxilla varied between 0.75 and
3.0 cm. Surgical correction of the abnor-
mality resulted in improved incisive
occlusion. Complete correction of the
malocclusion was more likely to occur if
foals were treated before 6 months of age. '

PERSISTENCE OF THE RIGHT
AORTIC ARCH

Persistence of the right aortic arch as a
fibrous band may occlude the esophagus :
and cause signs of obstruction, parti-
cularly chronic bloat in young calves.

CHOANAL ATRESIA

Failure of the bucconasal membrane to
rupture during fetal life prevents the j
animal breathing through the nostrils, j
The membrane separates the alimentary ]
tract and the nasal cavities in the pharynx.

It is incompatible with life in foals and
lambs, the two species in which it is
identified. 3 The defect is usually bilateral;
a unilateral lesion is tolerable. Surgical
correction is likely to be only partially
effective.

CONGENITAL ATRESIA OF THE
INTESTINE AND ANUS

Congenital intestinal atresia is charac-
terized by the complete closure of some
segment of the intestinal tract. Intestinal
atresia has been reported in calves, lambs,
foals and piglets and the affected new-
born usually dies of autointoxication
within a few days of birth. The incidence
of intestinal atresia in 31 Irish dairy herds
monitored over 1 year was 0.3% of all
| calves born. 4

ATRESIA OF THE ANUS

This is recorded as a congenital defect in
pigs, sheep and calves. 5 Its occurrence
is usually sporadic and no genetic or
management factors can be indicated as
causes. In other circumstances the occur-
rence can be suggestive of conditioning
by inheritance, or be at such a rate as to
suggest some environmental cause.
Atresia of the ileum and colon is probably
conditioned by inheritance in Swedish
Highland cattle. Congenital atresia of the
intestine can be differentiated from
retention of meconium in foals, and rarely
calves, by the passage of some fecal color
in the latter. Affected animals die at about
7-19 days of age unless the defect is
corrected surgically. The intestine is
grossly distended by then and the abdo-

men is obviously swollen as a result.
There is marked absence of feces. When
the rectal lumen is quite close to the
perineum, surgical intervention is easy
and the results, in terms of salvaging the
animals for meat production, are good.
These animals can usually be identified by
the way in which the rectal distension
bulges in the perineum where the anus
should be; pressure on the abdomen
provokes a tensing or further distension
of this bulge. Other signs include tenesmus
with anal pumping and inability to pass a
proctoscope or other instrument.

INTESTINAL ATRESIAS

Intestinal atresias have been classified
into type I - membrane atresia caused by
a diaphragm or membrane; type II - cord
atresia caused by blind ends joined by a
small cord of fibrous or muscular tissue or
both, with or without mesentery; and
type III - blind-end atresia, caused by
absence of a segment of the intestine,
with disconnected blind ends and a gap
in the mesentery, and often a short small
intestine. 6

ATRESIA OF THE TERMINAL COLON

This occurs in foals, 7 especially those of
the Overoo breed; the ileum and colon
are affected in calves 8 and the small
intestine in lambs. Atresia coli has been
reported in Holstein, Ayrshire, Shorthorn,
Simmental, Hereford, Angus and Maine
Anjou breeds and in crossbred cattle. In
one dairy herd over a 10-year period, the
overall incidence of atresia coli in calves
was 0.76%. 9 All the affected calves were
related to one another, some were inbred
and the frequency was higher in males
than females. Some affected calves were
aborted or born dead at term. More calves
were born with atresia coli from dams in
which pregnancy was diagnosed prior to
41 days of gestation than from dams
diagnosed as pregnant at a later date.

It is suggested that atresia coli in calves
j has an inherited basis and that affected
I calves are homozygous recessives for the
I defective allele for atresia coli. This is
j supported by planned matings between
j putative carrier sires and putative carrier
| dams. 10 The estimated minimum gene
1 frequency of atresia coli in cattle is 0.026
I and it is thought that the defective allele
| for atresia coli is at high frequency in
i Holstein cattle in the USA. It is also
I plausible that early pregnancy diagnosis
j by palpating the amniotic sac before
J 40 days of gestation may be a contributing
j factor, but it is not essential for all cases. 11
j Intestinal atresia can be produced experi-
j mentally by terminating the mesenteric
j blood supply to some parts of the intestine
during development.

In atresia coli, the abdomen may be
grossly distended before birth when the

Neoplasms of the alimentary tract

defect is 'in the small intestine and the
distension may interfere with normal
parturition. In defects of the large intestine,
distension usually occurs after birth. In
these the anus is normal and the part of
the intestine caudal to the obstructed
section may be normal or absent. The
principal clinical findings are depression,
anorexia and abdominal distension.
Frequently the owner has not seen the
calf pass meconium or feces. Thick mucus
may be passed through the anus if it is
patent or through the vagina in heifers
with concomitant rectovaginal fistula. In
many cases the animal has not sucked
since the first day and 5-6- day-old
animals are very weak and recumbent.
The intestine may rupture and acute
diffuse peritonitis develop. Intestinal
segmental atresia has been produced
experimentally by occluding the blood
supply to the intestine in fetal lambs. In
one large series of congenital defects in
calves the most common site of atresia
was the mid-portion of the spiral loop of
colon. 12 The passage of a rectal tube or the
infusion of barium and radiography may
assist in the detection of atresia of
the intestine. There are usually large
quantities of thick tenacious mucus in the
rectum with no evidence of meconium or
feces. In the latter case only exploratory
laparotomy can reveal the extent and
nature of the defect. 13 The differential
diagnosis of atresia coli in calves includes
acute intestinal obstructions such as
volvulus and intussusception, diffuse
peritonitis and septicemia. The presence
of feces in the rectum rules out the
presence of atresia coli.

Surgical repair appears to be a satis-
factory outcome in 30-50% of cases. 14 In a
series of intestinal atresia in calves
admitted to a veterinary teaching hospital
over a period of 10 years, the survival rate
was influenced by the atretic segments
affected. 15 In a series of 58 cases of intes-
tinal atresia in calves, seven of 18 cases
corrected surgically made a satisfactory
recovery; the remaining 40 calves were
euthanized for different reasons. 16

The incidence of atresia coli in foals
has been reported at 0.44% of foals under
2 weeks of age admitted to veterinary
teaching hospitals over a period of
27 years. 17 Clinical findings included pro-
gressive abdominal distension, colic, lack
of feces and lack of response to enemas. A
neutropenia may reflect the presence of
toxemia. The large transverse and/or
small colon is commonly involved.
Agenesis of the mesocolon in a 1-month-
old foal with colic has been described. 18
The prognosis for most cases is grave and
surgical correction is usually unsuccessful.

The common causes of colic in new-
born foals include ileus with or without

gas distension, intussusception, diaphrag-
matic hernia, gastroduodenal ulcers,
necrotizing enterocolitis, small and large
intestinal strangulation, large intestine
displacement, intraluminal obstruction
other than meconium, ruptured bladder
and congenital abnormalities of the
gastrointestinal tract.

MULTIPLE ORGAN DEFECTS

In many animals the congenital defects of
the intestine are accompanied by defects
in other organs, 8 ' 12 especially the lower
urinary tract, so that reparative surgery is
not possible. For example multiple gut
and urogenital defects are recorded in one
calf 19 and gut defects plus defects of the
pancreas and gallbladder in another. 20

Congenital constriction of the anus
and vagina is an inherited defect of Jersey
cattle and is recorded under that heading.
The defect may be combined with recto-
vaginal fistula manifested by the passage
of feces via the vulva or penile urethra. 21

REVIEW LITERATURE

Syed M, Shanks RD. Cornell Vet 1993; 83:261.

REFERENCES

1. Griffith J W et a I . J Comp Pathol 1987; 97:95.

2. Gift LJ et al. J Am Vet Med Assoc 1992; 200:715.

3. Crouch GM et al. Compend Contin Educ 1983;
5:S706.

4. MeeJF. Irish Vet J 1994; 47:63.

5. Cho DY, Taylor HW. Cornell Vet 1986; 76:11.

6. Young RL et al. Equine Vet J 1992; 24:60.

7. \&nderfecht SL et al.\fet Fhthol 1983; 20:65.

8. Anderson W1 et al. CornellVet 1987; 97:119.

9. Syed M, Shanks RD. J Dairy Sci 1992; 75:1357.

10. Syed M, Shanks RD. J Dairy Sci 1992; 75:1105.

11. Syed M, Shanks RD. CornellVet 1993; 83:261.

12. Ducharme NG et al. Can Vet J 1988; 29:818.

13. Constable PD et al. J Am Vet Med Assoc 1989;
195:118.

14. Smith DF et al. J Am Vet Med Assoc 1991;
199:1185.

15. Diyfuss DJ, Tulleners EP. J Am \fet Med Assoc
1989; 195:508.

16. Martens A et al. Vet Rec 1995; 136:141.

17. Nappert G et al. Equine Vet J Suppl 1992; 13:57.

18. Steinhaut M et al. \£t Rec 1991; 129:54.

19. Dunham BM et al. Vet Pathol 1989; 26:94.

20. Kramme PM. Vet Pathol 1989; 26:346.

21. Kingston RS, Park RD. Equine Pract 1982; 4:32.

Neoplasms of the
alimentary tract

MOUT H

Oral neoplasms in ruminants, other than
viral papillomas, may be associated with
heavy bracken intake. The tumors are
usually squamous cell carcinomas arising
from the gums and cause interference
with mastication. They occur most com-
monly in aged animals and probably arise
from alveolar epithelium after periodontitis
has caused chronic hyperplasia. Sporadic
occurrences of other tumors, e.g. adeno-

carcinoma, cause obvious local swelling
and dysphagia.

PHARYNX ANDJSOPHAGUS

Fhpillomas sometimes involve the pharynx,
esophagus, esophageal groove and
reticulum and cause chronic ruminal
tympany in cattle. A high incidence of
malignant neoplasia affecting the pharynx,
esophagus and rumen has been recorded
in one area in South Africa. The tumors
were multicentric in origin and showed
evidence of malignancy on histological
examination. The clinical disease was
chronic and confined to adult animals
with persistent, moderate tympany of the
rumen and progressive emaciation as
typical signs. A similar occurrence has
been recorded in cattle in western
Scotland and related to the long-term
consumption of bracken. The tumors
were squamous cell carcinoma in the
pharynx and dorsal esophagus. The prin-
cipal clinical abnormality was difficulty in
eating and swallowing. Many of the
carcinomas arise in pre-existing papillomas,
which are associated with a virus infec-
tion. The carcinomas occur only in cattle
more than 6 years of age.

STOM ACH AND RU MEN

Squamous cell carcinomas occasionally
develop in the mouth and stomach of
horses and the rumen of cattle. In the
stomach of the horse, they occur in the
cardiac portion and may cause obscure
indigestion syndromes, lack of appetite,
weight loss, anemia, obstruction of the
lower esophagus, 1 dysphagia, colic and
Occasionally chronic diarrhea. Or a tumor
may ulcerate to terminate with perfor-
ation of the stomach wall and the develop-
ment of peritonitis. Metastases may spread
to abdominal and thoracic cavities with
fluid accumulating there. Subcutaneous
edema is a common accompanying sign.
There may also be pleural effusion due to
metastases in the pleura. 2 Metastases
in the female genital tract have also
been noted. Most affected animals are
euthanized because of anorexia and
chronic weight loss. Large masses of
metastatic tumor tissue may be palpable
on rectal examination. In such cases an
examination of paracentesis fluid sample
cells should be valuable.

Lymphosarcoma in horses is often
manifested by chronic diarrhea due to
massive infiltration of the intestinal wall.
There is severe weight loss, even in the
absence of diarrhea in some cases, usually
a large appetite and often severe ascites,
and anasarca and sometimes colic. The
same signs are recorded in a case of
mesothelioma in a horse. The oral glucose
absorption test is abnormal with a poor

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

absorption response. Rectal examination |
may reveal large masses of hard nodular ;
tissue and hematological examination j
-may be of assistance in diagnosis. Fhra-
centesis and examination of cells in the
fluid for the presence of mitotic figures is
an essential part of an examination in
suspected cases of neoplasia in the ;
abdominal cavity. Nasal fibergastroscopy \
is an obvious technique for visualizing j
this tumor but suffers the limitation that j
standard instruments are not long j
enough. 3 The course of this disease in ;
horses is very variable, with the period of !
illness lasting from 3 weeks to 3 months. I

Ruminal tumors may obstruct the
cardia and cause chronic tympany. In
lymphomatosis of cattle, there is fre- j
quently gross involvement in the abo-
masal wall causing persistent diarrhea.
Ulceration, hemorrhage and pyloric
obstruction may also occur.

INTESTINES

A higher than normal rate of occurrence
of carcinoma of the small intestine has
been recorded in sheep in Iceland,
Norway 4 and New Zealand and in cows
only in New Zealand. 5 A series of
intestinal carcinomas is also recorded in
Europe, and another series in Australia. 6
The tumors in the Australian series were
located at abattoirs and were causing
intestinal stenosis. Metastasis to regional
lymph nodes occurred readily. In New
Zealand there appeared to be a much
higher prevalence in British-breed ewes
(0.9-0.15%) compared to Merino and
Corriedale ewes (0.2-0. 4%), and signifi-
cantly higher tumor rates were observed
in sheep that had been pastured on
foodstuffs sprayed recently with phenoxy
or picolinic acid herbicides. 7 The use of
the herbicides 2,4-D, 2,4,5-T, MCPA,
piclorum and clopyralid has been
associated with an increased incidence of
these tumors. A higher prevalence in
sheep kept at higher stocking rates was
also suggested.

Occasional tumors of the intestine are
recorded in abattoir findings but they can
cause clinical signs such as chronic bloat
and intermittent diarrhea 8 in cattle,
persistent colic due to partial intestinal
obstruction in horses 9 and anorexia and a
distended abdomen in sheep. 40 A series of
cases of lymphoma in horses were
characterized by malabsorption without
diarrhea but with anemia in some. 41

Occasional tumors recorded as causing
colic in horses include an intramural
ganglioneuroma occluding the jejunum, 42
an intraluminal leiomyoma causing an
intussusception of the small colon, 43 a
granulosa cell tumor of an ovary causing
external pressure and occlusion of a small

colon. 44 A juvenile granulosa cell tumor in j
a weanling filly caused a fatal volvulus j
and severe continuous colic. 45 Anorexia, j
weight loss, abdominal distension, con- i
stant chewing and swallowing movements |
are the prominent signs in gastric j
leiomyoma 46 and squamous cell j
carcinoma. 47 Metastases in the peritoneal
cavity are palpable in some cases.
Leiomyosarcomas have caused chronic
intermittent colic due to constriction of
the duodenum and partial intestinal
obstruction. 48 A colonic adenocarcinoma
has caused weight loss, intermittent colic,
poor appetite and scant feces and a mass |
palpable in the abdomen. 49

Tumors of the anus are rare: a j
mucoepidermoid carcinoma is recorded I
in a goat 20 but most tumors of the j
perineal area are anogenital papillomata.

REFERENCES

1. Tennant B et al. Equine Vet J 1982; 14:238.

2. Wrigley RR et al. Equine Vet J 1981; 13:99.

3. Keim DPet al. JAmVet Med Assoc 1982; 180:940.

4. Ulvund M. NZVet J 1983; 31:177.

5. Johnstone AC et al. NZVet J 1983; 31:147.

6. RossAD.AustVetJ 1980; 56:25.

7. Newell KW et al. Lancet 1984; 2:1301.

8. Cho DY, Archibald LF. Vet Fhthol 1985; 22:639.

9. Wright JA, Edwards GB. Equine Vet J 1984;
16:136.

10. Anderson BC. J Am Vet Med Assoc 1983; 183:
1467.

11. Platt H. J Comp Fhthol 1987; 97:1.

12. Allen D et al. Cornell Vet 1989; 79:133.

13. MairTS et al.Vet Rec 1992; 132:403.

14. Wilson DA et al. J Am Vht Med Assoc 1989;
194:681.

15. Hultgren BD et al. J Comp Rrthol 1987; 97:137.

16. Boy MG et al. JAmVet Med Assoc 1992; 200:1363.

17. Olsen SN.Vet Rec 1992; 131:170.

18. MairTS et al. J Comp Fhthol 1990; 102:119.

19. Rottman JB et al. J Am Vfet Med Assoc 1991;
198:657.

20. Turk JR et al.Vet Fhthol 1984; 21:364.

Diseases of the peritoneum

PERITONITIS

Inflammation of the peritoneum is
accompanied by abdominal pain, fever,
toxemia and a reduction in the amount of
feces. Symptoms vary in degree with the
severity and extent of the peritonitis.

ETIOLOGY

Peritonitis may occur as a primary disease
or secondarily as part of an etiologically
specific disease. As a primary disease it
results most commonly from injury of the
serosal surfaces of the alimentary tract
within the abdomen, allowing gastro-
intestinal contents to enter the peritoneal
cavity. Less commonly there is perforation
of the abdominal wall from the exterior
from traumatic injury, perforation of the
reproductive tract, or the introduction of
pathogens or irritating substances as
result of injections into the peritoneal

cavity or exploratory laparotomy. Some of
the more common individual causes are
as follows.

Cattle

3 Traumatic reticuloperitonitis
- Secondary to ruminal trocarization
° Perforation or leakage of abomasal
ulcer

« Concurrent abomasal displacement
and perforating ulcer 1
3 Necrosis and rupture of abomasal
wall after abomasal volvulus
° Rumenitis of cattle subsequent to
acute carbohydrate indigestion
3 Complication of caesarean section
3 Rupture of vagina in young heifers
during violent coitus with a young,
active bull

° Deposition of semen into the
peritoneal cavity by any means
’ Injection of sterile hypertonic
solutions, e.g. calcium preparations
for milk fever. The chemical peritonitis
that results may lead to formation of
constrictive adhesions between loops
of the coiled colon
Transection of small intestine that
becomes pinched between the
uterus and the pelvic cavity at
parturition

Intraperitoneal injection of nonsterile
solutions

Spontaneous uterine rupture during
parturition, or during manual
correction of dystocia
Sadistic rupture of vagina
Spontaneous rupture of rectum at
calving 2

As part of specific diseases such as
tuberculosis.

Horses

Peritonitis in horses is usually secondary
to infectious, chemical, or parasitic perito-
neal injuries, and can be a major compli-
cation after abdominal surgery. 3

Rupture of dorsal sac of cecum or
colon 4 at foaling, usually related to a
large meal given just beforehand
Cecal rupture in foals subjected to
anesthesia and gastric endoscopy 5
Administration of NSAIDs causing
cecal stasis and dilatation and
eventually perforation 6
Rectal rupture or tear during rectal
examination, predisposed to by
inflammation of mucosa and
overenthusiasm by the operator; this
subject is presented separately under
the heading of rectal tear
Extension from a retroperitoneal
infection, e.g. Streptococcus equi after
an attack of strangles, Rhodococcus
equi in foals under 1 year of age, both
probably assisted by migration of
Strongylus vulgaris larvae

«* Gastric erosion or rupture related to
ulceration associated with larvae of
Gasterophilus or Habronema spp.
n Colonic perforation associated with
aberrant migration of Gasterophilus
intestinalis 7

o Leakage from a cecal perforation
apparently associated with a heavy
infestation of Anoplocephala perfoliata
tapeworms

° Spontaneous gastric rupture
° Actinobacillus equuli infection by
unknown means. 8,9 Septicemia and
peritonitis due to A. equuli infection in
an adult horse has been described. 10

Pigs

Ileal perforation in regional ileitis
* Glasser's disease associated with
Haemophilus suis.

Sheep

4 Spread from intestinal wall abscess
following infestation with
Esophagostomum sp. larvae
Serositis- arthritis associated with
Mycoplasma sp.

Goats

- Serositis- arthritis associated with
Mycoplasma sp.

All species

Traumatic perforation from the
exterior of the abdominal wall by
horn gore, stake wound

- Faulty asepsis at laparotomy,
peritoneal injection, trocarization for
tympany of rumen or cecum
Leakage through wall of infarcted gut
segment

Spread from subperitoneal sites in
spleen, liver, umbilical vessels.

PATHOGENESIS

At least six factors account for the clinical
findings and the various consequences of :
peritonitis. They are toxemia or septicemia, \
shock and hemorrhage, abdominal pain, ;
paralytic ileus, accumulation of fluid
exudate and the development of adhesions, i

Toxemia and septicemia

Toxins produced by bacteria and by the
breakdown of tissue are absorbed readily
through the peritoneum. The resulting j
toxemia is the most important factor in
the production of clinical illness and its
severity is usually governed by the size of
the area of peritoneum involved. In acute
diffuse peritonitis, the toxemia is pro- ;
found; in local inflammation, it is negligible.
The type of infection present is obviously
important because of variations between
bacteria in their virulence and toxin
production. j

With rupture of the alimentary tract j
wall and the spillage of a large quantity of
gut contents into the peritoneal cavity,
some acute peritonitis does develop, but

Diseases of the peritoneum

283

death is usually too sudden, within
2-3 hours in horses, for more than an
early lesion to develop. These animals die
of endotoxic shock due to absorption of
toxins from the gut contents. In acute
diffuse peritonitis due solely to bacterial
contamination from the gut, the reaction j
depends on the bacteria that gain entry j
and the capacity of the omentum to deal j
with the peritonitis, and the amount of j
body movement that the animal has to !
perform. Cows that suffer penetration of
the reticular wall at calving have lowered
immunological competence, a greater
than normal negative pressure in the
peritoneal cavity, are invaded by
F. necrophorum, Corynebacterium spp. and
E. coli, and are required to walk to the
milking parlor, to the feed supply and so
on. They are likely to develop a massive
j diffuse purulent peritonitis and a pro-
found toxemia and die within 24 hours.
By contrast, horses that develop acute
peritonitis due to streptococci or A. equuli
show little toxemia and manifest only
abdominal pain due to the inflammatory
reaction of the peritoneum.

Shock and hemorrhage

The shock caused by sudden deposition
of gut contents, or infected uterine con-
tents, into the peritoneal cavity, plus the
hemorrhage resulting from the rupture,
may be significant contributors to the
common fatal outcome when an infected
viscus ruptures. Following rupture of the
uterus in cows, the shock and hemor-
rhage may be minor and peritonitis may
not develop if the uterine contents are not
contaminated. Failure of the uterus to
heal or be repaired may be followed by
peritonitis several days later.

Abdominal pain

Abdominal pain is a variable sign in
peritonitis. In acute, diffuse peritonitis,
the toxemia may be sufficiently severe to
depress the response of the animal to
pain stimuli, but in less severe cases the
animal usually adopts, an archcd-back
posture and shows evidence of pain on
palpation of the abdominal wall. Inflam-
mation of the serous surfaces of the
peritoneum causes pain, which may be
severe enough to result in rigidity of the
abdominal wall and the assumption of an
abnormal humped-up posture.

Paralytic ileus

Fhralytic ileus occurs as a result of reflex
inhibition of alimentary tract tone and
movement in acute peritonitis. It is also
an important sequel to intestinal obstruc-
tion and to traumatic abdominal surgery,
in which much handling cf viscera is :
unavoidable. Rarely, it arises because of j
ganglionitis and a loss of neural control of ;
peristalsis, similar to the idiopathic intes-

| tinal pseudo- obstruction of humans. 11
[ The net effect is functional obsfruction
of the intestine, which, if persistent, will
increase the likelihood of death. The end
result is a complete absence of defecation,
often with no feces present in the rectum.

Accumulation of fluid exudate

Accumulation of large quantities of
inflammatory exudate in the peritoneal
cavity may cause visible abdominal
distension and, if severe enough, interfere
| with respiration by obstruction of diaphrag-
matic movement. It is a comparatively rare
occurrence but needs to be considered in
the differential diagnosis of abdominal
distension.

Adhesions

Trauma to the peritoneum results in a
serosanguineous exudate, which contains
two closely bound proteins: fibrinogen
and plasminogen. Fibrinogen is con-
! verted by thrombin to fibrin, forming an
early fibrinous adhesion. Plasminogen
j may be converted by plasminogen acti-
j vators to plasmin, a specific fibrinolytic
; enzyme favoring lysis of the early
j adhesion. Peritoneal mesothelial cells are
! a source of plasminogen activators and
’ each species of domestic animal has its
own baseline peritoneal plasminogen
i activity. Cattle have a high capacity to
; respond to trauma with fibrin deposition. 6
i Intra -abdominal fibrin deposition and
adhesion formation is the most important
| factor in localizing peritonitis after
peritoneal trauma from penetrating
j foreign bodies or abomasal ulcers. How-
ever, these adhesions can cause mechanical
1 or functional intestinal obstruction.

In chronic peritonitis, the formation
I of adhesions is more important than
! either of the two preceding pathogenetic
! mechanisms. Adhesions are an essential
: part of the healing process and are
i important to localize the inflammation to
j a particular segment of the peritoneum. If
' this healing process is developing satis-
i factorily and the signs of peritonitis are
i diminishing, it is a common experience to
; find that vigorous exercise causes break-
j down of the adhesions, spread of the
i peritonitis and return of the clinical signs,
j Thus, a cow treated conservatively for
traumatic reticuloperitonitis by immobil-
ization may show an excellent recovery by
the third day but, if allowed to go out to
pasture at this time, may suffer an acute
relapse. The secondary adverse effects of
adhesions may cause partial or complete
obstruction of the intestine or stomach,
or by fixation to the body wall interfere
with normal gut motility. Adhesions are
important in the pathogenesis of vagus
indigestion in cattle.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

CLINICAL FINDINGS

Peritonitis is common in cattle, less com-
mon in horses and rarely, if ever,
identified clinically in sheep, pigs or goats.
There are general signs applicable to all
species and most forms of the disease in a
general way. In addition, there are special
findings peculiar to individual species and
to various forms of the disease.

Acute and subacute peritonitis

Inappetence and anorexia
Inappetence occurs in less severe and
chronic cases, and complete anorexia in
acute diffuse peritonitis.

Toxemia and fever

Toxemia, usually with a fever, is often
present but the severity varies depending
on the area of peritoneum involved, the
identity of the pathogens and the amount
of tissue injury. For example, in cattle with
acute local peritonitis the temperature
will be elevated (39.5°C; 103°F) for the
first 24-36 hours, but then return to
normal even though the animal may still
be partly or completely anorexic. A high
fever (up to 41.5°C; 106°F) suggests an
acute diffuse peritonitis, but in the
terminal stages the temperature usually
falls to subnormal. It is most noteworthy
that a normal temperature does not
preclude the presence of peritonitis. In
horses with peritonitis, the temperature
will usually exceed 38.5°C but the fever
may be intermittent. 12 There is usually a
moderate increase in heart and respir-
atory rates, the latter contributed to by the
relative fixation of the abdominal wall
because of pain. In some cases there is
spontaneous grunting at the end of each
expiratory movement.

Feces

The amount and composition of feces
is usually abnormal. The transit time of
ingesta through the alimentary tract is
increased and the dry matter content of
the feces increases. The amount of feces is
reduced, although in the early stages
there may be transient period of increased
frequency of passage of small volumes of
soft feces, which may give the false
impression of increased fecal output. In
some horses with peritonitis, periods of
diarrhea may occur but the feces are
usually reduced in amount. 12 Feces may
be completely absent for periods of up to
3 days, even in animals that recover, and
the rectum may be so dry and tacky,
because of the presence of small amounts
of tenacious mucus, that it is difficult to
do a rectal examination. This may suggest
a complete intestinal obstruction.

In pastured cattle with peritonitis the
feces are characteristically scant, dark and
like small fecal balls accompanied by
thick, jelly-like mucus. The feces may alter-

natively have a thick, sludge-like con-
sistency, be tenacious and difficult to
remove from a rubber glove, and have a
foul smell.

Alimentary tract stasis
As well as absence of feces, there are
other indicators of intestinal stasis. In
cows with acute peritonitis ruminal con-
tractions are reduced or absent; in chronic
peritonitis the contractions may be
present but are weaker than normal. In
the horse, intestinal stasis is evidenced by
an absence or reduction of typical intes-
tinal peristaltic sounds on auscultation,
although the tinkling sounds of paralytic
ileus may be audible. It is very important
to differentiate the two.

Abdominal pain evidenced by posture
and movement

In cattle with acute peritonitis there is a
disinclination to move, disinclination to
lie down, lying down with great care and
grunting with pain. The posture includes j
a characteristically arched back, the gait is
shuffling and cautious, with the back held
rigid and arched. Grunting at each step
and when feces or urine are passed is
common, and when urine is eventually
passed it is usually in a very large volume.
Sudden movements are avoided and
there is an absence of kicking or bellow-
ing or licking the coat.

In horses these overt signs of peritonitis
that characterize the condition in cattle
are uncommon, which makes the diag-
nosis difficult. In the horse peritonitis
is often manifested as an episode of
abdominal pain including flank watching,
kicking at the belly and going down and
rolling, which suggests colic caused by
intestinal obstruction. 8,11

In a series of 51 cases of peritonitis
associated with A. equuli in horses, most
had tachycardia, increased respiratory
rates, fever and reduced intestinal
borborygmi. 9 Affected horses were
depressed, lethargic and inapparent. Mild
to moderate abdominal pain was mani-
fested as reluctance to move, pawing on
the ground, lying down or splinting of
the abdominal musculature. The onset
of clinical signs was acute (<24h) in
30 horses, 1-4 days in 8 horses, or longer
and associated with weight loss in
3 horses. In 10 horses, there was no
record of the duration of clinical signs.

Abdominal pain as evidenced by deep
palpation

In cattle, deep firm palpation of the
abdominal wall elicits an easily recognized
pain response. It may be possible to elicit
pain over the entire abdominal wall if the
peritonitis is widespread. If it is localized
the response may be detectable over only
a very small area. Increased tenseness of

the abdominal wall is not usually detect-
able in the cow, although it is responsible
for the characteristic arched-back posture
and apparent gauntness of the abdomen,
because the wall is already tightly
stretched anyway.

Several methods are used to elicit a
grunt in cattle with abdominal pain. In
average-sized cows with acute local
peritonitis (most commonly traumatic
reticuloperitonitis), while listening over
the trachea with a stethoscope, a con-
trolled upward push with the closed fist of
the ventral body wall caudal to the
xiphoid sternum is most successful. In
large bulls, especially if the peritonitis is
subsiding, it may be difficult to elicit a
grunt with this method. In these cases,
the best technique is to use a heavy pole
held horizontally under the area imme-
diately caudal to the xiphoid sternum to
provide a sharp lift given by assistants
holding the pole on either side. Pinching
of the withers while auscultating over
the trachea is also used and with some
clinical experience is highly reliable.

In horses with acute or subacute
peritonitis, it is usually easy to elicit a pain
response manifested by the animal lifting
its leg and turning its head with anger
when its lower flank is firmly lifted, but
not punched. The abdominal wall also
feels tense if it is lifted firmly with the heel
of the hand. In all cases of peritonitis in all
species a pain response is always much
more evident in the early stages of the
disease and severe chronic peritonitis can
be present without pain being detected
on palpation.

Rectal examination

The general absence of feces is charac-
teristic. In cattle, it may be possible to
palpate slightly distended, saggy, thick-
walled loops of intestine in some cases.
Also, it may be possible to feel fibrinous
adhesions separating as the intestines are
manipulated. Adhesions are not often
palpable and their absence should not be
interpreted as precluding the presence of
peritonitis. Only adhesions in the caudal
part of the abdomen may be palpable.
Tough, fibrous adhesions may be present
in long-standing cases. In horses, there
are no specific rectal findings, other than
a reduced fecal output, to indicate the
presence of peritonitis. Distension of seg-
ments of both the small and large
intestines may provide indirect evidence
of paralytic ileus. However, there is a lack
of clarity as to what can be felt in chronic
cases because of the presence of fibrin
deposits and thickening of the peritoneum.
There may also be more than usual
pain when an inflamed area is palpated
or a mesenteric band or adhesion is
manipulated.

In rupture of the rectum associated with
a difficult dystocia, the rupture is usually
easily palpable rectally in the ventral
aspect of the rectum deep in the abdomen. 2
Distended loops of intestine may become
entrapped in the rectal tear.

Peracute diffuse peritonitis

In those cases in which profound toxemia
occurs, especially in cows immediately
after calving or when rupture of the
alimentary tract occurs, the syndrome is
quite different. There is severe weakness,
depression and circulatory failure. The
animal is recumbent and often unable to
rise, depressed almost to the point of
coma, has a subnormal temperature of
37-37.5°C (99-100°F), a high heart rate
(110-120/min) and a weak pulse. No
abdominal pain is evidenced sponta-
neously or on palpation of the abdominal
wall. In mares that rupture the dorsal sac
of the cecum during foaling, the owner
observes that the mare has been straining
and getting results when suddenly she
stops making violent muscular contrac-
tions, and progress towards expelling the
foal ceases. 13 Moderate abdominal pain
followed by shock are characteristic
developments. Death follows 4-15 hours
after the rupture.

The outcome in cases of acute, diffuse
peritonitis varies with the severity. Peracute
cases accompanied by severe toxemia
usually die within 24-48 hours. The more
common, less severe cases may be fatal in
4-7 days, but adequate treatment may
result in recovery in about the same
length of time.

In a series of 31 cases of generalized
peritonitis in cattle most cases occurred
peripartum. 14 The most consistent clinical
findings were depression, anorexia,
decreased fecal outpu t and varying degrees
of dehydration. The duration of illness
ranged from 1-90 days with a median of
4 days. In 19 animals, the duration of
clinical disease was less than 1 week and
in 12 cases the duration of illness was
more than 1 week. All animals died or
were euthanized.

Chronic peritonitis

Cattle

The development of adhesions, which
interfere with normal alimentary tract
movements, and gradual spread of infec-
tion as adhesions break down combine to
produce a chronic syndrome of indigestion
and toxemia that is punctuated by short,
recurrent attacks of more severe illness.
The adhesions may be detectable on
rectal examination but they are usually
situated in the anterior abdomen and are
impalpable. If partial intestinal obstruction
occurs, the bouts of pain are usually
accompanied by a' marked increase in
alimentary tract sounds and palpable

Diseases of the peritoneum

distension of intestinal loops with gas and
fluid. The course in chronic peritonitis
may be several weeks and the prognosis
is not favorable because of the presence of
physical lesions caused by scar tissue and
adhesions. In some cases there is marked
abdominal distension with many liters of
turbid -infected fluid present. This may be
restricted in its location to the omental
bursa. 15 Detection of fluid in the peri-
toneal cavity of a cow is not easy because
of the fluid nature of the ruminal con-
tents. Results obtained by testing for a
fluid wave should be interpreted cautiously.
Collection of fluid by paracentesis
abdominis is the critical test.

Horses

Horses with chronic peritonitis usually
have a history of ill-thrift for a period of
several weeks. Weight loss is severe and
there are usually intermittent episodes of
abdominal pain suggesting intestinal
colic. Gut sounds are greatly diminished
or absent, and subcutaneous edema of
the ventral abdominal wall occurs in
some cases. There may also be a con-
tiguous pleurisy. Identification of the
cause of the colic depends on the examin-
ation of a sample of peritoneal fluid.

Diagnostic medical imaging

In cattle with traumatic reticuloperitonitis,
inflammatory fibrinous changes, and
abscesses can be imaged 16 (see also Ch. 6).

In cattle, standing reticular radiography
is a useful aid for the diagnosis and
management of traumatic reticulo-
peritonitis. 5 It can accurately detect the
presence of a foreign body and in most
instances if that foreign body is perforating
the reticular wall.

CLINICAL PATHOLOGY
Hematology

The total and differential leukocyte count
is a useful aid in the diagnosis of
peritonitis and in assessing its severity. In
acute diffuse peritonitis with toxemia
there is usually a leukopenia, neutropenia
and a marked increase in immature
neutrophils (a degenerative left shift).
There is 'toxic' granulation of neutrophils.
In less severe forms of acute peritonitis of
a few days' duration there may be a
leukocytosis due to a neutrophilia with
the appearance of immature neutrophils.
In acute local peritonitis, commonly seen
in acute traumatic reticuloperitonitis in
cattle, there is commonly a normal total
leukocyte count, or a slight increase, with
regenerative left shift. In chronic peritonitis,
depending on the extent of the lesion
(diffuse or local), the total and differential
leukocyte count may be normal, or there
may be a leukocytosis with a marked
neutrophilia and occasionally an increase
in the total numbers of lymphocytes and

monocytes. The plasma fibrinogen levels
in cattle, in general, tend to increase as
the severity of acute peritonitis increases
and may be a useful adjunct to the cell
counts for assessing severity. 5

In horses with peritonitis associated
with A. equuli, there was hemoconcen-
tration, hypoproteinemia and a neutrophilia
count with a left shift.

Abdominocentesis and peritoneal
fluid

Examination of peritoneal fluid obtained
by paracentesis is a valuable aid in the
diagnosis of peritonitis and in assessing
its severity. It may also provide an indi-
cation of the kind of antibacterial treat-
ment required. The values in healthy
horses, and horses with various intestinal
or peritoneal diseases are provided in
Table 5.2. The maximum peritoneal fluid
nucleated cell counts in healthy foals is
much lower than reported maximum
values for adult horses 17 and similarly
for calves. Particular attention should be
paid to:

° The ease of collection of the sample
as a guide to the amount of fluid
present

° Whether it is bloodstained, indicating
damage to a wall of the viscus
° The presence of feed or fecal material,
indicating intestinal ischemic necrosis
or rupture

° Whether it clots and has a high
protein content, indicating
inflammation rather than simple
transudation

0 The number and kinds of leukocytes
present, as an indication of the
presence of inflammation, and also its
duration

° Microbiological examination.

When these results are available they
should be interpreted in conjunction with
the history, clinical signs and other results,
including hematology, serum chemistry
and possibly radiology. In particular, it
must be noted that failure to obtain a
sample does not preclude a possible diag-
nosis of peritonitis.

Interpretation of peritoneal fluid is also
influenced by simple manipulation of the
abdominal viscera and the response is
greater than that following opening and
closing of the abdomen without mani-
pulation of the viscera. Surgical mani-
pulation results in a significant and rapid
postoperative peritoneal inflammatory
reaction. 11

In peritonitis in horses associated with
A. equuli, the peritoneal fluid was turbid
and had an abnormal color in 98% of
cases. The protein content was elevated
above normal in 50 samples (range
25-84 g/L, mean 44 g/L, normal < 20 g/L).

286

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

Total nucleated celLcount was elevated in
all samples (range 46-810 x 10 9 cells/L,
mean 230 x 10 9 cells/L, normal < 10 x 10 9
cells/L). A nucleated cell count above
100 x 10 9 cells/L, was present in 88% of
animals. 9 Pleomorphic Gram-negative
rods were seen on cytology in 53% of
samples, and a positive culture of A equuli
was obtained in 72% of samples.

Experimentally, resection and anasto-
mosis of the small colon in healthy horses
causes a different inflammatory response
than does manipulation. Absolute values
in the peritoneal fluid for cell count, total
protein and differential count are in-
adequate to differentiate between a normal
surgical reaction and a postoperative
infection. Cytological examination of
peritoneal fluid is necessary to demon-
strate degenerative cell changes and the j
presence of bacteria and ingesta. The I
peripheral leukon and fibrinogen concen-
tration should always be compared with
the peritoneal fluid for evidence of post-
surgical infection. The nucleated cell and
red blood counts of peritoneal fluid are
commonly elevated for several days in
horses following open castration. 10 These
elevated counts may be mistaken for
peritonitis.

Septic peritonitis in the horse
Diagnosis of septic peritonitis is routinely
made on the basis of physical examin-
ation and hematologic findings, and
peritoneal fluid analysis. 18 After abdominal
surgery, differentiation between septic
peritonitis and other postoperative com-
plications can be difficult using physical
and hematological findings alone. As a
result of the exploratory process itself,
diagnosis of septic peritonitis is often
complicated in horses after surgery
because the total nucleated cell count and
protein concentration in the peritoneal
fluid are often high. Consequently, identi-
fication of bacteria on cytological evaluation
or isolation of bacteria from peritoneal
fluid is a more definitive indicator of
septic peritonitis, but sometimes there are
false-negative results. Although bacterial
cultures are considered the standard
criterion for the diagnosis of sepsis, posi-
tive results may not always be obtained
and results may be delayed by a minimum
of 24 hours for aerobic organisms and up to
10-14 days for anaerobic organisms. Thus
ancillary tests such as pH, glucose con-
centrations and lactate dehydrogenase
(LDH) activity in equine pleural and
synovial fluid have been used to detect
sepsis with the potential advantages of
speed, ease of measurement and lower
cost relative to bacterial cultures. 18

Horses with septic peritonitis have
significantly lower peritoneal fluid pH
and glucose concentrations than horses

with nonseptic peritonitis and healthy
horses. 18 Compared with other tests,
serum-to-peritoneal fluid glucose con-
centration differences of more than
50 mg/dL had the highest diagnostic use
for detection of septic peritonitis. Peritoneal
fluid pH below 7.3, glucose concentration
below 30 mg/dL and fibrinogen concen-
tration above 200 mg/dL were also highly
indicative of septic peritonitis.

NECROPSY FINDINGS

In acute diffuse peritonitis, the entire
peritoneum is involved but the most
severe lesions are usually in the ventral
abdomen. Gross hemorrhage into the
subserosa, exudation and fibrin deposits
in the peritoneal cavity and fresh
adhesions that are easily broken down are
present. In less acute cases, the exudate is
purulent and may be less fluid, often
forming a thick, cheesy covering over
most of the viscera. In cattle,
F. necrophorum and Actinomyces
(Corynebacterium) pyogenes are often
present in large numbers and produce a
typical, nauseating odor. Acute local
peritonitis and chronic peritonitis are not
usually fatal and the lesions are dis-
covered only if the animal dies of inter-
current disease such as traumatic peri-
! carditis or intestinal obstruction.

DIAGNOSIS

The diagnosis of peritonitis can be diffi-
cult because the predominant clinical
findings are often common to other
i diseases. The clinical features that are the
most reliable as indicators of peritonitis
are:

■ Abnormal feces - in amount and
composition

Alimentary tract stasis based on
auscultation and evaluation of the
passage of feces

Abdominal pain evinced as a groan
with each respiration or on light or
deep percussion of the abdomen
" Abnormality of intestines on rectal
palpation

Fibrinous or fibrous adhesions on
rectal palpation

Abnormal peritoneal fluid with an
increased leukocyte count collected by
paracentesis

A normal or low blood leukocyte
count with a degenerative left shift
The peritonitis may be chemical, so
that, although microbiological
examination usually yields positive
results, these are not essential to a
diagnosis of peritonitis.

PROGNOSIS

Case fatality rate in horses

Peritonitis in the horse is a potentially
life-threatening disease that must be
treated promptly and aggressively. 20

DIFFERENTIAL DIAGNOSIS

The diseases which could be considered in

the differential diagnosis of peritonitis are

as follows.

Cattle

• Acute local peritonitis - Traumatic
reticuloperitonitis, acute intestinal
obstruction, splenic or hepatic abscess,
simple indigestion, abomasal
displacement (right and left),
postpartum metritis, ketosis

• Acute diffuse peritonitis - Parturient
paresis, coliform mastitis (peracute
form), acute carbohydrate indigestion,
perforation of or rupture at abomasal
ulcer, acute intestinal obstruction,
uterine rupture, postpartum metritis

• Chronic peritonitis - Vagus
indigestion, lipomatosis or extensive fat
necrosis of the mesentery and
omentum, persistent minor leakage
from an intestinal lesion, large
accumulations of fluid as in ascites,
rupture of bladder, chronic pneumonia
and chronic toxemias due to a great
variety of causes

• Ascites associated most commonly with
primary or secondary cardiac disease,
cor pulmonale with chronic pneumonia,
endocarditis, thrombosis of the caudal
vena cava, and diffuse abdominal
epithelioid mesothelioma 19

Horses

• Acute and subacute peritonitis -

Acute intestinal obstruction and
thromboembolic colic

• Chronic peritonitis - Repeated
overeating causing colic, internal
abdominal abscess (retroperitoneal or
mesenteric abscess) may be classified as

I chronic peritonitis but is dealt with
separately under the heading of
retroperitoneal abscess. Horses with
both intra-abdominal neoplasms and
abscesses will have clinical findings
including anorexia, weight loss, fever,

! colic and depression . 13 Both groups may
also have peritoneal fluid that can be
! classified as an exudate

Pigs, sheep and goats

I Peritonitis is not usually diagnosed

| antemortem in these species.

j Therapy must be aimed at reducing
j systemic shock and hypovolemia, correc-
j tion of the primary cause, antibiotic
! therapy, and abdominal drainage and
| lavage. The reported case fatality rates for
1 peritonitis in horses range from 30-67%.
i In a series of 67 cases of peritonitis in
; horses, of those which developed
I peritonitis after abdominal surgery the
j case fatality was 56%. 3 Peritonitis not
■ associated with intestinal rupture or
j abdominal surgery had a lower case
j fatality rate of 43%. Horses that died had
j higher heart rates, red blood cell count,
1 serum creatinine concentration, PCV and
j anion gap; lower venous blood pH; and
i a greater number of bacterial species

Diseases of the peritoneum

28

cultured from the peritoneal fluid com-
pared with survivors. Those that died
were more likely to have clinical evidence
of abdominal pain, shock and bacteria in
the peritoneal fluid.

TREATMENT

The specific cause must be treated in each
case and the treatments used are described
under the specific diseases listed above.
An exploratory laparotomy may be indi-
cated to determine the cause of the
peritonitis and to effect repair. The
literature on the treatment of peritonitis
in horses has been reviewed. 20

Antimicrobials

Broad-spectrum antimicrobials given
intravenously or intramuscularly are indi-
cated for the infection and toxemia. How-
ever, there are no published reports of
clinical trials to evaluate the effectiveness
of various antimicrobials for the treat-
ment of peritonitis in cattle or horses.
Thus the recommendations are empirical.
In general, peritonitis in cattle is com-
monly treated with any of the broad-
spectrum antimicrobials, with the choice
dependent on ease of administration and
drug withdrawal times necessary in
lactating dairy cattle. Treatment for
traumatic reticuloperitonitis has commonly
been restricted to the use of anti-
microbials; supportive therapy has not
been indicated with the exception of
diffuse peritonitis.

Peritonitis in horses associated
with abdominal surgery or rupture of
the gastrointestinal tract is likely be
accompanied by a mixed flora of bacteria,
and broad-spectaim antimicrobials are
necessary. They must be given at doses
high enough to achieve high blood and
tissue levels and maintained daily until
recovery has occurred. In a series of cases
of peritonitis in horses, the most
commonly used antimicrobials were
gentamicin at 2.2-3.3 mg/kg BW intra-
venously every 8-12 hours; penicillin at
22 000 IU/kg BW intravenously or intra-
muscularly every 6-12 hours. Metroni-
dazole given orally at 15-25 mg/kg BW
has also been used in horses with
peritonitis. 3

Horses with peritonitis associated with
A. equuli respond quickly to treatment
with penicillin at 20 mg/kg BW intra-
muscularly twice daily for 5 days to
2 weeks. 9 Most isolates of the organism
are sensitive to penicillin but some are
resistant and gentamicin sulfate at
6.6 mg/kg BW intravenously once daily
for 5 days to 2 weeks in combination with
the penicillin has also been used
successfully. 9 In a series of 51 cases in
horses, the recovery rate following
treatment with penicillin and gentamicin
and supportive therapy was 100%. 9 Most

horses responded favorably within
48 hours following commencement of
treatment.

Administration of antimicrobials
into the peritoneal cavity has been
attempted on the basis that higher levels
of the drug may be achieved at the site of
the inflammation. However, there is no
scientific evidence that it is superior to
daily parenteral administration and there
is some danger of causing adhesions and
subsequent intestinal obstruction.

Fluid and electrolytes

Intensive intravenous fluid and electrolyte
therapy is a vital part of treatment of
peritonitis when accompanied by severe
toxemia and shock, especially during the
first 24-72 hours following abdominal
surgery in the horse. It is continued until
recovery is apparent and the animal is
drinking water voluntarily; water can
then be supplemented with electrolytes.
(See Ch. 2 for details of fluid and electro-
lyte therapy for the treatment of dehy-
dration and toxemia.)

Nonsteroidal anti-inflammatory
drugs

Flunixin meglumine is recommended at
0.25-1.1 mg/kg BW intravenously every
8-12 hours when the peritonitis is
accompanied by shock. However, no
information is available on efficacy.

Lavage

Peritoneal lavage with large volumes of
fluid containing antimicrobials is rational
and has been attempted when large
quantities of exudate are present. How-
ever, it is not easy to maintain the patency
of drains, especially in cattle. Also,
peritoneum is highly susceptible to
inflammation and chemical peritonitis is
common following the introduction of
certain materials into the peritoneal
cavity. Peritoneal lavage of ponies with
saline and antimicrobials induces a mild,
transient inflammatory response with
minimal change visible at necropsy. 21
Solutions containing povidone-iodine
induced chemical peritonitis, which was
severe when 10% povidone-iodine solu-
tion was used. A 3% solution also causes
peritonitis and the use of these solutions
is not recommended. Extreme caution is
required when foreign materials are
introduced into the cavity in order to
avoid exacerbating the existing inflam-
mation. The peritoneum is also a very
vascular organ and toxic material is
rapidly absorbed from it.

An active intra-abdominal drain has
been used successfully to treat abdominal
contamination in horses. 22 Closed -
suction abdominal drains were placed,
mostly under general anesthesia. Abdomi-
nal lavage was done every 4-12 hours and

about 83% of the peritoneal lavage solu-
tion was retrieved.

Prevention of adhesions

No attempt is made to prevent the develop-
ment of adhesions.

REVIEW LITERATURE

Dyson S. Review of 30 cases of peritonitis in the
horse. Equine Vet J 1983; 15:25-30.

Davis JL. Treatment of peritonitis. Vet Clin North Am
Equine Pract 2003; 19:765-778.

REFERENCES

1. Cable CS et al. J Am Vet Med Assoc 1998;
212:1442.

2. Tyler JW et al.VetRec 1998; 143:280.

3. Hawkins JF et al. J Am Vet Med Assoc 1993;
203:284.

4. Platt H. J Comp Pathol 1983; 93:343.

5. Edwards JF, RuoffWW. J Am Vet Med Assoc 1991;
198:1421.

6. Ross MW et al. J Am Vet Med Assoc 1985;
187:249.

7. Lapointe JM et al. Vat Pathol 2003; 40:338.

8. Fubini SL et al. J Am Vet Med Assoc 1990;
197:1060.

9. Matthews S et al. AustVet J 2001; 79:536.

10. Patterson -Kane JC et al. Vet Pathol 2001; 38:230.

11. Hanson RR et al. Am JVet Res 1992; 53:216.

12. MairTS et al.VetRec 1990; 126:567.

13. Zicker SC et al. J Am Vet Med Assoc 1990;
196:1130.

14. Ebeid M, Rings DM. Bovine Pract 1999; 33:144.

15. Schumacher J et al. JVet Intern Med 1988; 2:22.

16. Braun U. Vet J 2003; 166:112.

17. Grinden CB et al. Equine Vet J 1990; 22:359.

18. Van Hoogmoed Letal.J Am Vet Med Assoc 1999;
214:1032.

19. Milne MH et al.VetRec 2001; 148:341.

20. Davis JL. Vet Clin North Am Equine Pract 2003;
19:765.

21. Schneider RK et al. Am J Vet Res 1988; 49:889.

22. Nieto JE et al. Vet Surg 2003; 32:1.

RECTAL TEARS

Iatrogenic tears of the equine rectum are
a serious problem in equine practice. They
are a leading cause of malpractice suits for
the veterinarian, comprising approximately
7% of insurance claims against veteri-
narians in equine practice in the USA, 1
and can be a large economic loss for the
owner. Occurrence of rectal tears is often
an emotionally charged event because
they are unexpected and they usually
occur in otherwise healthy horses being
subjected to routine rectal examination.
Prompt diagnosis and vigorous treat-
ment, along with frank disclosure of the
event to the horse's owner or handler, is
essential in increasing the likelihood of a
good outcome both for the horse and for
the veterinarian-client relationship.

ETIOLOGY

The etiology of rectal tears is usually
readily apparent, with the vast majority of
rectal tears in horses being iatrogenic.
Iatrogenic rupture occurs during rectal
examination by veterinarians or lay-
persons for reproductive management
(brood mares), or examination of other

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

intra-abdominal structures, for example
during evaluation of a horse with colic. 2
Spontaneous or non-iatrogenic rupture
can occur associated with infarctive lesions
of the distal small colon or rectum, injuries
during parturition or coitus, and malicious
trauma caused by insertion of foreign
objects by attendants. 3 It is important that
rectal tears should not be assumed to be
iatrogenic until a thorough evaluation of
the animal and the history has been
performed.

EPIDEMIOLOGY

Risk factors for rectal tears in horses
have not been well quantified but include:

® Age - young animals appear to be at
increased risk, perhaps because they
are smaller and less accepting of rectal
palpation

® Sex - stallions and geldings have a
smaller pelvic inlet than do mares and
appear to have a rectum of smaller
diameter than mares, thus increasing
the risk of tension on the wall of the
rectum, with subsequent tearing
° Breed - Arabian horses appear to be
at increased risk of iatrogenic rectal
tears

° Size - smaller animals can be at
increased risk

° Inadequate restraint - horses must be
adequately restrained for rectal
examination (see Prevention, below)

° Inadequate preparation of the rectum
- the rectum and distal small colon
should be emptied of feces before an
examination of the reproductive
organs or gastrointestinal tract is
performed

® The experience of the examiner is not
a factor in the risk of rectal tears in
horses 4

® The use of ultrasonographic probes
per rectum does not appear to
increase the risk of rectal tears. 4

The case fatality rate varies depending
on the type of tear (see Clinical signs,
below). Horses with grade I or II tears
almost all survive, whereas the survival
rate for horses with grade III tears treated
appropriately is 60-70%. 3 Almost all
horses with Grade IV rectal tears die.

PATHOGENESIS

Rectal tears occur in horses because the
rectum of the horse is so sensitive and
fragile and powerful contractions occur
during rectal palpation. In contrast, the
bovine rectum is relatively durable and,
while often traumatized, is rarely ruptured.
Tears occur because of excessive tension
on the rectal wall. This usually occurs in
horses by peristalsis and contraction of the
rectum over the examiner's hand, with
splitting of the rectum often occurring over
the back (knuckles) of the hand.

Complete rupture of the peritoneal
portion of the rectum results in fecal
contamination of the abdomen and rapid
onset of septic peritonitis and death. Tears
in the nonperitoneal portion of the
rectum (that is, caudal to the peritoneal
reflection) cause perirectal cellulites and
abscessation.

CLINICAL SIGNS

The prominent clinical sign of the occur-
rence of a rectal tear is the presence of
blood on the rectal sleeve of the examiner.
Slight blood staining of mucus or lubri-
cant is usually not associated with rectal
tears (although this should be verified by
repeat examination) whereas the presence
of frank hemorrhage on the sleeve is
usually indicative of a rectal tear. The
rectum in an adult, 450 kg horse, is
approximately 30 cm long and is partially
within the abdomen, where it is covered
by peritoneum, and partially in the pelvic
canal, where it is not surrounded by
peritoneum but is supported by thick
connective tissue and muscle. The perito-
neal portion of the rectum is supported
dorsally by the mesorectum (mesocolon) .
Most iatrogenic rectal tears in horses
occur within 25-30 cm of the anus, but
can occur up to 60 cm from the anus, in
the peritoneal portion of the rectum. The
tears are almost always in the dorsal or
dorsolateral wall and are longitudinal
(parallel to the long axis of the rectum). It
is speculated that the dorsal wall of the
rectum is weaker than other segments
because it is not covered by serosa, and
blood vessels perforate the muscularis
layers, thereby weakening it. 5

Rectal tears in the horse have been
classified according to the layers of the
rectal wall disrupted. The classification is
also a useful guide to the clinical signs to
be expected and the treatment that is
indicated (see under 'Treatment' for
management of each grade of tear):

0 Grade I - Disruption of the mucosa
only, or the mucosa and submucosa.
There are usually no clinical signs
other than some blood on the
examiner's sleeve. Most of these
injuries occur to the mucosa of the
ventral aspect of the rectum 5
° Grade II - Disruption of the muscular
layer of the rectal wall with the
mucosal and serosal surfaces intact.
This is a rarely recognized form of
tear. There are minimal clinical signs
° Grade Ilia - Tear includes mucosa,
submucosa and muscularis but the
serosal surface is intact. This degree of
tear usually causes septic peritonitis. If
the tear is caudal to the peritoneal
reflection the pelvic fascia becomes
infected, but the infection may remain
contained within it for 7-10 days,

forming a local cellulitis or abscess.
During this period, the horse is likely -
to be affected by mild chronic
peritonitis, with mild abdominal pain,
fever and mild toxemia. At the end of
this time, the infection can erode
through the peritoneum and cause an
acute, severe, diffuse peritonitis, or
rupture through the perianal tissue
causing a fistula

0 Grade Illb - Tear is on the dorsal wall
and includes the mucosa, submucosa
and muscularis. Because there is no
serosa at this position, the tear
extends into the mesocolon. There is
usually septic peritonitis
° Grade IV - Complete rupture with
leakage of fecal material into the
peritoneal space. Clinical signs of
septic peritonitis are severe and death
is inevitable.

Horses with a rectal tear will not display
any immediate signs of discomfort. How-
ever, if there is grade III or grade IV tear,
the horse will have signs of septic
peritonitis, including elevated heart and
respiratory rates, sweating, colic, increased
capillary refill time and discolored mucus
membranes, within 1-2 hours.

CLINICAL PATHOLOGY

Hematological and serum biochemical
changes in horses with grade III and
grade IV tears are consistent with acute
septic peritonitis. These changes include
leukopenia and neutropenia, increased
band cell count, elevated hematocrit and
total protein concentration initially, after
which serum total protein concentration
can decline as protein leaks into the
abdomen. Peritoneal fluid has a high
white blood cell count and protein con-
centration. Cytological examination reveals
the presence of degenerate neutrophils,
intra- and extracellular bacteria and plant
material.

PROGNOSIS

The prognosis depends of the size, grade
and location of the tear and the time
between occurrence and treatment. All
horses with grade I or II lesions survive,
approximately 60-70% of horses with
grade III lesions survive, and almost all
horses with grade IV lesions die. 5

TREATMENT

If the person doing the rectal examination
feels the mucosa tear, if there is blood on
the rectal sleeve, or if a horse that has had
a rectal examination up to 2 hours
previously starts to sweat and manifest
abdominal pain, a rectal tear should be
suspected. A thorough examination
should be conducted immediately but
great care is necessary to avoid damaging
the rectum further. The principles of care
are to: verify the presence of a tear,

Diseases of the peritoneum

289

determine its severity, prevent leakage of
fecal material into the peritoneum or
tissues surrounding the tear, treat for
septic peritonitis, prevent extension of the
tear and provide pain relief.

Immediate care 6

If a rectal tear is suspected the horse
should be appropriately restrained and
examined immediately. There should
be no delay in conducting this examin-
ation. The client should be informed of
the concern about a rectal tear. First aid
measures taken at the time of a grade III
or IV tear can have a marked influence on
the outcome. 2,5 Horses with grade III or
IV rectal tears should receive first aid
treatment and then be referred for further
evaluation and treatment.

The existence of a tear should be deter-
mined and its severity assessed. This is best
achieved by sedating the horse, providing
local analgesia of the rectal mucosa and
anus, and careful manual and visual
examination of the rectal mucosa. Sedation
can be achieved by administration of
adrenergic agonists (xylazine, romifidine,
detomidine) with or without a narcotic drug
(butorphanol, meperidine, pethidine,
morphine). Analgesia of the rectum and
anus can be induced by epidural anesthesia
(lidocaine or xylazine) or local application of
lidocaine gel or lidocaine enema (10-15 mL
of 2% lidocaine in 50-60 mL of water
infused into the rectum). Peristalsis can be
reduced by administration of hyoscine
(N-butylscopolammonium bromide,
0.3 mg/kg intravenously).

Manual or visual examination of the
rectum can then be performed. Manual
examination is performed after generous
lubrication of the anus and examiner's
hand and arm. Some authorities prefer to
use bare hands, rather than gloves or a
rectal sleeve, for this examination because
of the decreased sensitivity when wearing
gloves. However, one should be aware of
the health risks to the examiner of not
using barrier protection (gloves) during a
rectal examination. The rectum should be
evacuated of feces and a careful and
thorough digital examination should be
performed. If a tear is detected, the
position, distance from the anus, length
and depth of the tear should be deter-
mined. Gentle digital examination should
be used to determine the number of layers
involved and if there is rupture of
the rectum and communication with the
peritoneal space.

Alternatively, the rectum can be
examined visually through a mare vaginal
speculum, or using an endoscope. Both
these approaches are likely to minimize
the risk of further damage to the rectum.
These examinations can be impaired by
the presence of fecal material.

If a grade III or TV rectal tear is detected,
then the horse should be administered
broad-spectrum antibiotics (penicillin,
aminoglycoside and possibly metroni-
dazole) and NSAIDs, and referred for
further evaluation. Some, but not all,
authorities recommend placement of a
rectal pack to prevent further contami-
nation of the rectal tear. This is formed
from a 3 inch (7.5 cm) stockinette into
which is inserted a roll of cotton (approxi-
mately 250 g) The roll is moistened with
povidone-iodine solution, lubricated and
inserted into the rectum in the region of
the tear. Epidural anesthesia will prevent
expulsion of the roll in the short term.

Prompt referral and care is essential for
maximizing the likelihood of a good
outcome in horses with grade III and TV
tears.

Grade I and grade II tears
Treatment of these tears is medical.
Horses should be administered broad-
spectrum antibiotics and feces should be
softened by the administration of mineral
oil. These wounds heal in 7-10 days.

Grade III tears

Both medical and surgical treatments are
effective in approximately 60-70% of
cases of grade III tears. 7-9 The choice of
treatment depends on the expertise and
experience of the attending clinician and
financial constraints imposed by the
horse's owner. Surgical treatment includes
direct repair of the tear (for those lesions
that can be readily exposed via the anus),
placement of a rectal sheath by ventral
laparotomy and placement of a loop
colostomy. Surgical repair is in addition to
aggressive treatment of peritonitis.

Medical treatment includes adminis-
tration of broad-spectrum antibiotics
(such as penicillin, aminoglycoside and
metronidazole), anti-endotoxin drugs
(such as hyperimmune serum or poly-
myxin sulfate), NSAIDs, crystalloid fluids,
colloidal fluids (hetastarch, plasma) and
heparin, and other care. Peritoneal lavage
might be indicated. Manual evacuation of
the rectum at frequent intervals (every
1-2 hours for 72 hours and then 4-6 times
daily for a further 7 days) was suggested
to improve the prognosis, 9 although
others caution against manual evacuation
of the rectum because of the risk of
worsening the tear. 8

Grade IV tears

Tears of this severity require immediate
surgical intervention to minimize fecal
contamination of the peritoneum. How-
ever, the grave prognosis and high cost of
treatment, and poor success of surgical
intervention in these cases, means that
most horses are euthanized. If surgical
care is attempted, there should also be

aggressive medical treatment of the
peritonitis.

PREVENTION

As noted above, rectal tears can occur
during examination by even the most
experienced operators. Ideally, the owner
should be informed of the risks of rectal
palpation and explicit consent to perform
the examination should be obtained. This
is especially important for animals that
are at increased risk of rectal tears.

The examination should be performed
only when there is a clear clinical reason
for performing a rectal examination,
when the animal is a suitable candidate
for rectal examination, and when the
animal can be adequately restrained to
permit a thorough examination to be
performed in relative safety for both the
examiner and the animal.

The examiner should proceed cautiously
with the examination. The gloved hand
and arm of the examiner should be well
lubricated with a water-based lubricant.
The anus should be gently dilated by
using fingers shaped into a cone. Feces
should be evacuated from the rectum
such that the rectum is empty to the most
cranial extent of the region to be examined.
If the horse is anxious and straining, or if
there is excessive peristalsis, then the
animal should be sedated and anti-
peristaltic drugs (such as hyoscine)
should be administered. The examination
should be halted if the horse begins
to struggle or resist the examination
excessively. Application of a nose twitch
often facilitates the examination.

During the examination care should be
exercised not to resist peristaltic waves -
the hand should be withdrawn in front of
these advancing waves and reinserted as
peristalsis passes. The fingers should not
be opened widely during the examination
and care should be taken not to put
excessive pressure on a small region of
rectum, such as might occur when trying
to grasp an ovary or loop of distended
intestine.

A rectal tear in a horse is a common
cause of a malpractice suit and the
veterinarian involved with the case is
advised to recommend to the owner that
a second opinion be solicited from another
veterinarian in order to minimize any
misunderstanding.

REFERENCES

1. Blikslager AT, Mansmann RA. Compend Contin

Educ PractVet 1996; 18:1140.

2. Watkins JP et al. Equine Vet J 1989; 21:186.

3. Guglick MA et al. J Am Vet Med Assoc 1996;

209:1125.

4. Sloet van Oldruitenborgh-Oosterbaan MM et al.

Tijdschr Diergeneeskd 2004; 129:624.

5. Eastman TG et al. Equine Vet Educ 2000; 12:263.

6. Sayegh Al et al. Compend Contin Educ PractVet

1996; 18:1131.

PART 1 GENERAL MEDICINE ■ Chapter 5: Diseases of the alimentary tract - I

7. Alexander GR, Gibson KT. AustVet } 2002; 80:137.

8. MairTS. Equine Vet J Suppl 2000; 32:104.

9. Katz LM, Ragle CA. J Am Vet Med Assoc 1999;
215:1473.

RETROPERITONEAL ABSCESS
(INTERNAL ABDOMINAL
ABSCESS, CHRONIC PERITONITIS,
OMENTAL BURSITIS)

A recognized form of chronic or rarely
intermittent colic is associated with an
abscess in the abdominal cavity. The
abscesses are usually retroperitoneal,
sometimes involving the omental bursa,
and chronic leakage from them into the
peritoneal cavity causes chronic or
recurrent peritonitis. Complete recovery is
difficult to effect and there is a high failure
rate in treatment. These abscesses result
from any of the following:

° Infection of a verminous aneurysm,
especially in young horses
° Post-strangles infection localizing
anywhere, but particularly in pre-
existing lesions such as verminous
aneurysms

° Minor perforations of intestinal
wall allowing minimal leakage of
intestinal contents so that omental
plugging is possible

° Erosion through a gastric granuloma
associated with Habronema sp. or a
squamous cell carcinoma of stomach
wall

° In mares, development of an abscess
in the pelvic fascia commonly results
after tearing of the rectal wall
during pregnancy diagnosis.

Clinical findings suggestive of the
disease include persistent or intermittent
chronic colic and weight loss. A fever is
common and varying degrees of anorexia
are typical. In cases with a concurrent
chronic peritonitis or an omental bursitis
the amount of inflammatory exudate may
be large enough to cause abdominal
distension. When the abscess is perirectal
and in the pelvic fascia there may be strain-
ing and constipation due to voluntary
retention of feces.

On rectal examination it may be

possible to feel an abscess, or adhesions
to one. They are often multiple and quite
large and adherent to one another, so that
tight bands of mesentery can be felt that
will lead the hand to the site of the
abscess. Pain is usually elicited by rectal
palpation of the infected sites and by firm
palpation of the external abdominal wall.
Ultrasonography through the abdominal
wall has been used to locate large
retroperitoneal abscesses in a foal.

The hemogram, especially in acute
cases, is characterized by a neutrophilia,
which may be as high as 30 000/pL with a
left shift. Chronic anemia due to bone

marrow depression may occur and
increased plasma fibrinogen and hypo-
albuminemia occur. Abdominocentesis
may yield turbid fluid with a protein
content greater than 2.5 g/dL and an
increase in leukocytes. If culture is
possible the causative bacteria are usually
S. equi, S. zooepidemicus, C. equi,
Corynebacterium pseudotuberculosis or
mixed infections if there has been
intestinal leakage. It is common, even
when there is an active infection in a
retroperitoneal abscess, to fail to grow
bacteria from a peritoneal effusion.

Intra-abdominal abscesses must be
differentiated from abdominal neoplasms
in the horse. 1 Anorexia, weight loss, fever,
colic and depression are common to both
syndromes. The laboratory findings in
both groups are similar but cytological
examination of the peritoneal fluid may
yield an accurate diagnosis in the case of
neoplasms. 1

Leakages from stomach wall may
result in adhesions to the spleen and
development of splenic abscesses. In
these animals a sharp pain response can
be elicited on finn palpation of the
abdomen in the left flank just behind the
last rib. Abscesses in liver are not so easily
located. Abscesses in pelvic fascia are
usually not very discrete but are instantly
noticeable on inserting the hand into the
rectum.

TREATMENT

Treatment with broad-spectrum anti-
microbials is indicated and the initial
response is good but often transitory
if the usual course of treatment is only
3-5 days' duration. The prognosis is
usually tentative because of the difficulty
of completely eliminating the infection.
Treatment must be continued for at least
2 weeks and in some cases for a period of
2 to even 4-5 months. Surgical treatment
may be possible hut is usually ineffectual
because of the deformity of the area by
adhesions and the usual outcome of
tearing the intestine and spillage into the
peritoneal cavity while attempting to
exteriorize the lesion.

REFERENCE

1. Zicker SC et al. J Am Vet Med Assoc 1990;

196:1130.

ABDOMINAL FAT NECROSIS
(LIPOMATOSIS)

The hard masses of necrotic fat that
occur relatively commonly in the perito-
neal cavity of adult cattle, especially the
Channel Island breeds and possibly
Aberdeen Angus, are commonly mistaken
for a developing fetus and can cause
intestinal obstruction. The latter usually
develops slowly, resulting in the appear-
ance of attacks of moderate abdominal

pain and the passage of small amounts of
feces. Many cases are detected during"
routine rectal examination of normal
animals. The lipomatous masses are
located in the small omentum, large
omentum and mesentery in cattle and
more diffusely to other parts of the body
in sheep and goats. 1 The composition of
the fatty deposits is identical with the fat
of normal cows and there is no
suggestion that the disease is neoplastic.
Sporadic cases are most common but
there are reports of a herd prevalence as
high as 67%. 2 The cause is unknown but
there appears to be a relation between
such high prevalence and the grazing of
tall fescue grass, 2 and an inherited
predisposition is suggested. The rate of
occurrence increases with age, the peak
occurrence being at 7 years of age. It has
been suggested that excessive fattiness of
abdominal adipose tissue may predispose
cattle to fat necrosis. 3 An unusual form of
the disease with many lesions in sub-
cutaneous sites has been recorded in
Holstein-Friesian cattle and is regarded
as being inherited. There is no treatment
and affected animals should be salvaged.
A generalized steatitis has been reported
in pony foals.

Pedunculated lipomas provide a
special problem especially in older horses.
Their pedicles may be 20-30 cm long and
during periods of active gut motility these
pedicles can become tied around a loop of
intestine anywhere from the pylorus to
the rectum. At the pylorus they cause
acute intestinal obstruction with gastric
dilatation. At the rectum they cause
subacute colic and a characteristic inability
to enter the rectum with the hand. This is
accompanied by a folded coning-down of
the mucosa, not unlike that in a torsion of
the uterus. Early diagnosis and surgical
intervention can produce a resolution but
delay is disastrous because the blood
supply is always compromised: it is
always a loop and its blood supply that
are strangulated. The pedicle is always
tied in a very tight knot.

REFERENCES

1. Xu LR. Acta Vet Zootechnol Sinica 1986; 17:113.

2. Stuedemann JA et al. Am JVet Res 1985; 46:1990.

3. Katamoto H et al. ResVet Sci 1996; 61:214.

TUMORS OF PERITONEUM

Disseminated peritoneal leiomyomatosis
has been reported occurring in a mature
Quarter horse. 1 Clinical findings included
inappetence, weight loss, intermittent
fever, chronic abdominal pain and enlarge-
ment of the abdomen. Rectal examination
revealed a prominent, firm, smooth-
walled mass in the ventral aspect of
the abdomen. Transabdominal ultra-
sonography was used to detect the mass,

Diseases of the peritoneum

2 '

which was a friable, polycystic structure
occupying a large portion of the abdomi-
nal cavity and weighing 34 kg. The mass
was removed and recovery was complete.

Mesothelioma has been reported in
cattle, predominantly in the peritoneal
cavity, but mesothelioma can also occur in
the pleural cavity and the vagina of adult
cattle. The cause of mesothelioma in cattle
is unknown but pleural mesothelioma in
humans is associated with asbestos
exposure. One report suggested that
the frequency of diagnosis in cattle is
increasing. 2 All ages of cattle can be
affected with peritoneal mesothelioma,
but affected animals are typically young,
with fetal and neonatal cases also being

reported. 3-4 Calves and adult cattle most
frequently present with moderate abdomi-
nal distension. 5 Other presenting signs
include scrotal edema in intact males 5 and
ventral pitting edema. Occasionally, small
2-20 mm, well demarcated'bumps'can be
felt on all serosal surfaces during pal-
pation per rectum in adult cattle.
Peritoneal fluid is easily obtained by
ventral abdominal paracentesis and has
the characteristics of a modified transudate
with a moderate to marked increase in
phagocytically active mesothelial cells.
Definitive diagnosis is made during a
right-sided exploratory laparotomy,
where numerous raised, white, well
demarcated masses are palpated on all

serosal surfaces, with copious abdominal
fluid being present. Biopsy of 'these
masses and microscopic examination
confirms the presumptive diagnosis of
mesothelioma. Extensive peritoneal
mesothelioma is fatal and there is no
known treatment. All cases reported to
date are sporadic and there is no apparent
association with asbestos or other toxic
agent in cattle.

REFERENCES

1. Johnson PJ et al. J Am Vet Med Assoc 1994;
205:725.

2. Pizarro M et al. J Vet Med A 1992; 39:476.

3. Klopfer U et al. Zentralbl Vet Med B 1983; 30:785.

4. Anderson BC et al.Vet Med 1984; 79:395.

5. Wolfe DF et al. J Am Vet Med Assoc 1991; 199:486.

PART 1 GENERAL MEDICINE

Diseases of the alimentary tract - II

DISEASES OF THE FORESTOMACH
OF RUMINANTS 293

Anatomy and physiology 293
Ruminant gastrointestinal
dysfunction 297

SPECIAL EXAMINATION OF THE
ALIMENTARY TRACT AND
ABDOMEN OF CATTLE 301

History 301

Systemic state, habitus and
appetite 301

Oral cavity and esophagus 301
Inspection of the abdomen 301
Examination of rumen fluid 304
Rectal palpation of abdomen 305
Gross examination of feces 305
Detection of abdominal pain 307
Clinical examination of the digestive
tract and abdomen of the calf 308
Laparoscopy 308
Diagnostic imaging 308
Exploratory laparotomy (exploratory
celiotomy) 309

Diseases of the
forestomach of ruminants

Forestomach motility of ruminants,
especially cattle, is of major concern to the
veterinarian. Evaluation of forestomach
motility is an integral part of the clinical
examination and differentiation of fore-
stomach abnormalities into primary and
secondary causes and is essential for
diagnosis and accurate therapy. Application
of the knowledge of the physiology of
normal reticulorumen motility can improve
the diagnosis, prognosis and therapy for
diseases of the forestomach. 1 ' 2 A brief
review of the clinical aspects of the motility
of the reticulorumen is presented here.

ANATOMY AND PHYSIOLOGY

The ruminant forestomach compartments,
consisting of the reticulum, rumen and
omasum, is like a fermentation vat. The
animal exerts some control over the fer-
mentation process by selecting the feed,
adding a buffer-like saliva, and providing
continual agitation and mixing with
specialized contractions of the forestomach.
Reticulorumen motility insures a con-
sistent flow of partially digested material
into the abomasum for further digestion.

The forestomach can be divided into
primary structures: the reticulorumen

DISEASES OF THE RUMEN,
RETICULUM AND OMASUM 311

Simple indigestion 311
Rumen impaction in sheep with
indigestible foreign bodies 313
Indigestion in calves fed milk replacers
(ruminal drinkers) 314
Acute carbohydrate engorgement of
ruminants (ruminal lactic acidosis,
rumen overload) 314
Ruminal parakeratosis 325
Ruminal tympany (bloat) 325
Traumatic reticuloperitonitis 337
Vagus indigestion 346
Diaphragmatic hernia 350
Traumatic pericarditis 351
Traumatic splenitis and hepatitis 352
Impaction of the omasum 352

DISEASES OF THE ABOMASUM 353

Clinical examination of the
abomasum 353

Applied anatomy and pathophysiology
of the abomasum 353
Abomasal reflux 354

and the omasum; they are functionally
separated by a sphincter: the reticulo-
omasal orifice. The reticulorumen of an
adult cow occupies almost the entire left
half of the abdominal cavity and has a
capacity of up to 90 kg of digesta. Because
of its large size and ease of clinical exam-
ination, rumen motility is considered
to represent digestive functions in the
ruminant.

Both parasympathetic and sympathetic
nerves supply the reticulorumen but only
the former nerves stimulate motility. Para-
sympathetic innervation occurs through
the vagus nerve, which is predominantly
sensory from the forestomach. Sympathetic
innervation to the forestomach consists of
numerous fibers from the thoracolumbar
segment; these fibers join at the celiac
plexus to form the splanchnic nerve. The
splanchnic nerve can inhibit motility, but
normally there is little or no tonic
sympathetic drive to the forestomach.

RETICULORUMEN MOTILITY

Four different specialized contraction pat-
terns can be identified in the forestomach:

0 Primary or mixing cycle
0 Secondary or eructation cycle
o Rumination (associated with cud
chewing and associated with the
primary cycle)

° Esophageal groove closure (associated
with sucking of milk).

6

Left-side displacement of the
abomasum 354
Right-side displacement of the
abomasum and abomasal
volvulus 362

Dietary abomasal impaction in
cattle 367

Abomasal impaction in sheep 369
Abomasal phytobezoars and
trichobezoars 370
Abomasal ulcers of cattle 370
Abomasal bloat (distension) in lambs
and calves 374
Omental bursitis 374

DISEASES OF THE INTESTINES OF
RUMINANTS 375

Cecal dilatation and volvulus in
cattle 375

Intestinal obstruction in cattle 376
Hemorrhagic bowel syndrome in cattle
(jejunal hemorrhage syndrome) 380
Intestinal obstruction in sheep 382
Terminal ileitis of lambs 382

It is important for the clinician to under-
stand the motility pattern of each cycle.
Specific diseases of the forestomach have
characteristic alterations in motility,
which aid in the diagnosis and prognosis.

Primary contraction cycle

The primary cyclic activity results in the
mixing and circulation of digesta in an
organized manner. The primary contrac-
tion in cattle begins with a biphasic
contraction of the reticulum. The first
reticular contraction forces ingesta dorsal
and caudad into the rumen, as does the
much stronger second reticular con-
traction. The dorsal ruminal sac then
begins to contract as the ventral sac
relaxes, thereby causing digesta to move
from the dorsal to the ventral sac.
Sequential contractions of the caudo-
ventral, caudodorsal and ventral ruminal
sacs force digesta back into the reticulum
and cranial sac. After a brief pause the
contraction sequence is repeated. During
each reticular contraction fluid and food
particles, particularly heavy grain, pass
into the reticulo-omasal orifice and into
the omasum and abomasum.

Reticulorumen motility results in
stratification of ruminal contents, with
firmer fibrous material floating on top of a
more fluid layer. Solid matter remains in
the rumen until the particle size is
sufficiently small (1-2 mm in sheep,

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

2-4 mm in cattle) to pass through the
reticulo-omasal orifice. The size of digested
plant fragments in ruminant feces can
therefore be considered an indirect
measurement of forestomach function.

Identification of ruminal contractions
requires both auscultation and obser-
vation of the left paralumbar fossa. Sound
is produced when fibrous material rubs
against the rumen during contraction.
Only slight sound is produced when the
rumen contains small quantities of fibrous
material.

External palpation of the rumen is
valuable in determining the nature of
ruminal contents. The normal rumen feels
doughy in the dorsal sac and more fluid
ventrally; the difference in consistency is
attributable to stratification of ruminal
contents. Very liquid ruminal contents
that splash and fluctuate on ballottement ;
(fluid-splashing sounds) are suggestive of j
lactic acidosis, vagal indigestion, ileus or j
prolonged anorexia.

Rumen hypomotility or hypermotility j
is usually associated with a change in the ;
type of sounds heard during auscultation, |
with gurgling, bubbling or distant rustling j
sounds replacing the normal crescendo- ;
decrescendo crackling sounds. The rumen j
can be examined and evaluated using a 1
combination of auscultation and simul- '
taneous ballottement or percussion, by ;
palpation through the left flank and by
rectal examination. Inspection and labora-
tory analysis of rumen contents is also
possible.

Control of primary contractions
The primary contraction cycle of the
reticulorumen is a complex and organized
contraction initiated, monitored and con-
trolled by the gastric center in the medulla
oblongata. These cycles are mediated by
the vagus nerve. The reticulorumen is
under extrinsic nervous control compared
to the remainder of the gastrointestinal
tract. It is also affected by hormones and
smooth muscle tone.

The gastric center is bilaterally paired
and located in the dorsal vagal nucleus in
the medulla. The gastric center has no
spontaneous rhythm of its own but acts
as a processor and integrator of afferent :
information. Various excitatory and inhibi- ■
tory inputs are brought together to .
determine both the rate and strength of I
contraction.

Ruminal atony

Ruminal atony, seen in lactic acidosis ;
and endotoxemia, can be attributed to
one or more of the following factors:

Direct depression of the gastric center, .

usually associated with generalized

depression and severe illness i

(toxemia)

° Absence of excitatory inputs to the
gastric center

0 Increase in excitatory inhibitory inputs
to the gastric center
c Failure of vagal motor pathway
(Table 6.1).

Hypomotility

Hypomotility is a reduction in the
frequency or strength of extrinsic contrac-
tions, or both, and usually is caused
by either a reduction in the excitatory
drive to the gastric center or an increase
in inhibitory inputs.

Properties of contractions
The frequency of primary contractions is
determined from information accumulated
during the quiescent phase of motility.
Frequency provides a rough estimate of
the overall health of a ruminant. In cows,
the frequency of primary contractions
averages 60 cycles per hour but decreases
to 50 cycles per hour during rumination j
and even lower when the cow is recum- i
bent. Feeding increases the rate to up to ;
105 cycles per hour. Because of this j
variability, the clinician should auscultate i
the rumen for at least two minutes before j
determining the frequency of contractions, j
The strength and duration of each \
contraction are determined by infor-
mation obtained just before and during
the contraction and are therefore more
dependent on the nature of the fore-
stomach contents than is frequency of
contraction. The strength of contraction is
subjectively determined by observing the
movement of the left paralumbar fossa
and assessing the loudness of any sounds
associated with ruminal contraction.

The distinction between frequency and
strength is important clinically, particularly
in reference to therapy of reticulorumen
hypomotility. When feed is withheld from
sheep for 4 days, the rate of forestomach
contractions remains unchanged but the
strength of contractions progressively
decreases because of changes in ruminal
contents.

Extrinsic control of primary
contractions

Excitatory inputs to the gastric center
Tension and chewing movements are two
major excitatory inputs to the gastric
center. Low-threshold tension receptors
deep in the circular smooth muscle layer
detect reticulorumen distension. The
greatest density of receptors is found in
the medial wall of the reticulum and
dorsal ruminal sac. These low-threshold
tension receptors send afferent impulses
along the dorsal or ventral vagus nerve to
the gastric center, where they excite
extrinsic reticulorumen contractions. Pro-
longed anorexia, leading to a smaller
reticulorumen volume, decreases this

excitatory input. Feeding increases
reticulorumen volume, thus leading to a
prolonged increase in forestomach
motility.

Buccal receptors, which are stimulated
during feeding, are also excitatory to the
gastric center. These are mechano-
receptors, and their effect is mediated by
the trigeminal nerve. This reflex increases
the rate of primary contractions only but
is short-lived and wanes with time. The
stimulatory response of feeding also has a
higher brain center component: the sight
of feed can increase the frequency of
primary contractions by 50% during a
period of 4-5 minutes. Rumination, in
comparison with feeding, is accompanied
by a lower than normal primary contrac-
tion rate.

Other relatively minor excitatory in-
puts to the gastric center include milking,
environmental cold and a decrease in
abomasal pH. Milking or udder massage
of dairy goats markedly increases the fre-
quency and strength of primary contrac-
tions. In a cold environment, the ruminant
increases the frequency of forestomach
contractions, thereby maximizing the
fermentation rate and helping to main-
tain body temperature.

Inhibitory inputs to the gastric center
The four most important inhibitory inputs
to the gastric center are fever, pain,
moderate to severe rumen distension
and increased ruminal volatile fatty acid
concentrations.

fever

Fever has been associated with decreased
rumen motility. Endogenous pyrogens
may cause prolonged forestomach hypo-
motility or atony often seen in cattle with
endotoxemia due to bacterial infections.
Pyrogens directly affect the gastric center
in the hypothalamus, and opioid receptors
mediate their action.

Endotoxemia

Endotoxemia is common in cattle and
often associated with fever, anorexia and
rumen atony. Inhibition of forestomach
motility during endotoxemia is thought to
be a combination of two different path-
ways: a prostaglandin -associated mech-
; anism and a temperature -independent
mechanism. The former can be attenuated
by administration of nonsteroidal anti-
: inflammatory drugs (NSAIDs). Therapy
for endotoxin-induced hypomotility or
atony includes the use of antimicrobials
for the underlying cause of the inflam-
| mation and NSAIDs for the effects of the
endotoxemia.
i

i Pain

I Pain may be associated with rumen
. hypomotility or atony. Painful stimuli act

Diseases of the forestomach of ruminants

Clinical afferent input Clinical findings and responses to treatment

Excitatory inputs

Low threshold reticular tension receptors

Increased reticular tension
After feeding
Mild ruminal tympany
Decreased reticular tension
Starvation
Anorexia

Lesions of medial wall of reticulum
Chronic induration and fibrosis due to traumatic
reticuloperitonitis
Acid receptors in abomasum

Increases in abomasal acidity following
emptying of organ
Buccal cavity receptors
Following eating
Inhibitory inputs

High-threshold reticular tension receptors

Peak of reticular contraction
Severe ruminal tympany
Ruminal impaction with forage, hay,
straw (not necessarily grain overload)

Abomasal tension receptors
Impaction, distension or displacement of
abomasum
Pain

Visceral pain due to distension of abomasum
or intestines. Severe pain from anywhere
in body

Depressant drugs

Anesthetics, central nervous system depressants

Prostaglandin E

Changes in rumen content

Marked decrease (< S) or increase (> 8)

in pH of ruminal fluid. Engorgement

with carbohydrates or protein-rich feeds.

Absence of protozoa in ruminal acidosis
and in lead and other chemical poisoning
Changes in body water, electrolytes and
acid-base balance
Hypocalcemia

Dehydration and electrolyte losses, acidosis,

alkalosis

Peritonitis

Traumatic reticuloperitonitis

Toxemia/fever

Peracute coliform mastitis

Acute bacterial pneumonia

Ruminal distension

Early ruminal tympany

Covering of cardia (fluid or form)

Ruminal tympany

Recumbent animal

Increases frequency, duration and amplitude of primary cycle contractions and mixing promotes
fermentation

Decreases frequency, duration and amplitude of primary cycle contractions and decreases
fermentation

Cause hypomotility of rumen contractions and may be explanation for atony in some cases of
vagus indigestion. Some cases are characterized by erratic hypermotility

Increase primary cycle movements, which increases flow of ruminal contents into abomasum to
maintain optimum volume and to decrease acidity

'Increased reticulorumen activity

Depression of primary cycle movements, ruminal hypomotility, depression of fermentation because
of failure of mixing

Abomasal impaction, dilatation and torsion may result in complete ruminal stasis. Left-side
displacement of abomasum usually does not cause clinically significant hypomotility

Moderate to total inhibition of reticulorumen movements possible with visceral pain. The degree of
inhibition from pain elsewhere will vary

Inhibition of primary and secondary cycle movements and of eructation, resulting in ruminal
tympany

Inhibition of primary and secondary cycle movement and lack of fermentation. Cud transfer
promotes return to normal activity

Inhibition of primary and secondary cycle movements and of eructation, resulting in ruminal
tympany which responds to treatment with calcium

Inhibition of primary and secondary cycle movements and of eructation, resulting in ruminal
tympany. Return of primary movements is good prognostic sign. Lesions must heal without
involvement of nerve receptors or adhesions that will interfere with normal motility

Inhibition of primary and secondary cycle movements, which return to normal with treatment of
toxemia

Increased frequency of secondary cycle movements and of eructation

Cardia does not open, failure of eructation, resulting in ruminal tympany. Clearance of cardia
results in eructation

Most of the sensory inputs are transmitted to gastric centers in the dorsal vagal nerve nuclei from which the efferent outputs originate and pass down the vagal
motor nerve fibers.

Source: modified from Leek BF. Vet Rec 1969: 84:238.

directly on the gastric center, although
modification of reticulorumen motility in
response to painful stretching of viscera
can be partially attributed to catecholamine
release. The sympathetic nervous system
response to pain can also stimulate
splanchnic motor nerves, thereby directly
inhibiting reticulorumen motility.

Because of their stoic nature, the only
clinical evidence of pain in ruminants

may be anorexia and depressed fore-
stomach motility. Prostaglandins have
been implicated in increasing the sensi-
tivity to pain both locally and centrally,
and NSAIDs are indicated for alleviation
of pain associated with inflammation.
Other analgesics are of limited usefulness
in the treatment of pain-induced fore-
stomach hypomotility. Xylazine, an excel-
lent sedative -analgesic for ruminants.

causes a dose-dependent inhibition of
reticulum contractions.

Distension of forestomach
Moderate to severe forestomach dis-
tension exerts an inhibitory influence on
reticulommen motility. Epithelial receptors
located in the ruminal pillars and papillae
of the reticulum and cranial rumen sac
respond to mechanical stimulation (stretch)

296

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

as well as changes in ruminal volatile fatty
acid concentration. These receptors,
also known as high-threshold tension
receptors, are stimulated continuously
during severe rumen distension. The
opposing actions of low- and high-
threshold tension receptors help to con-
trol the fermentation process and maintain
an optimum reticuloruminal volume.

A good example of their activities is the
motility changes evident with some forms
of vagus indigestion.

Ruminal volatile fatty acids
The ruminal volatile fatty acid concen-
tration also influences forestomach
motility. Epithelial receptors detect the
concentration of nondissolved volatile
fatty acids in ruminal fluid, which is
normally high enough to produce a tonic
inhibitor input to the gastric center.
Volatile fatty acids in the reticulorumen
exist in both the dissociated and non-
dissociated forms, with the degree of
ionization being governed by the rumen
pH and the pKa of each particular acid.
Ruminal atony in animals with lactic
acidosis results from elevated levels of
nondissociated volatile fatty acids in
ruminal fluid, with the decrease in rumen
pH changing more of the volatile fatty
acids into a nondissociated form. Systemic
acidosis does not appear to contribute to
ruminal atony, although increased volatile
fatty acid concentrations in the abomasum
may reduce forestomach motility.

Abomasal disease

Diseases of the abomasum influence
forestomach motility. Abomasal distension
may contribute to the decreased fore-
stomach motility often observed with
abomasal volvulus, impaction or right -
sided dilatation. Abomasal tension
receptors detect overfilling and reflexly
decrease reticuloruminal movements,
thus reducing the rate of flow of ingesta
into the abomasum. Ruminal hypo-
motility is not always observed in left-side
displacement of the abomasum even
though appetite may be decreased.

Effect of depressant drugs
General anesthetics and other depressant
drugs acting on the central nervous j
system also inhibit reticulorumen motility
by a direct effect on the gastric center.

Acid-base imbalance and blood glucose
Reticulorumen activity can be inhibited
by alterations in blood pH, electrolyte
imbalances, deprivation of water and j
hyperglycemia. j

Hormonal control of primary
contractions

Forestomach motility can be influenced
by the action of hormones. Both chole-
cystokinin and gastrin can reduce feed

intake and forestomach motility observed
in sheep with certain intestinal nematodes.

Intrinsic control of primary
contractions

The contribution of intrinsic smooth
muscle tone to forestomach motility is
not well understood. Intrinsic contrac-
tions are involved in maintaining normal
reticulorumen tone, directly influencing
the discharge of low-threshold tension
receptors to the gastric center. Calcium is
required for smooth muscle contraction
and hypocalcemia will usually cause
ruminal atony. The administration of
calcium borogluconate to cattle, sheep
and goats with hypocalcemia will restore
rumen motility and eructation commonly
occurs after the intravenous administration
of the calcium.

Treatment of forestomach
hypomotility

Anorexia and forestomach hypomotility
usually exist together. Reduced feed
intake reduces the two primary drives for
reticulorumen activity: moderate fore-
stomach distension and chewing activity.
A wide variety of drugs have been used
for many years to induce forestomach
motility with the aim of stimulating
anorexic cattle with forestomach hypo-
motility to begin eating. Most if not all of
these drugs have been unsuccessful.
Ruminatorics such as nux vomica, ginger,

| gentian and tartar given orally have not
i been effective. Parasympathomimetics,
j such as neostigmine or carbamylcholine,
should not be used to treat forestomach
atony. Neostigmine requires vagal activity
to be effective and therefore cannot incite
i normal primary contractions in atonic
j animals. Neostigmine may increase the
strength of a primary contraction without
altering rhythm or coordination. Carba-
mylcholine causes hypermotility in sheep
but the contractions are uncoordinated,
spastic and functionless.

Any effective drug must be able to
induce forestomach motility in a co-
ordinated sequence so that the ingesta
moves through the reticulo-omasal orifice,
into the omasum, out of the omasum, and
into the abomasum, and out of the abo-
masum into the small intestine. This
means that there must be a coordinated
sequence of contractions and relaxations
of sphincters. Experimentally, metoclo-
| pramide increases the rate of ruminal
contractions and therefore might be
beneficial in rumen hypomotility or
motility disturbances associated with
vagal nerve damage.

Secondary cycle contraction and
eructation

Secondary cycles are contractions that
involve only the rumen and are associated

with the eructation of gas. They occur
independently of the primary cycle con-
tractions and usually less frequently,
about once every 2 minutes. The con-
traction rate depends on the gas or fluid
pressure in the dorsal sac of the rumen.
Secondary cycles can be inhibited by
severe distension of the rumen.

Normally, the dorsal sac of the rumen
contains a pocket of gas composed of
C0 2/ , N 2 and CH 4 . Gas is produced at a
maximum rate of 1 L per minute in cattle,
with the rate depending on the speed of
microbial degradation of ingesta. Eructation
occurs during both primary and second-
ary contraction cycles but most gas is
removed during the latter. Eructation is
capable of removing much larger quan-
tities of gas than is produced at the maxi-
mum rates of fermentation and therefore
free gas bloat does not occur because of
excessive gas production but rather from
insufficient gas elimination.

Ruminal contractions are essential for
eructation. Tension receptors in the
medial wall of the dorsal ruminal sac
initiate the reflex by means of the dorsal
vagus nerve. Contractions begin in the
dorsal and caudodorsal ruminal sacs and
spread forward to move the gas cap
ventrally to the cardia region. Contraction
of the reticuloruminal fold is necessary to
stop fluid from moving forward to the
reticulum and covering the cardia.
Receptors in the cardia region detect the
presence of gas; the cardia remains firmly
closed if fluid or foam (as in frothy bloat)
contacts it. Injury to the dorsal vagal nerve
decreases the efficiency of eructation but
either the ventral or dorsal vagus nerve
alone can initiate enough eructation
activity to prevent bloat.

Despite the presence of normal second-
ary contractions, eructation may not occur
in recumbent animals when the cardia is
covered with fluid. Bloat is often observed
in ruminants in lateral recumbency.
Eructation occurs after the animal stands
or attains sternal recumbency as fluid
moves away from the cardia. Bloat can
also result from peritonitis, abscesses or
masses that distort the normal fore-
stomach anatomy and preventing active
removal of fluid from the cardia region.
Esophageal obstructions associated with
| intraluminal, intramural or extraluminal
! masses are a common cause of free gas
| bloat. Passage of a stomach tube usually
identifies these abnormalities, and fore-
; stomach motility is unimpaired unless the
■ vagal nerve is damaged.

Bloat is often observed in cattle with
I tetanus. Distension of the rumen is usually
I not severe and can be accompanied by
j strong and regular ruminal contractions,
j Because the ruminant esophagus is
j composed of striated muscle through-

Diseases of the forestomach of ruminants

2 '

out its length, tetanus-associated bloat j
may be due to spasm of the esophageal j
musculature. j

Persistent mild bloat is often observed j
in ruminants that have rumen atony or ;
hypomotility secondary to systemic
disease. Although the fermentation rate is i
lower than normal in these cases, ruminal ;
contractions are not strong enough to .
remove all the gas produced. The bloat !
usually requires no treatment and resolves ;
with return of normal forestomach motility.

Secondary contractions cannot be i
distinguished from primary contractions
by auscultation of the left paralumbar !
fossa only, unless a synchronous belch of ]
gas is heard. However, primary contrac-
tions can be identified by simultaneous
palpation of the left paralumbar fossa and
auscultation with the stethoscope over
the left costochondral junction between
the seventh and eighth ribs. Reticular
contractions indicating the beginning of a
primary contraction can be heard fol-
lowed by contraction of the dorsal sac and
lifting of the paralumbar fossa.

Secondary contractions are relatively
autonomous and are not subject to the
same central excitatory and/or inhibitory
influences as are primary contractions.
Agents that inhibit reticulorumen motility
by a central action have a lesser effect on
eructation than on primary contraction
cycles. However, high doses of xylazine
can inhibit secondary contractions
and the duration of inhibition is dose-
dependent.

No drugs are yet available to improve
secondary contractions as a means of
treating bloat. Severe bloat usually arises
from mechanical or diet-related causes,
and therapy should be directed specifically
to those causes.

Rumination

Rumination is a complex process and
consists of:

Regurgitation

Remastication

Insalivation
* Deglutition.

Rumination is initiated by the rumination
center close to the gastric center in the
medulla oblongata. Rumination allows
further physical breakdown of feed with
the addition of large quantities of saliva
and is an integral part of ruminal activity.
The time devoted to rumination is deter-
mined by the coarseness of ruminal
contents and the nature of the diet. Rumi-
nation usually commences 30-90 minutes
after feeding and proceeds for 10-60 min-
utes at a time, resulting in up to 7 hours
per day spent on this activity.

The epithelial receptors located in the
reticulum, esophageal groove area, reti-

culorumen fold and ruminal pillars detect j
coarse ingesta and initiate rumination. ;
The receptors can be activated by increases j
in volatile fatty acid concentration, \
stretching and mechanical rubbing.

An intact dorsal or ventral vagus nerve :
is necessary for regurgitation to proceed.
Regurgitation is associated with an extra
contraction of the reticulum immediately
preceding the normal reticular biphasic )
contraction of the primary cycle. The
glottis is closed, and an inspiratory move-
ment lowers the intrathoracic pressure.
The cardia then relaxes, and the distal ;
esophagus fills with ingesta. Reverse ;
peristalsis moves the bolus up to the mouth,
where it undergoes further mastication. :

The usual causes for a reduction or j
absence of rumination are: j

■’ Reticulorumen hypomotility or atony
o Central nervous system depression
* Excitement, pain or both
° Liquid ruminal contents such as a
high-concentrate diet with no coarse
fiber

^ Mechanical injury to the reticulum
(peritonitis).

Other less common causes include chronic
emphysema (difficulty in creating a
negative thoracic pressure) and extensive
damage to the epithelial receptors that
incite the reflex, as occurs in rumenitis.

Reticulorumen motility is required for
rumination to proceed. The extra reticular
contraction is not essentia] for regurgitation
because fixation or removal of the reticulum
does not prevent rumination from occur-
ring. Rumination can be easily inhibited by
higher brain centers, as disturbance of a
ruminating cow often stops the process
and is absent when animals are stressed
or in pain. Milking commonly elicits
rumination in cows and goats.

Pharmacologic stimulation of regurgi-
tation is not attempted.

Esophageal groove closure

The esophageal groove reflex allows milk
in the sucking preruminant to bypass the
forestomach, and directs milk from the
esophagus along the reticular groove and
omasal canal into the abomasum. Milk
initiates the reflex by chemical stimu-
lation of receptors in the oral cavity,
pharynx and cranial esophagus. Once the
reflex is established in neonatal ruminants,
sensory stimuli (visual, auditory, olfactory)
can cause esophageal groove closure with-
out milk contacting the chemoreceptors.
This occurs in calves teased with milk or
given water in an identical manner to
which the calf previously received milk.
The esophageal groove reflex continues to
operate during and after the development
of a functional rumen, provided the
animal continues to receive milk.

Liquid administered to calves with an
esophageal feeder (tube) does not cause
groove closure. In calves younger than
3 weeks of age, overflow of liquid from
the rumen into the abomasum begins
when 400 mL of liquid are given. Thus if
the goal of oral feeding is to insure that,
fluid administration by esophageal tube
rapidly enters the abomasum, more than
400 mL of liquid must be given.

Closure of the esophageal groove in
cattle younger than 2 years of age can be
induced by solutions of sodium chloride,
sodium bicarbonate or sugar. From
100-250 mL of 10% solution of sodium
bicarbonate induces esophageal groove
closure in 93% of cattle immediately and
it lasts for 1-2 minutes. Any other oral
solution administered during this time is
directed into the abomasum to avoid
dilution in the rumen. Closure of the
groove may be used to treat abomasal
ulcers if magnesium hydroxide or kaolin-
pectin solutions are given orally imme-
diately after a sodium bicarbonate solution.

RUMINANT GASTROINTESTINAL
DYSFUNCTION

The clinical findings which suggest pri-
mary ruminant gastrointestinal dysfunction
include the following:

o Inappetence to anorexia, failure to
ruminate

° Dropping regurgitated cuds occurs
occasionally and is associated with
straw impaction of the rumen, vagus
indigestion, esophageal dilatation and
rumenitis

° Visible distension of the abdomen,
which may be asymmetrical or
symmetrical, dorsal or ventral or both.
Distension of the left dorsal abdomen
because of ruminal tympany is most
common

° The abdomen may appear gaunt or
empty

° The rumen may feel abnormal on
palpation through the left paralumbar
fossa. It may feel more doughy than
normal, distended with gas, fluid
filled, or it may not be palpable
° Ruminal atony or hypermotility
observed visually and detectable on
auscultation and palpation
Abdominal pain, usually subacute and
characterized by humping of the back,
reluctance to move or acute colicky
signs of kicking at the abdomen and
stretching. Pain may also be
detectable on deep palpation of the
abdomen if there is peritonitis, either
local or diffuse

® Abnormal feces. The feces may be
absent, reduced in amount or
voluminous, and the composition may
be abnormal. In carbohydrate

298

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

engorgement th'e feces are usually
increased in amount and are
sweet-sour smelling. In most other

- diseases of the ruminant stomachs
the feces are reduced in amount
(scant), are pasty and foul-smelling
and appear overdigested because of
the increased transit time in the
alimentary tract. A complete absence
of feces for 24-48 hours is not
uncommon with diseases of the
ruminant stomach and may be
confused with an intestinal
obstruction or the earliest stages of
hypocalcemia in a recently calved
mature cow

o The temperature, heart rate and
respirations are variable and may be
within normal ranges. With an
inflammatory lesion such as acute
peritonitis, a fever is usually present.

In acute diffuse peritonitis with
toxemia, the temperature may be
normal or subnormal; in subacute and
chronic peritonitis the temperature is

usually normal. In most other diseases
of the ruminant stomachs except
carbohydrate engorgement and
abomasal torsion, where dehydration,
acidosis and gastric infarction occur,
vital signs may be within the normal
range.

The differential diagnosis of the diseases
associated with gastrointestinal dys-
function in cattle is summarized in
Table 6.2.

In contrast with most other parts of the
ruminant alimentary tract, and with the
stomach of nonruminants, specific lesions
of the mucosa of the forestomachs are
uncommon. Penetration of the reticular
wall by metallic foreign bodies is a
common disease and is dealt with below
under the heading of traumatic reticulo-
peritonitis, but it is the peritonitis that
causes interference with ruminal motility.
Rarely, there are actinomycotic or neo-
plastic lesions at the fundus of the
reticulum that interfere with the proper

functioning of the esophageal groove and
lead to a syndrome of vagus indigestion
described later. Rumenitis does occur
commonly but only as a secondary
change in acute carbohydrate engorge-
ment and it is this that has such
damaging effects on gut motility and fluid
and electrolyte status and eventually kills
most cows. The rumenitis may have a
long-term effect on ruminal motility but
its main significance is as a portal for
infection leading to the development of
hepatic abscesses. Ingested animal hairs,
plant spicules and fibers are also credited
with causing rumenitis but no clinical
signs have been associated with the
lesions. Because of the high prevalence
of rumenitis lesions in cattle on heavy
concentrated feed, especially when the
feed is awned barley, the awns have been
incriminated as traumatic agents. In acute
arsenic poisoning there is an early post-
mortem dehiscence of the ruminal
mucosa but no apparent lesions during
life.

Disease

Epidemiology and history

Clinical findings

Clinical pathology

Response to treatment

Simple indigestion

Dietary indiscretion, too much
of a palatable, or indigestible,
or change of, or damaged, or
frozen food. Can be outbreak.
Consumption of excessive
quantities of finely chopped
straw

Simple gastrointestinal
atony. Voluminous feces .
during recovery. Gross
distension of the rumen
and abdomen in straw
impaction

All values normal. Slight
changes in ruminal acidity,
should be self-buffered

Simple indigestion. Excellent
just with time. Usually a mild
purgative. Rumenotomy
necessary in case of
straw impaction

Carbohydrate

Access to large amount of

Severe gastrointestinal atony

Hemoconcentration with

Intensive intravenous

engorgement

readily fermentable carbohydrate
when not accustomed. Enzootic
in high-grain rations in feedlots

with complete cessation of
ruminal activity. Fluid splashing
sounds in rumen. Severe
dehydration, circulatory
failure. Apparent blindness,
then recumbency and too
weak to rise. Soft odoriferous
feces

severe acidosis, pH of rumen
juice < 5, serum phosphorus
levels up to 3-5 mmol/L,
serum calcium levels
depressed. No living
protozoa in rumen

fluid and electrolyte
therapy necessary for
survival. Rumenotomy
or rumen lavage may
be necessary. Alkalinizing
agents

Ruminal tympany

Frothy bloat on lush legume
pasture or low-roughage
feedlot ration, especially
lucerne hay. Free gas bloat
secondary, occasionally
primary on preserved feed

Gross distension of abdomen,
especially high up on left.
Sudden onset. Severe pain
and respiratory distress.
Rumen hypermotility
initially. Liquid feces.
Resonance on percussion
over rumen

Nil

Excellent if in time, stomach
tube for free gas. Froth-
dispersing agent in frothy
bloat. Severe cases may
require trocarization or
emergency rumenotomy

Acute traumatic
reticuloperitonitis

Exposure to pieces of metal.
Sporadic. Usually adult cattle

Sudden-onset reticulorumen
atony, mild fever. Pain on
movement and deep palpation
of ventral abdomen caudal to
xiphoid. Reduced amount of
feces. Lasts 3 days, then
improvement begins

Neutrophilia and shift to left

Good response to
antimicrobials for 3 days,
magnet, immobilize in stall.
If no recovery after 3 days
consider rumenotomy

Chronic traumatic

Previous history of acute

Inappetence to anorexia;

Hemogram depends on

Antimicrobials for several days.

reticuloperitonitis

local peritonitis

loss of weight; temperature,
heart rate and respirations
normal; rumen small and
atonic, chronic moderate
bloat common, feces scant,
grunt may be detectable on
deep palpation over xiphoid,
reticular adhesions on
laparotomy

stage and extent of
inflammation

Consider rumenotomy.

Small percentage will respond

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

.. v ■

Disease

Epidemiology and history

Clinical findings

Clinical pathology

Response to treatment

Torsion of

Sequel to RDA

History of RDA followed by

Dehydration alkalosis.

Laparotomy, abomasotomy

abomasum

sudden onset of acute

hypochloremia

and drainage. Survival rate

abdominal pain, distension

about 75% if treated early.

of right abdomen, loud
'ping'. Distended tense
abomasum palpable per
rectum in right lower quadrant,
marked circulatory failure,
weakness, bloodstained feces,
death in 48-60 h if not treated
surgically

Fluid therapy required

Primary

Insufficient intake of

Dullness, anorexia, reduced

Ketonuria and hypoglycemia

Dextrose intravenously and

acetonemia

energy in early lactation

feces, lose body condition,

propylene glycol oral^r, or

(wasting form)

milk yield down. Rumen

intramuscular corticosteroids.

activity depressed

Usually excellent response

Acute intestinal

May be heightened activity,

Sudden onset, short period

Progressive dehydration and

Surgery is necessary

obstruction

e.g. during sexual activity.

acute abdominal pain. Kicking

hemoconcentration over

Often no particular history

at belly, rolling. Complete
anorexia, failure to drink and
alimentary tract stasis.
Progressive dehydration.
Distended loops of intestine
may be palpable. Gray to red
foul-smelling rectal contents

3-4 days

Idiopathic

Few days postpartum, may

Anorexia, complete absence

Nil

Usually recover spontaneously

paralytic ileus

be change in diet

of feces for 24-48 h; may
detect ping over right flank

Obstruction of

Single animal usually. Area

Sudden onset acute

Hypochloremia,

Depends on nature of

small intestine

prevalence may be high

abdominal pain. Attack brief,

hypokalemia, severity

phytobezoar: dense fiber balls

by phytobezoar

some years. Depends on

often missed. Then anorexia,

depends on location

require surgery, crumbly

frequency of fibrous plants,

ruminal stasis, heart rate

masses may pass after

e.g. Romulea spp.

increases to 1 20/min
over 3-4 days. Abdomen
distends moderately, splashing
sounds and tympany right
flank. Rectal examination -
distended loops of intestine
if obstruction in distal small
intestine, may feel 5-6 cm
diameter fiber ball, feces pasty,
gray-yellow, foul-smelling, small
amount only. Untreated and
fatal cases have course of
4-8 days

mineral oil for several days

Abomasal ulcer

Soon after (2 weeks) parturition.

Gastrointestinal atony with

Melena or occult blood in

Alkalinizing agents orally.

High producers on heavy grain

melena and pallor. May be

feces. On perforation with

Surgery if medical treatment

feed. In intensive feeding systems

sufficient blood loss to cause

local peritonitis may be

unsuccessful

disease is becoming enzootic

death, prompt recovery after

leukocytosis and left shift

in some areas

4 days more likely. Perforation
and rupture of ulcer leads to
death in a few hours

Anemia due to hemorrhage

Pregnancy

Fat beef cattle deprived of feed

Complete anorexia, rumen

Ketonia, increase in

Poor response to therapy.

toxemia of beef

in last month of pregnancy.

stasis, scant feces, ketonuria,

nonesterified fatty acids,

Fluids, anabolic steroids,

cattle

Commonly have twin

weak and commonly

ketonuria, increase in

insulin

pregnancy

recumbent

liver enzymes

Fatty liver

Fat dairy cow, few days

Complete anorexia, rumen

Ketonemia, increase in liver

Poor response to therapy.

(fat cow)

following parturition or may

stasis, almost no milk yield.

enzymes

Glucose, insulin, anabolic

syndrome

have had LDA for several days

ketonuria initially but
may have more later

steroids

Cecal dilatation

Single case. Dairy cow, early

Systemically normal. Rumen

Nothing diagnostic, but has

Good response to surgical

and/or torsion

lactation, inappetence,

only slightly hypotonic, high-

hemoconcentration,

correction. Unfavorable

feces may be scant. Severe

pitched ping on percussion

compensated hypochloremia.

prognosis with severe

cases have history of mild

over right upper flank, which

hypokalemia and alkalosis

torsion and gangrene

abdominal pain

may be distended. Rectally
enlarged cylindrical movable
cecum with blind end can

of apex

be felt

(i cont'd)

Special examination of the alimentary tract and abdomen of cattle

31

^Differential diagnosis of cause

s of gastrointestinal 'dysfunct

•fi .*• ,, ,V:/- V 7 • ? -> S *> W • £

on of cattle A ' •'

Disease

Epidemiology and history

Clinical findings

Clinical pathology

Response to treatment

Acute diffuse
peritonitis

Following acute traumatic
reticuloperitonitis, uterine
rupture at parturition, rupture
of rectum, postsurgical

Acute toxemia, fever followed
by hypothermia, weakness,
tachycardia, recumbency,
groaning, moderate distension
scant feces, palpate
fibrinous adhesions rectally

Leukopenia, neutropenia,
degenerative left shift.
Hemoconcentration.
Paracentesis positive

Usually die

Chronic ruminal
tympany in
feeder calves

Beef calves 6-8 months of age
following weaning; feeder
cattle after arrival in feedlot

Chronic free-gas bloat,
relapses after treatment,
no other clinical findings

Nil

Good response to surgical
ruminal fistula or insertion of
corkscrew-type trocar and
cannula left in place for few
weeks

Omasal impaction

Uncommon. Single cases in
pregnant cows with vagus
indigestion. Feedlot cattle
with abomasal impaction dietary
in origin

Inappetence to anorexia. Scant
feces, abdominal distension.
Rectally, large distended
round hard viscus below
kidney can be felt

Nil

Slaughter for salvage. Treat
for abomasal impaction

Other lesions of the forestomachs are
parakeratosis, discussed below, and
villous atrophy, sometimes encountered
in weanling ruminants on special diets
low in fiber, even succulent young pas-
ture, but these are not known to influence
stomach function or motility. The factors
that principally affect ruminal motility are
those chemical and physical character-
istics of its contents that are dealt with in
simple indigestion and acute carbohydrate
engorgement. Lesions in, and mal-
functioning of, the abomasum are much
more akin to abnormalities of the stomach
in monogastric animals.

Some of the physiological factors that
affect reticulorumen function and the
clinical factors which cause reticulorumen
dysfunction are summarized in Table 6.1.
When reticulorumen hypomotility is
present the problem is to decide if the
cause is directly associated with the fore-
stomach and abomasum, or both, or other
parts of the alimentary tract, or if the cause
is due to an abnormality of another system.
Differentiation requires a careful clinical
examination, including simple laboratory
evaluation of the rumen contents.

The factors that affect the motility of
the rumen are presented in the section on
simple indigestion, as are the principles of
treatment in cases of ruminal atony.

REVIEW LITERATURE

Constable PD, Hoffsis GF, Rings DM. The
reticulorumen: normal and abnormal motor func-
tion. Fhrt I. Primary contraction cycle. Compend
Contin Educ PractVet 1990; 12:1008-1014.
Constable PD, Hoffsis GF, Rings DM. The reti-
culommen:normal and abnormal motor function.
Part II. Secondary contraction cycles, rumination,
and esophageal groove closure. Compend Contin
Educ PractVet 1990; 12:1169-1174.

REFERENCES

1. Constable PD et al. Compend Contin Educ Pract
Vet 1990; 12:1008.

2. Constable PD et al. Compend Contin Educ Pract
Vet 1990; 12:1169.

Special examination of the
alimentary tract and
abdomen of cattle

When gastrointestinal dysfunction is
suspected, a complete special clinical and
laboratory examination may be necessary
to determine the location and nature of
the lesion. A systematic method of exam-
ination is presented here.

HISTORY

A complete history, with as much detail as is
available, should be obtained. The stage of
the pregnancy-lactation cycle, days since
parturition, the nature of the diet, the speed
of onset and the duration of illness may
suggest diagnostic possibilities. An accurate
description of the appetite will suggest
whether the disease is acute or chronic. The
previous treatments used and the response
obtained should be determined. Any
evidence of abdominal pain and its
characteristics should be detennined. The
nature and volume of the feces may suggest
enteritis or alimentary tract stasis.

SYSTEMIC STATE, HABITUS AND
APPETITE

The vital signs indicate the severity of the
disease and suggest whether it is acute,

| subacute or chronic. In acute intestinal
I obstruction, abomasal torsion, acute
; diffuse peritonitis and acute carbohydrate
engorgement, the heart rate may be
100-120/min and dehydration is usually
obvious. Pallor of the mucous mem-
branes is an indicator of alimentary tract
hemorrhage, especially if there is con-
I current melena. If cattle with any of the
I above diseases are recumbent and unable
| to stand, the prognosis is usually
I unfavorable. A marked increase in the i
i rate and depth of respirations associated j

with alimentary tract disease usually
indicates the presence of fluid or electro-
lyte disturbances and possible subacute
pain. Grunting or moaning suggests
abdominal pain associated with distension
of a viscus or acute diffuse peritonitis.

The appetite and the presence or
absence of rumination are very reliable
indicators of the state of the alimentary
tract, including the liver. Complete anorexia
persisting for more than 3-5 days is
unfavorable. The return of appetite and
rumination with chewing of the cud
following medical or surgical treatment
for alimentary tract disease is a favorable
prognostic sign. Persistent inappetence
suggests a chronic lesion, usually with an
unfavorable prognosis.

ORAL CAVITY AND ESOPHAGUS

The oral cavity is easily examined by
inspection and manual palpation with the
aid of a suitable mouth speculum. The
patency of the esophagus is determined
by passage of a stomach tube into the
rumen through the oral cavity, with the
aid of a cylindrical metal speculum, or
through the nasal cavity.

INSPECTION OF THE ABDOMEN

The contour or silhouette of the abdo-
men should be examined from the rear,
and each lateral region viewed from an
oblique angle. Examination of the contour
can assist in determining the cause of
abdominal distension. Abdominal dis-
tension may be unilateral, bilaterally
symmetrical or asymmetrical or more
prominent in the dorsal or ventral
half. Recognition of the anatomical region
of maximum distension suggests diag-
nostic possibilities, which are set out in
Figure 6.1. The differential diagnosis
of abdominal distension of cattle is
summarized in Table 6.3.

i2

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

SPECIAL EXAMINATION OF THE ALIMENTARY TRACT AND ABDOMEN OF CATTLE

Hydrops

Paralytic ileus

Pneumoperitoneum

Right-side abomasum
dilated/torsion

Abomasal impaction

Fig. 6.1 Silhouettes of the contour of the abdomen of cattle, viewed from the rear, with different diseases of the
abdominal viscera. (After Stober M, Dirksen G. Bovine Pract 1977; 12:35-38.)

i ''Ml© si =xa n; l ©l I (pi^efern^-teijr, .irst (cgSfiHIip

Cause

Major clinical findings and methods of diagnosis

Distension of rumen

Acute ruminal tympany

Vagus indigestion

Grain overload
Simple indigestion

Distension of abomasum

Right displacement of
abomasum and torsion (volvulus)
Abomasal impaction

Left displacement of abomasum

Abomasal trichobezoars

Distension of intestines

Enteritis

Intestinal obstruction

Paralytic ileus

Cecal dilatation and torsion

Enlargement of uterus
Physiological

Marked distension of left abdomen, less of right. Very tense distended left paralumbar fossa, dull resonance on
percussion. Pass stomach tube and attempt to relieve gas or froth

Marked distension of left abdomen, less of right 'papple-shaped' abdomen. Fluctuating rumen on palpation. Excessive
rumen activity or complete atony. Large L-shaped rumen on rectal examination. Pass large-bore stomach tube to
remove contents to aid in diagnosis

Moderate distension of left flank, less of right. Rumen contents are doughy or fluctuate. Fluid-splashing sounds may
be audible on ballottement. Rumen static and systemic acidosis. Rumen pH below 5

Moderate distension of left flank; rumen pack easily palpable and doughy. Contractions may be present or absent
depending on severity. Systemically normal. May be dropping cuds

Right flank and paralumbar fossa normal to severely distended. Ping. Rectal palpation of fluctuating or tense viscus
in right lower quadrant

Right lower flank normal to moderately distended. Doughy viscus palpable caudal to costal arch. Rectal palpation feel
doughy viscus in right lower quadrant

Abdomen usually gaunt. Occasionally distended left paralumbar fossa due to displaced abomasum. Ping on percussion
over upper aspects of ribs 9-1 2

Older calves (2-4 months). Right lower flank distended. Fluid-splashing sounds. Painful grunt on deep palpation.
Confirm by laparotomy and abomasotomy

Slight to moderate distension of right abdomen. Fluid-rushing and splashing sounds on auscultation and ballottement.
Diarrhea and dehydration

Slight to moderate distension of right abdomen. Fluid tinkling, percolating and splashing sounds on auscultation and
ballottement. May palpate distended loops of intestine or intussusception rectally. Scant dark feces. Paracentesis
abdominis

Slight to moderate distension of right abdomen. Tinkling sounds on auscultation. Tympanitic ping on percussion.
Loops of distended intestine palpable per rectum. Scant feces but recover if no physical obstruction
Right flank may be normal or moderately distended. Ping present in right paralumbar fossa. Palpate movable blind
end cecum on rectal examination. Confirm by laparotomy

Gross distension of both flanks, especially right. Normal pregnancy with more than one fetus. May palpate rectally

Special examination of the alimentary tract and abdomen of cattle

3'

i

slS

Cause

Major clinical findings and methods of diagnosis

Pathological

Hydrops amnion

Hydrops allantosis

Fetal emphysema

Fluid accumulation in
peritoneal cavity
Ascites

Congestive heart failure,
ruptured bladder
Pneumoperitoneum
Perforated abomasal ulcer,
postsurgical laparotomy

Gradual enlargement of lower half of abdomen in late gestation. Flaccid uterus, fetus and placentomes are easily
palpable per rectum

Gradual distension of lower half of abdomen in late gestation. Palpable uterus rectally, cannot palpate placentomes
or fetus

History of dystocia or recent birth of one calf, twin in uterus and emphysematous. Diagnosis obvious on vaginal and
rectal examination

Bilateral distension of lower abdomen. Positive fluid waves. Paracentesis abdominis. May feel enlarged liver
behind right costal arch

Not common. Bilateral distension of dorsal half of abdomen. Ping both sides

DISTENSION OF THE ABDOMEN

The cause of distension of the abdomen
of cattle is determined by a combination
of the following examinations:

back drainage by gravity flow. After the
rumen is partially emptied it is usually
possible to more accurately assess the
rumen and the abdomen.

Nature of rumen contents
The nature of the rumen contents can be
assessed by palpation of the rumen
through the left paralumbar fossa. In the
roughage-fed animal, the rumen contents
are doughy and pit on pressure. In cattle
that have consumed large quantities of
unchopped cereal grain straw, the rumen
is large and the contents feel very firm but
not hard; they always pit on pressure. In
the dehydrated animal the contents may
feel almost firm. In the grain-fed animal
the contents may be soft and porridge-
like. When the rumen contains excessive
quantities of fluid, the left flank fluctuates
on deep palpation. In the atonic rumen
distended with excess gas the left flank
will be tense, resilient and tympanitic on
percussion.

In mature cattle that have been anorexic
for several days, the rumen may be smaller
than normal and the dorsal sac will be
collapsed (rumen collapse). There will be a
'pung' (low-pitched ping) in the left upper
abdomen extending dorsally to the
transverse processes of the lumbar
vertebrae, lack of abdominal distension,
absence of fluid upon succession of the
area of the ping, and on rectal palpation the
dorsal sac of the rumen will feel collapsed. 2

Auscultation of the rumen and left
flank

In the normal animal on a roughage diet
there are two independent contraction
sequences of the reticulorumen. The pri-
mary cycle recurs approximately every
minute and consists of a diphasic con-
traction of the reticulum followed by a
monophasic contraction of the dorsal
ruminal sac and then by a monophasic
contraction of the ventral ruminal sac.
These movements are concerned primarily
with'mixing'the rumen contents and with
assisting the passage of rumen contents
into the omasum.

The secondary cycle movements
occur at intervals of about 2 minutes and

>•’ Inspection of the contour or silhouette
of the abdomen to determine the
region of maximum distension

- If necessary, relief of rumen contents
with a stomach tube to determine if
the distension is due to an enlarged
rumen. The ruminal contents can also
be examined grossly at the same time

° Percussion or ballottement and
simultaneous auscultation to detect
fluid-splashing sounds indicating the
presence and location of gas- and
fluid-filled viscera

- Rectal examination to feel any
obvious enlargements or
abnormalities

0 Abdominocentesis to determine the
nature and amount of peritoneal fluid,
which may indicate the presence of
ischemic necrosis of intestines or
peritonitis

0 Trocarization of severely gas- filled
distended regions, such as an
abomasal volvulus in a calf.

LAVAGE OF DISTENDED RUMEN

In adult cattle presented with severe
abdominal distension due to gross dis-
tension of the rumen it is difficult, if not
impossible, to assess the status of the
abdomen. To determine if the rumen is
distended and/or to relieve the pressure, a
large-bore stomach tube should be
passed into the rumen. In vagus indiges-
tion, the rumen may be grossly distended
with fluid contents that will gush out
through a large-bore tube. In some cases
100-150 L of rumen contents may be
released. If no contents are released the
contents may be frothy or mushy and the
rumen end of the tube will plug almost
instantly. Rumen lavage may then be
attempted using a water hose to deliver
20-40 L of water at a time, followed by

LEFT SIDE OF ABDOMEN AND
RUMEN

Inspection and palpation
The primary and secondary cycle con-
tractions of the reticulorumen are
identified by simultaneous auscultation,
palpation and observation of the left
paralumbar fossa and the left lateral
abdominal region. During contractions of
the rumen there is an alternate rising and
sinking of the left paralumbar fossa in
conjunction with abdominal surface
ripples. The ripples reflect reticulorumen
contractions and occur during both the
primary (or mixing) cycle contraction
and the secondary (or eructation) cycle
contractions. 1 As the left paralumbar
fossa rises during the first part of the
primary cycle contraction there are two
horizontal ripples that move from the
lower left abdominal region up to the
paralumbar fossa. When the paralumbar
fossa sinks, during the second part of the
primary cycle, the ripple moves ventrally
and fades out at the lower part of the left
abdominal region. Similar ripples follow
up and down after the rising and sinking
of the paralumbar fossa associated with
the secondary cycle movements.

In vagus indigestion, there may be
three to five vigorous incomplete con-
tractions of the reticulorumen per minute.
These contractions may not be audible
because the rumen contents are porridge-
like and do not cause the normal crack-
ling and rustling sounds of the rumen
containing coarse fibrous ingesta. How-
ever, the contractions are visible and
palpable as waves of undulations of
the left flank. If reticulorumen motility
is assessed only on the basis of inspec-
tion and palpation, the results will be
misleading. _

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

are confined to the rumen and consist of
a contraction of the dorsal sac followed
by a contraction of the ventral sac. The

former causes the fluid contents of the
dorsal sac to be forced ventrally and the gas
layer to be forced cranially to the region of
the cardia where eructation takes place.
Contractions of the dorsal and ventral
sacs cause undulations of the left
paralumbar fossa and lower flanks that
are readily visible and palpable.

The clinical recognition of the presence
or absence of either the primary cycle or
secondary cycle contractions or both may
aid in determining the cause and severity
of the disease and the prognosis. These
are outlined in Table 6.1.

Auscultation of rumen
To auscultate the rumen, the stethoscope
is placed in the middle of the left
paralumbar fossa. After two complete
contractions have occurred, the stetho-
scope is moved cranially in the fossa and
cranial to the fossa over the dorsal third of
the 10th-13th ribs to determine if rumen
contractions are audible in the region,
which commonly becomes occupied with
a left-side displacement of the abomasum.
In the normal animal, ruminal contractions
are audible in this region.

The type, strength and frequency of
rumen movements should be noted.
The rumen sounds of the normal animal
consuming roughage are rasping, rustling,
exploding and booming-crackling sounds.
When the rumen contains less coarse
roughage or primarily grain, the sounds
may be much less distinct but still possess
a crackling characteristic.

Fluid-tinkling or fluid-splashing
sounds. The presence of fluid-tinkling or
fluid-splashing sounds over the left
paralumbar fossa, usually along with an
atonic rumen, suggests the presence of
excessive quantity of liquid contents in
the rumen, and that the coarse ingesta is
not floating on the fluid layer of the
rumen contents as in the normal animal.
Fluid-splashing sounds suggest diseases
such as grain overload, or an atonic
rumen associated with prolonged anorexia
(chronic diffuse peritonitis, abomasal or
omasal impaction). Fluid-splashing and
-tinkling sounds can also be elicited by
ballottement and simultaneous auscul-
tation of the left lower flank in left-side
displacement of the abomasum, because
of its liquid contents. To assist in the
differential diagnosis, the outline of the
rumen can be auscultated and percussed
to observe a much wider area of metallic
sound than is normally expected in left-
side displacement of the abomasum.

In vagus indigestion with an enlarged
hypermotile rumen, the contractions of
the rumen occur more frequently than

norma], at 3--6/min, and are easilyvisible as
prominent abdominal ripples over the left
flank. But characteristically, the ruminal
sounds are usually not audible or barely
so because the rumen contents are
homogeneous and porridge -like as a result
of prolonged maceration in the rumen. The
absence of coarse fiber in the ingesta and
the lack of coordinated reticulorumen
primary and secondary contractions
minimizes the intensity of the ruminal
sounds.The lack of effective secondary cycle
contractions and eructation results in frothy
bloat. Complete atony and gross distension
of the rumen is characteristic of advanced
vagus indigestion.

Percussion and simultaneous auscul-
tation of the left paralumbar fossa over an
area extending from the mid-point of the
ninth rib to the 13th rib is used to detect
the presence of a 'ping' or high-pitched
metallic tympanic sound associated with
left-side displacement of the abomasum.
Percussion is performed with a flick of the
flexed finger or most reliably with a
percussion hammer. The causes of
'pings' on percussion of the left abdo-
men in mature cattle include left-side
displacement of the abomasum, atonic
rumen and, rarely, pneumoperitoneum.
The tympanic sound associated with an
atonic rumen is lower-pitched than that
associated with a left-side displacement
of the abomasum and may be called a
'pung'.

For special investigations of reticulo-
rumen motility radiotelemetry capsules
can be placed in the rumen. 3

RIGHT SIDE OF ABDOMEN

The contour of the right side of the
abdomen should be examined by inspec-
tion for evidence of distension, which
may be due to a viscus filled with fluid,
gas or ingesta, ascites or a gravid
uterus. In severe distension of the rumen,
the ventral sac may also distend the lower
half of the right flank.

A combination of deep palpation,
ballottement and simultaneous percussion
and auscultation, and succussion (slightly
rocking the animal from side to side) is
used to detect the presence of viscera that
are distended with gas and/or fluid, or
ingesta.

The causes of 'pings' audible on
auscultation and percussion over the right
abdomen include:

° Right-sided dilatation and volvulus of

the abomasum

° Cecal dilatation and torsion
° Torsion of the coiled colon
0 Gas-filled descending colon and

rectum in a cow with persistent

tenesmus

° Intestinal tympany of unknown

etiology

s Torsion of the root of the mesentery
in young calves

° Intussusception causing intestinal
tympany

• Pneumoperitoneum
® Postpartum intestinal tympany, which
occurs in the postparturient cow (for
the first few days following parturition).

The causes of fluid-splashing sounds
on ballottement and auscultation of
the right flank include:

e Fluid-filled intestines in acute
intestinal obstruction and enteritis
° Fluid-filled abomasum in right-
sided dilatation.

Palpation of a firm viscus in the right
flank caudal or ventral to the right costal
arch may be due to:

° Omasal impaction
° Abomasal impaction
0 Enlarged ventral sac of the rumen,
which extends over to the right
abdominal wall

0 Enlargement of the liver. The liver
must be grossly enlarged before it is
palpable caudal to the right costal
arch.

A rectal examination is necessary to
identify the distended viscus associated
with these abnormal sounds, and often a
laparotomy is required.

EXAMINATION OF RUMEN FLUID

Examination of the rumen fluid is often
essential to establish an accurate diag-
nosis of diseases of the forestomach.
Rumen fluid can be obtained with a
stomach tube passed into the rumen, the
fluid being withdrawn with the vacuum of
a stomach pump. The major difficulty is
avoiding contamination of the sample
with saliva, which can be avoided if a free
flow of fluid is obtained. Specialized
stomach tubes are available that are
weighted and can be directed into the
ventral sac to collect up to 500 mL of
fluid. 4 Rumen fluid samples can also be
obtained by percutaneous aspiration of
the ventral sac of the rumen on the lower
left ventrolateral abdominal quadrant,
horizontal with the patella and 20 cm
caudal to the last rib. The site is prepared,
xylazine sedation given and a 12-15 cm
16-gauge needle is thrust firmly and
quickly perpendicular to the skin into the
rumen. Rumen fluid is withdrawn with a
syringe and pH is measured immediately
with a portable pH meter or wide-range
pH paper (pH values of 2-12).

ANALYSIS OF RUMEN FLUID

The color, depending on the feed to a
limited extent, will be a green, olive green
_or brown green. At pasture, the color is

Special examination of the alimentary tract and abdomen of cattle

• 3

very green; with root crops the color tends
to be gray; and with silage or straw the
color is mostly yellow-brown. The color of
the rumen contents is milky-gray in grain
overload and greenish-black in cases
where rumen stasis is of long duration
and where putrefaction is occurring
within the rumen.

The consistency of the rumen fluid is
normally slightly viscid, and watery
rumen contents are indicative of inactive
bacteria and protozoa. Excess froth is
associated with frothy bloat as in primary
ruminal tympany or vagus indigestion. The
odor is normally aromatic and, although
somewhat pungent, not objectionable to
the nose. A moldy, rotting odor usually
indicates protein putrefaction, and an
intensely sour odor indicates an excess
of lactic acid formation, due to grain or
carbohydrate engorgement.

The pH of the rumen fluid varies
according to the type of feed and the time
interval between the last feeding and
taking a sample for pH examination. The
normal range, however, is between 6.2
and 7.2. High pH values (8-10) will be
observed when putrefaction of protein is
occurring in the rumen or if the sample is
mixed with saliva. Low pH values (4-5)
are found after the feeding of carbo-
hydrates. In general, a value below 5 indi-
cates carbohydrate engorgement and this
pH level will be maintained for 6-24 hours
after the animal has actually consumed the
carbohydrate diet.

For experimental purposes, continuous
monitoring of the pH of the rumen
contents is possible with a pH probe
containing a commercial microelectrode
and a reference- electrode with a pressure-
equalizing system placed in the reticulum. 5
By feeding diets with changing com-
position it is possible to provoke marked
changes in rumen pH. The probes are
programmed to sample pH and tempera-
ture every 30 seconds.

Microscopic examination of a few
drops of rumen fluid on a glass slide with
a low-power field will reveal the level of
protozoon activity. Normally 5-7 proto-
zoons are active per low-power field. In
lactic acidosis the protozoa are usually
absent or a few dead ones are visible. The
rumen fluid can be stained with Gram
stain to determine the predominant
bacterial flora, which are normally Gram-
negative but in grain overload become
Gram-positive.

Chloride concentration can be deter-
mined by centrifuging the fluid and
analyzing the supernatant for chloride
levels. These are normally 10-25 mEq/L in
cattle and <15 mEq/L in sheep. Elevated
rumen chloride concentrations result
from abomasal reflux, ileus or high salt
intake.

RECTAL PALPATION OF
ABDOMEN

Some of the specific abnormalities of the
digestive tract, which are commonly
palpable on rectal palpation, include the
following, which relates to Figure 6.2
(a-1), illustrating the abnormalities
through a transverse section of the
abdomen.

(a) Normal

(b) L-shaped rumen: occurs commonly
in vagus indigestion and other
diseases of the rumen characterized
by gradual distension of the
rumen

(c) Cecal torsion: commonly palpable
as long distended organ, usually
movable, may feel the blind

end

(d) Abomasal torsion: commonly
palpable as tense viscus in lower
right half of abdomen

(e) Abomasal impaction: not usually
palpable in late pregnancy

(f) Left-side displacement of the
abomasum: usually cannot palpate
the displaced abomasum but can
often feel rumen, which is usually
smaller than normal

(g) Intussusception: not always
palpable, dependent on location of
intussusception and the size of the
animal

(h) Mesenteric torsion: usually palpable

(i) Intestinal incarceration: commonly
palpable

(j) Peritonitis: only palpable if
peritoneum of posterior aspect of
abdomen affected

(k) Lipomatosis: commonly palpable as
'lumps' in the abdomen and pelvic
cavity

(l) Omental bursitis: not common.

In Figure 6.2 (m-p) are included for the
differential diagnosis of the diseases each
represents.

As part of the differential diagnosis of
digestive tract disease in the post-
parturient cow, the uterus should be
examined carefully for evidence of
retained placenta and metritis. Both
vaginal and rectal examinations should
be performed. The toxemia caused by
retained fetal membranes and postpartum
metritis may cause anorexia, rumen stasis,
paralytic ileus, scant feces and sometimes
an idiopathic postpartum 'ping' in the
right flank, all of which may be mis-
interpreted as a primary digestive tract
disease.

GROSS EXAMINATION OF FECES

The gross appearance of the feces of cattle
is not only an indicator of disease of the
digestive tract but can provide valuable

clues for the differential diagnosis of
disease elsewhere.

AMOUNT

In adult cattle, the passage of ingesta
through the digestive tract takes 1.5-4 days.
Mature cattle generally pass some feces
every 1.5-2 hours, amounting to a total bf
30-50 kg/day in 10-24 portions.

A reduction in the bulk of feces can
be due to a decrease in feed or water in-
take or a retardation of the passage
through the alimentary tract. In diarrhea,
the feces are passed more frequently
and in greater amounts than normal and
contain a higher water content (>90%)
than normal.

ABSENCE OF OR SCANT FECES

Failure to pass any feces for 24 hours or
more is abnormal and the continued
absence of feces may be due to a physical
intestinal obstruction. However, in many
cases the intestine is not physically
obstructed but rather there is a functional
obstruction. Diseases causing disturb-
ances of motility of the rumen and abo-
masum often result in a relative absence
of feces. Paralytic ileus of the intestines
due to peritonitis or idiopathic intestinal
tympany also result in a marked reduction
in feces, sometimes a complete absence,
for up to 3 days. The marked reduction of
feces that occurs in functional obstruction
is a major source of diagnostic confusion
because it resembles physical obstruc-
tions of the intestines. The causes of
physical and functional obstruction of the
alimentary tract of cattle are summarized
in Figure 6.3.

COLOR

The color of the feces is influenced by the
nature of the feed, the concentration of
bile in the feces and the passage rate
through the digestive tract. Calves reared
on cows' milk normally produce gold-
yellow feces, which become pale brown
when hay or straw is eaten. The feeding of
milk substitutes adds a gray component
to a varying degree.

The feces of adult cattle on green forage
are dark olive-green, on a hay ration more
brown-olive, while the ingestion of large
amounts of grain produces gray-olive feces.
A retardation of the ingesta causes the
color to darken. The feces become ball-
shaped and dark brown with a shining
surface due to the coating with mucus.
Diarrheic feces tend to be paler than
normal because of their higher water
content and lower concentration of bile.

The presence of large amounts of bile
produces a dark olive -green to black-
green color such as in cattle with hemolytic
anemia. In cattle with obstruction of the
common bile duct, the feces are pale
olive-green because of the absence of bile
pigments.

Hydrops

Enlarged kidney

Palpation lymph nodes

Cystitis, ureteritis

Fig. 6.2 Schematic illustration of the rectal findings in cattle affected with different diseases of the abdominal viscera.
(After Stober M, Dirksen G. Bovine Pract 1977; 12:35-38.)

Special examination of the alimentary tract and abdomen of cattle

3i

r

Physical obstruction
(complete absence of feces
until obstruction relieved)

i

f

Obstruction of

Strangulation

lumen only

obstruction

(phytobezoars,

(intussusception,

trichobezoars,

torsion, coiled colon,

enteroliths)

torsion of root of
mesentery, cecal
torsion)

I

Functional obstruction
(scant or absence of feces for
2-4 days or until motility is restored)

r

Forestomach

Intestines

(traumatic

(paralytic ileus due to

reticuloperitonitis,

peritonitis, acute

vagus indigestion,

toxemias, severe fatty

omasal impaction)

liver, idiopathic
intestinal tympany)

Abomasum

(impaction (dietary or
secondary to vagal nerve
injury or peritonitis).
Left and right side
displacement and torsion.
Abomasal ulcers)

Fig. 6.3 Some common causes of physical and functional obstruction of the alimentary tract of cattle.

Blood in the feces may originate from
the following locations:

0 Hemorrhage into the abomasum:
acute hemorrhage usually appears as
black, tarry feces (melena); chronic
hemorrhage as occult blood
° Hemorrhagic enteritis of small
intestines: the feces are uniformly
dark red

0 Hemorrhagic enteritis of the large
intestines: in the cecum or colon,
blood appears evenly distributed
throughout the feces (dysentery); in
the rectum, blood appears as streaks
or chunks of frank blood unevenly
distributed throughout the feces
(hematochezia)

° 'Occult blood' is not visible grossly;
the color of the feces may be normal
or dark. An occult blood test
(Hemetest tablets) is required to
determine its presence. Occult blood
occurs most commonly when there
are only small quantities of blood in
the alimentary tract, as with minimal
hemorrhage insufficient to result in
melena. It also may be due to the
swallowing of blood coughed up from
pulmonary hemorrhage.

ODOR

Fresh bovine feces are not normally
malodorous. Objectionable odors are
usually due to putrefaction or fermen-
tation of ingesta, usually associated with
inflammation. For example, the feces in
cattle with salmonellosis may be fetid
while in advanced pericarditis with
visceral edema due to passive congestion
the feces are profuse but not odoriferous.

CONSISTENCY

The consistency of the feces is dependent
on the water content, the type of feed and
the length of time the ingesta has
remained in the digestive tract. Normally,
milk-fed calves excrete feces of a medium
to firm porridge-like consistency. After
transition to a plant diet, the first solid
particles begin to appear. Normal bovine
feces are of a medium porridge-like
consistency. A moderate thickening leads
to the passage of fecal disks of a more
solid consistency and severe dehydration
causes the formation of firm balls of feces
arranged in facets inside the rectum, the
surfaces of which are dark and coated
with mucus. The feces of cows with left-
side displacement of the abomasum are
commonly pasty in appearance. Sticky
and tenacious feces are commonly seen in
obstruction of the forestomachs (vagus
indigestion, chronic peritonitis).

DEGREE OF DIGESTION

The proportion of poorly digested plant
particles in the feces is dependent on the
duration and adequacy of rumination and
the rate of passage of ingesta through the
forestomach and abomasum. The length
of time the ingesta is in the postruminal
digestive tract seems to have no appreci-
able influence on its digestion. Inadequate
digestion indicates failure in rumination
and/or accelerated passage of ingesta
through the forestomach. Thus in some
cattle with acute traumatic reticulo-
peritonitis, the feces may contain small
walnut-sized chunks of undigested plant
fibers that have escaped the cellulose
digestive processes of the forestomachs.
The presence of large numbers of kernels

of grain in the feces is associated with the
ingestion of large quantities of unprocessed
grain such as wholewheat or barley.

OTHER SUBSTANCES IN THE FECES
Mucus

The presence of excessive mucus on the
surface of feces suggests increased transit
time of the ingesta in the large intestine.
The presence of a plug of mucus in the
rectum is suggestive of a functional
obstruction (paralytic ileus). In enteritis,
large quantities of clear, watery mucus
may be passed, which sometimes clot to
form gelatinous masses.

Fibrin

In fibrinous enteritis, fibrin may be
excreted in the form of long strands, which
may mold into a print of the intestinal
lumen (intestinal fibrinous casts).

DETECTION OF ABDOMINAL PAIN

Cattle with acute local or diffuse peritonitis
may grunt spontaneously with almost
every expiration; this is usually exaggerated
in the recumbent position. However,
grunting may also be caused by severe
pneumonia, pleurisy and severe pul-
monary emphysema. Careful auscul-
tation and percussion of the lungs is
therefore necessary to exclude the presence
of pulmonary disease.

Not all grunts occur spontaneously.
Deep palpation of the cranial part of
the abdomen using the closed hand or
knee is often necessary to elicit a grunt
in cattle. Auscultation over the trachea is
often necessary to hear the grunt. The
grunt is best elicited if pressure is applied
to the abdomen at the end of inspiration

308

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

and the beginning of expiration. The
inspiratory and expiratory sounds are
noted for 6-8 respirations by auscultation
over the trachea and then, without
warning to the animal, firm palpation is
applied to the abdomen. A grunt indicates
the presence of a peritoneal lesion
(stretching or inflammation of the perito-
neum regardless of cause) . The absence of
a grunt does not preclude the presence of
a peritoneal lesion. In acute traumatic
reticuloperitonitis the grunt may be
present for only 3-5 days after the initial
penetration of the reticulum.

A rigid bar or wooden pole may be
necessary to apply pressure in large cattle
(large cows and bulls). The bar is held by
two people in a horizontal position just
behind the xiphoid sternum while a third
person auscultates over the trachea when
the bar is lifted firmly up into the
abdomen. Simultaneous auscultation
over the trachea insures that the grunt is
heard. Several attempts should be made
to elicit a grunt before concluding the
absence of one. The ventral aspect and
both sides of the abdomen should be
examined beginning at the level of the
xiphoid sternum and moving caudally to
approximately the umbilicus. This will
insure that the cranial and caudal aspects
of the abdomen are examined for the
presence of points of abdominal pain.

Pinching of the withers is also used
to elicit a grunt. In the average-sized cow,
pinching of the withers causes the animal
to depress its back. In an animal with a
painful lesion of the peritoneum,
depression of its back will commonly result
in a grunt, which is clearly audible by
auscultation over the trachea and is often
audible without the use of the stethoscope.

The term anterior abdominal pain is
used to characterize the pain associated
with several diseases of anterior abdomen
of cattle, which would include traumatic
reticuloperitonitis, hepatic abscesses,
abomasal ulcers and intestinal obstruc-
tion. The differential diagnosis of the
anterior abdominal pain would include
diseases that cause thoracic pain such as
pleuritis, pericarditis and severe pulmon-
ary disease. 6

|

CLINICAL EXAMINATION OF THE
DIGESTIVE TRACT AND
ABDOMEN OF THE CALF

Clinical examination of the digestive tract j
and abdomen of the calf may be more !
difficult than in the adult animal. The j
rumen in the preruminant calf is not yet I
functional, and thus cannot be used as an *
indicator of the state of the alimentary j
tract as in adult cattle. Also, rectal exam- i
ination is not usually possible until the !
animal is about 10-12 months of age, ;

depending on the breed. A digital
examination of the rectum of young
calves is useful to determine the nature
and amount of feces. This may provide an
indication of the presence of impending
diarrhea. A complete absence of feces
suggests the presence of an acute intes-
tinal obstruction, acute diffuse peritonitis
or atresia coli.

The oral cavity of the calf is easily
examined and should be part of the
clinical examination of every sick calf.

ABDOMINAL DISTENSION IN CALVES

Abdominal distension occurs commonly in
calves under 2 months of age. If the
distension is symmetrical it may be difficult
to determine if it originates in the rumen,
abomasum, intestines or peritoneal cavity.

Examination of the abdomen of the
young calf includes inspection of the
contour of the abdomen to determine the
maximum area of any distension, deep
palpation and ballottement of each flank
to determine the presence of fluid-
splashing sounds that indicate a fluid-filled
viscus, and percussion and auscultation to
determine the presence of a gas-filled
viscus. Placing the calf's hindquarters on
the ground and allowing the viscera to
move to the caudal part of the abdomen
may allow visual inspection and palpation
of a distended abomasum below the
xiphoid sternum. With the calf in lateral
recumbency, careful palpation and simul-
taneous auscultation may reveal the
location of the distended viscus. However,
it is often necessary to do an exploratory
laparotomy to determine the cause. A
stomach tube should always be passed into
the rumen to relieve any pressure caused
by the accumulation of gas or fluid. In the
case of severe distension of the abdomen
accompanied by severe abdominal pain
(kicking, bellowing, rolling, getting up
and lying down) it may be necessary to
relieve pressure with a large-gauge needle
(12-14-gauge, 75-100 mm; 3-4 in). The
most common cause of severe abdominal
distension in a young calf that can be
relieved by trocarization is abomasal
torsion.

Abdominocentesis is easily done in the
calf and at least three punctures should be
attempted before concluding the absence
of fluid. To avoid puncture of the abo-
masum, sites that are caudal to the
umbilicus are used. (See Abdomino-
centesis in Ch. 5.)

The differential diagnosis of the com-
mon causes of abdominal distension in
the calf is set out in Table 6.4.

LAPAROSCOPY

Endoscopy of the abdomen through the
right paralumbar fossa, left paralumbar
fossa' and cranioventral midline provides

a safe alternative to exploratory celiotomy
in cattle. 8 Feed and water are withheld for -
24 hours and the animals are sedated with
acepromazine for both right and left
paralumbar fossa laparoscopies and
xylazine for the cranioventral approach. For
laparoscopy through the fossae, the sites
are prepared aseptically and a 2 cm incision
is made through the skin and abdominal
musculature after infiltration with 2%
lidocaine. Each incision is made 8 cm ven-
tral to the tip of the transverse process of
the third lumbar vertebra and 5 cm caudal
to the caudal aspect of the last rib. The
laparoscope is introduced by standard
technique and carbon dioxide gas is used to
insufflate the abdominal cavity, after intro-
duction of the trocar and cannula and prior
to introduction of the laparoscope. The
abdominal cavity is insufflated to a pressure
of 20-24 mmHg. Each examination is
completed by directing the laparoscope
cranially then moving counterclockwise to
examine the caudal portion of the abdo-
men. After the laparoscopy, the abdomen
is passively deflated through the cannula
and the skin is closed with sutures.

Cranioventral laparoscopy is per-
formed with the animal positioned in
dorsal recumbency. The incision for entry
is made on the midline, through the linea
alba, 10 cm caudal to the xiphoid process.
Examination of the cranioventral portion
of the abdomen is begun at the central
aspect of the diaphragm then circularly
moving the laparoscope counterclockwise.

Right paralumbar fossa laparoscopy
provides excellent viewing of the caudal
and right cranial portions of the abdomen
for evaluation of diseases involving the
right kidney, liver, diaphragm, small intes-
tine, cecum, colon, reproductive tract and
cranial part of the pelvic canal. Inadvertent
penetration of the greater omentum or
mesoduodenum may be avoided by careful
placement of the trocar and periodic
examination with the laparoscope to assess
proper positioning of the cannula. Left
paralumbar fossa laparoscopy provides
excellent viewing of the left cranial portion
of the abdomen and is appropriate for
evaluation of diseases involving the left
kidney, rumen, spleen and diaphragm. 8

The cranioventral midline laparoscopy
provides excellent visibility of the cranio-
ventral portion of the abdomen. It allows
evaluation of diseases involving the
abomasum, liver, reticulum, spleen and
diaphragm. 8

DIAGNOSTIC IMAGING

Radiography of the cranial abdomen
and reticulum of mature cattle is now

being performed more frequently.

| Radiological examination of the reticulum
| with the animal in dorsal recumbency

Special examination of the alimentary tract and abdomen of cattle

31

i

Disease History, clinical and laboratory findings, treatment

Abomasal torsion (volvulus)

Abomasal dilatation
(fluid, milk, hair balls
and often abomasal
ulcers)

Perforated abomasal ulcers

Torsion of root of
mesentery

Acute diffuse
peritonitis (not due
to perforated
abomasal ulcer)

Atresia coli

Intussusception

Peracute to acute enteritis

Omphalitis,
omphalophlebitis,
umbilical abscess

Gastrointestinal tympany
of dietary origin

Intestinal hairball

Always acute to peracute, 1 week to 6 months of age, acute
abdominal pain, bellowing, up and down, severe tight distension of
abdomen, loud ping and fluid-splashing right side, emergency surgery
necessary; recovery about 50% if recognized and corrected early
Chronic or acute onset, calves 1-6 months of age, history of
abnormal feces, may be unthrifty, mild to moderate abdominal
distension and pain, fluid-splashing sounds over right flank,
dehydration, negative peritoneal fluid, laparotomy and abomasotomy
required

Acute onset, sudden collapse, calves 2 weeks to 3 months, hand-fed
or nursing calves, weakness, recumbency, tachycardia, mild to
moderate abdominal distension, mild or no abdominal pain,
abdominal splinting occasionally, positive paracentesis, feces variable.
Laparotomy required; survival about 25%

Sudden onset, found in state of collapse, abdominal pain common,
moderate abdominal distension, distended loops of intestine visible
and palpable over right flank, bloodstained peritoneal tap, fluid-
splashing sounds on palpation and auscultation, scant feces,
emergency surgery

Usually in calves under 3 weeks of age. Toxemia, temperature
variable, weak, may be grunting, splinting of abdominal wall, mild
abdominal distension, scant feces, fluid-splashing sounds over
right flank (due to paralytic ileus), positive paracentesis, commonly
associated with enteric colibacillosis, polyarthritis and umbilical and
urachal abscess. Exploratory laparotomy. Prognosis poor
Calf usually under 10 days of age, progressive distension of abdomen,
bright and alert for first few days then becomes depressed, no feces
only thick mucus from rectum, insertion of tube into rectum may lead
to blind end but often blind end is near spiral colon. Surgery indicated
but often unrewarding

May have history of diarrhea, now scant bloodstained feces,
depressed, will not suck or drink, dehydrated, contour of abdomen
may appear normal or slightly distended, fluid-splashing sounds and
small 'ping' may be audible, bloodstained peritoneal fluid, presurgical
diagnosis often difficult, surgery necessary. Recovery rate good if
diagnosis early

Usually in calves under 3 weeks of age, acute onset of abdominal pain
(kicking, stretching), won't suck or drink, may not yet appear
dehydrated, temperature variable, mild to moderate abdominal
distension, fluid-splashing sounds on auscultation and succussion of
abdomen, continuous loud peristaltic sounds on auscultation,
diarrheic feces may not be present on first examination, digital
examination of rectum may stimulate defecation of foul-smelling, soft,
watery feces, peritoneal tap negative

Single calf, usually 2-6 weeks of age. May be unthrifty, chronic
toxemia. Large, painful swelling of umbilicus that may be obvious
externally or deep palpation dorsal to umbilicus reveals firm swellings
directed towards liver or bladder. Surgical excision required
Calves under 10 days of age. Nursing calves sucking good cows. May
be due to ingestion of excessive quantities of milk and excessive gas
formation in abomasum and large intestine. Abdominal pain (kicking
at abdomen), and pain on palpation of abdomen. Marked to severe
abdominal distension. At laparotomy there is gaseous distension of
the abomasum and cecum. Recovery is usually good
Calves 3-8 weeks of age. Sudden onset of failure to suck. Normal
vital signs. Total absence of feces. Slight to moderate distension of the
abdomen, fluid-splashing sounds over right abdomen, normal
peritoneal fluid. Will remain anorexic, and fail to pass any feces for up
to several days. Hemogram normal. Metabolic alkalosis with
hypokalemia, and hypochloremia may occur. Laparotomy and surgical
removal of hairball required

(dorsal reticulography) is an accurate
diagnostic method for the evaluation of
cattle with suspected traumatic reticulo-
peritonitis, and the techniques used are
presented under that heading.

Ultrasonography is a suitable method
for investigation of reticular contractions

in healthy ruminants and in cattle for the
diagnosis of traumatic reticuloperitonitis. 9
In contrast to radiography, ultra-
sonography provides more precise infor-
mation about the contour of the reticulum
and reticular motility. It is an ideal diag-
nostic aid for the examination of gastro-

intestinal diseases of cattle including left
and right displacement of the abomasum,
abnormal motility of the small and large
intestines, and cecal dilatation. 9 It is done
on the standing nonsedated animal
using a 3.5 MHz linear transducer. The
techniques used are presented under that
heading.

INTERPRETATION OF CLINICAL
FINDINGS

A guide to the interpretation of the
clinical findings associated with diseases
of the digestive tract and abdomen of
cattle is summarized in Table 6.5. In con-
junction with the history and the laboratory
findings, a differential diagnosis list can
be generated.

EXPLORATORY LAPAROTOMY
(EXPLORATORY CELIOTOMY)

An exploratory laparotomy can usually
assist in the diagnosis of diseases of the
digestive tract or abdomen. Identification
and evaluation of the abnormality allows
for a more accurate diagnosis, prognosis
and rational treatment. However, because
a properly done laparotomy is time-
consuming and expensive, the veterinarian
would like to minimize the number of
laparotomies in which no significant
lesions are present. The challenge is,
therefore, to improve the accuracy of
diagnosis and to evaluate the prognosis
as much as possible before doing a
laparotomy unnecessarily.

There are some well-recognized
diseases in which, if a clinical diagnosis
can be made, a laparotomy is indicated
(Table 6.6). (In some cases slaughter for
salvage may be more economical.)

Other than the rumenotomy for the
treatment of grain overload and the
cesarean section, the most common
indication for a laparotomy in cattle is for
the surgical correction of displacement or
obstruction of parts of the digestive tract
j (i.e. abomasal displacement, abomasal
dilatation and volvulus, intussusception
and volvulus, torsion of the root of the
mesentery, torsion of spiral colon, cecal
dilatation and torsion). If any of these
diagnoses can be made, a laparotomy or
slaughter is indicated.

In other cases, the diagnosis may be
suspected, but is not obvious and the
indications for a laparotomy, slaughter,
euthanasia or conservative medical treat-
ment are not clear. The major question is,
'Under what conditions is a laparotomy
indicated if the history and clinical and
laboratory findings suggest an obstruction
j (strangulation obstruction or functional)
j but the obstruction cannot be located on
j clinical examination?'

] Some examples of diseases that may
I elude diagnosis before laparotomy and

310

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

Clinical findings

Anorexia, inappetence
Scant feces, includes
small-volume diarrhea

Large-volume diarrhea

Dehydration

Tachycardia

Polypnea

Weakness and recumbency
Colic (abdominal pain)

Grunting with every
respiration

Presence of grunt on
deep palpation of
ventral abdominal wall
Abdominal distension

Rumen distension

Rumen stasis

Hyperactive rumen
Acidic rumen pH

Alkaline rumen pH

Reduced or absent
rumen protozoon activity

Abnormal foul-smelling
rumen contents
Presence of 'ping' or
'pung' over left flank
'Ping' over right flank

Presence of low-
pitched 'pings' not
clearly distinct over
right flank

Distended upper right
flank

Distended lower right flank

Fluid-splashing sounds on
ballottement of
abdomen or succussion

Dropping cuds

Pathogenesis, interpretation

Toxemia, distension of intestines and stomachs, enteritis, peritonitis
Reduced feed intake, functional obstruction of forestomachs and
abomasum, paralytic ileus, strangulation obstruction or obstruction of
lumen of intestine with phytobezoar or trichobezoar
Profuse, watery diarrhea usually associated with enteritis, simple
indigestion or carbohydrate engorgement

Failure to drink adequate amounts of water (due to toxemia or lesions
of oral cavity), malabsorption due to enteritis, diseases of the
forestomachs interfering with absorption of water, e.g. vagus
indigestion

Toxemia, acid-base imbalance, abdominal pain, distension of
intestines

Acid-base imbalance (torsion of the abomasum, severe enteritis,
vagus indigestion), distension of the abdomen due to gas- or fluid-
filled intestines

Toxemia, severe dehydration, severe distension of abdomen, peritonitis
Sudden onset of distension of forestomachs, abomasum or intestines.
Stretching of mesenteric bands. Strangulation of intestine in
mesenteric tear or scrotal hernia

Diffuse peritonitis (also pleuritis, pulmonary emphysema and advanced
pneumonia), distension of stomachs or intestines
Presence of peritoneal lesion (stretching of the peritoneum,
inflammation, edema, recent adhesions)

Most commonly due to gas- or fluid-filled intestines and/or
forestomachs and abomasum. Rarely due to pneumoperitoneum.

Also due to ascites and hydrops allantois/amnion
May be distended with gas, fluid or ingesta. Primary dietary ruminal
tympany and grain overload. Secondary ruminal tympany due to
peritonitis, vagus indigestion

Toxemia, metabolic (hypocalcemia), fever, ruminal acidosis, distension
of omasum or abomasum, peritonitis, vagal nerve injury
Early stages of primary dietary ruminal tympany; vagal nerve injury
Ruminal acidosis associated with carbohydrate engorgement; almost
no other cause known

Ruminal alkalosis associated with accidental consumption of high-
protein diet, urea poisoning

Ruminal acidosis (lactic acid inactivates protozoa); primary starvation
lasting more than 2-3 days; ingestion of lead, arsenic and other
poisonous substances

Putrefaction of rumen contents in static and defaunated rumen

Left displacement of abomasum (ping), atonic rumen with a gas
cap (pung), pneumoperitoneum (rarely)

Right-side dilatation displacement and torsion of the abomasum, cecal
dilatation and torsion, torsion of the spiral colon, gas in distended
colon and rectum

Tympany of right paralumbar fossa in recently calved cows (2-3 days).
Gas in distended colon and rectum. Fluid- and gas-filled intestines
with enteritis

Dilatation and torsion of abomasum. Cecal dilatation and torsion.
Torsion of spiral colon

Impaction of the abomasum. Enlarged L-shaped rumen and distension
of ventral sac to the right flank. Advanced pregnancy
Fluid-filled intestines or forestomachs or abomasum. Usually
associated with enteritis, paralytic ileus, or obstruction. Fluid-splashing
sounds are rarely due to fluid in the peritoneal cavity. Percolating
fluid sounds audible over right flank are common in cattle with acute
intestinal obstruction

Cattle rarely regurgitate uncontrollably (dropping cuds). It is usually
associated with chronic inflammatory lesions of the reticulum and
cardia resulting in lack of control of regurgitation and a larger than
normal bolus of rumen contents being regurgitated that cannot be
controlled by the animal. Also occurs in certain heavy-metal
poisonings such as arsenic poisoning. Cattle affected with straw
impaction of the rumen will also drop large, dry, fibrous cuds

that are or may be amenable to surgical
correction include the following.

INTUSSUSCEPTION AND OTHER
STRANGULATION OBSTRUCTIONS OF
THE SMALL INTESTINES

An intussusception may be located in the
anterior part of the abdomen and not
palpable per rectum. A clinical history of
acute onset of colic, absence of feces and
serosanguineous exudate on peritoneal
tap are indications for a laparotomy.
However, phytobezoars and trichobezoars
can cause acute intestinal obstruction
which may not be palpable rectally and
which becomes progressively more severe
with time, and only minimal, if any,
changes may occur in the peritoneal fluid.
A progressively worsening systemic state
warrants a laparotomy.

'ATYPICAL' LEFT-SIDE DISPLACEMENT
OF THE ABOMASUM (ATYPICAL LDA)

A small percentage of cases are difficult to
detect on auscultation and percussion.
When the typical LDA 'ping' cannot be
detected after several examinations over a
period of a few days, a presumptive
diagnosis may be made on the basis of
ketosis in a recently calved cow (within
the last week), the presence of rumen
contractions, but reduced intensity,
normal vital signs (unless fatty liver is
present) and spontaneous fluid-gurgling
sounds audible over the left flank or fluid-
splashing sounds on ballottement and
auscultation of the lower left flank.

TRAUMATIC RETICULOPERITONITIS

In traumatic reticuloperitonitis with a
persistently penetrating foreign body,
conservative medical treatment of immo-
bilization in a stanchion, antimicrobials
and a magnet may be unsuccessful even
after several days of antimicrobial therapy.
Diagnosis depends on continued anorexia,
mild fever, grunt, rumen stasis, a hemo-
gram indicating infection and peritoneal
fluid containing exudate.

The guidelines for the indications of an
exploratory laparotomy when a tentative
diagnosis is not made are set out in
Table 6.7.

REVIEW LITERATURE

Braun U, ed. Atlas und Lehrbuch der Ultraschall-
diagnostik beim Rind. Berlin: Parey Buchverlag
1997:1-279.

Braun U. Ultrasonography in gastrointestinal disease
in cattle. Vet J 2003; 166:112-124.

Cockcroft P, Jackson P Clinical examination of the
abdomen in adult cattle. In Pract 2004; June:
304-317.

Ivany JM, Rings DM, Anderson DE. Reticuloruminal
disturbances in the bovine. Bovine Pract 2002;
36:56-64.

Radostits OM. Clinical examination of the alimentary
system: Ruminants. In: Radostits OM, Mayhew
IGJ, Houston DM, eds.Veterinaiy clinical examin-
ation and diagnosis. London: WB Saunders
2000:409-468.

Diseases of the rumen, reticulum and omasum

311

. Table 6.6 Diseases of the
. laparotomy is indicated

1 -tTATTTT--::-; .

■ digestive tract and abdomen of cattle in which a ; - ! s

f the diagnosis can be made

v ; ;K: -A:?'' ; ; --.vudiAl 1

Disease

Major clinical findings

Left displacement of
the abomasum (LDA)

'Ping' over ribs 9-1 2 and other well -recognized findings

Right displacement (RDA)

Distension of upper right flank, 'ping' on percussion over ribs 9-12,

and torsion of the
abomasum

viscus palpable per rectum

Cecal dilatation and torsion

Distension of upper right flank, 'ping' in right paralumbar fossa, long
cylindrical mass palpable per rectum

Torsion of spiral colon

Distension of upper right flank, 'ping', distended loops of intestine
easily palpable

Intussusception

Abdominal pain, absence of feces, distended loops of intestine,
palpable intussusception

Phytobezoars or

Scant feces, subacute abdominal pain, distended loops, of intestine

trichobezoars

and hard lumps palpable rectally

Severe life-threatening

Severe distension of rumen,, skin over rumen cannot be picked up,

ruminal tympany

animal grunting, is lying down, mouth breathing,, cannot relieve with
stomach tube or trocar

Unidentifiable lumps

Chronic gastrointestinal atony, scant feces, large hard lumps palpable

palpable on rectal
examination, i.e. fat
necrosis

per rectum

Peracute grain overload

Weakness, recumbency, dehydration, tachycardia, rumen pH 5
(see Table 29.1 for guidelines in the treatment of grain overload)

Parameter/criterion Significance and interpretation of criteria

History Does the history suggest an acute surgically correctable condition?

Abdominal distension Laparotomy indicated if distension of abdomen caused by distension

of abomasum, cecum or intestines with fluid and gas

Volume and nature of feces Scant or absence of feces for more than 36-48 h indicates a physical
or functional obstruction. In functional obstruction (i.e. peritonitis)
some dark feces are usually present. In physical obstruction
(intussusception) feces are very scant and dark red due to leakage of
blood into intussusceptum. Laparotomy indicated unless can
determine that cause of absence of feces is not surgically correctable
(diffuse peritonitis or impaction of abomasum or omasum)

Distended viscera other than rumen (abomasum, cecum, small and
large intestines) warrant laparotomy. Palpable 'bread and butter'
fibrinous inflammation in caudal part of abdomen suggests acute
diffuse peritonitis and laparotomy would not be rewarding
Bloodstained peritoneal exudate and a degenerative left shift in the
leukocyte count suggest leakage of the intestinal wall and warrants
laparotomy if history and clinical findings suggest a strangulation
obstruction

Behavioral and postural signs of acute abdominal pain (colic) such as
kicking at the belly, stretching the body, suggest acute distension of
the stomachs or intestines with fluid and gas. Spontaneous grunting
with each respiration, which usually becomes pronounced in sternal
recumbency, or the presence of a grunt on deep palpation of the
abdomen suggests inflammation or stretching of the peritoneum

Rectal findings

Peritoneal fluid and
hemogram

Abdominal pain (colic)
and grunting

REFERENCES

1. McCarthy PH. Am J Vet Res 1981; 42:255.

2. Rebhun WC. CornellVet 1987; 77:244.

3. Kath GS et al. Am J Vet Res 1985; 46:136.

4. GeishauserT. Bovine Pract 1994; 28:109.

5. Enemark JMD et al. JVet Med A 2003; 50:62.

6. Henninger RW, Mullowney PC. Compend Contin
Educ RactVet 1984; 6:S453.

7. Wilson AD, Ferguson JG. Can Vet J 1984; 25:229.

8. Anderson DE et al. Am ] Vet Res 1993; 54:1170.

9. Braun U. Vet J 2003; 166:112.

Diseases of the rumen,
reticulum and omasum

SIMPL E IND IGESTION

ETIOLOGY

The disease is common in dairy cattle and
stall-fed beef cattle because of the vari-
ability in quality and the large amounts of

Etiology Excessive feed intake (grain,
silage); indigestible roughage
Epidemiology Usually in hand-fed dairy
cattle and stall-fed beef cattle
Signs Inappetence, drop in milk
production, lack of rumination, rumen
usually full and reticulorumen contractions
decreased or absent, vital signs are normal.
Spontaneous recovery in 12-24 hours
Clinical pathology None needed except
to rule out differential diagnoses. Lesions
not fatal

Diagnostic confirmation Spontaneous
recovery

Differential diagnosis list Early
parturient hypocalcemia, acetonemia,
traumatic reticuloperitonitis, carbohydrate
engorgement, left-side displacement of the
abomasum, right-side dilatation of
abomasum, abomasal volvulus, vagus
indigestion, phytobezoars, secondary
ruminal atony in toxemia
Treatment None required
Control Feeding management and
provision of digestible feeds

feed consumed. It is not commonly
observed in pastured beef cattle or sheep
because they are less heavily fed. The
common causes are dietary abnormalities
of minor degree including indigestible
roughage, particularly when the protein
intake is low, moldy, overheated and
frosted feeds, and moderate excesses of
grain and concentrate intake.

Cases occur under excellent feeding
regimens and are usually attributed to
overfeeding with grain. Although the
difference between simple indigestion
and carbohydrate engorgement (grain
overload) is one of degree, their separation
can be justified by the marked clinical
difference between the two syndromes.
Gross overfeeding usually occurs when
cattle or sheep gain accidental access to
large quantities of grain or are suddenly
introduced to high-grain diets in feedlots.
Indigestion is more common when
heavily fed cows are fed a little more
concentrate than they can digest ade-
quately. A sudden change to a new source
of grain, especially from oats to wheat or
barley, may have the same effect.

Indigestible roughage may include
straw, bedding or scrub fed during
drought periods. It is probable that
limitation of the available drinking water
may contribute to the occurrence of the
disease during dry seasons. Depraved
appetite may also contribute to the
ingestion of coarse indigestible material.
Although good-quality ensilage cannot
be considered an indigestible roughage,
cases of indigestion can occur in cattle
that are allowed unlimited access to it.
This is most likely to happen in heavy-
producing cows running outside in cold

2

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

weather whose hay and grain rations are
limited. It is not uncommon for large
Holstein cows to eat 45-50 kg of ensilage
daily in such circumstances and the high
intake of acetate and acetic acid may be
sufficient to depress their appetite. Pro-
longed or heavy oral dosing with
antimicrobials may cause indigestion due
to inhibition of the normal ruminal flora.
An unusual circumstance is the feeding of
a special diet to produce milk, and dairy
products, with a high content of poly-
unsaturated fats for special diets in
humans. Fats in the diet are protected
against hydrogenation in the rumen by a
coating of formalin. The efficiency and
safety of the diet depends on a thorough
mixing of the formalin with the con-
centrates. If this is not done the free
formalin causes severe rumenitis.

PATHOGENESIS

Primary atony caused by dietary abnor-
mality is difficult to explain. Changes in the
pH of its contents markedly affect the
motility of the rumen and in cases caused
by overeating on grain an increase in
acidity is probably of importance. High-
protein diets, including the feeding of
excessively large quantities of legumes or
urea, also depress motility because of the
sharp increase in alkalinity that results.
Atony that occurs after feeding on
damaged feeds may have the same basis
or be due to other unidentified agents in
the food. The simple accumulation of
indigestible food may physically impede
ruminal activity. Putrefaction of protein
may also play a part in the production of
atony. The toxic amides and amines
produced may include histamine, which
is known to cause ruminal atony when
given in travenously and to be reversed by
the administration of antihistamine
drugs. Histamine may contribute to the
ruminal atony that occurs in allergy, or
after heavy grain feeding, but the absorp-
tion of histamine from the forestomachs
in any circumstances is probably very
limited.

A marked fall in milk yield occurs,
caused probably by the sharp decrease in
volatile fatty acid production in a hypotonic
reticulorumen. Rumen contractions
appear to play the same role as hunger
contractions in simple stomachs and the
decreased food intake is probably due to
the ruminal atony.

CLINICAL FINDINGS

A reduction in appetite is the first clinical
finding, followed closely in milking cows
by a slight drop in milk production. Both
occur suddenly; the anorexia may be
partial or complete but the fall in milk
yield is relatively slight. The animal's
posture is unaffected but there is mild
depression and dullness. Rumination

ceases and the ruminal movements are
depressed in frequency and amplitude
and sometimes are almost absent. The
rumen may be larger than normal if the
cause is sudden access to an unlimited
supply of palatable feed. There may be
moderate tympany, especially with frozen
or damaged feeds or in allergy, but the
usual finding is a firm, doughy rumen
without obvious distension. The feces are
usually reduced in quantity and are drier
than normal on the first day. How-
ever, 24-48 hours later the animal is
commonly diarrheic; the feces are softer
than normal, voluminous and commonly
malodorous.

There is no systemic reaction and the
heart rate, temperature and respirations
are usually within normal ranges. Pain
cannot be elicited by deep palpation of
the ventral abdominal wall, although
cows that have consumed an excessive
quantity of a highly palatable feed such as
silage, after not having had any for a long
period of time, will have a grossly dis-
tended rumen, and mild abdominal dis-
comfort may be present for several hours.
The discomfort usually resolves when the
rumen movements return to normal and
the rumen returns to its normal size. Most
cases recover spontaneously or with
simple treatments in about 48 hours.

CLINICAL PATHOLOGY

Examination of the urine for ketone
bodies is usually necessary to differentiate
indigestion from acetonemia.

Two simple laboratory tests have been
introduced to assess the activity of the
ruminal microflora. The sediment activity
test is carried out on aspirated ruminal
fluid strained to remove coarse particles.
The strained fluid is allowed to stand in a
glass vessel at body temperature and the
time required for flotation of the parti-
culate material is recorded. The time in
normal animals varies between 3 minutes,
if the animal has just been fed, and
9 minutes, if the last feeding has occurred
some time previously. Settling of the par-
ticulate material indicates gross inactivity,
less severe degrees being manifested by
prolongation of the time required for
flotation. The cellulose digestion test is
also performed on aspirated rumen fluid
and depends upon the time required to
digest a thread of cotton. A bead is tied
to the end of the thread to indicate
when separation occurs. Digestion
times in excess of 30 hours indicate
abnormality.

The rumen juice can be examined for
pH using wide-range indicator paper.
Values between 6.5 and 7.0 are considered
normal. In cattle on grain diets, the pH
may range from 5.5-6.0 normally but in
cattle that have been on roughage diets

such low values should arouse suspicion
of lactic acidosis and careful monitoring is
necessary.

NECROPSY FINDINGS

The disease is not a fatal one.

DIFFERENTIAL DIAGNOSIS

Simple indigestion must be differentiated
from all the diseases of the forestomachs
and abomasum in which ruminal atony is a
common clinical finding, and from diseases
of other body systems that cause
secondary ruminal atony:

• Acetonemia: the appetite and milk
production decrease over a few days,
there is ketonuria and the rumen
contractions are present but weaker
than normal

• Traumatic reticuloperitonitis: there is
a sudden onset of anorexia and
agalactia, a mild fever, a painful grunt
on deep palpation of the xiphoid
sternum, and the rumen is static with
an increase in the size of the gas cap

• Carbohydrate engorgement:
characterized by depression,
dehydration, tachycardia, staggering,
recumbency, diarrhea and ruminal stasis
with the presence of fluid-splashing
sounds, and the pH of the ruminal fluid
is usually below 6 and commonly down
to 5

• Left-side displacement of the
abomasum (LDA): usually occurs
within a few days after parturition and
the rumen is usually smaller than
normal, the contractions are usually
reduced in amplitude, there is a ping on
percussion over the lower left flank, and
ketonuria

• Right-side dilatation of abomasum:

occurs most commonly in dairy cows
2-4 weeks post partum, there is
inappetence, reduced feces, ruminal
atony, reduced milk production and a
ping over the right flank, and a
distended viscus is palpable per rectum
in the lower right quadrant

• Abomasal volvulus: anorexia,
depression, reduced feces, dehydration,
tachycardia, a ping over the right flank
and a distended viscus in the lower
right quadrant are common

• Vagal indigestion: characterized by
gradual distension of the abdomen due
to distension of the rumen over a
period of several days, progressive
dehydration and scant feces. Initially
there is hypermotility of the rumen and
the development of secondary frothy
bloat. This is commonly followed by
ruminal atony

• Phytobezoars: cause inappetence to
anorexia, scant feces, and on rectal
examination distended loops of intestine
and the firm masses may be palpable

• Secondary ruminal atony: occurs in
many diseases in which septicemia or
toxemia (coliform mastitis) are present
but there are usually additional clinical
findings to indicate their presence

Diseases of the rumen, reticulum and omasum

3

• Ruminal atony with mild bloat is
common in the early stages of
hypocalcemia, which may last for
6-18 hours, and is usually accompanied
lay anorexia and a decreased amount of
feces: The ruminal motility and appetite
return to normal following 'treatment
with calcium borogluconate

• The rumen is also atonic in allergic and
anaphylactic states and returns to
normal following treatment,

TREATMENT
Spontaneous recovery

Most cases of simple indigestion recover
spontaneously. Small quantities of fresh,
good-quality, palatable hay should be
provided several times daily to encourage
eating and to stimulate reticulorumen
motility. Because anorexia and forestomach
hypomotility usually exist together the
objective is to stimulate both appetite and
motility. Reduced feed intake reduces
the two primary drives for reticulorumen
activity: moderate forestomach distension
and chewing activity.

Rumenatorics

A wide variety of oral preparations con-
taining rumenatorics were available for
many years and is was conventional to
administer these to stimulate reticulorumen
motility and to stimulate appetite. These
preparations contained nux vomica,
ginger and tartar emetic in powder form
to be added to water and pumped into
the rumen. However, there is no evidence
that they are effective and they are not
recommended. 1,2 The routine use of
magnesium hydroxide for rumen dis-
orders is not recommended unless there
is evidence of ruminal acidosis.

Magnesium hydroxide is a potent
alkalinizing agent for use in ruminants as
an antacid and mild laxative. It can
significantly decrease rumen microbial
activity and should be used only in cattle
with rumen acidosis and not for symp-
tomatic therapy of idiopathic rumen
disorders or hypomagnesemia. The oral
administration of boluses of magnesium
hydroxide (162 g) or a powdered form
(450 g) dissolved in 3.5 L of water daily
for 3 days resulted in a significant increase
in rumen pH after 48 and 24 hours,
respectively. 3 Both the boluses and the
powder forms of magnesium hydroxide
decreased rumen protozoal numbers and
increased methylene blue reduction times
compared with baseline values. There was
no change in blood pH, bicarbonate or
base excess values.

Parasympathomimetics

These agents have also been used to
stimulate reticulorumen activity but have
the disadvantage of inducing undesirable

side effects and being very transitory in
effect. Large doses depress reticulorumen
activity but small doses repeated at short
intervals increase ruminal activity and
promote vigorous emptying of the colon
in normal animals. The normal flow of
rumen contents from the reticulorumen
to the abomasum is the result of a
complex of synchronized contractions
and relaxations of various parts of the
forestomachs, orifices and abomasum
occurring simultaneously. One of the
major limitations of injectable para-
sympathomimetics used as rumenatorics
is that they do not provide these
synchronized movements and therefore
little movement of ingesta can occur.
Carbamylcholine chloride, physostigmine
and neostigmine are most commonly
used. Neostigmine is the most effective at
a dose of 2.5 mg/45 kg body weight (BW) .
Carbamylcholine acts on the musculature
only and causes uncoordinated and
functionless movements. These drugs are
not without danger, especially in very sick
animals or those with peritonitis, and are
specifically contraindicated during late
pregnancy.

Experimentally, metoclopramide in-
creases the rate of ruminal contractions
and therefore might be beneficial in
rumen hypomotility or motility disturb-
ances associated with vagal nerve
damage. 1,2

Epsom salts (0.5-1. 0 kg per adult cow)
and other magnesium salts are reason-
ably effective and have the merit of
simplicity and cheapness.

Alkalinizing and acidifying agents

If an excessive quantity of grain is the
cause of the simple indigestion, the use of
alkalinizers, such as magnesium hydronde,
at the rate of 400 g per adult cow (450 kg
BW), is recommended when the rumen
contents are excessively acid. Magnesium
oxide or hydroxide should be used only if
ruminal acidosis is present. The adminis-
tration of 400 g of magnesium oxide to
normal, mature, nonfasted cattle weighing
450 kg can cause metabolic alkalosis and
electrolyte disturbances for up to 24 hours
following treatment. A sample of rumen
fluid can be readily obtained and the pH
determined. If the rumen contents are dry,
15-30 L of water should be administered by
stomach tube.

Acetic acid or vinegar, 5-10 L, is used
when the rumen contents are alkaline as
a result of the ingestion of high-protein
concentrates.

Reconstitution of ruminal microflora

In cases of indigestion that have run a
course of more than a few days, and in
animals that have been anorexic for pro-
longed periods, there will be significant
loss of ruminal microflora, especially if

there have been marked changes, in pH.
Reconstitution of the flora by the use of
cud transfers from normal cows is highly
effective. An abattoir is the best source of
rumen contents (especially rumen fluid)
but it can be obtained from live animals
by reaching into the mouth during
rumination when the bolus is regurgi-
tated. Rumen fluid may also be removed
by siphoning from the rumen with a
stomach tube or by vacuum withdrawal
with a special pump. Best results are
obtained if 20-30 L of water is pumped
into the rumen and then allowed to
siphon by gravity flow (rumen lavage).
The rumen fluid to be transferred should
be strained and administered as an oral
drench or by stomach tube. Repeated
dosing is advisable. The infusion will keep
for several days at room temperature.
Commercial products comprising dried
rumen solids are available and provide
some bacteria and substrate for their
activity.

When affected animals resume eating
they are best tempted by good, stalky
meadow or cereal hay. Good-quality alfalfa
(lucerne) or clover hay, green feed and
concentrate may be added to the diet as
the appetite improves.

REVIEW LITERATURE

Constable PD, Hoffsis GF, Rings DM. The
reticulorumen: normal and abnormal motor func-
tion. Fhrt I. Primary contraction cycle. Compend
Contin Educ PractVet 1990; 12:1008-1014.
Constable PD, Hoffsis GF, Rings DM. The
reticulorumen: normal and abnormal motor func-
tion. Fhrt II. Secondary contraction cycles, rumi-
nation, and esophageal groove closure. Compend
Contin Educ PractVet 1990; 12:1169-1174.

REFERENCES

1. Constable PD et al. Compend Contin Educ Pract
Vet 1990; 12:1008.

2. Constable PD et al. Compend Contin Educ Pract
Vet 1990; 12:1169.

3. Smith GW, Correa MT. J Vet Intern Med 2004;
18:109.

RUMEN IMPACTION IN SHEEP
WITH INDIGESTIBLE FOREIGN
BODIES

Rumen impaction in sheep with indigest-
ible foreign bodies has been described in
a semi-arid region of Nigeria. 1 The sheep
had visited refuse dumps around a town.
Only certain breeds of sheep, theYankasa,
Uda and their crossbreeds, were found
feeding on refuse dumps. Rumen-
indigestible foreign bodies were present in
19.3% of the sheep slaughtered in the
local abattoir. The foreign bodies were
polythene/cellophane materials, ropes,
dry seeds, caked sand, metallic objects,
paper, fiber and hair balls. The poly-
thene/cellophane materials were present
in 81.6% of the sheep. Clinically, the
rumen impaction was characterized by

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

emaciation, abdominal distension and
symmetry, lack of feces in the rectum,
foamy salivation, recumbency and
inappetence.

At necropsy, the foreign bodies were
usually loosely matted together and
impacted with rumen ingesta.

Hyperglycemia, alkalosis, hyponatremia,
hypochloridemia, hypocalcemia, hypo-
proteinemia and hypoalbuminemia
occurred in some cases. The impaction
was related to the sheep scavenging on
refuse dumps and the blood biochemical
changes, along with the clinical signs,
might be of some diagnostic significance.

REFERENCE

1. Igbokwe IO et al. Smail Rumin Res 2003; 49:141.

INDIGESTION IN CALVES FED
MILK REPLACERS (RUMINAL
DRINKERS)

A form of indigestion known as ruminal
drinking occurs in veal calves and is
characterized clinically by recurrent ruminal
tympany, inappetence, unthriftiness and
the production of clay-like feces. 1 The
disease occurs most commonly in calves
5-6 weeks after being placed on a milk
diet and being fed with a bucket.

The cause is insufficient closure of the
reticular groove while drinking milk. The
ingested milk enters the rumen in large
quantities instead of flowing directly into
the abomasum. The experimental intra-
ruminal administration of milk to calves
at 6 weeks of age induces changes in the
rumen similar to those seen in spontaneous
cases of the disease. 2 The pH of the
rumen decreases and lactate concen-
trations increase rapidly. The daily oral
administration of untreated whole milk
via stomach tube into calves 5-23 days of
age results in a D-lactic metabolic acidosis
within a few days. 3 The onset of ruminal
acidosis occurred quickly and mean pH
values fell from 6.7 to 4.9 after the first
feeding. In the following days the rumen
pH values varied between 4 and 5. During
ruminal acidosis, both L- and D-lactic acid
are produced abundantly by bacterial
fermentative activity. Both isomers of
lactic acid are absorbed from the rumen,
or from the intestines, where they exert
an acidotic effect. The L-lactate can be
metabolized quickly by the body and does
accumulate despite the continuous influx
into the blood. However, D-lactate cannot
be metabolized at the same rate because
of a lack of specific metabolic pathway,
and it accumulates with the consequence
of the risk of hyper-D-lactatemia. 3

There is marked ruminal hyperkeratosis.
Villous atrophy occurs in proximal
jejunum accompanied by a reduction in
brush border enzyme activities. 4 Clinical
recovery occurs within several days after

returning to normal feeding practices,
with restoration of villous length and brush
border enzyme activities in 3-A weeks.

On clinical examination the tempera-
ture, heart rate and respiratory rates are
within normal range. The abdominal
contour is increased in size, especially
over the ventral half of the abdomen.
Distension is more obvious on the left
side. Ballottement of the left abdominal
wall commonly reveals fluid-splashing
sounds. 5,6 Auscultation of the left para-
lumbar fossa while the calf is drinking
reveals loud fluid-splashing sounds.
Large volumes of foul- or acid-smelling,
grayish-white fluid can be siphoned off
from the rumen. Examination of the
rumen contents after calves have con-
sumed milk reveals the presence of a
casein clot. Radiological examination
reveals that ingested milk enters the
rumen and reticulum and is only slowly
moved on to the abomasum.

Affected calves remain unthrifty while
they continue to drink milk. Esophageal
groove reflex dysfunction maybe a compli-
cation in some milk-fed calves affected
with diarrhea. 5 Weaning on to hay and
concentrates returns the calf to normal
very quickly. Rumen movements, via
eructation reflex, and ruminations become
normal within 1-2 weeks.

The administration of colostrum and
other fluids to calves using an esophageal
feeder does not induce the esophageal
groove reflex. However, colostrum and
other fluids administered directly into the
rumen with a feeder does move from the
forestomachs into the abomasum within
3 hours. 7 Feeding colostrum to newborn
calves by means of an esophageal feeder
is a labor-saving and effective method of
obtaining optimum levels of serum
immunoglobulins. This is particularly use-
ful in large dairy herds because colostrum
can be given to calves immediately after
birth.

At necropsy the rumen is enlarged and
there are varying degrees of hyper- and
parakeratosis. Villous atrophy is pro-
minent in the small intestine, which is
partially restored to normal when the
reticular groove reflex is restored. 8

Affected calves can be treated by
inducing them to suck on the herdsman's
fingers while they are being fed a small
quantity of cows' whole milk or milk
replacer.

REFERENCES

1. Breukink H et al.Vet Q 1988; 10:126.

2. Van Buisman WK et al. J Anim Physiol Anim Nutr

1990; 63:255.

3. Gentile A et al. J Vet Med A 2004; 51:64.

4. Van Buisman WK et al. \£t Res Commun 1990;

14:129.

5. Dirksen G, Din L. Bovine Pract 1989; 24:53, 54-60.

6. Dirksen G, Garay F. Compend Contin Educ Pract

Vet 1987; 9:140, 173.

I 7. Laleur-Rowet HJM et al.Vet Q 1983; 5:68.

8. Ivan Buisman WK et al.Vet Q 1988; 10:164.

ACUTE CARBOHYDRATE
ENGORGEMENT OF RUMINANTS
(RUMINAL LACTIC ACIDOSIS,
RUMEN OVERLOAD)

ETIOLOGY

The sudden ingestion of toxic doses of
carbohydrate-rich feed, such as grain, is
the most common cause of the acute form

iri ? V- V’tycy 1 .'?.' '

Etiology Sudden ingestion of large
amounts of highly fermentable
carbohydrates

Epidemiology Accidental consumption
by ruminating cattle of excessive quantities
of highly digestible feeds such as cereal
grains, corn, baker's bread, grapes, apples
and the like. Subacute ruminal acidosis is
considered an important problem in dairy
herds. In beef and lamb feedlots the rapid
introduction of high-level grain diets is a
major risk factor. Outbreaks occur when
animals gain access to a large quantity of
grain. High mortality rate when large
quantity of grain ingested
Signs Anorexia, depression, dehydration,
ruminal stasis, profuse diarrhea with
sweet-sour odor of feces, which may
contain undigested kernels, weakness and
ataxia leading to recumbency. Rumen may
or may not feel full but atonic and fluid-
splashing sounds audible on ballottement.
Laminitis, mycotic rumenitis are
complications

Clinical pathology Ruminal fluid pH
below 5, rumen protozoa absent or
inactive in rumen fluid;
hemoconcentration, blood lactate
increased, hypocalcemia
Lesions Acute congested and inflamed
rumenitis, sloughing ruminal mucosa;
mycotic inflammation and necrosis of
forestomach and fungal hepatitis if disease
lasts several days

Diagnostic confirmation Ruminal fluid
pH below 5

Differential diagnosis list 5imple
indigestion, parturient hypocalcemia,
peracute coliform mastitis, acute diffuse
peritonitis

Treatment Triage to determine which
animals need medical treatment, rumen
lavage or rumenotomy. Correct ruminal
and systemic acidosis with alkalinizing
agents parenterally or orally depending on
severity. Fluid and electrolyte therapy as
necessary. Restore forestomach and
intestinal motility by providing palatable
hay

Control Prevent accidental access to
grain. Gradual introduction to high-level
grain diets in feedlots. Total mixed rations
containing chopped roughage and grain to
insure controlled intake of carbohydrates.
Careful feeding management of dairy
cattle during late pregnancy and early
lactation. Use of ionophores in feed alter
rumen metabolism and potentially can
control ruminal acidosis

Diseases of the rumen, reticulum and omasum

35?

of the "disease. 1,2 Less common causes
include engorgement with apples, grapes,
bread, baker's dough, sugar beet, mangels,
sour wet brewers' grain that was
incompletely fermented in the brewery,
and concentrated sucrose solutions used
in apiculture. Subacute ruminal acidosis
(SARA) in dairy cattle is a disorder of
ruminal fermentation in dairy cattle
caused by the ingestion of large amounts
of concentrates and inadequate amounts
of fiber administered in order to increase
milk production in early lactation. 3,4

EPIDEMIOLOGY

Occurrence

All types of ruminant cattle and sheep
are susceptible but the disease occurs
most commonly in feedlot cattle and
dairy cattle fed on high-level grain diets.
The disease also occurs in lamb feedlots
and has been recorded in goats, wild deer
and farmed ungulates.

Previous diet and change of ration
Because the type and level of ration
consumed by a ruminant affects the num-
bers and species of bacteria and protozoa
in the rumen, a change from one ration to
another requires a period of microbial
adaptation, which is a variable interval of
time before stabilization occurs. Animals
being fed a low-energy ration are most
susceptible to a rapid change to a high-
energy ration because satisfactory
adaptation cannot occur quickly enough.
This results in the rapid onset of abnor-
mal fermentation.

Accidental consumption of excess
carbohydrates

The disease occurs commonly following
accidental consumption of toxic amounts
of grain by cattle gaining sudden access to
large quantities of grain. A single animal
or a group of hungry cows may break into
a grain storage bin or find a large supply
of unprotected grain, as not uncommonly
happens on a mixed cattle-grain farm.
Another common occurrence is when
cattle are left under the care of an assist-
ant who, being unaware of the feeding
schedule, gives the cattle an unaccustomed
quantity of grain. Outbreaks have occurred
in dairy herds following malfunction of
automatic feeders, which delivered many
times more than the usual amount of
grain. In a similar outbreak, recently
calved cows consumed an excessive
amount of feed delivered by an automatic
feeder but not eaten by other cows
because of hot weather.

Outbreaks have occurred when cattle
have been turned into unripe, green com
standing in the field, when cattle or sheep
have been placed on stubble fields in
which considerable grain lost by the
harvester was available on the ground.

and following the irregular feeding of
large quantities of other less common
animal feeds and byproducts, such as
bread, baker's dough and wet brewers'
grain. Problems usually arise with these
feeds when a larger than usual amount is
fed to cattle either for the first time or
because the usual supplementary feed is
in short supply.

Dairy cattle herds

Subacute ruminal acidosis occurs in
dairy cattle herds fed high-grain, low-
fiber rations in early lactation. 3,5 It is con-
sidered of major economic importance
because of the possible association with
laminitis in dairy herds. 2,6

The transition from the pregnant,
nonlactating state to the nonpregnant,
lactating state is the period during which
the majority of metabolic diseases occur
in the dairy cow. During this period,
which ranges from 3 weeks before until
3 weeks after calving, the cow is changed
from a high-fiber, low-concentrate diet to
a diet that is higher in concentrate feeds
and lower in fiber. Cows that have not
adapted to these high- grain diets are parti-
cularly susceptible to ruminal acidosis.
Subacute ruminal acidosis is characterized
by repeated bouts of depressed rumen pH
between 5.2 and 5.6. The abnormality
often results from a large intake of rapidly
fermentable carbohydrates that leads to
the accumulation of organic acids in the
rumen. Up to 20% of commercial dairy
farm cows in early to mid-lactation have a
rumen pH of less than 5.5, indicative of
subacute ruminal acidosis. 6 The economic
losses associated with SARA have been
estimated at $1.12 per cow per day. 7

Field observations suggest that peri-
parturient cows are at risk of subacute
ruminal acidosis because of the time
required for the rumen microflora
and papillae to adapt to increased intakes
of concentrates immediately before
parturition and during early lactation
when feed intake increases rapidly to
meet the energy needs of high-producing
dairy cows. The adaptation of the ruminal
microflora and papillae from a system
appropriate for forage to a system capable
of utilizing high-energy lactation rations
requires a gradual change during a period
of 3-5 weeks. 6

The need for individual cows to adapt
to high-energy rations and the common
practice of feeding dairy cows as groups
results in periparturient cows being at risk
of developing subacute ruminal acidosis.
For practical reasons, as total mixed
rations have become more common,
many dairy herds limit the number of
rations to a single dry-cow ration and a
single lactating-cow ration, because of the
time and labor required to mix -each

ration. This system has made it difficult to
introduce concentrates to individual cows
in the first few weeks after calving. If the
dry- cow ration has not resulted in
adaptation of the ruminal microflora
required for high-energy rations, acidosis
may occur when the cow is fed 'the
lactating-group ration. The net energy of
a ration can be safely increased in 10%
increments. For example, a change from
an energy density of 0.70 Mcal/lb NE 1
(net energy, lactation) to 0.77 Mcal/lb NE!
would be considered safe. The National
Research Council recommends that dry-
cow total mixed rations have 0.57 Mcal/lb
NE! and that a high-production lactation
cow ration have 0.78 Mcal/lb NE a 8 Using
the 10% guideline for gradual energy
change would require at least two inter-
mediate rations. 5

Dairy producers attempt to minimize
the negative energy balance of lactating
cows in early lactation by maximizing
concentrate intake early in the period
after parturition. The early lactation
period is a high-risk period for lactating
dairy cows if they are fed rations as
separate components, for three reasons:

° Concentrates are consumed by the
cow in preference to forage
0 Forage consumption is not usually
measured on an individual cow basis
and is commonly assumed to
approximate the herd average
° Dry matter intake of periparturient
cows is lower than commonly
thought and is very dynamic through
this period. 5

Thus high-producing lactating dairy cows
consuming large quantities of high-
energy grains are susceptible to subacute
ruminal acidosis during early lactation. 9

Field recommendations for feeding
component-fed concentrates during
the first 3 weeks of lactation are usually
excessive. 3,5 Feeding excessive quantities
of concentrate and insufficient forage
results in a fiber-deficient ration likely to
cause subacute acidosis. The same situ-
ation may occur during the last few days
before parturition if the ration is fed in
separate components; as dry matter
intake drops before calving, dry cows will
preferentially consume too much concen-
trate and insufficient fiber, and develop
acidosis.

Subacute ruminal acidosis may also be
caused by formulation of rations that
contain excessive amounts of rapidly
fermentable carbohydrates, a deficiency
of fiber, or errors in delivery of the rations.
Recommendations for the fiber content of
dairy rations are available in the National
Research Council (Nutrient Require-
ments of Dairy Cattle). 8 Dry-matter con-
tent errors in total mixed rations are

6

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

commonly related to a failure to adjust for
changes in moisture content of forages. 5

In a survey in Denmark, dairy cattle
'practitioners were asked to retrospectively
report on the occurrence and relative
importance of SARA in dairy herds
compared to the actual number of cases
reported to the national computer-based
dairy herd health recording system. 10 The
most common diagnoses believed to
occur were ketosis (26%), rumen acidosis
(22%), abomasal disorders (16%), sub-
clinical hypocalcemia (15%) and milk
fever (15%). Subclinical rumen acidosis
was considered to be a commonly occur-
ring underlying condition with significant
importance as a cause of reduced appetite,
and inadequate feeding strategies were
given as the main cause. However,
according to the national dairy health
recording system, SARA was rarely
reported as a diagnosis. The practitioners
were reluctant to imply that feeding
management was a problem. The clinical
signs of SARA were unclear to the
practitioners, and the diagnostic tests
necessary, such as rumenocentesis, were
considered time consuming and unreliable
because of the small size of the herds. 10

Feedlot cattle

The occurrence of grain overload in feed-
lot cattle, however, has gained the most
attention, presumably because of its
economic impact. Digestive disorders
account for approximately 25-35% of
deaths in feedlot cattle and may contri-
bute to decreased performance and
efficiency of production. 11 The economics
of feedlot beef production dictate that
cattle should gain weight at their
maximum potential rate and this usually
involves getting them on to a full feed of
a high concentration of grain quickly.
Economics also favor the processing of
grain by one of several methods available
that will increase the availability of starch
and thereby increase the rate of degra-
dation in the rumen. All these factors set
the stage for a high incidence of grain
overload in feedlot cattle. 12

There are some critical periods during
which grain overload occurs in feedlot
cattle. When starting cattle on feed,
animals with previous experience of
eating grain will commonly consume a
toxic dose if offered a ration with a high
percentage of grain. The disease occurs
commonly in feedlot cattle in which the
total daily feed intake has been brought
up to what is considered the same feed on
an ad libitum basis; they gorge themselves.
When increasing the concentration of
grain in the ration from one level to
another, if the increment is too high the
total amount of grain consumed by some
cattle will be excessive. Rapid changes in

barometric pressures may affect the
voluntary intake of cattle. A rapid change
to cold weather may result in a moderate
increase in feed intake in animals that are
fed ad libitum and outbreaks of grain over-
load may occur. When rain is involved and
feed becomes wet and possibly even
moldy, feed intake will drop, but when
fresh dry feed is offered again there may
be a marked increase in feed intake that
results in grain overload.

The disease also occurs when cattle
that have been on a high-level grain
ration (full feed) have become hungry
because they have been out of feed for
12-24 hours as a result of a breakdown in
the feed mill or handling facilities.
Offering an unlimited supply of feed to
these cattle will often result in severe
cases of grain overload. In large feedlots,
where communications can be a problem,
the accidental feeding of a high-level
grain ration to cattle that are on a high-
level roughage ration is a common cause
of the disease.

The ruminal lesions of rumenitis and
ruminal hyperkeratosis, which are com-
monly present in feedlot cattle at slaughter,
are thought to be associated with the
continuous feeding of grain. These lesions
are often remarkable at slaughter in well-
nourished cattle and their effect on live
weight gain and feed conversion is not
known.

Beef breeding herds

Cows in beef cow-calf herds may develop
acute ruminal acidosis if offered a high-
energy grain ration during the winter
feeding period without a period of
adjustment.

Lamb feedlots and liquid-fed calves
Outbreaks of the disease occur in lamb
feedlots in which lambs are started on a
high-level grain ration without a period of
adjustment. The disease is not as common
in lambs as in cattle, perhaps because
lambs are usually fed on oats.

Rumenitis and metabolic acidosis have
also been reported when newborn calves
were force-fed liquid feeds or nutrient-
electrolyte solutions containing easily
digestible carbohydrates. 13

Morbidity and case fatality rates

Outbreaks of the disease occur in cattle
herds kept on grain farms and in feedlots.
Depending on the species of grain, the
total amount eaten and the previous
experience of the animals, the morbidity
will vary from 10-50%. The case fatality
rate may be up to 90% in untreated cases,
while in treated cases it still may be up to
30-40%.

Types and toxic amounts of feeds

Wheat, barley and corn grains are the
most toxic when ingested in large

quantities. Oats and grain sorghum are
least toxic. All grains are more toxic when
ground finely or even crushed or just
cracked - processes that expose the starch
component of the grain to the ruminal
microflora. The experimental feeding of
unprocessed barley to cattle did not result
in rumenitis, whereas feeding rolled
barley was associated with ruminal
lesions. An unrestricted supply of stale
bread can cause outbreaks.

The amount of a feed required to cause
acute illness depends on the species of
grain, previous experience of the animal
with the grain, its nutritional status and
body condition score, and the nature of
the ruminal microflora. Dairy cattle
accustomed to high-level grain diets may
consume 15-20 kg of grain and develop
only moderate illness, while beef cows or
feedlot cattle may become acutely ill and
die after eating 10 kg of grain to which
they are unaccustomed. Amounts of feed
that are lethal range from 50-60 g of
crushed wheat/kg BW in undernourished
sheep to 75-80 g/kg BW in well-nourished
sheep, and in cattle doses ranging from
25-62 g/kg BW of ground cereal grain or
corn produced severe acidosis.

PATHOGENESIS

The details of the pathogenesis of ruminant
lactic acidosis have been reviewed. 1 A
summary of the events that occur in the
rumen and the systemic effects on the
animal is presented here. The disease is a
good example of metabolic acidosis in
ruminants.

Changes in rumen microflora

The ingestion of excessive quantities of
highly fermentable feeds by a ruminant is
followed within 2-6 hours by a marked
change in the microbial population in the
rumen. There is an increase in the number
of Streptococcus bovis, which utilize the
carbohydrate to produce large quantities
of lactic acid. In the presence of a suffi-
cient amount of carbohydrate (a toxic or a
lethal amount) the organism will continue
to produce lactic acid, which decreases
the rumen pH to 5 or less, which results
in the destruction of the cellulolytic
bacteria and protozoa. When large
amounts of starch are added to the diet,
growth of S. bovis is no longer restricted
by energy source and it multiplies faster
than any other species of bacteria.

Volatile fatty acids and lactic acid in
the rumen

The concentration of volatile fatty acids
increases initially, contributing to the fall
in ruminal pH. The low pH allows
lactobacilli to use the large quantities of
carbohydrate in the rumen to produce
excessive quantities of lactic acid, result-
ing in ruminal lactic acidosis. Both

Diseases of the rumen, reticulum and omasum

D and L forms of the acid are produced,
which markedly increases ruminal
osmolality, and water is drawn in from the
systemic circulation, causing hemo-
concentration and dehydration. Ruminal
osmolality increases from a normal of
280 mosmol/L to almost 400 mosmol/L. 1

Some of the lactic acid is buffered by
ruminal buffers but large amounts are
absorbed by the rumen and some moves
into and is absorbed further down the
intestinal tract. Lactate is a 10 times
stronger acid than the volatile fatty acids,
and accumulation of lactate eventually
exceeds the buffering capacity of rumen
fluid. As the ruminal pH declines, the
amplitude and frequency of the rumen
contractions are decreased and at about a
pH of 5 there is ruminal atony. The
increased ruminal levels of unassociated
volatile fatty acids may be more important
than increased lactic acid or increased
hydrogen ion concentration in causing
ruminal atony. Experimentally, increased
molar concentration of butyrate, not the
lactic acid, causes ruminal stasis. 1
Inhibition of ruminal activity may also be
due to lactic acid entering the duodenum
and exerting a reflex inhibitory action on
the rumen. Experimentally, ruminal atony
occurs in sheep within 8-12 hours after
grain engorgement but the precise
pathophysiological mechanism for loss of
forestomach motility is uncertain. The
diarrhea is considered to be due to the
reduction in net absorption of water from
the colon.

Systemic lactic acidosis

The absorbed lactic acid is buffered by the
plasma bicarbonate buffering system.
With nontoxic amounts of lactic acid, the
acid-base balance is maintained by
utilization of bicarbonate and elimination
of carbon dioxide by increased respir-
ations. In those which survive the acute
form of the disease, this compensatory
mechanism may overcompensate, result-
ing in alkalosis. In severe cases of lactic
acidosis the reserves of plasma bicarbonate
are reduced, the blood pH declines
steadily, the blood pressure declines,
causing a decrease in perfusion pressure
and oxygen supply to peripheral tissues
and resulting in a further increase in lactic
acid from cellular respiration. Lactic acid
given intravenously to cattle causes
hypertension, increased responses to j
norepinephrine, slight bradycardia and i
slight hyperventilation.

Both D- and L-lactic acids are |
produced. The L-lactic acid is utilized j
much more rapidly than the D-isomer
which accumulates and causes a severe
D-lactic acidosis. If the rate of entry of
lactic acid into body fluids is not too rapid,
compensatory mechanisms are able to

maintain the blood pH at a compatible
level until the crisis is over, and recovery is
usually rapid. This may explain the
common observation that feedlot cattle
may be ill for a few days after being
introduced to a grain ration but quickly
recover, while in other cases when the
rate of entry is rapid the compensatory
mechanisms are overcome and urgent
treatment is necessary.

In experimental lactic acidosis using
sucrose in sheep, feed intake does not
resume until rumen pH has returned to
6.0 or higher and lactic acid is no longer
detectable in the rumen. Renal blood flow
and glomerular filtration rate are also
decreased, resulting in anuria. Eventually
there is shock and death. All these events
can occur within 24 hours after engorge-
ment of a lethal dose of carbohydrate;
with toxic doses the course of events may
take 24-48 hours.

Chemical and mycotic rumenitis

The high concentration of lactic acid in
the rumen causes chemical rumenitis,
which is the precursor for mycotic
rumenitis in those that survive; this
occurs about 4-6 days later. The low pH of
the rumen favors the growth of Mucor,
Rhizopus and Absidia spp. which invade
the ruminal vessels, causing thrombosis
and infarction. Inoculation of Absidia
corymbifera orally into sheep with
experimental ruminal acidosis produced
with barley causes desquamation of the
superficial layers of the mucosae and focal
necrosis from lamina propria to muscular
layers. Severe bacterial rumenitis also
occurs. Widespread necrosis and gangrene
may affect the entire ventral half of the
ruminal walls and lead to the develop-
ment of an acute peritonitis. The damage
to the viscus causes complete atony and
this, together with the toxemia resulting
from the gangrene, is usually sufficient to
| cause death. Mycotic omasitis and
rumenitis may also occur without a
! history of grain engorgement in cattle,
j Anorexia and forestomach atonicity
associated with a primary illness in other
I body systems may predispose the
mucosae to fungal infection because of
abomasal reflux of acid and the prolonged
use of antimicrobials.

Chronic rumenitis and ruminal hyper-
: keratosis are common in cattle fed for
long periods on grain rations, and the
lesions are attributed to the chronic
acidosis, but it is possible that barley awns
and ingested hair may contribute to the
severity of the lesions.

Hepatic abscesses

In uncomplicated chemical rumenitis, the
ruminal mucosa sloughs and heals with
scar tissue and some mucosal regeneration.
Hepatic abscesses commonly occur as a-

' 3

complication as a result of a combination
of rumenitis caused by lactic acidosis and
allowing Fusobacterium necrophorum and
Arcanobacter (Corynebacterium) pyogenes to
enter directly into ruminal vessels and
spread to the liver, which may have also
undergone injury from the lactic acidosis.
Severe diffuse coagulation necrosis and
hyperplasia of the bile duct epithelium
and degeneration of renal tubules may
also be present histologically.

In cattle being placed on a grain ration,
even with control of the daily intake,
hepatic cell damage and liver dysfunction
occur even though dietary adaptation
may have occurred in 2-3 weeks. The bio-
chemical profile indicates that complete
metabolic adaptation requires at least
40 days following the start of grain
feeding.

Laminitis

Laminitis occurs in acute, subclinical and
chronic forms associated with varying
degrees of severity of ruminal acidosis.
The association between acidosis and
laminitis appears to be associated with
altered hemodynamics of the peripheral
microvasculature. Vasoactive substances
(histamine and endotoxins) are released
during the decline of rumen pH and the
bacteriolysis and tissue degradation.
These substances cause vasoconstriction
and dilation, which injure the micro-
vasculature of the corium. Ischemia results,
which causes a reduction in oxygen and
nutrients reaching the extremities of the
corium. Ischemia causes physical degra-
dation of junctures between tissues that
are structurally critical for locomotion. The
insidious rotation of the distal phalanx
(pedal bone) can result in permanent
anatomical change. Manifestations of
subclinical laminitis are sole hemorrhages
and yellowish discoloration. Other
clinical manifestations include double
soles, heel erosion, dorsal wall concavity
and ridging of the dorsal wall. 2

\ Other toxic substances produced

I Several toxic substances other than lactic
| acid have been suggested as contributory
j to the disease. Increased concentrations
j of histamine have been found in the
j rumen of experimentally engorged cattle,
j but its possible role in the disease remains
j unknown. Histamine is not absorbed
| from the rumen except at abnormally
I high pH values, but is absorbed from
| intestinal loops. Laminitis occurs in some
| cases of rumen overload but the patho-
j genesis is unknown.

Other substances that have been
I recovered from the rumen in grain over-
i load include a suspected endotoxin,
j ethanol and methanol. In experimental
j lactic acidosis induced in cattle with 70 g
barley/kg BW, endotoxin and arachidonic

318

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

acid metabolites are produced and may
be important. However, the role of the
endotoxin is uncertain. Endotoxin
■administered into the intestine of lactic
addotic sheep is not absorbed. Clostridium
perfringens and coliform bacteria have also
been found in increased numbers but
their significance is uncertain. The
electrolyte changes that occur include a
mild hypocalcemia due to temporary
malabsorption, loss of serum chloride due
to sequestration in the rumen, and an
increase in serum phosphate due to renal
failure.

Experimental lactic acidosis

The disease can be reproduced in cattle
and sheep with a variety of grains, fruits,
sugars and pure solutions of lactic acid.
The oral administration of sucrose at
18 g/kg BW to goats can cause lactic
acidosis. In cattle the sucrose is used to
induce rumen lactic acidosis experi-
mentally. 14 The severity of the experimental
disease and the magnitude of the
pathophysiological changes vary depend-
ing on the substance used, but changes
similar to the natural disease occur.

Lesions in the brain have been recorded
in the experimental disease in sheep and
naturally occurring cases in cattle, but
their pathogenesis and significance are
uncertain. There are detectable changes in
the cellular and biochemical composition
of the cerebrospinal fluid, which suggests
that the blood-brain barrier may be
affected. Experimentally, sublethal doses
of volatile fatty acids, lactate and
succinate have an effect on liver function.
Toxic and lethal doses of butyrate can
cause sudden flaccid paralysis and death
from asphyxia.

Adaptation to grain-based diets in
beef cattle

The health and ruminal variables during
adaptation to grain -based diets in beef
cattle have been examined experi-
mentally. Successive diets with forage -to-
grain ratios of 75:25 (diet 1), 50:50 (diet 2),
25:75 (diet 3) and 10:90 (diet!) were each
fed for 7 days. The health variables such as
rectal temperature, heart rate, respiratory
rate, rumen motility rates, fecal consistency,
demeanor, blood pH, and blood glucose
and L + -lactate concentrations remained
within reference range limits through-
out the adaptation period. Blood pH
continually decreased during feeding of
the four diets. The pH of the ruminal
contents decreased progressively from 6.8
to 5.3. By the end of the period, the
ruminal contents were acidic (pH < 5.5)
and, on the basis of the amounts of
ruminal glucose and DL-lactate, it was
concluded that ruminal microbial
equilibrium had not yet been achieved. In
addition, an increase in the heart and

respiratory rates in animals fed diets 2
and 4 indicated stress. During normal
fermentation, glucose is not detectable in
ruminal fluid because its production is
closely linked with its assimilation. In
general, changing from a high-roughage
to low-roughage diet is stressful for cattle
and their resident ruminal microflora.

Subacute ruminal acidosis (dairy
cattle)

The pathogenesis of SARA in lactating
dairy cows is not as well understood as
acute ruminal acidosis associated with the
sudden ingestion of large amounts of
readily fermentable carbohydrates, for
example, most commonly in beef cattle
that gain accidental access to large
quantities of grain. In early-lactating dairy
cows, SARA is usually caused by the
consumption of diets with high levels
of rapidly fermentable carbohydrates
and/or marginal, often deficient, levels of
physically active fiber. 8

The biochemical changes that occur in
lactating dairy cows in early lactation that
are affected with SARA have not been
examined in detail. In SARA, fermen-
tation of nonstructural carbohydrates
leads to the production of large quantities
of volatile fatty acids and lactate, which
accumulate in the rumen and sub-
sequently decrease rumen pH. It has been
difficult to reproduce SARA in early-
lactation dairy cows even with diets such
as high-moisture com, cracked dried com
grain and rolled barley. 7 These feeds did
not induce SARA, either because of an
inability of the feeds to depress the rumen
pH rapidly enough or because of the
cow's refusal to consume them.

Wheat/barley pellets were readily con-
sumed by lactating dairy cows and did
result in a sustained reduction in rumen
pH. 7 When cows with experimental
SARA are given a choice between alfalfa
hay and alfalfa pellets, cows will choose
the alfalfa hay more strongly, which
implies that dairy cows would increase
their dietary preference for a feed of
longer particle size when given the
appropriate choice during a bout of
SARA. 7 As intake of long hay will result in
more saliva production and rumen
buffering than intake of pelleted alfalfa,
this indicates that cows select feeds with
high rumen buffering capacity in an
attempt to prevent SARA. When cows
with SARA were offered sodium bicar-
bonate ad libitum, they did not select the
compound in order to attenuate the
ruminal acidosis. 15 When cows with SARA
were offered a choice between two test
pellets, one containing 4% sodium bicar-
bonate and the other 4.5% sodium chloride,
the intake of the sodium bicarbonate
pellets increased over time, but the

intake of sodium chloride pellets remained
unaltered. 16

There is some evidence that lactic acid
is not the causal reason for the prolonged
reduction in pH of the ruminal contents.
Studies have shown only low lactate levels
between 0.45 mmolVL and 0.74 mmol/L in
cows with suspected SARA. Excessive
volatile fatty acid production may be a
more important contributor to SARA in
lactating dairy cows.

The induction of SARA by excess
feeding of wheat/barley pellets reduces
the rumen digestion of neutral detergent
fiber from grass hay, legume hay and com
silage. 17 It is thought that SARA affects
the productivity of dairy cows by reducing
the fiber digestion, because low pH
negatively affects cellulolytic bacteria. The
induction of SARA in lactating dairy cows
by replacing 25% of the total mixed ration
intake with pellets consisting of 50%
wheat and 50% barley reduced the in-situ
dry matter and neutral detergent fiber
digestion of mixed hay. Disappearance of
neutral detergent fiber was reduced from
39.5% to 30. 9%. 18

In experimentally induced SARA,
lipopolysaccharide concentration in the
rumen increases during periods of grain
feeding compared with times when only
hay is fed. 19 The concentration of serum
amyloid- A and serum haptoglobin indicate
a systemic inflammatory response.

Rumen pH drops considerably in dairy
cows after calving when the diet is
changed. Monitoring rumen pH through-
out the transition period of dairy cows in
which the concentrate to forage ration
was changed from 70:30 to 55:45 at
calving found that 1 week prior to calving
the average daily pH was 6.83, average
daily time with rumen pH below 6 was
25.5 minutes and average daily time with
mmen pH below 5.6 was 5.6 minutes.
During the first week after calving,
average daily pH was 6.51, and average
daily time with rumen pH below 6 and 5.6
were 312 and 59.6 minutes respectively. 18
The drop in rumen pH is associated with
an increase in the rate of production of
volatile fatty acids, which temporarily
increases the concentration of volatile
fatty acids in the rumen, until the absorp-
tive capacity of the rumen mucosa for
volatile fatty acids has been increased.

The pathogenesis of rumenitis, hepatic
abnormalities and laminitis associated
with SARA is considered to be similar to
those described above for acute ruminal
acidosis.

CLINICAL FINDINGS

Speed of onset and severity

The speed of onset of the illness varies
with the nature of the feed, being more
rapid with ground feed than with whole

Diseases of the rumen, reticulum and omasum

3

grain. The' severity increases with the
amount of feed eaten. If cattle are
examined clinically within a few hours
after engorgement, the only abnor-
malities that may be detectable are a
distended rumen and abdomen, and
occasionally some abdominal discomfort,
evidenced by kicking at the belly. In the
mild form, affected cattle are anorexic
and still fairly bright and alert, and the
feces may be softer than normal. Rumen
movements are reduced but not entirely
absent. Affected cattle do not ruminate
for a few days but usually begin to eat on
the third or fourth day without any
specific treatment.

In outbreaks of the severe form,

within 24-48 hours some animals will be
recumbent, some staggering and others
standing quietly alone. Most affected
cattle are anorexic, apathetic and depressed.
Teeth grinding may occur in about 25% of
affected sheep and goats. Once they are ill
they usually do not drink water, but cattle
may engorge themselves on water if it is
readily available immediately after
consuming large quantities of dry grain.
In an outbreak, inspection of the feces on
the ground will usually reveal many spots
of soft to watery feces.

Individual animals

Depression, dehydration, inactivity,
weakness, abdominal distension,
diarrhea and anorexia are typical. The
temperature is usually below normal,
36.5-38.5°C (98-101°F), but animals
exposed to the sun may have tempera-
tures up to 41°C (106°F). In sheep and
goats, the rectal temperatures may be
slightly higher than normal. The heart
rate in cattle is usually increased and
continues to increase with the severity of
the acidosis and circulatory failure. In
general, the prognosis is better in those
with heart rates below 100/min than
those with rates up to 120-140/min. In
sheep and goats, the heart rate may be
higher than 100/min. The respirations are
usually shallow and increased up to
60-90/min. A mucopurulent discharge
is common because animals fail to lick
their nares.

Diarrhea is almost always present

and usually profuse, and the feces are
light-colored with an obvious sweet-sour
odor. The feces commonly contain an
excessive quantity of kernels of grain in
grain overload, and pips and skins when
grapes or apples have been eaten. An
absence of feces is considered by some
veterinarians as a grave prognostic sign
but diarrhea is much more common. The
dehydration is severe and progressive.
In mild cases, the dehydration is about
4-6% BW, and with severe involvement
up to 10-12% BW. Anuria is a common

finding in acute cases and diuresis follow-
ing fluid therapy is a good prognostic
sign.

Careful examination of the rumen is
important. The rumen contents palpated
through the left paralumbar fossa may
feel firm and doughy in cattle that were
previously on a roughage diet and have
consumed a large amount of grain. In
cattle that have become ill on smaller
amounts of grain, the rumen will not
necessarily feel full but rather resilient
because the excessive fluid contents are
being palpated. Therefore, the findings on
palpation of the rumen may be deceptive
and a source of error. The primary con-
tractions of the reticulorumen are usually
totally absent, although low-pitched
tinkling and gurgling sounds associ-
ated with the excessive quantity of fluid in
the rumen are commonly audible on
auscultation of the rumen. The ruminal
fluid is a milky green to olive brown color
and has a pungent acid smell. Collection
of a sample of ruminal fluid in a glass
beaker will reveal an absence of foam.
The pH of the rumen fluid is usually
below 5.

Severely affected animals have a
staggery, drunken gait and their eye-
sight is impaired. They bump into objects
and their palpebral eye preservation reflex
is sluggish or absent. The pupillary light
reflex is usually present but slower than
normal. Acute laminitis may be present
and is most common in cases that are not
severely affected and appear to be good
treatment risks. Affected animals are lame
in all four feet, shuffle while they walk
slowly and may be reluctant to stand.
The lameness commonly resolves if the
animals recover from the acute acidosis.
Evidence of chronic laminitis may develop
several weeks later.

Recumbency usually follows after
about 48 hours but may occur earlier.
Affected animals lie quietly, often with
their heads turned into the flank, and
their response to any stimulus is much
decreased so that they resemble parturient
paresis. A rapid onset of recumbency
suggests an unfavorable prognosis and
the necessity for urgent treatment,
because death may occur in 24-72 hours
after the ingestion of the feed. Evidence of
improvement during this time includes a
fall in heart rate, rise in temperature,
return of ruminal movement and passage
of large amounts of soft feces.

The clinical findings described. above
are most common but when a group of
animals have been exposed to over-
feeding there are all degrees of severity
from simple indigestion, cases of which
recover spontaneously, to the severe cases
that need intensive therapy. The prog-
nosis varies with the severity, and the

clinical variables that are useful in
deciding on a course of treatment or
action are summarized in Table 6.8.

Mycotic rumenitis

Some animals appear to recover follow-
ing treatment but become severely ill
again on the third or fourth day. Mycotic
rumenitis is common in these animals
and is characterized by a fluid-filled
atonic rumen, dehydration in spite of fluid
therapy, diarrhea, anorexia, weakness
leading to recumbency and death in
2-3 days due to acute diffuse peritonitis.

Complications

Chronic laminitis may occur several
weeks or months later. This is particularly
important in dairy cattle herds affected
with subacute acidosis. 5

Abortions may occur 10 days to
2 weeks later in pregnant cattle that
survive the severe form of the disease.

Subacute ruminal acidosis in dairy
cattle

Subacute ruminal acidosis (SARA) is
being recognized with increased fre-
quency in dairy herds. 3-5 However, the
case definition is not yet well described.
Clinical findings include laminitis, inter-
mittent diarrhea, suboptimal appetite or
cyclic feed intake, a high herd culling rate,
loss of body condition in spite of adequate
energy intake, liver abscesses, and
hemoptysis and epistaxis associated with
venal caval thrombosis and pulmonary
hemorrhage. Milk-fat depression and
suboptimal milk production in the
second- and subsequent- lactation cows
compared to the first-lactation cows may
occur. 3

A decrease in dry matter intake is
commonly reported in herds with SARA. 4
The causes of a lowered dry matter intake
are uncertain but may be related to weaker
rumen motility during low pH phases,
bacterial endotoxins and changes in the
osmolarity of the rumen contents.

The laminitis is characterized by ridges
in the dorsal hoof wall, sole ulceration,
white line lesions, sole hemorrhages and
misshapen hooves. 20 It is suggested that
when the incidence of laminitis exceeds
10% of the herd, it should be considered a
herd problem related to the feeding
program.

CLINICAL PATHOLOGY

The severity of the disease can usually be
determined by clinical examination, but
field and laboratory tests are of some
additional value.

Ruminal fluid pH

The pH of the ruminal fluid obtained by
stomach tube or by rumenocentesis
through the left paralumbar fossa can be
measured in the field using wide-range

.MEDICINE ■ Chapter 6: Diseases of the alimentary tract - I

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Diseases of the rumen, reticulum and omasum

32

pH (2-12) Indicator paper. The ruminal
fluid must be examined immediately
because the pH will increase upon
exposure to air. Cattle that have been fed
a roughage diet will have a ruminal pH of
6-7; for those on a grain diet it will be
5.5-6. A ruminal pH of 5-6 in roughage-
fed cattle suggests a moderate degree of
abnormality but a pH of less than 5
suggests severe grain overload and the
need for energetic treatment. Feedlot
cattle that have been on grain for several
days or weeks and are affected with grain
overload usually have a pH below 5.

Rumenocentesis has become a com-
monly used diagnostic test for subacute
ruminal acidosis. 13,20 A hypodermic
needle of 1.6 (outer diameter) x 130 mm
(length) is inserted into the ventral rumen
and rumen contents aspirated with a
syringe. Landmarks for the puncture site
are the left side, on a horizontal line level
with the top of the patella about 15-20 cm
posterior to the last rib. The hair of the site
is clipped and prepared using a standard
scrub. The cow is restrained in a stanchion
or head-gate and one assistant elevates
the tail of the cow while another assistant
inserts a 'nose leader' and pulls the cow's
head to the right side. The needle will
usually become obstructed by ingesta,
which is cleared by forcing a small
amount of air or fluid back through the
needle. When the needle becomes
obstructed it is important to avoid
creating a negative pressure within the
syringe, as carbon dioxide will leave the
fluid and increase the pH. Typically,
3-5 mL of rumen fluid can be collected
with minimal difficulty.

The pH is measured immediately using
a pH meter with a digital readout. Samples
should be collected when the pH is likely to
be near the lowest point of the day. If the
ration is fed as separate components,
rumenocentesis should be performed
2-4 hours after the cows are fed the
primary concentrate of the day. If the ration
is fed as a total mixed ration, the samples
should be collected 4-8 hours later. A pH of
5.5 is recommended as the cut-point
between nonnal and abnormal. 20 At least
12 or more cows should be sampled from
any group in which acidosis is suspected. If
30% of 10 or more sampled cows are
below 5.5, the group is classified as in a
state of ruminal acidosis. A subsample of
12 cows from a herd or diet group and a
critical number of three cows with a
niminal pH less than or equal to 5.5 may
effectively differentiate between herds with
15% or less or greater than 30% prevalence
of cows with a low ruminal pH. 13

Ruminal protozoa

Microscopic examination of a few drops
of ruminal fluid on a glass slide (with a

coverslip) at low power will reveal the
absence of ruminal protozoa, which is a
reliable indicator of an abnormal state of
the rumen, usually acidosis. The pre-
dominantly Gram-negative bacterial flora
of the rumen is replaced by a Gram-
positive one.

Serum biochemistry

The degree of hemoconcentration, as
indicated by hematocrit, increases with
the amount of fluid withdrawn from the
extracellular fluid space into the rumen.
The hematocrit rises from a normal of
30-32% to 50-60% in the terminal stages
and is accompanied by a fall in blood
pressure. Blood lactate and inorganic
phosphate levels rise and blood pH and
bicarbonate fall markedly. In almost all
cases there is a mild hypocalcemia,
which is presumably due to a temporary
malabsorption. Serum levels may drop to
between 6-8 mg/dL (1.5-2 mmol/L).

The serum enzyme activities of cattle
fed on barley for several months has been
measured and suggest that hepatocellular
damage occurs during the early stages of
feeding grain but that recovery occurs
after about 1 month.

Urine pH

The urine pH falls to about 5 and
becomes progressively more concen-
trated; terminally there is anuria.

NECROPSY FINDINGS

In acute cases where the animal dies in
24-48 hours the contents of the rumen
and reticulum are thin and porridge-like
and have a typical odor suggestive of
fermentation. The cornified epithelium
may be mushy and easily wiped off, leaving
a dark, hemorrhagic surface beneath. This
change may be patchy, caused probably
by the production of excess lactic acid in
pockets where the grain collects, but is
generally restricted to the ventral half of
the sacs. Abomasitis and enteritis are also
evident in many cases. The abomasum
may contain large quantities of grain.
There is a pronounced thickening and
darkening of the blood and the visceral
veins stand out prominently.

In cases that have persisted for 3-4 days
the wall of the reticulum and rumen may
be gangrenous. This change is again
patchy but may be widespread. In affected
areas the wall may be three or four times
the normal thickness, show a soft black
mucosal surface raised above surrounding
normal areas and have a dark red appear-
ance visible through the serous surface.
The thickened area is very friable and
on cutting has a gelatinous appearance.
Histological preparations show infil-
tration of the area by fungal mycelia and a
severe hemorrhagic necrosis. A fungal
hepatitis is common in those with fungal

rumenitis. In the nervous system, in cases
of 72 hours or more duration, demyeli-
nation has been reported. A terminal
ischemic nephrosis is present in varying
degrees in most fatal cases of more than
several days' duration.

If the examination takes place less ,
than an hour after death, estimation of
ruminal pH may be of value in confirming
the diagnosis but after 1 hour the pH of
the rumen contents begins to increase
and its measurement may not be reliable.
A secondary enteritis is common in
animals that have been ill for several days.

DIFFERENTIAL DIAGNOSIS

When outbreaks of the disease with an
appropriate history are encountered, the
diagnosis is usually readily obvious and
confirmed by the clinical findings and
examination of the ruminal fluid for pH
and rumen protozoa.

When the disease occurs in a single
animal without a history of engorgement,
the diagnosis may not be readily obvious.
The anorexia, depression, ruminal stasis
with gurgling fluid sounds from the rumen,
diarrhea and a staggery gait with a normal
temperature are characteristics of rumen
overload.

Acute and subacute carbohydrate
engorgement must be differentiated from:

• Simple indigestion. The consumption
of large quantities of palatable feed,
such as ensiled green feed offered to
cattle for the first time, may cause
simple indigestion, which may resemble
grain overload. The rumen is full, the
movements are reduced in frequency
and amplitude, there may be mild
abdominal pain due to the distension,
but the ruminal pH and protozoan
numbers and activity are normal

• Parturient paresis. Severe cases that
are recumbent may resemble parturient
paresis, but in the latter the feces are
usually firm and dry, marked
dehydration does not occur, the
absolute intensity of the heart sounds is
reduced and the response to calcium
injection is favorable

• Toxemias. Common toxemias of cattle
that may resemble ruminal overload
include peracute coliform mastitis and
acute diffuse peritonitis, but clinical
examination will usually reveal the
cause of the toxemia

• Subacute ruminal acidosis must be
differentiated from diseases of dairy
cows in early lactation in which there is
reduced appetite and milk production.
These include simple indigestion, left-
side displacement of the abomasum,
ketosis and other causes of suboptimal
milk production in dairy cows in early
lactation. 2 ' Feeding management
problems such as poor-quality forage or
poor feeding bunk management are
common causes of suboptimal
performance in lactating dairy cows
that are not affected with SARA

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

TREATMENT

The principles of treatment are:

° Correct the ruminal and systemic
acidosis and prevent further
production of lactic acid
° Restore fluid and electrolyte losses
and maintain circulating blood
volumes

0 Restore forestomach and intestinal
motility to normal.

There are at least two common clinical
situations encountered. One is when cattle
have been found accidentally eating large
quantities of grain, are not yet ill and all
appear similar clinically except for varying
degrees of distension depending on the
amount each animal has consumed. In the
other situation, the engorgement occurred
24-48 hours previously and the animals
have clinical evidence of lactic acidosis.

When cattle are found engorging
themselves, the following procedures
are recommended:

° Prevent further access to feed
0 Do not provide any water for
12-24 hours

0 Offer a supply of good-quality

palatable hay equal to one-half of the
daily allowance per head
0 Exercise all animals every hour for
12-24 hours to encourage movement
of the ingesta through the digestive
tract.

Those cattle that have consumed a toxic
amount of grain will show signs of
anorexia, inactivity and depression in
approximately 6-8 hours and should be
identified and removed from the group
for individual treatment. Those cattle that
did not consume a toxic amount are
usually bright and alert and will usually
begin eating hay if it is offered. Not all
cattle found engorging themselves with
grain will have consumed a toxic dose and
careful monitoring over a 24-48- hour
period will usually distinguish between
those that need treatment and those that
do not.

After 18-24 hours, those cattle that
have continued to eat hay may be allowed
free access to water. Those with clinical
evidence of grain overload must be
identified and treated accordingly. They
will engorge themselves with water if
allowed free access to it. The rumen
becomes grossly distended with fluid and
affected cattle may die 18-24 hours later
from electrolyte disturbances and acid-
base imbalance.

In certain situations, if feasible and
warranted by economics, such as when
finished beef cattle have accidentally
engorged on grain, emergency slaughter
may be the most economical course of
action.

Triage

The recommendations for treatment
given in Table 6.8 are guidelines. In an
outbreak, some animals will not require
any treatment while severely affected
cases will obviously need a rumenotomy.
For those that are not severely affected, it
is often difficult to decide whether to treat
them only medically with antacids orally
and systemically or to do a rumenotomy.
Each case must be examined clinically
and the most appropriate treatment
selected. The degree of mental depression,
muscular strength, degree of dehydration,
heart rate, body temperature, and rumen
pH are clinical parameters that can be
used to assess severity and to determine
the treatment likely to be most successful.

Rumenotomy

In severe cases, in which there is recum-
bency, severe depression, hypothermia,
prominent ruminal distension with fluid,
a heart rate of 110-130/min and a rumen
pH of 5 or below, a rumenotomy is the
best course of action. The rumen is
emptied, washed out with a siphon and
examined for evidence of and the extent
of chemical rumenitis, and a cud transfer
(10-20 L of rumen juice) is placed in the
rumen along with a few handfuls of hay.
The rumenotomy will usually correct the
ruminal acidosis and an alkalinizing
agent in the rumen is not necessary. A
large quantity of the lactic acid and its
substrate can be removed. The oral or
intraruminal administration of compounds
such as magnesium oxide or magnesium
hydroxide to cattle following complete
evacuation of the rumen may cause
metabolic alkalosis for up to 24-36 hours.
Not all of the feed consumed will be
removed because considerable quantities
may have moved into the omasum and
abomasum, where fermentation may also
occur. The major disadvantages of a
rumenotomy are time and cost, parti-
cularly when many animals are involved.

Intravenous sodium bicarbonate and
fluid therapy

The systemic acidosis and the dehydration
are treated with intravenous solutions of
5% sodium bicarbonate at the rate of 5 L
for a 450 kg animal given initially over a
period of about 30 minutes. This will
usually correct the systemic acidosis. This is
followed by isotonic sodium bicarbonate
(1.3%) at 150 mL/kg BW intravenously
over the next 6-12 hours. Cattle that
respond favorably to the rumenotomy and
fluid therapy will show improved muscular
strength, begin to urinate within 1 hour
and attempt to stand within 6-12 hours.

Rumen lavage

In less severe cases, in which affected
cattle are still standing but are depressed.

their heart rate is 90-100/min, there is
moderate ruminal distension and the
rumen pH is between 5 and 6, an alter-
native to a rumenotomy is rumen lavage if
the necessary facilities are available. A large
25-28 mm inside-diameter rubber tube is
passed into the rumen and warm water is
pumped in until there is an obvious dis-
tension of the left paralumbar fossa; the
rumen is then allowed to empty by gravity
flow. The rumen can be almost completely
emptied by 10-15 irrigations. With success-
ful gastric lavage, alkalinizing agents are
not placed in the rumen but the systemic
acidosis is treated as described above.

Intraruminal alkalinizing agents

In moderately affected cases, the use of
500 g of magnesium hydroxide per 450 kg
BW, or magnesium oxide in 10 L of warm
water pumped into the rumen and followed
by kneading of the rumen to promote
mixing will usually suffice.

Magnesium hydroxide is a potent
alkalinizing agent for use in ruminants as
an antacid and mild laxative. It can
significantly decrease rumen microbial
activity and should be used only in cattle
with rumen acidosis and not for symp-
tomatic therapy of idiopathic rumen
disorders or hypomagnesemia. 22 The oral
administration of boluses of magnesium
hydroxide (162 g) or a powdered fonn
(450 g) dissolved in 3.5 L of water daily for
3 days resulted in a significant increase in
rumen pH after 48 and 24 hours, respect-
ively. Both the boluses and the powder
forms of magnesium hydroxide decreased
rumen protozoal numbers and increased
methylene blue reduction times compared
with baseline values. There was no
change in blood pH, bicarbonate or base
excess values. Serum magnesium values
were significantly increased in cows
receiving the powder.

Ancillary therapy

Ancillary treatment has included anti-
histamines for laminitis, NSAIDs for
shock therapy, thiamin or brewer's yeast
to promote the metabolism of lactic acid,
and parasympathomimetics to stimulate
gut motility. Their efficacy has been
difficult to evaluate and it is unlikely that
any of them would be of much value.
Calcium borogluconate is used widely
because there is a mild hypocalcemia and
a beneficial but temporary response does
occur, but it is of doubtful value.

Orally administered antimicrobials
including penicillin and the tetracyclines
have been used to control growth of
the bacteria that produce lactic acid, but
appear to be of limited value.

Monitor response to therapy

Regardless of the treatment used, all cases
must be monitored several times daily

until recovery is obvious, for evidence of
unexpected deterioration. Following
treatment, cattle should begin eating hay
by the third day, some ruminal move-
ments should be present, large quantities
of soft feces should be passed and they
should maintain hydration. In those that
become worse, the heart rate increases,
depression is marked, the rumen fills with
fluid and weakness and recumbency
occur. During treatment, the water supply
should be restricted because some cattle,
either immediately after they have
engorged themselves or once they become
ill, appear to have an intense thirst and
will drink excessive quantities of water
and die precipitously within a few hours.

The fungal rumenitis that may occur
about 3-5 days after engorgement is best
prevented by early effective treatment of
the ruminal acidosis.

CONTROL AND PREVENTION

Cattle can be started, grown and finished
on high-level grain rations successfully,
providing they are allowed a gradual
period of adaptation during the critical
period of introduction. The important
principle of prevention is that the
ruminant can adapt to an all-concentrate
ration. For animals that have just arrived
in the feedlot, the length of the adaptation
period required will depend on the
immediate nutritional history of the
animals, their appetite and the composition
of the ration to be used.

Total mixed rations

One of the safest procedures is to feed a
milled mixed ration, consisting of 50-60%
roughage and 40-50% grain, as the start-
ing ration for 7-10 days and monitor the
response. If results are satisfactory, the
level of roughage is decreased by 10%
every 2-4 days down to a level of 10-15%
roughage, with the remainder grain and
vitamins-mineral-salt supplement. The
use of roughage-grain mixtures insures
that cattle do not engorge themselves on
grain, and adaptation can occur in about
21 days.

Small incremental increases in
concentrate

Another method is to begin with small
amounts of concentrate 8-10 g/kg BW,
which is increased every 2-4 days by
increments of 10-12%. A source of
roughage is supplied separately. The
disadvantages of this system are that
hungry or dominant cattle may eat much
more than their calculated share and
there is no assurance that sufficient
roughage will be consumed. In this
system, on a practical basis, the cattle are
usually fed twice daily and brought up to
a daily intake of concentrate that satisfies
their appetite and then the concentrate

Diseases of the rumen, reticulum and omasum

ration is offered free-choice from self-
feeders. Unless there is sufficient feeding
space in the self-feeders, competitive and
dominant animals will often overeat and
careful monitoring is necessary.

Feedlot starter rations

Feedlot starter rations consisting of a
mixture of roughage and grain, offered
free-choice along with hay and gradually
replaced by a finishing ration have
successfully adapted cattle in 10 days. The
starter ration contains about 2500 kcal
(10 460 kj) DE (digestible energy) per kg
of feed. The finishing ration contains
about 3100 kcal (12 970 kj), and control-
ling the rate of increase of DE concen-
tration of the ration was a major factor in
getting cattle on feed.

A comparison of the effect of rapid or
gradual grain adaptation on subacute
acidosis and feed intake by feedlot cattle
indicates a range of individual responses
to grain challenge and current manage-
ment strategies for preventing acidosis in
pens of cattle are based on responses of
the most susceptible individuals. 23 Using
this approach requires consideration of
individual animal responses. The data
suggest that most cattle can be rapidly
adapted to high-grain diets in few incre-
mental steps; minimizing acidosis in the
most susceptible individuals requires
decreasing the pace of grain adaptation
for the entire group.

Dietary buffers

The incorporation of buffers, such as
sodium bicarbonate, into the ration of
feedlot cattle has been studied extensively
but to date the results are inconclusive
and reliable recommendations cannot
be made. A level of 2% dietary sodium
bicarbonate, sodium bentonite or lime-
stone provided some protection from
acidosis during the early adaptation
phase of high-concentrate feeding; but
they were no more effective than 10%
alfalfa hay. Buffers have been most
effective in reducing acidosis early in the
feeding period and have little or no effect
later. They may be associated with an
increased incidence of urinary calculi,
bloat and vitamin deficiencies. The
experimental results to date are conflict-
ing. Some trials indicate that buffers
maintain a Gram-negative rumen flora in
sheep fed grain compared to a shift to
Gram-positive rumen flora in animals not
fed buffers. Liveweight performance is
also improved in some trials but not in
others fed 0.75, 1.0 or 2.25% of diet as
sodium bicarbonate.

The potential efficiency of products for
the control of ruminal acidosis has been
examined through the measurement of
the increase in buffer capacity and acid-
consuming capacity. 24 Sodium bicarbonate

provided the highest increment in
buffering capacity and acid-consuming
capacity compared to calcium carbonate.
Magnesium oxide provided higher acid-
consuming capacity but had no effect on
buffer capacity.

Dietary supplementation of sodium
bicarbonate at a level of 1 .5% for 90 days
in high-concentrate diets fed to lambs
improved cellulose digestibility, ciliate
protozoal number, ruminal pH and total
nitrogen concentration, resulting in
improved growth of lambs maintained on
a high-concentrate diet. 25

lonophores

The ionophores salinomycin, monensin
and lasalocid have been compared for
their protective effects, and salinomycin is
more effective than the other two;
monensin also shows some promise.
Laidlomycin propionate does not prevent
ruminal acidosis but may reduce the
severity of ruminal acidosis during adap-
tation to a 100% concentrated diet.
Monensin supplementation did not affect
dry matter intake, milk yield and compo-
sition, and ruminal pH characteristics in
experimentally induced SARA. 16 The rates
of ruminal forage fiber degradability were
similar between control and monensin-
treated cows; however, monensin supple-
mentation increased total digestive tract
fiber digestion, especially at postruminal
sites. Thus monensin could be used for
the improvement of nutrient digestion
during grain-induced SARA in dairy
cows. 26

Subacute ruminal acidosis in dairy
cattle

The basic principles of preventing SARA
in dairy herds include:

° Limiting the intake of rapidly

fermentable carbohydrates
• Providing adequate ruminal buffering
° Allowing for ruminal adaptation to

high-grain diets. 27

Prevention of subacute ruminal acidosis
includes proper adaptation of rumen
papillae during the prepartum period,
adequate intake of forage in early
lactation, and adequate fiber nutrition
throughout lactation. Successful manage-
ment of energy balance through the peri-
parturient transition period depends on
providing adequate energy density in the
prepartum diet. Increasing energy density
of the prepartum diet also promotes dry
matter intake before and after calving.
The energy density in the prepartum diet
should be 1.54-1.63 Mcal/kgNE,.

Dry cows should be fed according to
their needs; cows in the early and middle
portion of the dry period (far-off cows)
and cows in the final 3 weeks prior to
calving (pre-fresh cows) have different

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

nutritional requirements in order to
achieve optimal milk production and
maintain the health and fertility of early-
lactation cows.

Prepartum diets should be offered,
starting at least 3 weeks prior to calving.
Because of the different calving dates of
dry cows fed in groups, the use of a
prepartum diet over a prepartum feeding
period of 21 days will usually allow each
cow to consume the diet for a minimum
of 5 days. The nutrient requirements for
pre-fresh dry cows is controversial. The
National Research Council does not
provide recommendations for pre-fresh
cows and it is recommended that a dairy
cattle nutritionist be consulted for for-
mulation of such rations. In general, a
pre-fresh diet will provide about
0.50-0.75% BW per day as concentrates.
Pre-fresh diets should be similar to early
lactation diets so that the transition
occurs effectively. The forages fed in the
pre-fresh diet should be similar to those
fed in early lactation.

Dairy cows are usually fed total mixed
rations, where the concentrates and
forages are mixed and fed as a total ration,
or separate component rations in which
the concentrates and forage are fed
independently. In herds using separate
component diets, the concentrates in the
pre-fresh diet should be gradually
introduced over a period of 3-5 days, and
preferably fed individually. Forages
should also be fed individually so that
intake can be evaluated.

Limiting the intake of rapidly
fermentable carbohydrates
As a guideline, cows should not receive
more than 8-12 lb (3-5 kg) of dry matter
from grain in the first week after calving. 27
Grain feeding should then increase by
about 0.25-0.50 lb (110-220 g) per cow
per day until peak grain feeding is
reached at 6-8 weeks post calving.

The physical form of the feed ingre-
dients is as important as their chemical
composition in determining how rapidly
and completely they are fermented in the
rumen. Grains that are finely ground,
steam-flaked, extruded and/or very wet
will ferment more rapidly and completely
in the rumen than unprocessed or diy
grains. Starch from wheat or barley is
more rapidly and completely fermented
than starch from corn (maize). Corn
silage that is very wet, finely chopped or
kernel-processed is also a greater risk
for SARA than drier, coarsely chopped,
or unprocessed corn silage. Particle
size analysis of grains is a useful
adjunct test when assessing the risk for
SARA in a dairy herd. Grain particle size
length can be determined using metal
sieves.

Providing adequate ruminal buffering
Ruminal buffering includes dietary and
endogenous buffering. 27

Dietary buffering is the inherent
buffering capacity of the diet and is
dependent on cation-anion difference
(DCAD). Diets high in sodium and
potassium relative to chloride and sulfur
have higher DCAD concentrations, tend
to support higher ruminal pH, and
increase dry matter intake and milk yield.
Optimal DCAD for early lactation diets is
approximately +400 mEq/kg of (Na + K) -
(Cl + S). Mid-lactation cows have an
optimal DCAD of +275 to +400 mEq/kg.
Formulating diets with a high DCAD
requires the addition of buffers such as
sodium bicarbonate. Alfalfa forages have
a higher DCAD than corn (maize) silage,
depending on the mineral composition of
the soil. Concentrate feeds typically have
a low or negative DCAD, which adds to
their already high potential to cause
ruminal acidosis because of their high
fermentable carbohydrate content.

Endogenous buffers are produced by
the cow and secreted into the rumen via
saliva. The amount of physical fiber in the
diet determines the extent of buffer
production by the salivary glands. Coarse,
fibrous feeds contain more effective fiber
and stimulate more saliva production
during eating than do finely ground feeds
or fresh pasture. Coarse, fibrous feeds also
make up the mat layer of the rumen,
which is the stimulus for rumination.
Fiber particles must be at least 4 cm in
length in order to contribute to mat layer
formation. Rumination promotes much
chewing activity and the secretion of large
amounts of saliva into the rumen.
Ruminal pH increases during bouts of
rumination.

The ability of a diet and feeding pro-
gram to promote maximal amounts of
ruminal buffering must be evaluated in
herds with SARA. Wet chemistry analysis
of a carefully collected total mixed ration
bunk sample can be used to determine
the actual DCAD of the diet actually con-
sumed by the cows. Diets with measured
DCAD values below +275-400 mEq/kg of
(Na + K) - (Cl + S) should be supple-
mented with additional buffers to provide
more Na or K relative to Cl and S.

Endogenous buffering can be estimated
by observing the number of cows
ruminating (a goal is at least 40% of cows
ruminating at any given time) and by
measuring the particle length of the total
mixed ration actually consumed by the
cows using the Ffennsylvania State Forage
Particle Separator. 27 Diets with less than
7% long particles render cows at increased
risk of SARA, especially if the diets are
also borderline or low in chemical fiber
content. Diets with excessive (over 15%)

long forage particles can paradoxically
increase the risk of SARA if the long
particles are unpalatable and sortable.
Sorting of the long particles occurs soon
after delivery of the feed, resulting in the
cows consuming a diet low in physically
effective fiber after feeding. The diet
consumed later in the feeding period is
then excessively high in physically effective
fiber and low in energy. Socially dominant
cows are particularly susceptible to SARA
in this situation because they are likely to
consume more of the fine total mixed
ration particles soon after delivery of the
feed. Cows lower on the social order then
consume a very low-energy diet. Limiting
feed bunk space to less than 75 cm per cow
exacerbates the effect of total mixed ration
sorting in a group of cows.

Allowing for ruminal adaptation to high-
grain diets 27

Cows in early lactation are susceptible to
SARA if they are poorly adapted for the
lactation diet. Ruminal adaptation to diets
high in fermentable carbohydrates depends
on microbial adaptation (particularly the
lactate-utilizing bacteria, which grow
more slowly than the lactate-producing
bacteria) and the length of the ruminal
papillae (longer rumen papillae promote
greater volatile fatty acid absorption and
thus lower ruminal pH).

In herds with total mixed rations, the
pre-fresh diets can be offered to pre-fresh
cows as they approach calving, usually
with success. With total mixed rations,
cows cannot eat excessive quantities of
concentrate at the expense of forage.
Cows that have become adapted on a
well-formulated pre-calving total mixed
ration during the prepartum period can
go directly on to the high-producing
lactating total mixed ration after calving
without any further adaptation.

In summary, one of the most challeng-
ing aspects of diet formulation for lactating
dairy cows is balancing for carbohydrates.
Adequate effective fiber must be provided
to stimulate chewing and secretion of
salivary buffers. However, effective fiber is
more filling than other nutritional
components of the diet and the filling
effect often limits the energy intake of
high-producing cows. Therefore, diets for
high-producing cows should be balanced
to provide adequate effective fiber with
the least filling effect. A balance must also
be attained for ruminal carbohydrate
fermentation, which is desirable to provide
nutrients for microbial growth and protein.
However, the fermentability of the diet
must be limited to prevent excessive pro-
duction of acids of fermentation. 28

Feeding management in early lactation
This consists of ensuring that concen-
trates are introduced gradually, and

Diseases of the rumen, reticulum and omasum

preferably- at the same rate as dry matter
intake increases in the first 6 weeks of
lactation. Formulation strategies for feed-
ing concentrates in the first 6 weeks of
lactation without compromising fiber
nutrition have been developed. Weekly
dry matter predictions were used and the
proper increase in concentrate feeding is
only 0.9-1 .6 kg/week. At the same time, it
is necessary to insure that cows receive
adequate dietary energy to prevent pri-
mary acetonemia.

Routine monitoring of the dry-matter
content of feed ingredients is an import-
ant strategy in preparing total mixed
rations for dairy cattle. Electronic silage
testers are available and recommended.

Ionophores, such as monensin sodium,
alter rumen metabolism and have the
potential to control ruminal acidosis in
dairy cattle, increase milk production,
modify milk composition and improve
health. Monensin alters the volatile fatty
acid profile in the rumen towards
increased propionate production, which
induces glucogenesis. Milk production is
increased but the percentage of milk fat is
depressed, which is effective in reducing
the incidence of ketosis. Monensin
decreases the population of S. bovis in the
rumen, resulting in a reduction in the pro-
duction of lactic acid; it increases the
clearance of lactate from the rumen and
increases ruminal pH. This has the
potential to reduce the incidence of
subacute ruminal acidosis in dairy cattle
and the sequelae of rumenitis, laminitis
and hepatic abscessation. Monensin also
decreases ruminal methanogenesis,
ruminal ammonia and blood levels of
ketone bodies. Thus monensin has the
potential to improve health of dairy cows
and prevent ruminal acidosis during the
transition period of the periparturient
cow as described above. Ionophores have
not yet been approved for use in lactating
dairy cows in North America but
extensive studies are under way.

Vaccination against lactic acidosis

Some preliminary research has investi-
gated the immunization of cattle against
lactic -acid -producing bacteria, S. bovis
and Lactobacillus. Immunization induced
high levels of persistent saliva antibody
responses against S. bovis and Lactobacillus,
which reduced the risk of lactic acidosis in
cattle. 29

REVIEW LITERATURE

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Loerch SC, Fluharty FL. Physiological changes an
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2. Nocek JE. J Dairy Sci 1997; 80:1005.

3. Oetzel GR. In: Proceedings of the 33rd Annual
Meeting of the American Association of Bovine
Practitioners. Opelika, AL: AABP, 2000:46.

4. Kleen JL et al. JVet Med A 2003; 50:406^114.

5. Nordlund K. In: Proceedings of the 33rd Annual
Meeting of the American Association of Bovine
Practitioners. Opelika, AL: AABP, 2000:58.

6. Oetzel GR. 2003: http://www.vetmed.wisc.
edu/dms/fapm/fapmtools/2nutr/saralaabp.pdf.

7. Keunen JE et al. J Dairy Sci 2002; 85:3304.

8. National Research Council. Nutrient require-
ments of dairy cattle, 7th ed. Washington, DC:
National Academy Press, 2001.

9. Nordlund K. 2003: http://www.vetmed.wisc.edu/
dms/fapm/fapmtools/2nutr/sarafacters.pdf.

10. Enemark JMD, Jorgensen RJ.Vet Q 2001; 23:206.

11. Galyean ML, Rivera JD. Can J Anim Sci 2003;
83:13.

12. Loerch SC, Fluharty FL. J Anim Sci 1999; 77:1113.

13. Garrett EF et al. J Dairy Sci 1999; 82:1170.

14. Ortolani EL. Vet Hum Toxicol 1995; 37:462.

15. Keunen JE et al. J Dairy Sci 2003; 86:954.

16. Cumby JL et al. Can J Anim Sci 2001; 81:149.

17. Krajcarski-Hunt H et al. J Dairy Sci 2002; 85:570.

18. Plaizer JC et al. Can J Anim Sci 2001; 81:421.

19. Gozho GN et al. J Dairy Sci 2005; 88:1399.

20. Nordlund K. 2003; http://www.vetmed.wisc.edu/
dms/fapm/fapmtools/2nutr/sara2aabp.pdf.

21. Steen A. Acta Vfet Scand 2001; 42:219.

22. Smith GW, Correa MT. J Vet Intern Merl 2004;
18:109.

23. Bevans DW et al. J Anim Sci 2005; 83:1116.

24. Zammarreno AM et al. J Sci Food Agric 2003;
83:1607.

25. Santra A ct al. Small Rumin Res 2003; 47:203.

26. Osborne JK et al. J Dairy Sci 2004; 87:1840.

27. Oetzel GR. 2003: http://www.vetmed.wisc.
edu/dms/fapm/fapmtools/2nutr/sara3aabp.pdf.

28. Allen M. In: Proceedings of the 33rd Annual
Meeting of the American Association of Bovine
Practitioners. Opelika, AL: AABP, 2003:1.

29. Shu Q et al. ResVet Sci 1999; 67:65.

RUMINAL PARAKERATOSIS

Parakeratosis of the ruminal epithelium
does not, as far as is known, cause clinical
illness but opinions on its effect on weight
gain and productivity vary. There is
evidence that the development of para-
keratosis increases and then reduces the
absorption of volatile fatty acids from the
rumen and that the addition of volatile
fatty acids to a calf starter increases the
incidence of the condition. The abnor-
mality has been observed most commonly
in cattle and sheep fed high-concentrate
rations of alfalfa pellets that have been
subjected to heat treatment, and does not
occur in cattle fed on rations containing
normal quantities of unpelleted roughage.
The incidence of the disease does not
appear to be related to the feeding of
antibiotics or protein concentrates.

In affected rumens the papillae are
enlarged, leathery, dark in color and often
adhered to form clumps. Histologically
there is an increase in thickness of the
cornified portion of the ruminal epi-
thelium and a persistence of nuclei in the
cornified cells. Some of the affected cells
contain vacuoles. The greatest severity of
lesions is present on the dorsal surface of
the rumen about the level of the fluid
ruminal contents. It is thought that they
are caused by the lowered pH and the
increased volatile fatty acid content in the
rumen liquor. The fact that unprocessed,
whole grain - on which animals gain
weight as readily as on processed grain -
does not lead to the development of the
disease is probably related to the higher
pH and higher concentration of acetic
versus longer-chain volatile fatty acids in
the ruminal liquor. The incidence of
affected animals in a group may be as
high as 40%.

RUMINAL TYMPANY (BLOAT)

Ruminal tympany is abnormal distension
of the rumen and reticulum caused by
excessive retention of the gases of fer-
mentation, either in the form of a
persistent foam mixed with the rumen
contents or as free gas separated from the
ingesta. Normally, gas bubbles produced
in the rumen coalesce, separate from the

326

PART 1 GENFRAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

rumen contents to form pockets of free
gas above the level of the contents and
finally are eliminated by eructation.

Etiology Ingestion of bloating forages or
interference with eructation mechanism
Epidemiology Primary ruminal tympany
(frothy bloat) is a major problem in cattle
pastured on bloating forages (legumes)
and in feedlot cattle fed high-level grain
rations with minimal roughage. Occurs
within few days after turning into bloating
pasture. High morbidity and mortality
possible and cost of control makes pasture
bloat an economically important disease.
Bloating forages most dangerous in
prebloom stage and when covered with
dew in the morning. Feedlot bloat
common when feed contains 80% grain
and is ground fine. Secondary ruminal
tympany (free-gas bloat) occurs in single
animals due to interference with eructation
because of physical obstruction of
esophagus or eructation mechanism, as in
reticular adhesions

Clinical signs Cattle may be found dead
on pasture. Mild to marked distension of
left abdomen, which is tympanic; when
severe, distends right abdomen also.

Severe distress, dyspnea, protrusion of
tongue. Passage of stomach tube in frothy
bloat reveals froth and failure to release
significant amount of gas; in secondary
free-gas bloat, large quantities of gas
released with ease. If severe, animal may
die in few hours or less if tympany not
relieved

Lesions Marked congestion and
hemorrhages of tissues of cranial aspect of
body (tongue, nasal sinuses, lymph nodes
and proximal part of esophagus - bloat
line) compared to caudal because of
ruminal tympany. Distended rumen, frothy
contents if examined early; later the froth
dissipates

Diagnostic confirmation Excessive
quantity of froth or free-gas in rumen

Differential diagnosis Primary bloat is
easily recognizable and there are no other
diseases of the reticulorumen that result in
ruminal tympany. Secondary bloat must be
differentiated from causes of failure of
eructation, including esophageal
obstruction, chronic reticuloperitonitis,
vagus indigestion and tetanus
Treatment Remove animals from
bloating pasture. In severe cases,
emergency rumenotomy. In less severe
cases, passage of stomach tube or trocar
and cannula to release rumen gas.
Antifoaming agents into rumen
Control Pasture bloat Management
strategies to reduce rate of rumen
fermentation. Use of grass-legume
mixtures. Delay grazing each day until dew
is off; feed hay before grazing. Feed forage
supplements prior to grazing. Strategic use
of antifoaming agents to pastured cattle.
Sustained-release antifoaming agents such
as monensin. Feedlot bloat Use total mixed
rations containing chopped roughage and
grain

ETIOLOGY

Primary ruminal tympany (frothy
bloat)

Primary ruminal tympany or frothy bloat
is caused by the production of a stable
foam that traps the normal gases of
fermentation in the rumen. The essential
feature is that coalescence of the small gas
bubbles is inhibited and intraruminal
pressure increases because eructation
cannot occur.

Pasture and feedlot bloat
Leguminous or pasture bloat is due to

the foaming qualities of the soluble leaf
proteins in bloating legumes and other
bloating forages ingested by cattle on
pasture. Alfalfa hay may also cause bloat.
Feedlot bloat is caused by feeding finely
ground grain, which promotes frothiness
of rumen contents; the cause is not clear. 1
The feeding of large quantities of grain to
cattle results in marked changes in the
total numbers and proportions of certain
ruminal protozoa and bacteria. Some
species of encapsulated bacteria increase
in numbers and produce a slime which
may result in a stable foam. 2

Feedlot bloat may also be of the free-
gas type based on the observations that
gas may be easily released with a stomach
tube. Feedlot cattle are susceptible to
esophagitis, ruminal acidosis, rumenitis,
overfill and ruminal atony each of which
can interfere with eructation and cause
secondary ruminal tympany and free-gas
bloat.

Frothy rumen contents
Frothiness of the ruminal contents is the
vital factor in pasture bloat. The froth in
the rumen contents is not a true foam but
rather a dispersion of gas and particles in
liquid. 3 The liquid lamellae between the
bubbles are wide, and fragments of
chloroplast membranes are dispersed in
the fluid. The stable dispersion of small
feed particles is primarily responsible for
the frothiness of the rumen fluid. The
concentration of chloroplast membrane
particles (measured as chlorophyl) is
higher in frothy rumen fluid than in
nonfrothy liquid.

The soluble leaf cytoplasmic proteins
were once considered to be the principal
foaming agents but their role is now
questioned. 3 It is now accepted that
bloat-causing legumes are more rapidly
digested by rumen microflora than non-
bloat-causing forages and that rupture of
leaf mesophyll cells leads to the release of
chloroplast particles. These particles are
readily colonized by rumen microflora
and gas bubbles are trapped among the
particles, which prevent coalescence of
bubbles by preventing drainage of rumen
fluid from the liquid lamellae between the
bubbles. The higher foam production in

bloat-prone cattle is attributed to slower
rates of passage of the liquid phase of
ruminal contents. 4 The slower clearance
enhances microbial activity and promotes
gas production, which contributes to
stable foam formation. Rapid clearance
decreases microbial gas production,
enhances protein bypass and reduces the
probability of bloat.

In general, bloat-causing legumes
are susceptible to rapid digestion by
rumen microflora, while bloat-safe
legumes are digested more slowly.

The condition of the rumen prior to
feeding is an important factor in the
immediate susceptibility of an animal to
pasture bloat. 3 A predisposed rumen is
characterized by an excess of dispersed
particulate matter with adherent
microbes, which provides an active
inoculum for the fermentation of
incoming feedstuffs. The soluble leaf
protein may contribute to the frothiness
but is not the primary foaming agent. The
chloroplast particles in the rumen have a
slower rate of clearance from the rumen in
bloating animals than in nonbloating ones.
It is also known that bloatinganimals have
larger rumen volumes than nonbloating
animals. Since chloroplast particles are
negatively charged, it is possible that the
concentrations of ions such as sodium,
potassium, calcium and magnesium in the
rumen fluid prior to feeding are associated
with the onset of bloat. 3

The froth in feedlot bloat is associ-
ated with high-level grain diets. The
viscosity of the ruminal fluid is markedly
increased because of the production of
insoluble slime by certain species of
bacteria that proliferate to large numbers
in cattle on a high-carbohydrate diet. The
slime may entrap the gases of fer-
mentation. The delay in occurrence of
feedlot bloat suggests that a gradual
change in the microbial population of the
rumen may be an important factor in
explaining the cause. The physical form of
a grain ration appears to be related to
grain bloat. As in frothy legume bloat,
where a rapid release of leaf nutrients is
important in producing bloat, it seems
likely that the small particle size of
ground feed could have the same effect.

Fine particulate matter can markedly
increase foam stability. The feeding of
ground grain of fine particle size (geometric
mean particle size 388 pm) was associated
with more rumen froth than the use of a
coarse particle size (715 pm). The pH
of the rumen contents also plays an
important part in the stability of the foam
(maximum stability occurs at a pH of
about 6) and the composition of the diet
and the activity and composition of the
rumen microflora are known to influence
this factor.

Diseases of the rumen, reticulum and omasum

327

Role of saliva

The rate of flow and composition of the
saliva has an effect on the tendency for
bloat to occur. Saliva may have a buffering
effect on the pH of the rumen contents or
it may influence the contents because of
variation in its content of mucoproteins.
The physical effects of dilution of ruminal
ingesta by saliva may also be important.
There is a negative correlation between
the moisture content of the feed and the
incidence of bloat. Feed of a low fiber and
high water content depresses the volume
of saliva secreted. Also, bloat-susceptible
cows secrete significantly less saliva than
nonsusceptible cows and there are differ-
ences in the composition of saliva that are
genetically determined. 3

In summary, primary frothy pasture
bloat occurs when there is rapid digestion
of leaf material by rumen microorganisms,
leading to the release of chloroplast par-
ticles into the liquid phase of the rumen
contents, which prevents the coalescence
of the gas bubbles. In addition, there is a
slower rate of clearance of these particles
from the rumen in bloating cows, which
also have larger rumen volumes. In
primary frothy feedlot bloat, the fine
particle size of the feed and the presence
of rumen microorganisms that produce
slime may be important factors.

Secondary ruminal tympany
(free-gas bloat)

Physical obstruction to eructation occurs
in esophageal obstruction caused by a
foreign body, by stenosis of the esophagus,
by pressure from enlargements outside
the esophagus, such as tuberculous
lymphadenitis or bovine viral leukosis
involvement of bronchial lymph nodes, or
by obstruction of the cardia. Interference
with esophageal groove function in vagus
indigestion and diaphragmatic hernia
may cause chronic ruminal tympany and
the condition also occurs in tetanus,
particularly in young animals and in
poisoning with the fungus Rhizoctonia
leguminicola, probably as a result of spasm
ofthe esophageal musculature. Carcinoma,
granulomatous lesions associated with
Actinomyces bovis near the esophageal
groove and in the reticular wall, and
papillomata of the esophageal groove and
reticulum are less common causes of
obstructive bloat. Tetanus in cattle is
usually accompanied by secondary free-
gas bloat due to spasm of the esophagus
and inability to eructate normally.

Interference with the nerve pathways
responsible for maintenance of the
eructation reflex may also occur. The
receptor organs in this reflex are situated
in the dorsal aspect of the reticulum and
can discriminate between gas, foam and
liquid. The afferent and efferent nerve

fibers are contained in the vagus nerve
but the location of the central coordinating
mechanism has not been defined.
Depression of this center or lesions of the
vagus nerve can interrupt the reflex,
which is essential for removal of gas from
the rumen.

Normal tone and motility of the
musculature of the rumen and reticulum
are also necessary for eructation. In
anaphylaxis, bloat occurs commonly
because of ruminal atony and is relieved
by the administration of epinephrine or
antihistamine drugs. A sudden marked
change in the pH of the rumen contents
due to either acidity or alkalinity causes
ruminal atony but the tympany that
results is usually of a minor degree only,
probably because the gas-producing
activity of the microflora is greatly
reduced. Hypocalcemia in milk fever of
cattle is commonly associated with
secondary free-gas bloat due to ruminal
atony, which is reversible following
treatment with calcium salts.

While most cases of feedlot bloat
associated with outbreaks are of the
frothy type (primary) and cannot be easily
relieved with a stomach tube, sporadic
cases are of the free-gas type, which
suggests that they are secondary. Possible
causes of the ruminal atony and failure of
eructation include: esophagitis, acidosis,
rumenitis and failure of rumination
because of an all-grain diet. Feedlot
cattle on high-level grain diets for long
periods will not ruminate normally and
their rumen movements are significantly
reduced.

Chronic ruminal tympany
Chronic ruminal tympany occurs in
calves up to 6 months of age. Persistence
of an enlarged thymus, continued feeding
on coarse indigestible roughage, and the
passage of unpalatable milk replacer into
the rumen, where it undergoes fermen-
tation and gas production, instead of into
the abomasum, have all been suggested
as causes but the condition usually
disappears spontaneously in time and in
most cases the cause is undetermined. 5
Necropsy examination of a number of
cases has failed to detect any physical
abnormality, although a developmental
defect appears to be likely because of the
age at which it occurs. Unusual postures,
particularly lateral recumbency, are
commonly characterized by secondary
tympany. Cattle may die from secondary
tympany if they become accidentally cast
in dorsal recumbency in handling
facilities, crowded transportation vehicles,
irrigation ditches and other restrictive
positions.

In some cases of vagus indigestion
characterized by ruminal hyperactivity the

secondary bloat may be of the frothy type
because of ruminal hyperactivity. '

EPIDEMIOLOGY

Occurrence

Pasture bloat

Pasture bloat occurs in both dairy and
beef cattle that graze pastures consisting
of bloating forages. The incidence is
highest when the pasture is lushest.
Spring and autumn are the most
dangerous seasons, when the pastures are
lush and young and the leaves of the
plants contain a high concentration of
soluble proteins. Dry hot conditions and
matured plants, and thus midsummer, are
the forerunners of a decline in incidence.
Sheep can also be affected but appear to
be much less susceptible than cattle. 6

Feedlot bloat

Feedlot bloat occurs in feedlot cattle
during the 50-100 days when cattle are
fed large quantities of grain and small
quantities of roughage. In some cases the
use of pelleted, finely ground feed has
been associated with outbreaks of feedlot
bloat. High-producing dairy cows that are
fed 12-22 kg of grain daily may also
develop grain bloat.

Morbidity and case fatality

Pasture bloat

Reliable current field data on the inci-
dence of pasture bloat in cattle are not
available. Canadian observations in 1975
indicated that cattle fed fresh alfalfa
typically bloat on 35% of the feeding
days and 10% of the total animal days.
Frothiness of rumen contents, observed in
fistulated cattle, occurs on about 50% of
the feeding days and 25% of the animal
days. 3 In dairy herds in New Zealand, the
average death rate due to legume pasture
bloat has ranged from 0.3-1. 2%. A survey
of 312 dairy farms in New Zealand over a
period of 2 months revealed that 87% of
all farms experienced bloat, ranging from
mild to severe. 7 The percentage of
lactating cows dying of bloat in spring of
1986 averaged 0.83%. The highest death
rate of milking cows in an individual herd
was 16% and in young stock 48%. 7 The
majority of variation among farms in
bloat severity was not accounted for by
any of the management, soil or pasture
factors measured.

Feedlot bloat

In a survey of Kansas feedlots (60 lots
totalling 450 000 head of cattle) the
incidence of deaths due to bloat was
0.1%; 0.2% of cattle had severe bloat and
0.6% moderate bloat. In a Colorado
feedlot, during one full year, bloat was the
cause of 3% of all mortalities. In the same
study, bloat was among the four most
common causes of sudden death or of
cattle found dead without having been

328

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

seen ill. Outbreaks -of feedlot bloat are
usually of the frothy type (primary), while
the sporadic cases are of the free-gas type
and secondary to lesions that cause
dysfunction of eructation.

Risk factors that influence the
occurrence of primary ruminal
tympany

Several risk factors have an influence on
the occurrence of primary bloat and
possibly contribute to its causation.
Dietary, weather and animal factors have
received most attention.

Dietary risk factors
Bloating forages

Alfalfa ( Medicago sativa), red clover
(' Trifolium pratense) and white clover
(' Trifolium repens) are the principal bloat-
causing legumes.

Alfalfa has been recognized for its
superior yield and quality in seeded pas-
tures. Alfalfa is the most productive and
most widely adapted forage species and is
considered the 'queen of forages'.

Sweet clover and alsike clover are also
bloat-causing forages.

Bloat also occurs occasionally when
cattle are grazed on cereal crops, rape,
cabbages, leguminous vegetable crops,
including peas and beans, and young
grass pasture with a high protein content.
An increasing occurrence of bloat is noted
when cattle are grazed on young green
cereal crops such as winter wheat,
especially if it is heavily fertilized and
irrigated.

Frothy bloat may also occur in cattle
fed alfalfa hay, even when mixed with
cereal grains and another hay. Outbreaks
are commonly associated with particular
lots of hay, often containing fine particles.
Alfalfa hay produces a frothy bloat with a
typical viscous consistency of the rumen
contents but it is commonly more sub-
acute and chronic rather than acute and
peracute as in pasture bloat.

Nonbloating forages

Bird's foot trefoil ( Lotus comiculatus), cicer
milk vetch ( Astragalus cicer), arrowleaf
clover (Trifolium vesiculosum), sainfoin
( Onobrychis viciifolia), and crown vetch
(Coronilla varia) are the bloat- safe forages.
The bloat-safe forages contain tannins
that bind with soluble proteins and inhibit
microbial digestion. 3

Condensed tannins (CTs) or pro-
anthocyanidins comprise polymerized
flavan-3-ol-units, and those occurring in
temperate forages have a relative mol-
ecular mass of 2000-4000, comprising
10-12 units condensed together. 8 Tannins
normally occur in plant vacuoles. CTs
from L. comiculatus (bird's foot trefoil) and
Lotus pedunculatus (big trefoil) differ
considerably in their chemical structures.

Forage

Total

(g/kg DM)

Legumes

Big trefoil ( Lotus pedunculatus)

77

Bird's foot trefoil ( Lotus

47

comiculatus)

Sulla (Hedysanum cornonarium)

45

Sainfoin ( Onobrychis vicifolia)

29

Red clover ( Trifolium pratense)

1.7

Alfalfa ( Medicago sativa)

0.5

Grasses

Perennial ryegrass

1.8

( Lolium pervenne)

Herbs

Chicory ( Chicorum inly bus)

4.2

Sheep's burnet

3.4

(. Sanguisorba minor)

Source: modified from Barry & McNabb. 8

The levels of CTs in big trefoil and bird's
foot trefoil are 45 times greater than in red
clover (T. pratense) and 150 times greater
than in alfalfa ( Medicago saliva) . 8 The
protein-precipitating properties of grazing
CT- containing legumes has long been
known to eliminate bloat. The minimum
plant CT concentration needed to make
forage bloat-safe has not been discovered
but 5 g CT/kg dry matter (DM) or greater
has been proposed. Most common
legumes and grasses used in temperate
agriculture have CT concentrations well
below this value, and both conventional
plant breeding and genetic engineering
techniques are being examined to increase
these levels (Table 6.9).

Crop maturity

The maturity of the forage is the major
plant factor affecting the incidence of
pasture bloat. 4 Grazing very succulent
pasture - immature, rapidly growing
legumes in the prebloom stage - is the
biggest single risk of bloat in cattle. 4 The
bloat potential of alfalfa varies signifi-
cantly with the phenological stage of the
■ plant. The greatest risk to cattle occurs
during the vegetative stage of growth,
and the risk declines during the bud stage
and may be absent during the bloom
stage. 9 Feeding cattle freshly chopped
j alfalfa herbage daily at different stages of
growth resulted in animal-days of bloat of
62, 10 and 0, respectively, for the vege-
tative, bud and bloom stages of the
alfalfa. 9 The leaf:stem ratio decreased
from 1.2 to 0.5 and 1.5 to 0.4 in two
different years as the crop matured from
vegetative to bloom stage. 9 The absence
of bloat during bloom can be attributed to
the much lower leaf:stem ratio at that
stage. As most chloroplasts are within the
leaves, the lower leaf:stem ratio at bloom

would reduce the concentration of these
fragments. A leaf:stem ratio of less than
0.5 (1:2) could be used as an indicator of a
low potential for bloat in alfalfa.

The rapid rate of digestion of the
immature bloating forages results in
the production of a foam. In the summer
months, especially under irrigated con-
ditions when the growth rate of alfalfa is
rapid, bloat occurs in cattle fed alfalfa
herbage at the vegetative to prebud
stages of growth. Alfalfa's potential for
causing bloat is highest when moisture
conditions are optimal for vegetative
growth. Under these conditions the stems
become turgid and fleshy but not fibrous;
the leaves are soft and easily crushed
between the fingers. In autumn, the
growth rate of alfalfa is slower because of
lower temperatures. A rapid rate of
growth of the alfalfa is a necessary
condition for bloat. Field observations of
the relationship between plant factors to
alfalfa bloat found that the percentages of
dry matter and acid detergent fiber were
lower, and the concentration of chlorophyl,
total nitrogen and soluble nitrogen were
higher on days when bloat occurred. 10

Ingestion of the more succulent
parts of plants and avoidance of the
more mature portions can be a precipitating
factor and tympany is less likely to occur
if the crop is harvested and fed than if it is
grazed. Restriction of the grazing area has
a similar effect, by forcing the cattle to eat
the entire plants. A high incidence is
recorded when pasture is wet but this is
probably due to the rapid growth of the
plants during heavy rainfall periods rather
than to the physical wetness of the crop.
Under experimental conditions the pro-
duction of tympany is not influenced by
the water content of clover or by wilting.
Other plant factors that are known to be
associated with an increased tendency to
bloat are liberal administration of urea to
the pasture, a high intake of glucose,
calcium and magnesium, and a high
nitrogen intake.

A high herbage potassium to sodium
ratio can increase the risk of bloat in
cattle, which may be caused by digestion
rate. 11 There is some indication that
sodium fertilizer can affect the digestion
rate of perennial ryegrass and white
clover. 11 Sodium fertilizer increased maxi-
mum gas output from grass and rate of
production, which was associated with an
increase in grass digestibility; however, in
clover it had the opposite effect, thereby
potentially reducing bloat in cows fed a
high-legume diet.

Results from two decades of bloat
research (1973-1993) at Kamloops have
been reviewed. 4 Every cultivar of alfalfa
tested in its vegetative to early bloom
stages of growth caused bloat. The dry

Diseases of the rumen, reticulum and omasum

329

matter -disappearance over the first
6-8 hours was highest in alfalfa that is
bloat-inducing. 12 Lower rates of dry
matter disappearance were found in
sainfoin, bird's foot trefoil and cicer milk
vetch, which confirms the bloat-safe
features of these alternative legume
forages. 4 Bloat was positively associated
with the level of fraction 1 protein and
total soluble protein in alfalfa, supporting
the concept of a decreased probability of
bloat with advancing stages of plant
maturity. To maintain a high incidence of
bloat at the research station, it was
necessary to harvest the forage at vege-
tative to early bloom stages of growth.
The risk of bloat was twice as great when
the forage height was less than 25 cm
than when it was more than 50 cm. 4

The risk of bloat was reduced by
waiting until the dew was off the alfalfa
before allowing cattle to graze. 13 This
confirms the practice of many cattlemen
of delaying morning grazing 'until the
dew has dried'. Bloat was observed 2-17
times more often when cattle were fed
between 0700 and 0800 hours than when
they were fed 4 hours later in both grazing
and feedlot trials. Ruminal chlorophyl
was higher before the early feeding than
before the late feeding, suggesting that
feeding later in the morning reduced the
predisposition of cattle to bloat by
increasing particle clearance from the
rumen.

The risk of bloat was also reduced
when cattle grazed alfalfa continuously
than when grazing was interrupted and
cattle were allowed to graze for only
6 hours daily. Fhsture management systems
that promote continuous and rapid ruminal
clearance (more bypass, less gas pro-
duction) are most likely to reduce the
incidence of bloat.

Weather risk factors

The relationship of weather conditions to
the occurrence and incidence of pasture
bloat has been examined under Canadian
conditions. 10 Under ordinary grazing con-
ditions, bloat occurs sporadically over
large parts of the growing season. The
occurrence of pasture bloat was not
associated with a simple, unique weather
variable. 4 The effect of temperature on the
incidence of bloat is complex. Bloat seems
to occur when moderate daytime tem-
peratures (20-25°C) permit optimum
vegetative growth. Cool overnight tem-
peratures in combination with moderate
daytime temperatures may induce bloat
in the fall. Cool temperatures delay
maturation and extend the vegetative
growth phase of forage crops, and
optimize conditions for bloat. On a daily
basis, bloat tended to be preceded
immediately by nights and days that were

cooler than usual. Bloat can also occur
after a killing frost. 10

Feedlot bloat

This occurs in hand-fed cattle confined in
feedlots and barns when insufficient
roughage is fed or the feed is too finely
ground. Two separate sets of circum-
stances conducive to feedlot bloat have
been identified. In one, the cattle are
being fed a high-level grain finishing
ration in which grain comprises more
than 80% of the weight of the ration. The
effect of these rations on the rumen is a
tendency to acidity and a shortage of
rumen-stimulating roughage, which may
interfere with motility and eructation. In
the other situation, grain comprises
30-70% of the ration, with the same but
less marked effect as above, but the
roughage component is alfalfa hay
with its own bloat-inducing capacity. 3

Animal risk factors

Cattle vary in their susceptibility to
primary ruminal tympany, especially that
caused by legumes, and this individual
susceptibility may be inherited. Cows can
be classified according to their suscep-
tibility to pasture bloat into high or low
susceptibility and their progeny are
similar. 3,14 Total exchange of rumen con-
tents between high-susceptibility and
low-susceptibility animals produces a
temporary exchange of susceptibilities
that lasts about 24 hours. A number of
inherited characteristics are related to
bloat. 3,14 They include ruminal structure
and motility, composition of salivary
proteins, rate of salivation and the greater
capacity of the rumen contents of high-
susceptibility animals to degrade muco-
proteins that would either reduce
antifoaming activity or increase foam-
stabilizing activity. 3,14 A salivary protein,
bSP30, is correlated with susceptibility to
bloat in cattle herds selected for high or
low bloat susceptibility. 15 One obvious
application for such a protein marker for
bloat would be to screen cattle to
eliminate highly susceptible herds. Blood
and urinary metabolites in cattle have also
differed with respect to susceptibility
to bloat. 16

There may also be differences between
animals in the rate and extent of physical
breakdown of feed in the rumen and the
rate of passage of solids out of the
rumen. 17 However, neither differences in
gas production nor foam production nor
the stability of the foam are important
factors in distinguishing between high-
susceptibility and low-susceptibility
cows. 18

One major physiological difference
between high and low susceptibility is
volume of rumen fluid. 19 It is suggested
that low-susceptibility cows do not bloat

because they have a lower relative volume
of rumen digesta than high-susceptibility
cows.

Under experimental conditions the
production of tympany is not influenced
by the rate of intake or the total intake of
dry matter. Susceptibility increases with
time when a tympany-producing diet is
fed for a relatively short period. However,
animals accustomed over very long
periods to grazing bloating pastures may
be less susceptible than other animals.
Accordingly the mortality rate in young
cattle is much higher than in mature
animals.

There may be a common biological
basis for partial preference for grass and
clover in sheep and cattle. Dairy heifers
select between 50% and 65% white clover
when given a free choice between
adjacent ryegrass and white clover mono-
cultures. 20 There is also a diurnal pattern
to preference, with a stronger preference
for clover in the morning, with the
preference for grass increasing towards
evening. Providing animals with anti-
bloat treatment (slow-release monensin
capsules) did not have any effect on the
proportion of clover selected.

Economic importance

Primary ruminal tympany causes heavy
losses through death, severe loss of
production and the strict limitations
placed on the use of some high-
producing pastures for grazing. For
example, it is estimated that bloat costs
the dairy industry in New Zealand $50
million annually. The incidence of the
disease has increased markedly with the
improvement of pastures by heavy appli-
cations of fertilizers and the use of high-
producing leguminous pasture plants,
and losses in cattle at times have reached
enormous proportions.

The most obvious form of loss is
sudden death. Although this is the
dramatic loss, especially when a large
number of cattle are unexpectedly found
dead, an equivalent loss occurs as the
result of reduced food intake. For example,
on clover-dominant pasture (60-80%
white clover) where bloat was common
the weight gains of cattle grazing it were
20-30% less than normal. It has been
argued that the returns achieved by good
bloat prevention in pastured cattle would
not compensate for the costs incurred, but
the opposite view is strongly held.

PATHOGENESIS

Normally, gas bubbles produced in the
rumen fluid coalesce, separate from the
rumen contents to form pockets of free
gas above the level of the contents, and
are finally eliminated by eructation. Much
of the gas of fermentation and acidification

330

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

of bicarbonate will be eructated. A grass-
fed cow can produce 100 L during the first
hour of feeding. A cow maintained on a
legume diet may produce 200 L per hour. 21

The composition and kinetics of the
gas in the rumen headspace of lactating
dairy cattle grazing white clover and
perennial ryegrass pastures has been
determined. 22 Before grazing, rumen
headspace gas was composed of carbon
dioxide 65%, methane 31% and nitrogen
4%; 1 hour after grazing, the headspace
gas was composed of carbon dioxide 76%,
methane 22% and nitrogen 2%. The
composition of the headspace gas was
not affected by antibloat capsules that
release 250 mg/d of monensin. The head-
space gas from bloated cows contained
slightly less carbon dioxide and slightly
more nitrogen than that from nonbloated
cows.

In frothy bloat, the gas bubbles
remain dispersed throughout fhe rumen
contents, producing an abnormal increase
in the volume of the ruminoreticular
contents and, consequently, inhibiting
eructation. The characteristic frothiness
of ruminal contents is caused by in-
adequate coalescence of gas bubbles.

In free-gas bloat the gas bubbles
coalesce and separate from the rumen
fluid but the animals cannot eructate the
pockets of free gas because of abnor-
malities of the reticulorumen or esophagus.

Most cases of naturally occurring pas-
ture or feedlot bloat are not accompanied
by ruminal atony. In the early stages there
is unusually pronounced hypermotility.
Most of the gas is mixed with the solid
and fluid ruminal contents to form a
dense, stable froth. Some free gas is
present but the amount that can be
removed by a stomach tube or trocar and
cannula does little to relieve the
distension of the rumen. In general, free-
gas bloat characterized by the accu-
mulation of free gas is due to esophageal
obstaiction or ruminal atony.

If the eructation reflex is functional,
the experimental introduction of very
large amounts of gas does not cause
tympany, since eructation removes the
excess. Bloat-producing forages do not
produce more gas than safe feeds and the
simple production of excessive gas is
known not to be a precipitating factor.

Frothiness of the ruminal contents
interferes with function of the cardia
and inhibits the eructation reflex. Rumen
movements are initially stimulated by the
distension and the resulting hypermotility
exacerbates the frothiness of the ruminal
contents. Terminally there is a loss of
muscle tone and ruminal motility.

The most distinctive aspect of bloated
cattle is abdominal distension, particularly
the left abdomen, due to distension of the

rumen. Experimentally there is a relation-
ship between reticulorumen volume,
intraruminal pressure and the abdomen
of cows fed fresh alfalfa. 21 The volumes of
gas in a bloated cow are large, 50-70 L,
and there is an exponential increase in
intraruminal pressure with increasing
rumen volume, especially as the potential
for further increases in the abdomen
diminishes. Most severely bloated cows
will attempt to urinate and defecate when
intraruminal pressures exceeds 25 cmH 2 0
but some cows can tolerate pressures in
excess of 50 cmH 2 0. As the intraruminal
pressure increases, occlusion of the vena
cava occurs, causing congestion of the
caudal part of the body. In addition, the
pressure exerted by the distended rumen
on the diaphragm is very high, which
results in reduced lung capacity and death
from hypoxia.

CLINICAL FINDINGS

Primary pasture or feedlot bloat

Bloat is a common cause of sudden
death (or found dead) in cattle. Pastured
beef cattle that die of bloat are usually
found dead because they are not observed
as regularly as dairy cattle. Feedlot cattle
that die of bloat are commonly found
dead in the morning, which may be due
to their relative inactivity during the night
or to the lack of observation, detection
and treatment. Dairy cattle that are
being milked and observed regularly will
commonly begin to bloat within 1 hour
after being turned into a bloat-producing
pasture. There is commonly a lag period
of 24-48 hours before bloating occurs in
cattle that have been placed on a bloat-
producing pasture for the first time. They
may bloat on the first day but more
commonly they bloat on the second and
third days. A similar situation has been
observed in pastured beef cattle, which
have been on a particular pasture for
several days or weeks before bloat occurs.
This is always a surprise to the owner and
the veterinarian, who find it difficult to
explain why bloat suddenly becomes a
] problem on a pasture that cattle have
grazed safely for some time.

In primary pasture bloat, obvious
distension of the rumen occurs quickly,
sometimes as soon as 15 minutes after
going on to bloat-producing pasture, and
the animal stops grazing. The distension
is usually more obvious in the upper left
paralumbar fossa but the entire abdomen
is enlarged. There is discomfort and the
animal may stand and lie down
frequently, kick at its abdomen and even
roll. Frequent defecation and urination
are common. Dyspnea is marked and is
accompanied by mouth breathing,
protrusion of the tongue, salivation and
extension of the head. The respiratory rate

is increased up to 60/min. Occasionally,
projectile vomiting occurs and soft feces
may be expelled in a stream.

In mild bloat, the left paralumbar
fossa is distended, the animal is not in
distress, and 5-7 cm of skin over the left
paralumbar fossa may be easily grasped
and 'tented', which provides a measure of
the degree of abdominal distension and
tautness of the skin.

In moderate bloat, a more obvious
distension of the abdomen is evident, the
animal may appear anxious and slightly
uncomfortable, and the skin over the
paralumbar fossa is usually taut but some
can be grasped and tented.

In severe bloat, there is prominent
distension of both sides of the abdomen,
the animal may breathe through its
mouth and protrude the tongue. It is
usually uncomfortable, anxious and may
be staggering. The skin over the left flank
is very tense and cannot be grasped and
tented.

Ruminal contractions are usually
increased in strength and frequency in the
early stages and may be almost continuous,
but the sounds are reduced in volume
because of the frothy nature of the
ingesta. Later, when the distension is
extreme, contractions are decreased and
may be completely absent. The low-
pitched tympanic sound produced by
percussion over the rumen is charac-
teristic. Before clinical tympany occurs,
there is a temporary increase in eructation,
but this disappears in the acute stages.
The course in ruminal tympany is short
but death does not usually occur in less
than 3-4 hours of the onset of clinical
signs. Collapse and death almost without
struggle occur quickly.

If animals are treated by trocarization
or the passage of a stomach tube, only
small amounts of gas are released
before froth blocks the cannula or tube. In
a group of affected cattle, some will be
bloated and the remainder have mild to
moderate distension of the abdomen.
These animals are uncomfortable, graze
for only short periods and their milk
production is decreased. The drop in
production may be caused by depression
of food intake or by failure of milk
letdown.

Secondary bloat

In secondary bloat, the excess gas is
present as a free gas cap on top of the
ruminal contents, although frothy bloat
may occur in vagus indigestion with
increased ruminal motility (see vagus
indigestion) . There is usually an increase
in the frequency and strength of ruminal
movements in the early stages followed
by atony. Fhssage of a stomach tube or
trocarization results in the release of large

Diseases of the rumen, reticulum and omasum

331

quantities of gas and subsidence of the
ruminal distension. If an esophageal
obstruction is present it will be detected
when the stomach tube is passed.

Dyspnea and tachycardia in severe
bloat

In both severe primary and secondary
bloat there is dyspnea and a marked
elevation of the heart rate up to
100-120/min in the acute stages. A
systolic murmur may be audible, caused
probably by distortion of the base of the
heart by the forward displacement of the
diaphragm. This murmur has been
observed in ruminal tympany associated
with tetanus, diaphragmatic hernia, vagus
indigestion and esophageal obstruction
and disappears immediately if the bloat is
relieved.

CLINICAL PATHOLOGY

Laboratory tests are not necessary for the
diagnosis of ruminal tympany.

NECROPSY FINDINGS

I n cattle that have died from bloat within
an hour previously there is protrusion and
congestion of the tongue, marked con-
gestion and hemorrhages of lymph nodes
to the head and neck, epicardium and
upper respiratory tract, friable kidneys
and mucosal hyperemia in the small
intestine. The lungs are compressed and
there is congestion and hemorrhage of
the cervical portion of the esophagus but
the thoracic portion of the esophagus is
pale and blanched. In general, congestion
is marked in the front quarters and less
marked or absent in the hindquarters. The
rumen is distended but the contents are
much less frothy than before death. A
marked erythema is evident beneath the
ruminal mucosa, especially in the ventral
sacs. The liver is pale because of expulsion
of blood from the organ. Occasionally, the
rumen or diaphragm have ruptured. In
animals dead for several hours there is
subcutaneous emphysema, almost com-
plete absence of froth in the rumen, and
exfoliation of the cornified epithelium of
the rumen with marked congestion of
submucosal tissues.

TREATMENT

The approach to treatment depends on
the circumstances in which bloat occurs,
whether the bloat is frothy or due to free
gas, and whether or not the bloat is life-
threatening.

First-aid emergency measures

Emergency rumenotomy
It is often necessary to advise an owner to
use some first-aid measures before the
veterinarian arrives on the farm. All
animals should be removed immediately
from the source of the bloating pasture or
feed. In severe cases in which there is

DIFFERENTIAL DIAGNOSIS

When presented with ruminating cattle
with a distended abdomen and with
marked distension of the left paralumbar
fossa the most obvious diagnosis is ruminal
tympany.

• Primary bloat is likely if the dietary
conditions are present and the passage
of a stomach tube reveals the presence
of froth and the inability to release gas

• Secondary bloat is likely if the history
indicates that distension of the
abdomen and left flank has been
present for a few days or if the bloat
has been intermittent within the last
several days. Passage of a stomach tube
will detect esophageal obstruction or
stenosis, both of which are
accompanied by difficult swallowing
and, in acute cases, by violent attempts
at vomiting

• In secondary bloat associated with
vagus indigestion, the history usually
indicates that distension of the
abdomen has been progressive over the
last several days or few weeks with loss
of weight and scant feces. In addition,
the rumen is grossly enlarged and the
ventral sac is commonly enlarged and
distends the right lower flank

• Tetanus is manifested by limb and tail
rigidity, free-gas bloat, prolapse of the
third eyelid and hyperesthesia

• Carcinoma and papillomata of the
esophageal groove and reticulum and
actinobacillosis of the reticulum cannot
usually be diagnosed antemortem
without exploratory rumenotomy

• Animals found dead. One of the
difficult situations encountered in
veterinary practice is the postmortem
diagnosis of bloat, especially in animals
found dead at pasture in warm weather.
Blackleg, lightning strike, anthrax
and snakebite are common causes of
cattle being found dead and the
necropsy findings are characteristic. A
diagnosis of bloat must depend on an
absence of local lesions characteristic of
these diseases, the presence of marked
ruminal tympany in the absence of
other signs of postmortem
decomposition, the relative pallor of the
liver and the other lesions described
above

gross distension, mouth-breathing with
protrusion of the tongue and staggering,
an emergency rumenotomy is necessary
to save the life of the animal. Once the
animal falls down death occurs within a
few minutes and many animals have died
unnecessarily because owners are unable
or reluctant to do an emergency
rumenotomy. Using a sharp knife, a quick
incision 10-20 cm in length is made over
the midpoint of the left paralumbar
fossa through the skin and abdominal
musculature and directly into the rumen.
There will be an explosive release of
rumen contents and marked relief for the

animal. There is remarkably little con-
tamination of the peritoneal cavity, and
irrigation and cleaning of the incision site
followed by standard surgical closure
usually results in uneventful recovery with
only occasional minor complications.

Trocar and cannula

The trocar and cannula have been used
for many years for the emergency release
of rumen contents and gas in bloat.
However, the standard-sized trocar and
cannula does not have a large enough
diameter to allow the very viscous stable
foam in peracute frothy bloat to escape
quickly enough to save an animal's life. A
larger-bore instrument (2.5 cm in diameter)
is necessary and an incision with a scalpel
or knife must be made through the skin
before it can be inserted into the rumen. If
any size of trocar and cannula fails to
reduce the intraruminal pressure and the
animal's life is being compromised by the
pressure, an emergency rumenotomy
should be performed. If the trocar is
successful in reducing the pressure, the
antifoaming agent of choice can be
administered through the cannula, which
can be left in place until the animal has
returned to normal in a few hours.
Owners should be advised on the proper
use of the trocar and cannula, the method
of insertion and the need for a small
incision in the skin, and the care of
cannulas left in place for several hours
or days.

A corkscrew-type trocar and cannula
has been recommended for long-term
insertion in cases of chronic bloat that
occur in feedlot cattle and in beef calves
following weaning. The etiology of these
is usually uncertain; insertion of a cannula
for several days or use of a rumen fistula
will often yield good results.

Promote salivation

For less severe cases, owners may be
advised to tie a stick in the mouth like a
bit on a horse bridle to promote the
production of excessive saliva, which is
alkaline and may assist in denaturation of
the stable foam. Careful drenching with
sodium bicarbonate (150-200 g in 1 L of
water) or any nontoxic oil as described
below is also satisfactory.

Stomach tube

The passage of a stomach tube of the
largest bore possible is recommended for
cases in which the animal's life is not
being threatened. The use of a Frick oral
speculum and passage of the tube through
the oral cavity permits the passage of
tubes measuring up to 2cm in diameter,
whereas this may not be possible if
passed through the nasal cavity. In free-
gas bloat, there is a sudden release of gas
and the intraruminal pressure may return

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

to normal. While the tube is in place, the
antifoaming agent can be administered.
In frothy bloat, the tube may become
plugged immediately on entering the
rumen. A few attempts should be made to
clear the tube by blowing through the
proximal end of the tube and moving it
back and forth in an attempt to locate
large pockets of rumen gas that can be
released. However, in frothy bloat it may
be impossible to reduce the pressure with
the stomach tube and the antifoaming
agent should be administered while the
tube is in place.

If the bloat cannot be relieved but an
antifoaming agent has been administered,
the animal must be observed closely for
the next hour to determine if the
treatment has been successful or if the
bloat is becoming worse, which requires
an alternative treatment.

Feedlot bloat

In an outbreak of feedlot bloat, the acute
and peracute cases should be treated
individually as necessary. There may be
many 'swellers', which are moderate
cases of bloat that will usually resolve if
the cattle are coaxed to walk. After a few
minutes of walking they usually begin
to eructate. Shaking of experimentally
reproduced foam results in loss of stability
of foam and coalescence into large
bubbles and the movement of walking
has the same effect. If walking is effective
in reducing the foam, the animals should
be kept under close surveillance for
several hours for evidence of continued
bloating, which is unusual.

Antifoaming agents

Details of the oils and synthetic
surfactants used as antifoaming agents in
treatment are described in the section on
control because the same compounds are
used in prevention. Any nontoxic oil,
especially a mineral one that persists in
the rumen, not being biodegradable, is
effective and there are no other significant
differences between them. Their effect is
to reduce surface tension and foam. A
dose of 250 mL is suggested for cattle but
doses of up to 500 mL are commonly
used. An emulsified oil or one containing
a detergent such as dioctyl sodium
sulfosuccinate is preferred because it
mixes effectively with ruminal contents.
Of the synthetic surfactants, poloxalene
is the one in most general use for
leguminous bloat and a dose of 25-50 g is
recommended for treatment. It is not as
effective for feedlot or grain bloat. Alcohol
ethoxylates are a promising new group of
compounds for use as bloat remedies and
both poloxalene and the ethoxylates are
more effective and faster than oil, which is
relatively slow and better suited to
prevention than treatment. All three are

recommended as being satisfactory for
legume hay bloat, but poloxalene is not
recommended for feedlot bloat. All of
them can be given by drench, stomach
tube or through a ruminal cannula. The
effect of all is enhanced if they are
thoroughly mixed with the ruminal
contents; if rumen movements are still
present mixing will occur. If the rumen is
static it should be kneaded through the
left flank.

Alfasure (a water-soluble pluronic
detergent) is effective for the treatment of
alfalfa bloat when 30 mL is given intra-
ruminally using a 6 cm 14-gauge hypo-
dermic needle directly into the rumen
through the abdominal wall in the middle
of the paralumbar fossa. 23 The median
time of disappearance after treatment was
25 minutes; the swelling returned to
normal within 52 minutes.

Return to pasture or feed

Following the treatment of the individual
cases of bloat the major problem remain-
ing is the decision about whether or not,
or when, or under what conditions, to
return the cattle to the bloat-producing
pasture or to the concentrate ration in the
case of feedlot cattle. The possible pre-
ventive measures are presented under
control but, unless one of the reliable
ones can be instituted, the cattle should
not be returned until the hazardous
period has passed. This is difficult on
some farms because the bloat-producing
pasture may be the sole source of feed.

CONTROL
Pasture bloat

Management strategies to reduce rate of
rumen fermentation

The prevention of pasture bloat is
difficult. Grazing management strategies
are the principal methods used for the
prevention of pasture bloat, along with
controlling pasture yields and quality. 24
Several different management practices
have been recommended, including the
prior feeding of dry, scabrous hay, parti-
cularly Sudan grass, cereal hay and straw,
restricting the grazing to 20 minutes at a
time or until the first cow stops eating,
harvesting the crop and feeding it in
troughs, and strip grazing to insure that
all available pasture is utilized each day.
The principle of each of these strategies
is to decrease the rate of rumen fer-
mentation. These methods have value
when the pasture is only moderately
dangerous but may be ineffective when
the bloat-producing potential is high. In
these circumstances the use of simple
management procedures is unreliable
because the occurrence of bloat is
unpredictable. In other cases, the strategies
such as limited grazing are impractical.
Generally, the farmer does not know if

the pastures are dangerous until bloat
occurs and, once effective prophylactic "
methods are being used, it is difficult to
know when they are no longer required.
The bloat-producing potential of a
pasture can change dramatically almost
overnight and the management strategy
can be quickly nullified.

Stage of growth

The probability of legume bloat decreases
with advancing stages of plant maturity
due to a decrease in the soluble protein
content of the legume. Alfalfa at the
vegetative stage of growth results in the
highest incidence of bloat compared with
the bud and bloom stages, with moderate
and no bloat, respectively. 25 These results
indicate the potential for grazing manage-
ment through selection of plant phenology
(periodic phases of plant growth) as a
method of bloat control. In practice, it
would be essential to recognize the
predominant stage of growth of the stand
before turning cattle into the pasture. The
leaf:stem ratio should also be considered
as a factor.

Choice of forages

Seeding cultivated pastures to grass-
legume mixtures is the most effective and
least costly method of minimizing pasture
bloat, particularly for beef herds grazing
over large areas under continuous grazing
systems. In a grass-legume mixture, a
legume content of 50% is suggested as
the maximum bloat-safe level. However,
this ratio may be impractical for large
areas, especially on rolling terrain, where
it is impossible to maintain a uniform
50:50 stand. If cattle have a tendency to
avoid the grass and select the legume, the
potential for bloat increases. Bloat can
occur in mixed pastures where the
proportion of legume is less than 15%,
possibly because of selective grazing.

Because of the potential for causing
bloat, grasses alone or nonbloating
forages may be used. Sainfoin, bird's foot
trefoil, cicer milk vetch and crown vetch
are useful bloat-safe legumes in regions
where they are adapted. However, their
yield, vigor, regrowth, winter-hardiness
and persistence are well below the superior
growth and production characteristics of
alfalfa. Seeding grasses alone avoids the
problem of bloat but the benefits of
including a legume in the mixture include
much greater production, higher protein
and nutritional value and lower fertilization
costs. A decision to use grass with or
without bloat-safe legumes should be
based on the economic benefits of the
greater protein from alfalfa or clover
compared with the possible losses from
bloat.

At present, a pasture comprising equal
quantities of clovers and grasses comes

Diseases of the rumen, reticulum and omasum

closest to achieving this ideal but with
available pasture plants and current
methods of pasture management this
clovengrass ratio is not easy to maintain.
Research work in this area is directed
towards selecting cattle that are less
susceptible to bloat. More practical are the
moves being made to breed varieties of
legume that are low on bloat-producing
potential.

The incidence of frothy bloat can be
substantially reduced if alfalfa herbage
contains as little as 25% orchardgrass. 26

Condensed tannins in forages
Proanthocynanidins, also known as CTs,
are phenolic plant secondary compounds
widely distributed through the plant
kingdom, especially in woody plants and
in certain forages. 27 In ruminants fed
high-quality fresh forage diets (25-35 g
nitrogen (N/kg DM) and 10-11 MJ of
metabolizable energy (ME)/kg DM) most
proteins are rapidly solubilized and
release between 56% and 65% of the N
concentration in the rumen during masti-
cation; consequently large losses of
nitrogen occur (250-25%) as ammonia is
absorbed from the rumen. Thus, the
inefficient use of nitrogen by ruminants
needs research to focus on improving
nitrogen retention by the animal and
natural plant compounds with known
ability to reduce proteolysis, such as CTs,
which exert their effects by complexing
with proteins.

Forages containing moderate concen-
trations of CTs can exert beneficial effects
on protein metabolism in sheep, slowing
degradation of dietary protein to ammonia
by rumen microflora and increasing
protein outflow from the rumen, thus
increasing absorption of amino acids in
the small intestine of the animal. This can
result in increases in lactation, wool
growth and live weight gain, without
changing voluntary feed intake. Dietary
CTs can also contribute to improved
animal health by reducing the detrimental
effects of internal parasites in sheep and
the risk of bloat in cattle. In contrast, high
dietary CT concentrations (6-12% DM)
depress voluntary feed intake, digestive
efficiency and animal productivity. 27

The literature on the effect of CTs on
the nutrition and health of ruminants fed
fresh temperate forages has been
reviewed. 28 Forages containing substantial
amounts of CTs are non bloating because
of the protein-precipitating properties of
CTs. 8,28 CTs interact with proteins in feed,
saliva and microbial cells, with microbial
exoenzymes and with endogenous
proteins and other feed components,
which alters digestive processes compared
with diets free from CT. 29 Tannin levels
exceeding 40-50 g/kg DM in forages may

reduce protein and DM digestibility of the
forages by ruminants. At low to moderate
levels, CTs increase the quantity of dietary
protein, especially essential amino acids,
flowing to the small intestine. Unlike
alfalfa, legumes that contain CTs do not
cause bloat. Dietary CTs may provide a
means to beneficially manipulate protein
digestion and/or prevent pasture bloat in
ruminants.

White clover and alfalfa (lucerne)
contain only trace amounts of CT s in their
leaves but are used extensively in animal
production because of their high nutritive
value. A minimum concentration of 5 g/kg
DM of CTs is necessary for a high prob-
ability of preventing bloat. The transfer of
DNA coding for CT production in leaves
from plant species such as lotus, sulla and
sainfoin into legumes such as white
clover and alfalfa that normally only
express low levels of CTs in leaf tissue has
been proposed. Investigations to produce
alfalfa and white clover containing 5 g
CT/kg DM using gene transfer tech-
nology have been conducted in Australia
and Canada with the objective of
producing a nonbloating alfalfa cultivar. 30
Concentrations of 0.75-1.25 g CT/kg DM
have been achieved but are well below
the value of 5 g/kg DM estimated to
reduce bloat.

Alternative temperate forages
The literature on the use of alternative
temperate forages to improve the sustain-
able productivity of grazing ruminants,
relative to grass-based pastures has been
reviewed. 30

Forages comprise a major proportion
of the diet in most ruminant animal pro-
duction systems. Grazed forages are used
especially during the late spring, summer
and early autumn in many countries,
while in some regions such as Australasia
and South America, ruminant animal
production is based on year-round
grazing of forages, with no indoor
housing. Grazing systems are generally
based on swards of which the major
portion consists of grasses (perennial
ryegrass ( Lolium perenne) in the case of
New Zealand), with a legume (white
clover (T. repens) in the case of New
Zealand) forming a minor portion
(approximately 20%), mainly to fix
atmospheric nitrogen and to provide a
higher-quality feed. Different grasses and
legumes form the grazed pastures in
other countries. The grazing of alternative
forages is being developed for the
sustainable control of internal parasites,
with reduced anthelmintic use, for
increasing reproductive performance in
sheep and the growth rate in young
animals, and for reducing the incidence of
bloat in cattle. 30

It has been long accepted in ruminant
nutrition that the feeding value of legufhes
is greater than that of grasses, owing to
their more rapid particle breakdown,
faster rumen fermentation, lower rumen
mean retention time and consequently
greater voluntary feed intake. Despite
these advantages, legumes have never
attained their true potential in many
grazing systems because of three principal
disadvantages: legumes generally grow
slowly in winter, producing less feed per
hectare than grasses; rumen frothy bloat
in cattle is caused by rapid solubilization
of protein in many legumes; and the
presence in some legumes of estrogenic
substances depresses reproductive per-
formance when grazed by ewes during
the breeding season. Thus the identification
of legumes that could overcome these
limitations would offer major advantages.
The herb chicory ( Chicorum intybus) and
the CT-containing legumes bird's foot
trefoil (L comiculatus) and sulla ( Hedysarum
coronarium ) offer the most advantages. 30
Chicory and sulla promoted faster growth
rates in young sheep and deer in the
presence of internal parasites, and showed
reduced methane production. Grazing
on L comiculatus was associated with
increases in reproductive rate in sheep,
increases in milk production in both ewes
and dairy cows and reduced methane
production, effects that were mainly due
to its content of CTs. The risk of frothy
bloat in cattle grazing legumes is reduced
when the forage contains 5 g CT/kg DM
or greater.

The degree to which sulla, chicory and
bird's foot trefoil are adopted by livestock
farmers will depend upon their agronomy
under grazing, as well as their nutritive
and feeding values. All three have no
means of vegetative propagation under
grazing and thus plant density declines
with time. With careful management,
such as not grazing during wet winter
weather, stands of chicory can last
4-6 years under New Zealand conditions
and is gaining acceptance by farmers.
Chicory is often seeded with a legume
such as red clover, which has a similar
lifespan and fixes nitrogen. L. comiculatus
is best suited to hot, dry summer climates
and warm winter climates and stands will
persist for 3-4 years under these con-
ditions, indicating a role in future dryland
grazing systems. When grown in environ-
ments that have regular summer rainfall,
a stand of L. comiculatus lasts only 2 years,
as a result of competition from grasses,
volunteer legumes and weeds. 30 Sulla is
biennial, with a life of one winter and two
grazing seasons; it has a specialized
requirement for inoculation with Rhizobium
bacteria. These factors and the lack of
commercial seed supply have reduced the

334

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

acceptance of sulla by livestock producers
in New Zealand, despite its obviously
high nutritive value and high feeding
value.

Nonbloating alfalfa cultivars
Based on research initiated in western
Canada in the 1970s, alfalfa cultivars have
been selected with a low potential for
bloating based on low initial rates of
digestion. 25 In field trials, a new alfalfa
cultivar (AC Grazeland) reduced the
incidence and severity of bloat on pasture
compared with the control cultivar
Beaver. 31 The initial rate of digestion was
85% of unselected alfalfa, and the
incidence of bloat at three locations over
3 years was significantly reduced. 32 How-
ever, the new cultivars are not bloat-safe;
they are bloat-reduced cultivars. 24

Field management

Fertilization and grazing management
may be used to maintain a 50:50 mixture
of grass and alfalfa. Nitrogen fertilizer and
heavy or frequent grazing promote grass
growth at the expense of alfalfa. In areas
where the incidence of bloat is high, the
critical upper limit of alfalfa may be as low
as 25-30%. In addition to seeding alfalfa
to form 25-30% of the total stand,
mixtures grown in sandy areas, which are
more prone to drought than heavy soils,
are less likely to produce bloat. Although
alfalfa-grass mixtures may be seeded to
produce the desired proportion of alfalfa
and grass, selective grazing and variation
in the terrain of the field may allow
excessive intake of alfalfa, resulting in
bloat. The period following mechanical
harvesting or intensive grazing of alfalfa-
grass mixtures may pose a potential risk
of bloat, because alfalfa generally recovers
faster than grass after cutting.

The ideal companion grass should
have the same seasonal growth pattern
and regrowth characteristics as alfalfa.
Smooth bromegrass is widely grown in a
mixture with alfalfa but its regrowth after
grazing or cutting is lower than alfalfa.
Consequently, pasture bloat may occur
when an alfalfa-bromegrass mixture is
used in rotational grazing systems.
Sufficient time must elapse between rota-
tions to allow regrowth of the bromegrass.

Meadowgrass has faster regrowth than
smooth bromegrass. Similarly, orchardgrass
and timothy have fast regrowth charac-
teristics and are the best choices in areas
where they are adapted.

Grazing management
Uniform and regular intake is the key to
managing cattle on legume pastures.
Waitinguntil the dew is off before placing
animals on pasture is a common practice
and is probably useful when animals are
first exposed to a legume pasture. Before

animals are placed on a legume pasture
they should be fed coarse hay to satiety.
This prevents them from gorging
themselves and overeating the fresh and
lush legume forage. Thereafter, they
should stay on the pasture. Mild bloat
may occur on first exposure, but the
problem should disappear in a few days
because animals usually adapt to legume
pastures with continuous grazing. If the
legume pasture continues to have a high
bloat potential, the animals should be
removed until the legume becomes more
mature and less bloat-provoking.

Forage supplements prior to grazing
The effect of feeding a forage supplement
such as chopped straw combined with
cane molasses and soyabean meal to
dairy cattle prior to being placed on a
clover pasture twice daily has been
examined as a strategy to reduce the inci-
dence of bloat. 33 The energy and protein
content were varied by the content of
molasses and soyabean meal. A high-
energy, high-protein supplement increased
the incidence of bloat, and a low-energy,
high-protein supplement reduced the
incidence compared to grazing alone. The
feeding of silage prior to grazing reduced
the incidence of bloat among cows
grazing both tall and short swards. The
most suitable forages to feed when there
is a risk of bloat are those that are slowly
fermented in the rumen but are eaten in
sufficient quantity to reduce periods of
rapid forage intake.

Grazing patterns and strip grazing
Bloat is often associated with discontinuous
grazing such as removal of animals from
the legume pasture for a period of time,
e.g. overnight. Similarly, outbreaks may
occur when grazing is interrupted by
adverse weather, such as storms, and
by biting flies or other insect pests. These
factors alter normal grazing habits,
generally resulting in more intensive,
shorter feeding periods that may increase
j the incidence of bloat.

In strip grazing the field is grazed in
strips that are changed every 1-3 days.
This is done by careful placement of an
electric fence so that the grazing strip is
moved further and further away from the
entrance. In this way the animals are forced
to graze a greater proportion of the entire
plant, which increases the dry matter
intake and proportionately decreases the
intake of soluble protein, which results in
a decrease in the rate of digestion in
the rumen. In some situations, the most
reliable methods for the prevention of
bloat in dairy cows are either strip grazing
of pasture sprayed daily with oil or
pluronics, or twice-daily drenching with
the same preparations.

Swathing and wilting
The frequency of alfalfa bloat can be
decreased by grazing pastures that have
been swathed and wilted. Wilting swathed
alfalfa for 24 hours produces changes in
the protein configuration of the sulfhydryl
and disulfide content of the proteins. 25
Compared with feeding a fresh swath,
wilting a swath for 24 or 48 hours reduces
the incidence of alfalfa bloat. The reduc-
tion is greatest by 48 hours and may be
eliminated after 48 hours. A reduction in
moisture content during wilting may be
sufficient to eliminate the risk of bloat.
Alfalfa silage is virtually bloat-free because
of protein degradation by proteolysis
during ensiling.

Alfalfa hay bloat prevention
The bloat-potential of alfalfa hay is
unpredictable. The best indicators are leafy,
immature hay with soft stems. Hay grown
under cool, moist conditions is more likely
to cause bloat than hay produced in hot,
dry areas. Reports of bloat on damp, moldy
hay are common but not documented and
are unexplained. Since fine particles and
leaves are especially dangerous, chopping
hay can increase the incidence of bloat.

When alternative roughages are avail-
able, a coarse grass hay, cereal grain hay
or straw can be substituted for a portion
of the bloat-causing hay. In dairy herds,
alfalfa hay can be fed in the morning and
grass hay in the evening. Animals should
be adjusted gradually to new lots of alfalfa
hay; old and new lots should be mixed for
the first 5 days of feeding.

Rations containing a 50:50 mixture of
alfalfa hay and grain are most dangerous
but the risk of bloat is low when grain
consists of less than 35% of the mixture.

Antifoaming agents

One satisfactory strategy for the prevention
of pasture bloat is the administration of
antifoaming agents.

Oils and fats

Oils and fats have achieved great success
for the control of pasture bloat in New
Zealand and Australia.

Individual drenching

Individual drenching is sometimes prac-
ticed but because of the time and labor
involved it is most suited to short-term
prophylaxis. It is popular as an effective
standard practice in pastured cattle in
New Zealand. The common practice is
to administer the antifoaming agent
(antibloat drench) at the time of milking
using an automatic dose syringe that is
moved up and down to reach each cow in
the milking parlor. Cows become con-
ditioned quickly and turn their heads to
the operator to receive their twice-daily
dose of 60-120 mL of the oil. The duration
of the foam-preventing effect is short,

Diseases of the rumen, reticulum and omasum

335

lasting only a few hours, and increasing
the dose does not significantly lengthen
the period of protection.

The combined use of sodium chloride
and antibloat drenching of lactating dairy
cows in New Zealand may stimulate the
closure of the reticular groove, causing the
swallowed fluid to by-pass the reticulo-
rumen, rendering the drenching with the
antibloat solution ineffective. 34 The
proportion of antibloat-sodium-chloride
fluid bypassed was considered to be of no
practical significance to the protection
from bloat in most animals. However,
there may be decreased protection in
10-15% of drenched cows. Thus, cows
should be drenched with these compounds
at separate times, morning for one,
evening for the other, or, if drenching at
the same milking, drench with the anti-
bloat solution first, followed by a separate
drench with sodium chloride.

Application of oil to pasture
If the oil or fat is emulsified with water it
can be sprayed on to a limited pasture
area that provides part or all of the
anticipated food requirements for the day.
Backgrazing must be prevented and care
is required during rainy periods when the
oil is likely to be washed from the pasture.
The method is ideal where strip-grazing
is practiced on irrigated pasture but is
ineffective when grazing is uncontrolled.

Addition to feed and water
The oil can be administered at the rate of
120 g per head in concentrates fed before
the cattle go on to the pasture or by
addition to the drinking water to make a
2% emulsion. Oil can be added to water
in all available troughs, turning off the
water supply and refilling the troughs
when they are emptied. However, the
actual intake of the oil cannot be
guaranteed. Climatic conditions also
cause variations in the amount of water
that is taken, with consequent variation in
the oil intake. Thus it is best to make
provision for a daily intake of 240-300 g
of oil per head during those periods when
the risk of bloating is highest. The
recommended procedure is to provide an
automatic watering pump that injects
antifoaming agents into all the drinking
water supplies in amounts that will
maintain a concentration of 1% of the
antifrothing agent. Hand replenishment
means that the preparation must be
added twice daily. Surfactants are pre-
ferred to oils because of their faster
action, the smaller dose rates (5-8 mL in
10-20 mL of water) and their longer
period of effectiveness (10-18 h) .

Application to flanks

Antifoaming agents can be applied with a
large paint brush to the flanks of cows as

they go out of the milking shed. A
preparation that is palatable to cattle and
encourages them to lick their flanks is
preferred. This has been a popular
method of controlling bloat in dairy cows
in Australia, but failures are not infrequent,
especially in individual cows.

Types of oil

Many different oils have been used and
most vegetable oils, mineral oil and
emulsified tallow are effective. The choice
of oil to be used depends on local
availability and cost. If the oils are to be
used over an extended period, some
consideration must be given to the effects
of the oil on the animal. Continued
administration of mineral oil causes
restriction of carotene absorption and
reduces the carotene and tocopherol
content of the butter produced. Linseed
oil, soya oil and whale oil have undesirable
effects on the quality and flavor of the
milk and butter. Peanut oil and tallow are
the most satisfactory. In most areas the
tympany-producing effect of pasture is
short-lived and may last for only 2-3 weeks.
During this time the pasture can be grazed
under the protection of oil administration
until the bloat-producing period is passed.

Water-soluble feed supplements
Commercially available sources of CTs,
and plant extracts of Yucca schidigera
(yucca) are a natural source of steroidal
saponins. 35 Both compounds were
ineffective in preventing bloat in cattle fed
fresh alfalfa herbage when used as a
water-soluble feed supplement added
to the drinking water or given as a top-
dressing.

Synthetic non-ionic surfactants
Poloxalene

Poloxalene is a non-ionic surfactant
(surface active agent) that has been used
successfully for the prevention of
leguminous bloat for 25 years. 36 It is a
polyoxythylene polyoxypropylene block
polymer and highly effective for use in
cattle grazing lush legume pasture or
young cereal crops such as wheat pasture.
Poloxalene moderates the ingestive
behavior of cattle grazing immature
alfalfa. 37 In cattle the recommended daily
level of poloxalene for prevention of bloat
is 2 g/100 kg BW. In high-risk situations it
may be advisable to administer the drug
at least twice daily. Poloxalene is unpalat-
able and its use in drinking water was not
possible until the introduction of the
pluronic L64, which is suitable for mixing
with drinking water and is effective. It
needs to be introduced to the cattle
several weeks before the bloat season
commences. It is commonly used as an
additive to grain mixtures, in feed pellets
and in mineral blocks. The use of

pluronics administered by mixing with
molasses to be licked from a roller drum
was popular for a short period of time for
the control of bloat in pastured beef cattle
but consumption was erratic and control
of bloat unreliable. The alternative of
mixing pluronics with the drinking water
is also not dependable. Pluronic poison-
ing has occurred in grass- and milk-fed
young calves given a pluronic-type
detergent bloat drench because the
attendant thought the calves were mildly
bloated. 38 Dyspnea, bellowing, convulsions
and death in 24 hours occurred.

Alfasure

Alfasure, a polyoxypropylene-poly-
oxyethylene glycol surfactant polymer, is
very effective for the prevention of bloat
when used at 0.05% in drinking water of
cattle fed fresh alfalfa herbage and when
added as a top dressing. 35 An Alfasure
spray on pasture is completely effective in
eliminating the occurrence of bloat in
cattle grazing alfalfa at the vegetative to
bud stage of growth. 23

Alcohol ethoxylate detergents
These products are known to have equal
foam-reducing qualities to poloxalene
and have the advantage of better
palatability so that they can be administered
by a voluntary intake method such as
medicated blocks. Small-scale field trials
show that these blocks are palatable and
attractive and should be satisfactory in
reducing the severity and prevalence of
bloat. Not all cattle visit them voluntarily,
so some cases cf bloat are likely to occur.
The blocks contain 10% of the alcohol
ethoxylate, known as Teric, and a daily
consumption of 17-19 g of it is usual.
Application of Teric to the flanks of cows
has not been as successful as a bloat
prevention as has similar application
of oils.

Alcohol ethoxylate and pluronic deter-
gents controlled the occurrence of bloat in
sheep fed freshly harvested alfalfa in
confinement and in grazing studies
wherein the products were added to the
water supply. 39 In cattle grazing early to
late bud alfalfa stands, the addition of the
products to the water supplies prevented
the occurrence of bloat.

lonophores

Rumen modifiers such as the ionophore
monensin have been used to control bloat
using controlled-release capsules and
liquid formulations. 40

Controlled-release monensin capsules
Sustained-release capsules containing
antifoaming agents are available for the
control of pasture bloat. The capsule is
administered into the rumen, where it
opens, exposing an antifoaming agent,
which diffuses slowly from a matrix.

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

Monensin, a polyether ionophore anti-
biotic, is potentially an important agent
for bloat relief in dairy cows grazing
legume-based pasture. 17 A monensin
controlled-release intraruminal capsule is
available that releases approximately
300 mg/head per day for 100 days. 17
Experimental and field studies indicate
that monensin can reduce the severity of
bloat and increase milk production in
dairy cows grazing legume pastures. 17 In
dairy farms in Australia, sustained-release
monensin capsules were effective in
reducing the incidence of clinical bloat in
pasture-fed cattle. 41 There was also a
significant decrease in the use of pasture
spraying, drinking water administration
and flank-spraying of antifoaming agents
on the farms using the capsules, with no
compensatory rise in the use of other
bloat-prevention techniques.

A controlled-release monensin capsule
reduced the incidence of bloat by about
50% in experimental steers fed alfalfa
at the vegetative to early bud stages of
growth. 42

Liquid formulation of monensin
Oral drenching with a liquid formulation
of monensin is effective in reducing bloat
in milking cows grazing white-clover-
ryegrass or red-clover pastures. 40 A daily
dose of 300 mg per cow given as an oral
drench in a volume of 100 mL daily pro-
vided protection for 24 hours.

Feedlot bloat

Roughage in ration

Feedlot high-level grain rations should
contain at least 10-15% roughage, which
is cut or chopped and mixed into a
complete feed. This ensures that cattle
will consume a minimum amount of
roughage. The roughage should be a
cereal grain straw or grass hay. The use of
leafy alfalfa hay may be hazardous. The
roughage may be fed separately in the
long form as a supplement to the grain
ration but this practice is dangerous
because the voluntary intake of roughage
will very considerably. The more palatable
the grain ration, the less total roughage
will be eaten and outbreaks of feedlot
bloat may occur.

Consistency of grain

Best results in feedlot bloat are achieved
by the incorporation of nonbloating
roughages in the grain ration at a level of
at least 10%, and avoiding fine grinding
of the grain. Grains for feedlot rations
should be only rolled or cracked, not
finely ground. If the grain is very dry, the
addition of water during processing will
prevent pulverization to fine particles. The
use of pelleted rations for feedlot cattle
cannot be recommended because a fine
grind of the grain is normally necessary to

process a solid pellet. When the pellet
dissolves in the rumen, a fine pasty
rumen content forms, which may be
associated with the development of a
stable foam. In addition, it is difficult to
incorporate a sufficient quantity of
roughage into a pellet.

Antifoaming agents

The use of dietary antifoaming agents for
the prevention of feedlot bloat has had
variable success. The addition of tallow at
the level of 3-5% of the total ration has
been successful, judged empirically, but
controlled trials did not reduce bloat
scores. 17 If animal fats are effective in
preventing feedlot bloat they would be
useful as a source of energy and for the
control of dust in dusty feeds. Poloxalene
is ineffective for the prevention of feedlot
bloat.

Dietary salt

The addition of a 4% salt to feedlot
rations has been recommended when
other methods are not readily available.
However, feed intake and rate of body
weight gain will be reduced. A high salt
diet increased water intake, causes an
alteration in the proportion of disrupted
cells in the forage due to changes in
fermentation, and increases the rate of
flow of particulate material out of the
rumen. Other management factors con-
sidered to be important in the prevention
of feedlot bloat generally include: avoid
overfeeding after a period of temporary
starvation, e.g. after bad weather,
machinery failure, transportation or feed
handling failure, and insure that the
water supply is available at all times.

Genetic control of pasture bloat

Because of the high costs of bloat from
deaths, lost production, treatment costs
and extra labor, one possible long-term
solution is to breed cattle with reduced
susceptibility to bloat. 14 Bloat score on a
single day is heritable but the required
testing procedures are expensive in labor
; and can put the lives of otherwise
j valuable animals at risk. Selection on
I bloat score has been achieved successfully
I in an experimental herd, and genetic
markers and candidate genes for bloat
susceptibility are now being explored. 14
The ultimate aim is to assist the dairy
industry to identify bloat-susceptible
animals, so that they can be culled or used
less frequently as parents in the national
herd. Work in New Zealand suggests that
the prospects are good for providing the
dairy industry with a means of removing
bloat-susceptible cattle. Carrier sires
could be identified, using a marker, and
these sires could be withheld from the
teams of widely used proven sires avail-
able for commercial use. The use of non-

carrier artificial insemination sires in the
dairy cattle industry could minimize the
bloat problem in one generation, by
removing all homozygous bloat-susceptible
progeny from the population. 14 There has
been no recent research on this aspect of
bloat in cattle.

General comments

Apart from the impressive reduction in
clinical and fatal cases of ruminal
tympany resulting from the prophylactic
use of oils, there are the added advant-
ages of being able to utilize dangerous
pasture with impunity and the reduction
of subclinical bloat and its attendant
lowering of food intake. Production may
rise by as much as 25% in 24 hours after
the use of oil. Nevertheless, these pre-
ventive methods should be considered as
temporary measures only. The ultimate
aim should be the development of a pas-
ture of high net productivity where the
maximum productivity is consistent with
a low incidence of bloat and diarrhea.

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Mathison GW. Effects of processing on the utilization
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Cheng KJ, McAllister TA, Popp JD et al. A review of
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Acrts RJ Barry TN, McNabb WC. Polyphenols and
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anthocyanidins in forages. Agric Ecosystem
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Barry TN, McNabb WC. The implications of
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Berg BP, Majak W, McAllister T A et al. Bloat in cattle
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Coulman B, Goplcn B, Majak W et al. A review of the
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McMahon LR, McAllister TA, Berg BP et al. A review
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Popp JD, McCaughey WP, Cohen RDH, Me AllisterTA,
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3. Howarth RE et al. In: Milligan LP, Grovum WL,
Dobson A, eds. Control of digestion and
metabolism in ruminants. Proceedings of the 6th
International Symposium on Ruminant Physiology,
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TRAUMATIC

RETICULOPERITONITIS

Perforation of the wall of the reticulum by
a sharp foreign body initially produces an
acute local peritonitis, which may spread
to cause acute diffuse peritonitis or
remain localized to cause subsequent
damage, including vagal indigestion and
diaphragmatic hernia. The penetration of
the foreign body may proceed beyond
the peritoneum and cause involvement
of other organs resulting in pericarditis,
cardiac tamponade, pneumonia, pleurisy
and mediastinitis, and hepatic, splenic
or diaphragmatic abscess. These sequelae
of traumatic perforation of the reticular
wall are set out diagrammatically in
Figure 6.4.

This complexity of development makes
diagnosis and prognosis difficulCand the
possibility that a number of syndromes
may occur together further complicates
the picture. All these entities except
endocarditis are dealt with together here,
even though many of them are diseases of
other systems.

ETIOLOGY

Traumatic reticuloperitonitis is caused by
the penetration of the reticulum by metallic
foreign objects that have been ingested in
prepared feed. Baling or fencing wire that
has passed through a chaff-cutter, feed
chopper or forage harvester is one of the
most common causes. In one series of 1400
necropsies, 59% of lesions were caused by
pieces of wire, 36% by nails and 6% by
miscellaneous objects. The metal objects
may be in the roughage or concentrate or
may originate on the fann when repairs are
made to fences, yards and in the vicinity
of feed troughs.

The wire from motor vehicle radial
tires may be the cause. 1-3 Used tires are
commonly used to hold down plastic
sheeting over silage piles. The wire is
gradually released from the tires, which
are in a state of deterioration, and is mixed
with the feed supply, or the tires may be
inadvertently dropped into a feed mixer
wagon and become fragmented, mixing
the pieces of wire throughout the ration.

Fig. 6.4 Sequelae of traumatic perforation of the reticular wall.

!8

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract- II

Synopsis

Etiology Penetration of reticulum by
metallic foreign objects such as nails and
pieces of wire, including tire wire, that
were ingested by the animal and located in
the reticulum

Epidemiology Most common in adult
dairy cattle fed prepared feeds
Signs Sudden anorexia and fall in milk
yield, mild fever, ruminal stasis and local
pain in the abdomen. Rapid recovery may
occur, or the disease may persist in a
chronic form or spread widely to produce
an acute, diffuse peritonitis
Clinical pathology In acute local
peritonitis, neutrophilia and regenerative
left shift; in chronic form, leukopenia and
degenerative left shift. Peritoneal fluid
contains marked increase in nucleated cells
and total protein. Plasma protein
concentration increased. Radiography and
ultrasonography of abdomen
Lesions Localized reticuloperitonitis and
varying degrees of locally extensive
fibrinous adhesions. Abnormal peritoneal
fluid. Abscesses and adhesions possible
throughout the peritoneal cavity
Diagnostic confirmation
Reticuloperitonitis and metallic foreign
body

Differential diagnosis list:

• Acute local traumatic reticuloperitonitis
must be differentiated from: simple
indigestion, acute carbohydrate
engorgement, acute intestinal
obstruction, abomasal volvulus,
pericarditis, acute pleuritis, perforated
abomasal ulcer, postpartum septic
metritis, pyelonephritis acute hepatitis,
acetonemia

• Acute diffuse or generalized peritonitis
must be differentiated from those
diseases causing severe toxemia or
acid-base imbalance, dehydration, and
shock which include the following:
carbohydrate engorgement, acute
intestinal obstruction, advanced vagus
indigestion, abomasal volvulus,
perforated abomasal ulcer, and
miscellaneous causes of generalized
peritonitis

• Chronic traumatic reticuloperitonitis
must be differentiated from early stages
of vagus indigestion, hepatic
abscessation, traumatic splenitis, chronic
pneumonia and pleuritis, and
miscellaneous causes of chronic
peritonitis such as peritoneal abscesses
secondary to intraperitoneal injections

Treatment Antimicrobials daily for several
days, reticular magnet and immobilization
in stall to promote adhesions.

Rumenotomy to remove foreign body if
medical treatment unsuccessful or in
valuable animal

Control Prevent exposure of cattle to
metallic foreign objects that can be
ingested. Feed processing equipment
should be equipped with magnets to
remove metallic foreign bodies

In an abattoir survey of the gastro-
intestinal tract of 1491 slaughter cows in
Denmark, foreign bodies were found in
16% of the cows. Of 286 foreign bodies,
11% were tire wires, 14% fencing wires,
5% screws, 9% nails, 37% mixed pieces of
metal, 2% copper and 22% remnants of
boluses containing antiparasitic drugs. 3 A
significant association was found between
the type of foreign body and the presence
of lesions, and a significant association
between the cross-section of the foreign
body and the presence of lesions. There
was also an association between the end
shape of the foreign body and the presence
of lesions. Tire wire was the most com-
mon traumatizing foreign body, as 81% of
all lesions were associated with tire wires.

EPIDEMIOLOGY

Occurrence

Adult dairy cattle are most commonly
affected because of their more frequent
exposure but cases occur infrequently in
yearlings, beef cattle, dairy bulls, sheep
and goats. In the series of 1400 referred to
above, 93% were in cattle over 2 years old
and 87% were in dairy cattle. In the
Danish abattoir survey of cows (see
Etiology), foreign body lesions were
present in 10% of the cows. 3 Magnets,
one or two, were found in only 7% of the
cows. All magnets collected iron filings
and fencing wire (30%), and 'other pieces
of metal' (39%) were the predominant
contents of the magnet. There were no
lesions in 97% of the cows with magnets,
and a significant association was found
between the use of magnets and the
absence of lesions.

The disease is much more common in
cattle fed on prepared feeds, especially
those fed inside for part of the year. It is
almost unknown in cattle fed entirely on
pasture. Accordingly, it is much more
common in the winter months in the
northern hemisphere. The incidence is
low in sheep and goats.

The incidence is usually sporadic but
outbreaks have occurred when sources of
wire have become mixed into feed
supplies, as in the case of perforation of
the alimentary tract by pieces of tire wire. 2
Over a period of 6 months, 30% of 170
lactating dairy cows in one herd exhibited
clinical signs suggestive of hardware
disease associated with the ingestion of
tire wire in the feed supplies.

Risk factors

There are few studies of the epidemiology
of traumatic reticuloperitonitis. The effects
of 23 veterinary diagnoses, host charac-
teristics and production were examined
on the risks of ruminal acidosis and
traumatic reticuloperitonitis. 4 The lacta-
tional incidence risk for the disease in
Finnish Ayrshire dairy cattle was 0.6%, 4

which is similar to observations made in
Holstein-Friesian cows. 5 The risk of the "
disease in the former study increased with
early metritis, nonparturient paresis,
ketosis, acute and chronic mastitis, and
foot and leg problems. It is unknown how
metritis and mastitis could be risk factors
for traumatic reticuloperitonitis. The median
day of occurrence was on 113 days after
calving, which makes it unlikely that
calving was a risk factor. Similarly,
dystocia was not found to be a risk factor.

When several or more cases occur in a
cluster outbreak, the nature of the feed
supply should be considered as a risk
factor. The use of used tires to secure
plastic sheeting over silage piles may be
an important risk factor.

Economic importance

The disease is economically important
because of the severe loss of production it
causes and the high mortality rate. Many
cases go unrecognized and many more
make spontaneous recoveries. In indus-
trialized countries, metallic foreign bodies
may be present in the reticulum in up to
90% of normal cattle and residual
traumatic lesions may be present in as
many as 70% of dairy cows. Among the
clinically affected animals, about 25%
develop incurable complications. The
other 75% can be expected to recover
completely with conservative treatment
or routine surgical intervention.

PATHOGENESIS
Ingestion of foreign body

Lack of oral discrimination by cattle leads
to the ingestion of foreign bodies that
would be rejected by other species.
Swallowed foreign bodies may lodge in
the upper esophagus and cause obstruc-
tion or in the esophageal groove and
cause vomiting, but in most instances
they pass to the reticulum. Radiological
examination of goats that have been fed
foreign bodies experimentally indicate
that they may first enter various sacs of
the reticulorumen before reaching the
reticulum. Many lie there without causing
harm but the honeycomb-like structure of
the reticulum provides many sites for
fixation of the foreign body, and contrac-
tions of the reticulum are sufficient to
push a sharp-pointed object through
the wall.

Penetration of reticulum

Most perforations occur in the lower part
of the cranial wall of the reticulum but
some occur laterally in the direction of the
spleen and medially towards the liver.

If the reticular wall is injured without
penetration to the serous surface no
detectable illness occurs, and the foreign
body may remain fixed in the site for long
periods and gradually be corroded away.

Diseases of the rumen, reticulum and omasum

A piece of wire can disappear in 6 weeks
but certain nails last much longer and are
unlikely to corrode away in less than
1 year. The ease with which perforation
occurs has been illustrated by the artificial
production of the disease. Sharpened
foreign bodies were given to 10 cows in
gelatin capsules. Of 20 pieces of wire and
10 nails, 25 were found in the reticulum.
Of the 20 pieces of wire 18 had perforated
or were embedded in the wall or plicae.
Only one of the nails was embedded.
Complete perforations were caused by 13
foreign bodies and incomplete by six. All
cows suffered at least one perforation,
showed clinical signs of acute local
peritonitis and recovered after surgical
removal of the foreign bodies.

Many foreign bodies may not remain
embedded but are commonly found free
in the reticulum if surgery is carried out
about 72 hours after illness commences.
This may be due to necrosis around the
penetrating object and the reticular
contractions moving the foreign body
back into the reticulum. Objects that are
deeply embedded or have kinks, barbs or
large diameters tend to remain in situ and
cause persistent peritonitis.

Acute local peritonitis

The initial reaction to perforation is one of
acute local peritonitis and, in experi-
mentally induced cases, clinical signs
commence about 24 hours after pene-
tration. The peritonitis causes ruminal
atony and abdominal pain. If the foreign
body moves back into the reticulum
spontaneous recovery may occur.

Resolution of acute fibrinous local
peritonitis is characterized by the develop-
ment of fibrous adhesions, which
gradually become long, stringy strands
over a period of weeks and months;
motility of the reticulum is restored
and the animal may recover fully. Follow-
up ultrasonographic examinations of
cows with traumatic reticuloperitonitis in
which rumenotomies were done found
that the adhesions disappeared in most of
the animals by 6 months. 6

Depending on the severity of the local
peritonitis, the ventral aspect of the
reticulum becomes adherent to varying
degrees to the abdominal floor and
diaphragm. This results in decreased
reticular motility. Ultrasonography of
cows with traumatic reticuloperitonitis
reveals that the biphasic contractions of
the reticulum are slower than normal
or indistinct and the number of con-
tractions are reduced.' Reticular
abscesses are common complications
and may be located between the
reticulum and the ventral body wall,
between the reticulum and the right
thoracic wall and between the reticulum

and the spleen. 8 Persistent local peri-
tonitis with or without abscesses results
in reduced reticulorumen motility, in-
appetence to anorexia, a capricious appetite
(may eat hay not concentrate), chronic
ruminal tympany, persistent mild fever,
abdominal pain on deep palpation, and
changes in the hemogram and feces.
Immobilization of the reticulum impairs
the clearance function of the reticulum,
which results in the passage of poorly
comminuted feces characterized by an
increased proportion of large particles. 9

Generalized peritonitis and
extension of disease

Spread of the inflammation causing
generalized or diffuse peritonitis may

occur in cows that calve at the time of
perforation and in cattle that are forced to
exercise. Immobility is a prominent
clinical finding and may be a protective
mechanism so that adhesions are able to
form and localize the peritonitis. Animals
made to walk or transported long
distances frequently suffer relapses when
these adhesions are broken during body
movements. Generalized peritonitis results
in toxemia, alimentary tract stasis, dehy-
dration and shock.

During the initial penetration of the
reticulum, the foreign body may penetrate
beyond the peritoneal cavity and into the
pleural or pericardial sacs. This may
occur more commonly in cows in advanced
pregnancy than in nonpregnant cows,
because of the gravid uterus, although
this is uncertain. Complications such as
pericarditis occur most commonly in cows
after the sixth month of pregnancy.

Details of the pathogenesis of the
more common complications are presented
under traumatic pericarditis, vagus
indigestion, diaphragmatic hernia and
traumatic abscess of the spleen and
liver. Less common sequelae include
rupture of the left gastroepiploic artery
causing sudden death due to internal
hemorrhage and the development of a
diaphragmatic abscess, which infiltrates
tissues to the ventral abdominal wall at
the xiphoid process, rupturing to the
exterior and sometimes discharging the
foreign body. Hematogenous spread of
infection from a diaphragmatic abscess or
chronic local peritonitis is a common
cause of endocarditis and its sequelae of
polysynovitis and arthritis, nephritis and
pulmonary abscessation. Penetration into
the pleural cavity causes acute sup-
purative pleurisy and pneumonia. In
rare cases the infection is localized to the
mediastinum causing abscessation, which
causes pressure on the pericardial sac and
congestive heart failure. Rarely, the foreign
body penetrates to the abomasum, causing
abomasitis, pyloric stenosis and abomagal

ulceration. Even more rarely, puncture of
the reticular vein by a migrating metal
wire may lead to fatal hemorrhage
causing sudden death. 10

CLINICAL FINDINGS
Acute local peritonitis

Characteristically, the onset is sudden
with complete anorexia and a marked
drop in milk yield, usually to about a
third or less of the previous milking.
These changes occur within a 12-hour
period and their abrupt appearance is
typical. Subacute abdominal pain is com-
mon in most cases. The animal is
reluctant to move and does so slowly.
Walking, particularly downhill, is often
accompanied by grunting. Most animals
prefer to remain standing for long periods
and lie down with great care; habitual
recumbency is characteristic in others.
Arching of the back occurs in about 50%
of cases, along with the appearance of
tenseness of the back and the abdominal
muscles so that the animal appears gaunt
or 'tucked-up'. Defecation and urination
cause pain and the acts are performed
infrequently and usually with grunting.
This results in constipation, scant feces
and in some cases retention of urine.
Rarely, acute abdominal pain with kicking
at the belly and stretching occurs. In
others there is recumbency and reluc-
tance to stand.

A moderate systemic reaction is
common in acute localized peritonitis.
The temperature ranges from 39.5-40°C
(103-104°F), rarely higher, the heart rate
is about 80/min and the respiratory rate
about 30/min. Temperatures above 40°C
(104°F) accompanied by heart rates greater
than 90/min suggest severe complications.
The respirations are usually shallow and,
if the pleural cavity has been penetrated,
are painful and accompanied by an
audible expiratory grunt.

Rumination is absent and reticulo-
rumen movements are markedly
depressed and usually absent. The rumen
may appear to be full because of the
presence of a free-gas bloat with moderate
distension of the left paralumbar fossa.
On palpation of the fossa, the ruminal gas
cap is usually larger than usual and the
rumen contents more doughy than
normal. Deep palpation of the gas cap in
the fossa may be required to feel the
rumen pack below the gas cap.

Pain can be elicited by deep pal-
pation of the abdominal wall just
caudal to the xiphisternum. Palpation is
done using short, sharp pushes with the
closed fist or knee over an imaginary
band about 20 cm wide covering the
ventral third of the abdomen from the left
to the right side with the cranial border of
the band being the point just caudal to

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

the xiphisternum. This area should be
probed with at least six deep palpations on
both sides of the abdomen while listening
with a stethoscope over the trachea for
evidence of a grunt. Pinching the withers to
cause depression of the back and eliciting a
grunt is also an effective diagnostic aid,
except in large adult cows and bulls; for
these the sharp elevation of a solid rail held
horizontally under the abdomen is a useful
method for eliciting a grunt. A positive
response to any of these tests is a grunt of
pain, which may be audible some distance
away but is best detected by auscultation of
the trachea. Rarely, a grunt may also be
audible by auscultation over the trachea
when infrequent reticulorumen contrac-
tions occur.

The course of acute local peritonitis is
short and the findings described above
are most obvious on the first day; in most
cases they subside quickly and may be
difficult to detect by the third day. In these
cases, in addition to persistent anorexia
and ruminal atony, the most constant
finding is the abdominal pain, which may
require deep palpation for its demon-
stration. In cases that recover sponta-
neously or respond satisfactorily to
conservative treatment there may be
no detectable signs of illness by the
fourth day.

Chronic local peritonitis

In chronic peritonitis the appetite and
milk yield do not return to normal after
prolonged therapy with antimicrobials.
The body condition is usually poor, the
feces are reduced in quantity and there is
an increase in undigested particles. In
some cases, the temperature may be
within the normal range, which makes
the diagnosis uncertain. A persistent
slightly elevated temperature is sup-
portive evidence of the presence of a
chronic inflammatory lesion. The grunt
test may be positive or negative; often it is
uncertain. The gait may be slow and
careful and, occasionally, grunting may
occur during rumination, defecation and
urination. Rumination activities are
infrequent, the rumen is usually smaller
than normal, chronic moderate bloat is
common and there is ruminal atony or
some moderate reticulorumen activity.

Reticular abscesses in cows are
characterized by poor body condition, a
relatively full rumen but with reduced
ruminal contractions or almost complete
ruminal atony, persistent mild bloat, an
arched back with a tense abdomen and a
grunt indicating abdominal pain, and
undigested particles in the feces. Most
have a clinical history of not responding
to prolonged therapy with antimicrobials.
These can be diagnosed with radiography
and ultrasonography.

Rectal examination
Rectal examination of cattle with acute
or local traumatic reticuloperitonitis may
cause a painful grunt when the animal
strains during the examination. The feces
are usually dry and firm and covered by a
thin coating of mucus because of pro-
longed retention. In acute localized
peritonitis the rumen may feel larger than
normal and the gas cap is easily palpable.
In acute and chronic generalized peritonitis,
fibrinous adhesions may be palpable
between the rumen and the left abdomi-
nal wall or between loops of intestine, or
in the pelvic cavity.

Acute diffuse (generalized)
peritonitis

Acute diffuse peritonitis is characterized
by the appearance of profound toxemia
within a day or two of the onset of local
peritonitis. Alimentary tract motility is
reduced, mental depression is marked
and the temperature is elevated or sub-
normal in severe cases, especially those
that occur immediately after calving. The
heart rate increases to 100-120/min and a
painful grunt may be elicited by deep
digital palpation at almost any location
over the ventral abdominal wall. This
stage is usually followed by rapid collapse
and peripheral circulatory failure and an
absence of pain responses. Terminally,
recumbency and depression are common.

Sudden death

There is a record of sudden death in a 20-
month-old pregnant heifer in which the
reticular vein was punctured by a migrating
piece of metal wire, causing fatal hemor-
rhage into the reticulum. At necropsy, a
large blood clot was present in the
reticulum, the rumen contents were red
brown and no reticular adhesions were
present. 10

Iatrogenic reticulitis

There is a record of iatrogenic reticulitis
that occurred as a result of the oral
administration of intraluminal anthelmintic
boluses, which may have lodged in the
reticulum and become filled with other
foreign objects ingested by the animal,
resulting in a syndrome similar to acute
traumatic reticuloperitonitis. 11 Inappetence,
reduced milk production, reduced
reticulorumen motility, abdominal pain
and scant feces were present. On explor-
atory rumenotomy the reticulum contained
two cylindrical boluses filled with stones,
nuts and bolts. Removal of the boluses
was followed by prompt recovery.

CLINICAL PATHOLOGY
Hemogram

The total and differential leukocyte
counts provide useful diagnostic and
prognostic data. The differential leukocyte
count is usually considerably more indi-

cative of acute peritonitis than the total
count.

In acute local peritonitis a neutro-
philia (mature neutrophils above 400/pL)
and a left shift (immature neutrophils
above 200/pL) are common. This is a
regenerative left shift Both the
neutrophilia and the left shift will be
increased on the first day and will last for
up to 3 days, when in uncomplicated
cases the count begins to return to
normal. In chronic cases the levels do not
return completely to normal for several
days or longer periods and there is usually
a moderate leukocytosis, neutrophilia and
a monocytosis.

In acute diffuse peritonitis a

leukopenia (total count below 4000/pL)
with a greater absolute number of
immature neutrophils than mature
neutrophils (degenerative left shift)
occurs, which suggests an unfavorable
prognosis if severe. The degree of
lymphopenia (lymphocyte count below
2500-3000/pL) is an indication of a stress
reaction to inflammation.

Plasma protein and fibrinogen

There is a significant difference in total
plasma protein levels between cattle with
traumatic reticuloperitonitis and those
with other diseases of the gastrointestinal
tract that might be confused with the
former. 12 The mean plasma protein
concentrations, measured before surgery,
were 88 + 13 g/L for traumatic reticulo-
peritonitis and 77 ± 12 g/L for controls. In
severe diffuse peritonitis the fibrinogen
levels may be increased up to 10-20 g/L. 12

Cut-off points for total plasma protein
(TPP) and plasma fibrinogen (PF) were
determined to differentiate between
traumatic reticuloperitonitis and other
gastrointestinal diseases with similar
clinical findings. 13 There was moderate
negative dependence between sensitivities
of TPP and PF at the 8.82 g/dL and
766 mg/dL cut-off points, and mild negative
dependence between their specificities at
the 7.78 g/dL and 691 mg/dL cut-off
points, respectively. 13 Acceptable accuracy
(98% or 86% specificity with 62% or 88%
sensitivity, respectively) was obtained
with serial interpretation of the tests.

Abdominocentesis and peritoneal
fluid

Abdominocentesis and analysis of peri-
toneal fluid can be a valuable diagnostic
aid. The best site for abdominocentesis is
uncertain because the rumen occupies a
large portion of the ventral abdominal
wall and avoiding penetration of it is
difficult. Cattle have a low volume of
peritoneal fluid and failure to obtain a
sample is not unusual. Empirically, the
best sites are those in which, on an
anatomical basis, there are recesses

Diseases of the rumen, reticulum and omasum

341

between the forestomachs, abomasum,
diaphragm and liver. These are usually
10-12 cm caudal to the xiphistemum and
10-15 cm lateral to the midline. A blunt-
ended teat cannula is recommended but
with care and caution a 16-gauge 5 cm
hypodermic needle may also be used. The
hair of the site is clipped, the skin is
prepared aseptically and a local anesthetic
is applied. The skin in incised with a stab
scalpel and the cannula is pushed
carefully and slowly through the abdomi-
nal wall. The latter will twitch and a 'pop'
will be felt when the peritoneum is
punctured. When the cannula is in the
peritoneal cavity the fluid may leak out
without the aid of a vacuum. If it does not,
a syringe may be used to apply a vacuum
while the needle is manipulated in an
attempt to locate some fluid.

If no fluid can be obtained, a trocar and
cannula 80 mm long and with a 4 mm
internal diameter can be used with
success. The trocar and cannula are
inserted into the abdomen, the trocar is
removed and an 80 cm long 10 French
gauge infant feeding tube is inserted into
the abdomen through the cannula,
leaving about 10-20 cm outside. The tube
acts as a wick and within several minutes
fluid can be collected into vials. At least
three different sites should be attempted
to obtain peritoneal fluid. Peritonitis in
cattle is characterized by a marked
fibrinous response and localization of a
lesion, and the amount of exudative fluid
available at the abdominocentesis sites
may be minimal. Thus the failure to obtain
fluid does not preclude the presence of
peritonitis.

Laboratory evaluation of peritoneal
fluid consists of determinations of total
white blood cell count, differential cell
count, total protein and culture for
pathogens. The interpretation of the
analysis of the peritoneal fluid can be
unreliable because to date only a few
correlations have been made between the
laboratory findings and the presence or
absence of peritoneal lesions. A nucleated
cell count above 6000 cells/pL and total
protein above 3g/dL is consistent with
the diagnosis of peritonitis in 80% of cases.
Using a differential cell count, a relative
neutrophil count more than 40% and a
relative eosinophil count less than 10%
was frequently associated with the diag-
nosis of peritonitis.

METAL DETECTION

Metal detectors were used at one time to
aid in the diagnosis of traumatic reticulo-
peritonitis. Ferrous metallic foreign bodies
can be detected with metal detectors but
the instruments are of limited use
because most normal dairy cows are
positive for metal over the reticular area.

LAPAROSCOPY

Right flank laparoscopy using a flexible
fiberoptic laparoscope, 14 mm diameter
and 1120 mm working length, is a reliable
diagnostic aid for the presence of traumatic
reticuloperitonitis.

RADIOGRAPHY OF CRANIAL
ABDOMEN AND RETICULUM

Radiological examination of the reticulum
with the animal in dorsal recumbency
(dorsal reticulography) is an accurate
diagnostic method for the evaluation of
cattle with suspected traumatic reticulo-
peritonitis. 14 However, the lack of adequate
radiographic equipment in private veter-
inary practices precludes its routine use.
Also, the technical difficulties of position-
ing the animal and the increased
potential for personnel exposure associ-
ated with manual restraint suggests that it
may not be practical except for valuable
animals that may warrant referral to a
veterinary medical center.

The cranioventral abdomen of cattle
can be evaluated using two cranial
abdominal and one caudal thoracic radio-
graphs. An X-ray machine with a capacity
of 1000-1250 mA and 150 kV is necessary,
which is usually only available in veter-
inary teaching hospitals. However,
such techniques may be appropriate in
valuable animals in which an accurate
diagnosis and prognosis for surgical
treatment may be desirable. 15 In a con-
secutive series of standing lateral cranial
abdominal radiographs, the sensitivity
and specificity for detecting traumatic
reticuloperitonitis or pericarditis was 83%
and 90%, respectively. 16 These values are
higher than those achieved with dorsal
recumbency. In standing lateral radio-
graphs, an enlarged reticulum was
associated with a final diagnosis of vagal
indigestion. Alteration in reticulo-
diaphragmatic separation does not cor-
relate with any specific disease process.
The presence of focal perireticular gas
collections and reticular foreign bodies
greater than 1 cm in length unattached to
a magnet were good indicators of traumatic
reticuloperitonitis. Radiography is best
suited for identification of radiodense
foreign bodies in and outside the
reticulum (these cannot be visualized
ultrasonographically ) . 14

Features found to be reliable in the
diagnosis of traumatic reticuloperitonitis
using lateral radiographs of the reticulum
include:

° Atypically positioned foreign
bodies

° Abnormal gas shadows in the
region of the reticulum
° Depressions in the cranioventral
margin of the reticulum . 17

The reticulum is commonly markedly
displaced caudallyfrom the diaphragm or
dorsally or caudodorsaliy from the ventral
abdominal wall. Space-occupying masses
of the density of soft tissue, with or with-
out gas inclusions, gas shadows and gas-
fluid interfaces in the region of, the
reticulum, were highly predictive of peri-
tonitis (specificity 97%, positive predictive
value 96%).

ULTRASONOGRAPHY OF THE
RETICULUM

Ultrasonography is a suitable method for
investigation of reticular contractions in
healthy ruminants and in cattle for
the diagnosis of traumatic reticulo-
peritonitis. 18 ' 19 The literature on the use of
ultrasonography as a diagnostic aid in
gastrointestinal disease in cattle has been
reviewed. 20 The reader is referred to an
excellent atlas and textbook on the use of
ultrasonography in cattle. 19

The reticulum and adjacent organs of
cows can be examined with ultra-
sonography using a 3.5 MHz linear
transducer applied to the ventral midline
of the thorax over the sixth and seventh
intercostal spaces and from the left and
right sides of the midline. 21 ' 22 It may not
be possible to image the reticulum in
large cows in good body condition
because of the high proportion of fat in
the muscle layers. In older cows, calcifi-
cation of the xiphistemum may interfere
with imaging. The most common reason
for being unable to visualize the reticulum
in sick animals is the displacement of the
reticulum by a markedly distended rumen
or by space-occupying lesions such as
abscesses and fibrin-containing effusions.
The pattern, number, amplitude and
duration of the interval between con-
tractions can be visualized. 21 The contour
of reticulum, the reticular contractions
and the organs adjacent to the reticulum
can be imaged. The biphasic reticular
contractions can be visualized at the rate
of 4 during a 4-minute period. 21-22 During
the first incomplete contraction, the
reticulum contracts by a mean of about
7.2 cm and during the second contraction
the reticulum disappears from the screen.

Ultrasonography for traumatic
reticuloperitonitis

In contrast to radiography, ultra-
sonography provides more precise infor-
mation about the contour of the reticulum
and reticular motility. 7,22 In cattle
with traumatic reticuloperitonitis, ultra-
sonography can be used to identify
morphological changes in the region of
the cranial, ventral or caudal reticular
wall. 20 The caudoventral reticular wall is
the most frequently affected, often in

342

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

association with the craniodorsal blind
sac of the rumen. The changes in the
contour of the reticulum depend on the
severity of the inflammatory changes.

The reticulum can be visualized in
more than 90% of cows in spite of
interference by the ribs and sternum. In
cows with disturbed reticular motility,
biphasic contractions are slower than
normal, or indistinct, and the number of
contractions is reduced. Fibrinous
material appears as echogenic deposits,
sometimes accompanied by hypo-
echogenic fluid. Reticular abscesses have
an echogenic capsule with a hypoechogenic
center. Involvement of the spleen,
omasum, liver and abomasum may
also be imaged. Neither magnets nor
foreign bodies can be visualized by
ultrasonography. 22

Reticular activity is almost always
affected in cattle with traumatic reticulo-
peritonitis. The frequency, amplitude or
velocity of contractions, singly or com-
bined, may be abnormal. The frequency
can be reduced from 3 to 2, 1 or no
contractions per 3 minutes. The reduction
in the amplitude of contractions varies:
when formation of adhesions is extensive,
reticular contractions appear indistinct.
Although the pattern of biphasic con-
traction is often maintained, the reticulum
contracts only 1-3 cm. The velocity of
reticular contractions may be normal but
can be markedly reduced. In cattle with
reticulo-omasal obstruction due to a
foreign body, the frequency of reticular
contractions may be increased. 23

Reticular abscesses associated with
traumatic reticuloperitonitis can be
visualized by ultrasonography 8 (Fig. 6.5).
The amplitude of reticular contractions
is reduced, the reticulum is displaced
from the ventral body wall, and the
abscesses have hypoechogenic centers
and echogenic capsules.

Peritoneal effusion is visible as an
accumulation of fluid without an echogenic
margin and restricted to the reticular area.
Depending on the fibrin and cell content,
the fluid may be anechoic or hypo-
echogenic. Fibrinous deposits are easily
identified in the fluid and bands of fibrin
are sometimes seen within the effusion.
Occasionally, the peritoneal effusion is
considerable and extends to the caudal
abdomen.

The spleen, particularly its distal
portion, is often affected. Fibrinous changes
are frequently seen as echogenic deposits
of varying thickness, often surrounded by
fluid, between the spleen and reticulum
or rumen. The spleen may be covered by
fibrinous deposits. Occasionally, one or
more splenic abscesses are visible, and
the vasculature may be dilated, indicating
splenitis. 20

Ultrasonography and radiography of
cattle with traumatic
reticuloperitonitis

These two techniques have been compared
in cows with traumatic reticuloperitonitis.
The major advantages of radiography are
that metallic foreign bodies can be
visualized and their position determined.
It has a specificity of 82%, a positive
predictive value of 88% and a sensitivity
of 71%. 24 Abnormal gas shadows or
gas-fluid interfaces observed on radio-
graphs are highly diagnostic for the
disease and have a specificity of 97% and
positive predictive value of 88%. How-
ever, they are seldom seen on radiographs
and their sensitivity is only 19%. The
position of the reticulum is a good
criterion for the diagnosis of traumatic
reticuloperitonitis, with a specificity of
80% and a positive predictive value of
82%. Thick-walled changes or abscessation
should be suspected when the reticulum
is displaced caudodorsally from the
sternum. Changes in the contour of the
reticulum such as indentations are highly
suggestive of inflammation, with a speci-
ficity of 95% and positive predictive value
but a low sensitivity of only 34%.

The major advantage of ultra-
sonography is being able to visualize and
assess reticular motility! 9,22,24 Even in
the presence of severe adhesions and
abscessation, the reticulum may maintain
its basic contractile rhythm, but much
reduced. Abscesses have an echogenic
capsule of varying width and a central
cavity filled with hypoechogenic material.
Purely fibrous deposits are echogenic, and

fibrinous deposits containing an accu-
mulation of fluid from inflammatory
processes are echogenic interspersed with
hypoechogenic accumulations of fluid
(Fig. 6. 6). 24 Radiography and ultra-
sonography complement each other and
the combined results can be used to
decide whether an exploratory laparotomy
is indicated, if the animal should be
treated conservatively with antibiotics, or
if it should be slaughtered for salvage. 22

NECROPSY FINDINGS

Localized traumatic reticuloperitonitis is
characterized by varying degrees of locally
extensive fibrinous adhesions between
the cranioventral aspects of the reticulum
and the ventral abdominal wall and the
diaphragm. Adhesions and multiple
abscesses may extend to either side of the
reticulum involving the spleen, omasum,
liver, abomasum and ventral aspects of
the rumen. Large quantities of turbid,
foul-smelling peritoneal fluid may be
present, containing fibrinous clots. Some
cases of reticular abscesses are solitary
and there are adhesions between the
reticulum, diaphragm and ventral body
wall, which are strictly localized. The size of
the abscess varies. It may be from 5-10 cm
in diameter or else a single one may be
irregularly shaped and measure 30 x 10 x
10 cm, along with multiple smaller ones
measuring around 3x3x3 cm. 24 The
foreign body can usually be found
perforating the cranioventral aspect of the
reticulum, although it may have fallen
back into the reticulum, leaving only the
perforation site and its surrounding

Fig. 6.5 Ultrasonogram and schematic of a reticular abscess in a cow with
chronic traumatic reticuloperitonitis. The abscess is between the reticulum and
the ventral abdominal wall. The ultrasonogram was obtained from the sternal
region with a 5.0 MHz-linear transducer. 1 = Ventral abdominal wall;

2 = Abscess; 3 = Capsule of the abscess; 4 = Reticulum. Cr, Cranial; Cd, Caudal.
(Reproduced with kind permission of U. Braun.)

f • v • r

I V':- ■

■ -.Vvj.c

b :

f : : " A

Fig. 6.6 Ultrasonogram and
schematic of the reticulum in a cow
with chronic traumatic
reticuloperitonitis. The reticulum is
covered with fibrinous deposits. The
ultrasonogram was obtained from
the sternal region with a 5.0 MHz-
linear scanner. 1 = Lateral abdominal
wall; 2 = Fibrinous deposits;

3 = Anechoic fluid; 4 = Reticulum.

Cr, Cranial; Cd, Caudal. (Reproduced
with permission from U. Braun.)

inflammation as evidence of the site of
penetration. A reticular magnet with
many pieces of metallic foreign bodies
stuck to it may be present in the

DIFFERENTIAL DIAGNOSIS

Typical acute traumatic reticuloperitonitis is
characterized by a sudden onset of
complete anorexia, marked drop in milk
production, mild fever, ruminal atony, pain
on deep palpation of the ventral abdomen,
an elevated leukocyte count with a left
shift in the hemogram and a peritoneal
fluid sample that indicates inflammation.

However, the times at which cases of
traumatic reticuloperitonitis are seen varies
from day 1, when the syndrome is typical,
to day 3 or 4, by which time the acuteness
has subsided so much clinically that
confusion with other diseases is a
significant possibility. The sudden onset of
anorexia and marked drop in milk
production will usually be noted in
lactating dairy cattle but not in dry dairy
cattle or beef cattle, including mature bulls
whose feed intake and behaviors are not
monitored daily. In these animals the
clinical findings can change in a few days
and be characterized by anorexia to
inappetence, normal temperature, ruminal
hypotonicity or atony and no evidence of
abdominal pain on deep palpation of the
abdomen.

The clinician must review the history
carefully, conduct a thorough clinical
examination and attempt to intensify the
diagnostic efforts on those abnormalities
that are present.

The differential diagnosis of
gastrointestinal dysfunction of cattle is
summarized in Table 6.2. An algorithm for
the causes of grunting in cattle is shown in
Fig. 6.7.

Acute local traumatic
reticuloperitonitis

Acute local traumatic reticuloperitonitis
must be differentiated from those diseases
in which sudden anorexia, sudden drop in
milk production, ruminal atony, abdominal
pain and abnormal feces are common.

They include the following:

• Simple indigestion characterized by
sudden anorexia or inappetence, normal
mental state, full rumen but atonic,
perhaps uncomfortable if ingested large
quantities of palatable feed like fresh
silage, normal vital signs, abnormal
feces and spontaneous recovery in
24 hours are typical

• Obstruction of reticulo-omasal ^
orifice with a foreign body such as a
roll of polyethylene twine causes
intermittent inappetence, a slightly
enlarged rumen with normal motility,
slight reduction in the amount of feces,
a decrease in milk yield for 24-48 hours
followed by a return to normal and
then subsequent relapses. A grunt is not
present, the temperature, heart and
respiratory rates are normal and the
hemogram is normal. Obstruction of the
reticulo-omasal orifice with foreign
bodies such as rope can cause
distension and hypermotility of the
rumen and persistent vomiting. 23 A
rumenotomy must be done to make the
diagnosis

• Acute carbohydrate engorgement

characterized by sudden anorexia,
diarrhea and dehydration, weakness,
tachycardia, staggering, ruminal
distension and atony, fluid-splashing
sounds in the rumen with a rumen pH
of less than 5 and a history of access to
grain

• Acute intestinal obstruction

characterized by sudden anorexia, mild
abdominal pain perhaps with kicking at
the abdomen and stretching, ruminal
atony, mild dehydration, scant feces or
complete absence of feces, straining on
rectal examination, dark blood-stained
feces and perhaps distended loops of
intestine palpable on rectal examination

• Abomasal volvulus (following right-
side dilatation) characterized by
anorexia, dehydration, tachycardia,
distended right abdomen, ping audible
over right flank, distended viscus
palpable on rectal examination. Usually
in lactating dairy cows a few weeks
after parturition and following the
clinical findings of right-side dilatation
of the abomasum that lasts several days
culminating in the volvulus but may
occur spontaneously in some cows with
no immediate history of previous illness

• Pericarditis. Continued high fever,
toxemia, anorexia, tachycardia and
muffled heart sounds suggest
pericarditis, which is marked by
markedly elevated total leukocyte and
neutrophil counts. In pericarditis, the
heart sounds are muffled and the typical
to and fro fluid-splashing sounds are
audible. The jugular veins are engorged
and other signs of congestive heart
failure such as anasarca are present.
Pericardiocentesis to obtain foul-
smelling, turbid fluid is diagnostic

• Acute pleuritis is characterized by a
fever, toxemia, anorexia, painful
respirations that may be accompanied
by a grunt, pain on digital palpation of
intercostal spaces, ruminal atony, and
abnormal and muffled lung sounds.

Fluid on thoracentesis

• Perforated abomasal ulcer causes
acute local peritonitis characterized by
marked pain on palpation over a much
larger area of the abdominal wall and in
the early stages is most marked on the
right-hand side. If, as is usual, the
peritonitis becomes diffuse the
syndrome cannot be distinguished

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

clinically from that caused by traumatic
reticuloperitonitis. Extension from a
metritis to involve the peritoneum is
suggested by other signs of the primary
disease

• Postpartum septic metritis occurs a
few days after parturition and is
characterized by anorexia, fever,
tachycardia, ruminal hypotonicity to
atony, reduced amount of feces and
foul-smelling vaginal discharge, and
retained placenta may be present. Very
important to examine the uterus
vaginally for the presence of the
placenta, which may be protruding
through the cervix

• Acute local peritonitis due to
penetration of the uterine wall by a
catheter or of the rectal wall by a
foreign body thrust sadistically into the
rectum may be difficult to differentiate
unless the painful area of the
peritoneum can be determined. Acute
local peritonitis can be differentiated
from indigestion, acute ruminal
impaction and acetonemia by the
presence of fever, local abdominal pain
and the abrupt fall in milk yield and
appetite

• Pyelonephritis is occasionally
accompanied by mild abdominal pain
but can be distinguished by the
presence of pus and blood in the urine

• Acute hepatitis or severe hepatic
abscess is characterized by anorexia,
fever, decreased ruminal movements,
reluctance to move, a painful grunt on
deep palpation over the cranial aspects
of the right lower flank, icterus if
obstruction of the bile ducts has
occurred, and a poor response to
therapy. A marked neutrophilia is typical
of hepatic abscessation secondary to
traumatic reticuloperitonitis

• Acetonemia. Traumatic
reticuloperitonitis usually causes a
secondary acetonemia when it occurs
during early lactation and the presence
of ketonuria should not be used as the
sole basis for differentiation of the
diseases. Differentiation may be
extremely difficult if the peritonitis is of
3-4 days' duration. Response to
treatment may also serve as a guide.

The history is often helpful; the appetite
and milk yield fall abruptly in traumatic
reticuloperitonitis but slowly over a
period of several days and not to the
same degree in acetonemia

Acute diffuse or generalized
peritonitis

Acute diffuse peritonitis is characterized
by anorexia, fever, toxemia, tachycardia,
dehydration, weakness leading to
recumbency, distended abdomen, ruminal
atony, spontaneous grunting or a grunt on
deep palpation over the abdomen, fluid-
splashing sounds and pings on auscultation
and percussion or ballottement of the
abdomen due to ileus, scant feces, perhaps
palpable fibrinous adhesions on rectal
palpation, profuse quantities of abnormal
peritoneal fluid and marked changes in
the hemogram. It must be differentiated
from those diseases causing severe
toxemia or

acid-base imbalance, dehydration and
shock, which include: carbohydrate
engorgement, acute intestinal obstruction,
advanced vagus indigestion, abomasal
volvulus, perforated abomasal ulcer and
miscellaneous causes of generalized
peritonitis.

Chronic reticuloperitonitis

The clinical findings of chronic traumatic
reticuloperitonitis are not typical. Each
chronic case may have a different
combination of clinical findings, which
makes the diagnosis uncertain. The clinical
findings that may be present include
inappetence to anorexia, mild fever, loss of
body condition, lack of rumination, ruminal
hypotonicity to atony, moderate bloat,
scant feces containing increased amounts
of undigested feed particles, possibly a
grunt on deep palpation of abdomen, and
changes in the hemogram. The presence of
abnormal peritoneal fluid is highly
supportive. It must be differentiated from
early stages of vagus indigestion, hepatic
abscessation, traumatic splenitis, chronic
pneumonia and pleuritis, and
miscellaneous causes of chronic peritonitis
such as peritoneal abscesses secondary to
intraperitoneal injections.

TREATMENT

Two methods of treatment are in general
use: conservative treatment with or with-
out the use of a magnet, and rumenotomy.
Both have advantages and each case must
be considered when deciding on the form
of treatment to be used.

Conservative medical therapy

Conservative treatment comprises immo-
bilization of the animal, administration of
antimicrobials for the inflammation and
the oral administration of a magnet to
immobilize the foreign body. The cow
is tied, stanchioned or confined in a box
stall for several days. Immobilization of
the animal facilitates the formation of
adhesions.

Antimicrobials

Penicillin or broad-spectrum anti-
microbials given parenterally daily for
3-5 days are widely used with empirical
success. Because of the high probability
that a mixed gastrointestinal flora is the
cause of the lesion it is more rational to use
a broad-spectrum antimicrobial such as the
tetracyclines or trimethoprim-potentiated
sulfonamides rather than penicillin, which
is commonly used because of cost and a
short withdrawal period in the event that
the animal does not respond favorably in a
few days. For lactating dairy cattle, those
antimicrobials with a short milk withdrawal
period are desirable. However, there are no
published clinical trials to indicate the
preferential value of any particular
antimicrobial. The general effect appears
to be good and a high rate of recovery is
recorded with antimicrobials parenterally

combined with immobilization provided
treatment is begun in the early stages of
the disease. Cows past their sixth month
of pregnancy are unlikely to recover
completely and commonly relapse.

Rumenotomy

Surgical removal of the foreign body
through a rumenotomy incision is widely
used as a primary treatment. It has the
advantage of being both a diagnostic
procedure in the first instance and a
satisfactory treatment. The recovery rate
varies, depending on when the surgery is
done relative to the time of initial
penetration, but is approximately the
same as that obtained with the con-
servative treatment described above. In
both instances 80-90% of animals recover
compared with about 60% in untreated
animals. Failure to improve is usually due
to involvement of other organs or to the
development of locally extensive peritonitis
and reticular abscesses associated with
persistent penetration of the foreign body
or, uncommonly, generalized peritonitis.

Based on follow-up ultrasonography
of cows that had surgery for traumatic
reticuloperitonitis, the inflammatory
adhesions resolved and disappeared in
the majority of animals by 6 months. 6 As
a consequence, reticular function nor-
malizes. In animals with severe adhesions,
there is a marked disturbance of digesta
passage and, in these animals, extensive
abscesses are present.

Persistent penetration by the foreign
body necessitates removal for optimum
results but a rumenotomy is necessary to
determine the extent of the lesion. Radi-
ography and ultrasonography as described
above may assist in determining the
presence and location of the foreign body.
A single preoperative dose of anti-
microbial such as potassium penicillin G
at 10 million IU given intravenously is
recommended to avoid complications
after a rumenotomy in cattle.

The recovery rate after surgery is likely
to be much lower if only complicated
cases are selected for rumenotomy and
conservative treatment is given to the
early mild cases. In one series the recovery
rate in the cases treated conservatively
was 84% and in those difficult cases
treated surgically it was 47%.

Drainage of reticular abscesses

Reticular abscesses may be drained
through an ultrasound-guided trans-
cutaneous incision. 8

Choice of treatment

The choice of treatment is largely
governed by economics and the facilities
and time available for surgery. A
rumenotomy, satisfactorily performed, is
the best treatment but is unnecessary in
many cases because of the tendency of

Diseases of the rumen, reticulum and omasum

345

Fig. 6.7 Causes of grunting in cattle.

the foreign body to return to the
reticulum. A commonly used practice is to
treat the animal conservatively for 3 days
and if marked improvement has not
occurred by that time to consider a
rumenotomy. A rumenotomy is highly
desirable in cows in the last 3 months of
pregnancy if severe sequelae are to be
avoided. Movement of the cow during the
early stages of the disease is undesirable
because of the risk of disrupting the ;
adhesions that localize the infection.

Cases of chronic traumatic reticulo- !
peritonitis are best treated by rumenotomy j
because of the probability that the foreign j
body is still embedded in the wall. Acute
diffuse peritonitis is highly fatal but if
detected early daily treatment with
broad-spectrum antimicrobials may be
effective.

PREVENTION

All processed feed should be passed over
magnets to remove metallic material
before being fed to cattle. The use of syn-
thetic string instead of wire has resulted
in a major decrease in the incidence of the
disease.

Reticular magnets

Small cylindrical or bar magnets, 7.5 cm
long by 1. 0-2.5 cm diameter with rounded i
ends, are used to prevent the disease but I
are also used in acute cases to minimize ;
penetration of the foreign body. When j
given orally to normal healthy animals j
the magnets locate in the reticulum j
within a few days, where they remain
indefinitely and maintain their magnetic
pull. The magnets attract foreign bodies,
which then do not penetrate the reticular
wall as easily as when they are free. The

extensive prophylactic use of these
magnets in a dairy herd has reduced
the incidence of the disease and its
complications by 90-98%. The magnets
are given to herd replacement heifers at
18 months to 2 years of age as part of a
herd health program.

The effects of magnets in traumatic
reticulitis was examined in the Danish
study of cows at slaughter (see under j
Etiology). 3 Two magnets tested were i
cylindrical cage magnets with different j
fields of magnetic force. Magnet I had a j
magnetic force of attraction of 110 mT; j
magnet II had a force of 210 mT. Magnets |
were found in only 7% of the cows. There j
were no lesions in 97% of the cows j
j with magnets. Magnet II was superior to I
■ magnet I in attracting all types of foreign j
' bodies, including tire wires. Thus the j
i prophylactic use of magnets should be ;
j promoted to reduce the occurrence of
I foreign body lesions. 3

It is unlikely that magnets will extract a :
1 firmly embedded foreign body from the \
\ wall of the reticulum but loosely j
embedded ones with long free ends may I
be returned to the reticulum and loose
foreign bodies will be immobilized. The
position of the foreign body within
the reticulum greatly influences the ;
efficacy of treatment with a magnet. A ;
foreign body at an angle to the ventral I
aspect of the reticulum of more than 30° j
is less likely to become attached to a i
magnet than a foreign body situated '
horizontally on the ventral aspect of the I
reticulum. 25 There have been only a j
few reports of physical injury to the wall ;
of the reticulum being caused by the j
magnets or the foreign bodies that may ;
be attached to them. A compass can be I

used to locate the presence and position

of the magnet.

REVIEW LITERATURE

Braun U. Atlas und Lehrbuch der Ultraschall-
diagnostik beim Rind. Berlin: Blackwell

Wissenschafts-Verlag, 1997.

Braun U. Ultrasonography in gastrointestinal disease
in cattle. Vet J 2003; 166:112-124.

Braun U. Ultrasound as a decision-making tool in
abdominal surgery in cows. Vet Clin North Am
Food Anim Pract2005; 21:33-53.

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23. Braun U.Vet Rec 2002; 150:580.

24. Braun U et al. Vet Rec 1994; 135:470.

25. Braun U et al. Am J Vet Res 2003; 64:115.

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

VAGUS INDIGESTION

Etiology Reticular adhesions from
traumatic reticuloperitonitis and failure of
passage of ingesta from reticulorumen and
abomasum resulting in accumulation in
forestomach and abomasum. Abomasal
emptying defect in sheep (uncertain
etiology)

Epidemiology Primarily mature dairy
cattle; also in mature beef cows and bulls.
Also occurs in sheep as abomasal emptying
defect of uncertain etiology
Signs Gradual distension of abdomen,
especially left upper abdomen and bilateral
aspects of ventral abdomen. Inappetence
to anorexia and scant feces containing
undigested long particles. Large L-shaped
rumen viewed from rear. Rumen
hypermotility or atony. Dehydration
Clinical pathology Hemoconcentration,
metabolic alkalosis with hypochloremia and
hypokalemia, increased ruminal chloride
levels

Lesions Reticular adhesions. Enlarged
rumen containing pasty and frothy material
or fluid contents. Abomasum impacted
with semi-dry ingesta
Differential diagnosis Ruminal
distension with hypermotility, indigestion
of late pregnancy, obstruction of the
reticulo-omasal orifice. Ruminal distension
with atony: chronic traumatic
reticuloperitonitis. Abomasal impaction :
abomasal impaction, dietary in origin.
Omasa I impaction : phytobezoars blocking
the abomasal pylorus, abomasal ulceration
without melena

Treatment Fluid and electrolyte therapy,
rumen lavage, rumenotomy, drain reticular
abscess, slaughter for salvage
Control Prevent traumatic
reticuloperitonitis

ETIOLOGY

The etiology has been controversial but
has been divided into two major sub-
categories of complications of traumatic
reticuloperitonitis: vagal nerve injury and
reticular adhesions. In addition there are
some other causes.

Complications of traumatic
reticuloperitonitis

Vagal nerve injury and dysfunction
Historically, it was thought that vagus
indigestion was caused by vagal nerve
dysfunction due to vagal nerve injury
associated with complications of traumatic
reticuloperitonitis. It was hypothesized
that the inflammatory and scar tissue
lesions affected vagal nerve fibers supply-
ing the forestomach and abomasum. The
naturally occurring syndrome was similar
to the Hoflund syndrome created by
experimentally sectioning the vagus nerves
and thus the term 'vagus indigestion' was
coined.

The prevailing explanation was that
dorsal vagal nerve injury resulted in
achalasia of the reticulo-omasal orifice
(anterior stenosis) and inhibited the
passage of ingesta from the reticulo-
rumen into the omasum and abomasum,
resulting in an enlarged rumen with
abnormal rumen contents. Similarly,
injury of the pyloric branch of the ventral
vagus nerve resulted in achalasia of the
pylorus (posterior stenosis) and inhibited
the flow of ingesta from the abomasum
resulting in abomasal impaction. Both
abnormalities resulted in scant feces
containing undigested long feed particles.

However, while in many cases of vagus
indigestion there are extensive adhesions
between the reticulum and adjacent
organs, there is little evidence of vagal
nerve injury. It is also known that the
syndrome can occur without any gross
evidence of inflammation of the serosa of
the forestomach and abomasum over
which the vagus nerves are located. In the
absence of gross lesions, it has been
suggested that microscopic lesions of the
medial reticular wall where vagal tension
receptors are located may interfere with
forestomach motility and esophageal
groove reflexes.

New information based on clinical-
pathological examination of clinical cases
has questioned the long-held view that
vagal nerve injury is an important cause of
this syndrome.

Reticular adhesions

Mechanical impairment of reticular
motility and esophageal groove dys-
function as a result of reticular adhesions
is probably the most important cause of
the syndrome. 1 An examination of 42 dairy
cows with complications of traumatic
reticuloperitonitis found that the primary
mechanism was a disturbance in particle-
separation processes in the reticulo-
rumen attributable to mechanical
inhibition of reticular motility associ-
ated with extensive inflammatory para-
reticular adhesions . 1 Based on examin-
ation of necropsy tissue grossly and
j histologically, there was no evidence of
j vagal nerve injury. Perireticular abscesses
! near the reticulo-omasal orifice of cattle
i can cause the disease. 2

Other causes

Several causes unrelated to traumatic
reticuloperitonitis have been recorded.
Actinobacillosis of the rumen and reti-
culum is a less common cause. In sheep,
peritonitis associated with Sarcosporidia
and Cysticercus tenuicollis maybe a cause.
Fibropapillomas of the cardia can
mechanically occlude the distal esophagus
and cause interference with forestomach
motility. 3 Abomasal impaction in sheep
has been recorded but the etiology and

pathogenesis have not been determined.
Disturbances similar to those that occur
under natural conditions have been
produced by sectioning the vagus nerve.
Following surgery for right-sided abo-
masal displacement or volvulus, some
cattle develop a vagus-indigestion-like
syndrome characterized by anorexia, scant
feces, ruminal distension and abdominal
distension. It has been suggested
that distension of the abomasum and
thrombosis of its vessels may have caused
injury to the ventral vagus nerve. 4

Pyloric achalasia is described as part
of a secondary indigestion due to
septicemia and toxemia but this is not
well documented. There is also ruminal
distension with fluid material, abomasal
reflux into the reticulorumen, dehydration,
hypochloremia, hypokalemic metabolic
alkalosis and uremia.

Indigestion of late pregnancy of
cows is considered a type of vagus
indigestion in which the rumen and
abomasum are grossly distended, but the
cause is uncertain. 5 There is no evidence
that the effects of an advanced pregnancy
alone will cause a vagus-indigestion-like
syndrome.

Peripheral nerve sheath tumors, such
as a solitary schwannoma have been
described causing a syndrome similar to
vagus indigestion in a mature cow. 6

A vagal indigestion-like syndrome
may be a postsurgical complication of
] right abomasal displacement . 7 Gastric
wall injury, peritonitis and vagal nerve
lesions may be causative factors. It occurs
in 14-21% of cases, and only 12-20% of
cases return to normal production. (See
under Right-side displacement of the
abomasum and abomasal volvulus.)

EPIDEMIOLOGY

The syndrome occurs most commonly in
dairy cows that have a history of
traumatic reticuloperitonitis, which may
have occurred several weeks or a few
months previously. The disease is not
restricted to dairy cows - it also occurs in
beef cattle and in mature bulls.

PATHOGENESIS

The syndrome of vagus indigestion is
characterized by disturbances in the
passage of ingesta through the reticulo-
omasal orifice (failure of omasal trans-
; port, anterior functional stenosis) and
disturbances in the passage of ingesta
through the pylorus (pyloric stenosis,
posterior functional stenosis). Stenosis
is a misnomer because there is no
evidence of stenosis but achalasia of the
sphincters may occur. The characteristic
clinical findings are distension of the
rumen with pasty and/or frothy contents
because of increased time and maceration
-in the reticulorumen, alterations in

Diseases ot the rumen, reticulum and omasum

347

reticulorumen motility, with consequences
such as dehydration, an increase in
undigested particles in the feces, scant
feces, acid-base imbalance and secondary
starvation. It is an outflow abnormality
of the reticulorumen and abomasum.

Based on careful clinicopathological
observations of 42 cows with complications
of traumatic reticuloperitonitis including
'vagus indigestion', it is now proposed that
the disturbances in the flow of ingesta are
associated with particle-separation in the
reticulorumen caused by mechanical
inhibition of reticular motility associated
with extensive adhesions of the reticulum. 1
Experimentally impaired reticular contrac-
tions in sheep support the central role of
reticular motility for the separation of
particles in the forestomach, the outflow of
digesta from the reticulorumen and
transpyloric digesta flow. 8

Normally, reticulorumen motility results
in stratification of ruminal contents
into three layers of ingesta in addition
to the most dorsal gas pocket. The top
layer, consisting of firm fibrous material
of low-density particles (coarse hay),
floats on the middle layer of liquid
ingesta, consisting of particles of medium
density; the bottom layer consists of fine
particles of high density. The solid
material remains in the rumen and is
digested until the particle size is suffi-
ciently small (1-4 mm in cattle) to pass
through the reticulo-omasal orifice. The
size of the digested plant fragments in
ruminant feces can be considered an
indirect measurement of forestomach
function. In cows, the presence of large
plant particles (> 0.5 cm) in the feces
indicates inadequate rumination or
abnormalities in forestomach motility. 9

In normal cattle, the mean retention
time of particles in the reticulorumen
depends on particle size and density. The
density of large feed particles is low
because of their air-filled interior. During
biphasic reticular contractions, most of
these large, light particles are pushed
caudodorsally in the rumen. Thus, large
particles are retained in the reticulo-
rumen, because outflow through the
reticulo-omasal orifice occurs mainly
during the maximum portion of the
second reticular contraction. Feed particles
with a high density (small and well
digested) are moved out of the reticulo-
rumen preferentially, because the majority
of them remain in the reticulum during
the biphasic contraction.

If reticular motility is inhibited, the
balance of particle retention time and
particle outflow in the reticulorumen is
disturbed. Immobilization of the reticulum
experimentally causes a decrease in feed
intake, an increase in ruminal volume, a
decrease of mean retention time of light

plastic particles, a four-fold increase in
mean retention time of heavy plastic
particles, a marked increase in the amount
of large particles in the feces, and an
increase in abomasal volume. Such
changes reflect the changes occurring in
naturally occurring vagus indigestion. An
increase in the amount of large particles
in the feces of cows with traumatic
reticuloperitonitis is indicative of inhibited
clearance function of the reticulum.

Liquid consistency of the abomasal
contents is important to insure physio-
logical transpyloric flow. In cows with
uncomplicated traumatic reticuloperitonitis,
the process of particle separation in the
reticulorumen is disturbed, which results
in an increase in the amount of large
particles in the feces. In uncomplicated
traumatic reticuloperitonitis, the reticulo-
rumen is not large and the abomasum is
not impacted because the fluid outflow is
probably adequate to flush even large
particles out of the abomasum.

In cows with pyloric stenosis and an
increase in the size of the abomasum, the
rumen contents are homogeneous and
pasty and not stratified. Thus, consistency
of rumen outflow contents changes
markedly. Normally, transpyloric digesta
flow depends predominantly on hydro-
dynamic factors, especially viscosity. Even
small increases in viscosity of abomasal
contents may cause a marked decrease in
abomasal outflow.

Disturbances of the passage of digesta
in cows with traumatic reticuloperitonitis
develop in three phases.

° In the first phase, reticulorumen
motility is decreased because of
immobilization of the reticulum
caused by the inflammation, pain and
fever. Immobilization of the reticulum
impairs clearance function of the
reticulum, resulting in poorly
comminuted feces

° The second phase occurs when the
adhesions are extensive enough to
cause additional impairment of
reticular motility. Particle distribution
within the reticulorumen is changed,
resulting in a loss of stratification.
Although feed intake decreases, the
volume of the reticulorumen increases
because rumen outflow is decreased.
During the second phase,
comparatively small amounts of
rumen outflow contents can exit the
abomasum, because the dry-matter
content of the material is similar to
that of a clinically normal cow. During
this phase, the rumen may become
hypermotile because of excitation of
low-threshold tension receptors as a
consequence of moderate rumen
distension

r The third phase is characterized by a
further change in the consistency of
rumen contents, resulting in a
homogeneous pasty mass of relatively
high viscosity. The increase in dry-
matter content of the rumen outflow
material inhibits transpyloric digesta
flow. The abomasum enlarges, and
reflux of abomasal contents may
occur. It is suggested that the primary
underlying process of reflux of
abomasal contents in cows with
posterior stenosis is a disturbance of
ruminal outflow. 1

In summary, the current hypothesis for
the pathogenesis indicates that disturb-
ances of the passage of ingesta consists of
two phases of the same syndrome. Pyloric
stenosis represents the phase with the
most severe clinical consequences. The
prognosis is poorer for cows with anterior
stenosis than for those with uncomplicated
traumatic reticuloperitonitis and is poorer
for cows with posterior stenosis than for
those with anterior stenosis. Only a small
percentage of cows with traumatic
reticuloperitonitis develop disturbances
of digesta passage through the reticulo-
omasal orifice and not all cows with
anterior stenosis develop posterior
stenosis. The extent and location may
determine the course of the syndrome
and how rapidly it develops. In cows with
acute traumatic reticuloperitonitis the
consistency of the adhesions changes
from a widespread fibrous type to a
stringy type after several months, and
with time the reticulum may regain
sufficient motility to provide its clearance
function.

Anterior functional stenosis
(achalasia)

This is characterized by accumulation of
ingesta in the reticulorumen, known also
as failure of omasal transport. If the
ruminal wall is atonic the ingesta
accumulates without bloat occurring; if it
has normal motility the ruminal wall
responds to the distension by increased
motility and the production of frothy
bloat. Ruminal motility will be almost
continuous (3-6/min) but the contrac-
tions are ineffective in propelling the
ingesta into the omasum. As a result the
rumen enlarges to fill the majority of the
abdomen, which accounts for the gross
distension of the abdomen. The dorsal sac
of the rumen enlarges to the right of the
midline, and the ventral sac enlarges to fill
most or all of the right lower quadrant of
the abdomen; this results in the'L-shaped'
rumen as viewed from the rear of the
animal. The continuous rumen contrac-
tions also result in frothy rumen contents,
which can be fatal if progressive and not
relieved. Occasionally there is free gas

PART TCiENEKAL medicine ■ cnapter a: Diseases onne anmemary xracx - n

bloat. Bradycardia occurs commonly and
has been attributed to increased vagal
tone of the injured nerve, causing para-
sympathetic slowing of the heart, but this
has not been documented.

Obstruction of the reticulo-omasal
orifice by foreign bodies such as poly-
ethylene twine ingested by the animal
may cause a syndrome indistinguishable
from anterior functional stenosis. 10

Posterior functional stenosis
(achalasia)

This is characterized by failure of trans-
pyloric outflow resulting in abomasal
impaction with large particles. Abomasal
fluid containing hydrochloric acid may
reflux into the rumen if the fluid does not
move from the abomasum into the small
intestines. 11 This is known as the abomasal
reflux syndrome. The chloride concen-
trations in the rumen fluid increase and
there is a hypochloremia and hypokalemia.
Bile acids may also reflux from the
duodenum into the rumen of animals with
an ileus of the small intestine. 12 Associated
with pyloric achalasia there is in some cases
an apparent failure of the esophageal
groove to permit the passage of ingesta
into the rumen, this organ containing only
fluid. The syndrome observed depends on
the stage of the disease at which the animal
is first examined.

Metabolic alkalosis, abomasal reflux

Depending on the location and severity of
the functional obstruction and distension
or impaction, there will be varying
degrees of dehydration and a tendency
towards a metabolic hypochloremic,
hypokalemic alkalosis. In pyloric
stenosis with abomasal impaction there is
sequestration of abomasal fluid in the
abomasum and a reflux of abomasal
contents into the rumen, resulting in a
ruminal chloride concentration of more
than 20 mmol/L. In anterior stenosis, the
abomasal fluid can pass into the duo-
denum and neither metabolic alkalosis
nor dehydration can be expected.

Postsurgical complication in right-
side displacement of the abomasum
or abomasal volvulus

A vagus-indigestion-like syndrome may
occur in cattle treated for right-side dis-
placement of the abomasum or abomasal
volvulus. 7 Possible mechanisms include
vagus nerve injury, overstretching of the
abomasal wall during prolonged dis-
tension resulting in neuromuscular junction
alterations and autonomic motility
modification, thrombosis and abomasal
wall necrosis, and peritonitis.

Abomasal impaction in sheep

Abomasal emptying defects associated
with dilatation and impaction of the
abomasum in Suffolk sheep have been

reported. 13,14 The electrolyte imbalances
that occur in cattle with abomasal impac-
tion do not occur in sheep.

CLINICAL FINDINGS

Three similar but separate clinical syn-
dromes have been recognized, with some
clinical findings characteristic of all three,
including:

0 Inappetence for several days or

complete anorexia with evidence of
loss of body weight
» An enlarged 'papple'-shaped

abdomen (pear-shaped on the right
and apple-shaped on the left) with or
without bloat. The upper left
abdomen is distended and the lower
half of the abdomen is distended
bilaterally

° Dehydration and electrolyte
imbalance with metabolic alkalosis
® Enlarged rumen palpable on rectal
examination

= Scant feces with an increase in
undigested particles

“ Enlarged ingesta-impacted or fluid-
distended abomasum palpable
through right flank or on rectal
examination (except cannot be easily
palpated in advanced pregnancy)

Vital signs within the normal range
- Inadequate response to treatment.

Ruminal distension with
j hypermotility

I The occurrence of this type is not parti-
| cularly related to pregnancy or parturition.

: Moderate to severe bloat is common. There
; is evidence of loss of body weight. The
■ animal has usually been inappetent or
anorexic intermittently for the past few
weeks. The abdomen is prominently
distended and the rumen movements
represented by the abdominal ripples are
often unusually prominent and may occur
at the rate of 4-6 per minute. The sounds
of the rumen contractions are often
reduced or almost absent in spite of
hyperactivity because the rumen contents
; are pasty and frothy. Initially, this contra-
diction is misleading because the hyper-
activity of the rumen tends to indicate
normal reticulorumen activity. Fluid-
splashing sounds may be audible on
ballottement of the left and right flanks if
the rumen is distended with excessive
quantities of fluid. The feces are scant and
pasty and contain undigested particles.The
temperature is usually normal and brady-
cardia (44-60 beats/min) may be present. A
systolic murmur that waxes and wanes
with respiration, being loudest at the peak
of inspiration, may be present because of
the ruminal distension and tympany
causing compression of the heart and
distortion of the valves. The murmur
disappears when the tympany is relieved.

Ruminal distension is obvious on
rectal examination. The dorsal sac of the

rumen is grossly distended to the right of
the midline and is pushed back against
the brim of the pelvis; the ventral sac is
also enlarged and occupies much of the
right lower quadrant of the abdomen.
This may be difficult to appreciate in
advanced pregnancy. Viewed from the
rear the enlarged rumen is L-shaped,
giving an external silhouette with the left
flank distended from top to bottom and
the right flank distended only in the lower
half - the 'papple'-shaped abdomen.

An important aspect of the clinical
history of 'vagus indigestion' cases is that
standard treatments for ruminal tympany
and impaction usually have no effect on
the course of the disease. If the acid-base
imbalances can be corrected and hydration
maintained and adequate nutritional
status maintained until parturition occurs
in these cows, the prognosis is favorable
and the recovery rate is high.

Ruminal distension with atony

This type occurs most commonly in late
pregnancy and may persist after calving.
The cow is clinically normal in all respects
except that she is anorexic, passes only
scant amounts of soft pasty feces, has a
distended abdomen and will not respond
to treatment with purgatives, lubricants or
parasympathetic stimulants. Ruminal
movements are seriously reduced or
absent and there may be persistent mild
bloat. Fluid-splashing sounds may also be
! audible on ballottement of the left and
j right flanks if the rumen is distended with
| excessive quantities of fluid. The tempera-
i ture and heart rate are usually normal,
j There is no pain on deep palpation of the
| ventral abdomen. On rectal examination
j the primary abnormality is gross dis-
I tension of the rumen, which may almost
j block the pelvic inlet. The animal loses
\ weight rapidly, becoming weak and
j recumbent. At this stage the heart rate
i increases markedly. The animal dies
i slowly of inanition.

Pyloric obstruction and abomasal
; impaction

Most cases of abomasal impaction also
j occur late in pregnancy and are manifested
i by anorexia and a reduced volume of
1 pasty feces. There may be no abdominal
i distension and no systemic reaction until
' the late stages, when the heart rate rises
rapidly. The distended and impacted
abomasum may be palpable in the lower
■ right abdomen as a heavy, doughy viscus.

: On rectal examination the impacted
: abomasum may be palpable as a doughy
viscus that pits on pressure in the right
lower quadrant. If the animal is in
advanced pregnancy the impacted abo-
masum may not be palpable through the

abdominal wall or by rectal palpation but
the gravid uterus may feel as if it is
displaced into the pelvic cavity by the
enlarged abomasum. Rumen movements
are usually completely absent. As in the
first type, affected animals usually become
weak and recumbent and die slowly of
inanition and electrolyte and acid-base
imbalances. In some cases, the impacted
abomasum may rupture and cause death
in a few hours.

Combinations of these types may
occur; in particular, distension of the
rumen with atony combined with
abomasal impaction is the most commonly
observed syndrome.

Indigestion of late pregnancy in cattle
characterized by distension and hyper-
motility of the rumen with distension of the
abomasum has been described but is
probably not due to advanced pregnancy
alone. 5 In late pregnancy, the abomasum is
difficult to examine clinically either through
the abdominal wall or by rectal exam-
ination. The presence of fluid-splashing
sounds on ballottement and auscultation
over the right lower flank is indirect
evidence of distension of the abomasum
with fluid. The distended abomasum can
be palpated and evaluated by left or right
side laparotomy (celiotomy).

CLINICAL PATHOLOGY
Hemogram

In most cases there are no abnormalities
on hematological examination although a
moderate neutrophilia, a shift to the left
and a relative monocytosis may suggest
the presence of chronic traumatic
reticuloperitonitis. Hemoconcentration is
common, associated with the clinical
dehydration. Total plasma protein con-
centrations may be increased, similar to
traumatic reticuloperitonitis.

Peritoneal fluid

This may be indicative of a chronic
reticuloperitonitis.

Serum biochemistry

In abomasal impaction there is metabolic
hypochloremic, hypokalemic alkalosis.

Ruminal chloride concentrations

These are normally below 30 mmol/L and
increased in posterior stenosis to levels
above 40 mmol/L due to abomasal reflux. 1
Levels of 66 mmol/L have been recorded
in cows with indigestion of late pregnancy. 5

NECROPSY FINDINGS

The rumen is grossly enlarged and the
contents are pasty and may be frothy. The
contents may have undergone some
putrefaction. In some cases the rumen is
grossly distended with liquid rumen
contents containing floating large particles
of ingesta. The reticulum and omasum are
usually grossly enlarged and the reticulo-

omasal orifice is commonly dilated and
filled with rumen contents. The omasum
may be almost twice its normal size and is
firmer than normal. Sectioning of the
omasum reveals rumen contents impacted
between its leaves. The abomasum may
be up to twice its normal size and firm on
palpation. The abomasum is impacted
and grossly distended with semi-dry
partially digested ingesta that resembles
partially dried rumen contents. Erosions
and ulcers may be present in the pyloric
part of the abomasum.The intestines may
be relatively empty and the feces in the
large intestine are pasty, containing an
increased amount of undigested particles.

Lesions between the reticulum and
ventral abdominal floor and the diaphragm
vary considerably from thick fibrinous sup-
purative adhesions to multiple abscesses
containing a foreign body or non-
inflammatory fibrous bands and strings.

DIFFERENTIAL DIAGNOSIS

The salient clinical features of vagus
indigestion in cattle are inappetence for
several days leading to anorexia, a
gradually enlarging abdomen, especially on
the left side, scant feces, failure to respond
to common medical therapy, loss of body
condition and varying degrees of
dehydration. Obtaining an accurate history
is of paramount importance. Most cases of
vagus indigestion have been affected for at
least several days or a few weeks. The
diagnosis can be perplexing in those cases
that occur in late pregnancy because the
animal has usually been housed and fed
with other dry cows and daily observation
of feed intake and fecal output have not
been made, so it is difficult to obtain an
accurate and helpful history. The clinical
examination should focus on the state of
the rumen and the abomasum. In valuable
animals a left-side exploratory laparotomy
and rumenotomy will often be necessary in
order to make a diagnosis. This will allow
the determination of the presence of
reticular adhesions, obstructions of the
reticulo-omasal orifice and the state of the
abomasum.

The various forms of vagus indigestion
must be differentiated from diseases of the
forestomach and abomasum resulting in
distension and hypermotility or atony of the
rumen and enlargement of the abomasum.

• Ruminal distension with
hypermotility is typical of vagus
indigestion and, if accompanied by
anorexia, dehydration, scant and
abnormal feces, and a large L-shaped
rumen on rectal examination, it must be
differentiated from:

• Indigestion of late pregnancy,
characterized by anorexia, lethargy,
dehydration, grossly distended
papple-shaped abdomen, ruminal
distension with hypermotility,
abomasal distension with fluid,
elevated ruminal chloride levels and
hypochloremic, hypokalemic alkalosis

• Obstruction of the reticulo-omasal
orifice by ingested baling twine, "plastic
sleeves and bags may cause distension
of the rumen indistinguishable from
vagus indigestion . 10 The rumen is
moderately distended but its size will
vary daily and reticulorumen motility is
normal. The animal is bright and alert ,
but the feed intake, amount of feces
and milk production varies daily from
normal to subnormal for no obvious
reason. Rumenotomy is the only
method of making the diagnosis. The
ruminal foreign body will be floating in
the rumen or may be partially lodged
in the reticulo-omasal orifice

• Ruminal distension with atony must

be differentiated from diseases of the

forestomach and abomasum in which

there is failure of passage of ingesta.

These include:

• Chronic traumatic
reticuloperitonitis, which is
characterized by inappetence to
anorexia, a usually smaller than
normal rumen with atony - but in
some cases the rumen feels larger
that normal with free-gas bloat, loss
of body weight, persistent slight
fever, perhaps the presence of a
grunt, an absence of rumination,
scant feces with an increased amount
of undigested particles, and changes
in the hemogram indicating chronic
inflammation

• Abomasal impaction in vagus
indigestion, characterized by a
papple-shaped abdomen, perhaps
prominent enlargement of the right
lower abdomen, ruminal distension
with hypermotility or atony, the
presence of a palpable heavy viscus
in the right lower abdomen, scant
feces with long undigested particles
of ingesta, loss of body weight,
dehydration and hypochloremic,
hypokalemic alkalosis. The gravid
uterus is easily palpable on rectal
examination and the fetus may be
displaced into the pelvic cavity
because of the impacted and
enlarged abomasum. Ruminal
chloride levels are elevated

• Abomasal impaction dietary in
origin due to ingestion of straw or
sand occurs in cattle with unlimited
access to chopped straw during cold
weather or consuming tuber crops
contaminated with sand. The rumen is
grossly distended with coarse ruminal
ingesta or liquid contents and is
atonic. Ballottement of the rumen
elicits fluid-splashing sounds. The right
flank is distended and the impacted
abomasum can be palpated as a
heavy, firm viscus in the right lower
flank (except in late pregnancy when it
cannot be palpated). Hypochloremic,
hypokalemic alkalosis is present

• Omasa! impaction occurs
sporadically and commonly part of
the vagus indigestion syndrome but
its cause is uncertain. Anorexia,
ruminal distension and atony, scant
inadequately digested feces

• Phytobezoars blocking the
abomasal pylorus causes loss of body
weight, abomasal distension with
fluid-splashing sounds on
ballottement over the right lower
flank, ruminal distension and
hypotonicity, anorexia and
hypochloremic, hypokalemic
alkalosis. Right flank laparotomy and
abomasotomy is necessary to make
the diagnosis

• Abomasal ulceration without
melena is uncommon but occurs in
dairy cows with a history of chronic
inappetence and decreased milk
production. There is distension of the
abomasum with fluid-splashing
sounds on ballottement, ruminal
hypotonicity, inappetence and loss of
body weight, occult blood and
moderate dehydration. Diagnosis is
only made surgically or at necropsy

• Peripheral nerve sheath tumors of
the vagus nerve may cause a
syndrome similar to vagus
indigestion. Clinically, there is chronic
ruminal stasis and tympany,
persistently distended loops of
intestine palpable per rectum,
inappetence to anorexia and
progressive loss of body weight. The
diagnosis cannot be made clinically;
lesions are present on the vagus
nerve above the base of the heart

TREATMENT

The prognosis in most cases in
unfavorable but also unpredictable. The
problem is to determine the location and
extent of the lesion, which may be
difficult or impossible even on exploratory
laparotomy or rumenotomy.

Rumen lavage

If the rumen is grossly distended with
fluid or mushy rumen contents, it can be
emptied using a large-bore (25 mm inside
diameter) stomach tube followed by
flushing warm water into the rumen and
lavaging it by gravity flow. The contents
are usually well macerated and foul-
smelling. Emptying the rumen not only
relieves the pressure but allows for easier
examination of the abdomen.

Fluid and electrolyte therapy and
laxatives

Some cases respond beneficially follow-
ing fluid and balanced electrolyte therapy
for 3 days combined with the oral
administration of mineral oil (5-10 L)
daily for 3 days or dioctyl sodium sulfo-
succinate as described under the treat-
ment of abomasal impaction of dietary
origin. Other cases do not respond but
there is no reliable method of knowing
which ones will respond other than by
attempting treatment for a few days.
Valuable pregnant cows near parturition
may be maintained on fluid and electro-
lyte therapy for several days or until near

enough to term to Induce parturition and
hopefully obtain a live calf. Some cows will
recover following parturition but the
syndrome may recur in the next pregnancy.
The use of hypertonic saline solution, 1.8%,
is effective for the correction of experi-
mentally induced hypochloremic metabolic
alkalosis in sheep and could be of beneficial
value for use in cattle. 15

Rumenotomy

Rumenotomy and emptying of the rumen
is usually followed by slow recovery over
a period of 7-10 days when there is
ruminal hypermotility. The creation of a
permanent ruminal fistula to permit the
escape of gas in cases where gas retention
is a problem may cause dramatic improve-
ment. Surgical correction of abomasal
distension or impaction by abomasotomy
is usually unsatisfactory because the
motility of the abomasum does not
return. Surgical drainage of perireticular
abscesses into the reticulum or omasum
at the site of the lesion through a
rumenotomy incision has been successful
in prolonging survival of affected cattle
for at least 1 year. 2 Reticular abscesses
may be drained successfully by ultra-
sound-guided transcutaneous incision. 16
For some cases of vagus indigestion, the
most satisfactory procedure may be to
recommend slaughter for salvage. In
suspected cases of obstruction of the
reticulo-omasal orifice by rope or twine,
an exploratory rumenotomy is required to
remove the foreign object.

PREVENTION

This is dependent on preventing traumatic
reticuloperitonitis through management
of the environment and the adminis-
tration of reticular magnets.

REFERENCES

1. Rehage J et al. J Am Vet Med Assoc 1995;
207:1607.

2. Fubini SL et al. J Am Vet Med Assoc 1989;
194:811.

3. Gordon PJ. \£t Rec 1997; 140:69.

4. Rebhun WC et al. Compend Contin Educ Pract
Vet 1988; 10:387.

5. Vin Mere DC et al. J Am Vet Med Assoc 1995;
206:625.

6. Bradshaw J et al. Vet Rec 2003; 153:784.

7. SattlerN et al. Can Vet J 2000; 41:777.

8. Kaske M, Midasch A. Br J Nutr 1997; 78:97.

9. Constable PD et al. Compend Contin Educ Pract
Vet 1990; 12:1008, 1169.

10. Braun U. Vet Rec 2002; 150:580.

11. Braun U et al. Vet Rec 1990; 126:107.

12. Braun U et al. Vet Rec 1989; 124:373.

13. Kopcha M. J Am Vet Med Assoc 1988; 192:783.

14. Ruegg PL et al. J Am Vet Med Assoc 1988;
193:1534.

15. Fubini SL et al. Am J Vet Res 1991; 52:1898.

16. Braun U et al.Vet Rec 1998; 142:184.

DIAPHRAGMATIC HERNIA

Herniation of a portion of the reticulum
through a diaphragmatic rupture causes

chronic ruminal tympany, anorexia and
displacement of the heart.

ETIOLOGY

Most cases occur because of weakening of
the diaphragm by lesions of traumatic
reticuloperitonitis, but diaphragmatic
rupture can occur independently of a
foreign body and congenital defects of the
diaphragm may be a cause in some
animals. An unusually high incidence of
herniation of the reticulum through the
diaphragm, sometimes accompanied by
the abomasum, has been recorded in
buffalo in India.

PATHOGENESIS

The usual syndrome is similar to that of
vagus indigestion in which ruminal hyper-
motility is present. It seems probable that
there is either achalasia of the reticulo-
omasal sphincter due to involvement of
the vagus nerve or impairment of func-
tion of the esophageal groove caused by
the fixation of the reticulum to the ventral
diaphragm. The disturbance of function in
the forestomachs suggests that food can
get into the rumen but cannot pass from
there to the abomasum. The hypermotility
is thought to be due to overdistension of
the rumen and to be the cause of the
frothy bloat.

There is usually no interference with
respiration without major herniation but
displacement and compression of the
heart occur commonly.

CLINICAL FINDINGS

There is a capricious appetite and loss of
condition for several weeks before abdomi-
nal distension due to accumulation of
fluid and froth in the rumen, persistent
moderate tympany of the rumen, occurs.
Grinding of the teeth may occur and the
feces are pasty and reduced in volume.
Rumination does not occur but occasion-
ally animals regurgitate when a stomach
tube is passed.

The temperature is normal and brady-
cardia may be present (40-60/min).
Breathing is usually normal. A systolic
murmur may be present and the intensity
of the heart sounds may suggest displace-
ment of the heart, usually anteriorly or to
the left. Reticular sounds are audible just
posterior to the cardiac area in many
normal cows and they are not significantly
increased in diaphragmatic hernia.

A more severe syndrome is recorded in
cases where viscera other than a portion
of the reticulum is herniated. Peristaltic
sounds may be audible in the thorax and
there may be interference with respiration
and signs of pain with each reticular
contraction. Affected animals usually die
from inanition in 3-4 weeks after the
onset of bloat.

Diseases of the rumen, reticulum and omasum

351

CLINICAL PATHOLOGY

Laboratory examinations are of no value
in diagnosis. Radiological examination
after a barium meal has facilitated
diagnosis.

NECROPSY FINDINGS

The majority of cases are complications of
traumatic reticuloperitonitis and a fistulous
tract is often found in the vicinity of the
diaphragmatic rupture which is usually
15-20 cm in diameter. A portion of the
reticulum protrudes into the right pleural
cavity to form a spherical distension usually
20-30 cm in diameter, but more extensive in
some cases. The reticulum is very tightly
adherent to the hernial ring which is
thickened by fibrous tissue. The omasum
and abomasum are relatively empty but the
rumen is overfilled with frothy, porridge-
like material which contains very little fiber.
Less common cases are those in which part
of the reticulum, the omasum and part of
the abomasum are herniated.

DIFFERENTIAL DIAGNOSIS-

• Other causes of chronic bloat must be
considered in the differential diagnosis,
especially vagus indigestion with
hypermotility, which is also often
accompanied by a systolic murmur. The
two can only be differentiated by
rumenotomy but there is the hazard that
cases of diaphragmatic hernia are not
relieved by the operation and tympany
returns rapidly, sometimes necessitating a
permanent ruminal fistula

• Passage of a stomach tube is usually
necessary to determine whether or not a
physical obstruction is present in the
esophagus. Regurgitation is likely to occur
in cases of diaphragmatic hernia and this
occasionally causes blockage of the
esophagus with ingesta, simulating choke

• Causes of diaphragmatic hernia other
than traumatic reticuloperitonitis include
violent trauma to the abdomen and
straining at parturition. In both
instances there is probably a primary
weakness of the diaphragm. In buffalo
this is thought to be an anatomical
characteristic of the species, the
weakness being located in the right half
of the diaphragm

TREATMENT

Most recorded attempts at surgical repair
in cattle have been unsuccessful and treat-
ment has not usually been recommended.
The animals could not be left as they
were, so salvage by slaughter has been
the usual outcome.

The ruminal contents are frothy, and
trocarization or passing a stomach tube
has virtually no effect in reducing the
tympany, nor have standard antifrothing
agents. The tympany is usually not suffi-
ciently severe to require emergency
rumenotomy. The signs may be partly

relieved by keeping the animal confined
with the forequarters elevated.

TRAUMATIC PERICARDITIS

Perforation of the pericardial sac by a
sharp foreign body originating in the
reticulum causes pericarditis with the
development of toxemia and congestive
heart failure. Tachycardia, fever, engorge-
ment of the jugular veins, anasarca,
hydrothorax and ascites, and abnormalities
of the heart sounds are the diagnostic
features of the disease.

Etiology Perforation of pericardial sac by
foreign body originating from the
reticulum

Epidemiology Usually mature cattle;
may have had history of traumatic
reticuloperitonitis
Signs Depression, toxemia, fever,
inappetence to anorexia, engorged jugular
veins, brisket edema, heart sounds muffled
and accompanied by pericardial friction
rubs and to-and-fro fluid movement
sounds

Clinical pathology Marked
neutrophilia. Pericardiocentesis yields foul-
smelling and turbid fluid
Lesions Distension of pericardial sac, foul-
smelling, grayish fluid containing fibrin.
Adhesions and sinus tracts to reticulum
Diagnostic confirmation
Pericardiocentesis

Differential diagnosis Common
causes of congestive heart failure in cattle
include endocarditis, myocardiopathy
(lymphomatosis), congenital cardiac defect
Treatment Antimicrobials. Prognosis
unfavorable. Euthanasia commonly
recommended

ETIOLOGY

Traumatic pericarditis is caused by pene-
tration of the pericardial sac by a
migrating metal foreign body from the
reticulum. The incidence is greater during
the last 3 months of pregnancy and at
parturition than at other times. Approxi-
mately 8% of all cases of traumatic
reticuloperitonitis will develop pericarditis.
Most affected animals die or suffer from
chronic pericarditis and do not return to
completely normal health.

PATHOGENESIS

The penetration of the pericardial sac may
occur with the initial perforation of the
reticular wall. However, the animal may
have had a history of traumatic reticulo-
peritonitis some time previously, followed
by pericarditis, usually during late preg-
nancy or at parturition. In this case it is
probable that the foreign body remains in
a sinus in the reticular wall after the initial
perforation and penetrates the pericardia]
sac at a later date. Physical penetration of

the sac is not essential to the develop-
ment of pericarditis, infection sometimes
penetrating through the pericardium
from a traumatic mediastinitis.

Introduction of a mixed bacterial
infection from the reticulum causes a
severe local inflammation, and persistence
of the foreign body in the tissues is not
essential for the further progress of the
disease. The first effect of the inflam-
mation is hyperemia of the pericardial
surfaces and the production of friction
sounds synchronous with the heart beats.
Two mechanisms then operate to produce
signs: the toxemia due to the infection
and the pressure on the heart from the
fluid which accumulates in the sac and
produces congestive heart failure. In
individual cases one or other of these two
factors may be more important. Depression
is characteristic of the first and edema of
the second. Thus an affected animal may
be severely ill for several weeks with
edema developing only gradually, or
extreme edema may develop within
2-3 days. The rapid development of
edema usually indicates early death.

If chronic pericarditis persists there is
restriction of the heart action due to
adhesion of the pericardium to the heart.
Congestive heart failure results in most
cases but some animals may recover. An
uncommon sequel after perforation of the
pericardial sac by a foreign body is
rupture of a coronary artery or the ventri-
cular wall. Death usually occurs suddenly
due to acute, congestive heart failure
from compression of the heart by the
hemopericardium, and often without
premonitory illness.

CLINICAL FINDINGS

Depression, anorexia, habitual recum-
bency and rapid weight loss are common.
Diarrhea or scant feces may be present
and grinding of the teeth, salivation and
nasal discharge are occasionally observed.
The animal stands with the back arched
and the elbows abducted. Respiratory
movements are more obvious, being
mainly abdominal, shallow, increased in
rate to 40-50/min and often accompanied
by grunting. Engorgement of the
jugular veins, and edema of the brisket
and ventral abdominal wall are com-
mon and in severe cases there may even
be edema of the conjunctiva with grape-
like masses of edematous conjunctiva
hanging over the eyelids. A prominent
jugular venous pulse is usually visible and
extends proximally up the neck.

Pyrexia (40-41°C, 104-106°F) is com-
mon in the early stages and an increase in
the heart rate to 100/min and a dimi-
nution in the pulse amplitude are constant.
Rumen movements are usually present
but depressed. Pinching of the withers to

352

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

depress the back or deep palpation of the
ventral abdominal wall behind the xiphoid
sternum commonly elicits a marked
painful grunt. A grunt and an increased
area of cardiac dullness can also be
detected by percussion over the precordial
area, preferably with a pleximeter and
hammer.

Auscultation of the thorax reveals
the diagnostic findings. In the early
stages before effusion commences, the
heart sounds are normal but are
accompanied by a pericardial friction
rub, which may wax and wane with
respiratory movements. Care must be
taken to differentiate this from a pleural
friction rub due to inflammation of the
mediastinum. In this case the rub is much
louder and the heart rate will not be so
high. Several days later when there is
marked effusion, the heart sounds are
muffled and there may be gurgling,
splashing or tinkling sounds. In all
cases of suspected pericarditis, careful
auscultation of the entire precordium on
both sides of the thorax is essential as
abnormal sounds may be audible only
over restricted areas. This is especially so
in chronic cases.

Most affected animals die within a
period of 1-2 weeks, although a small pro-
portion persist with chronic pericarditis.
The obvious clinical findings in the
terminal stages are gross edema, dyspnea,
severe watery diarrhea, depression,
recumbency and complete anorexia.
Enlargement of the liver may be
detectable by palpation behind the upper
part of the right costal arch in the cranial
part of the right paralumbar fossa. Death
is usually due to asphyxia and toxemia.

Animals which have recovered from an
initial pericarditis are usually affected by
the chronic form of the disease. Body
condition is poor, the appetite is variable,
there is no systemic reaction and the
demeanor is bright. Edema of the brisket
is usually not prominent but there is
jugular engorgement. Auscultation reveals
variable findings. The heart sounds are
muffled and fluid splashing sounds
may be heard over small discrete areas
corresponding to the loculi of fluid in
the sac, or there may be irregularity of
the heart beat. The heart rate is rapid
(90-100/min) and the pulse is small in
amplitude. These animals remain unthrifty
and are unlikely to withstand the stress of
another pregnancy or lactation.

CLINICAL PATHOLOGY
Hemogram

A pronounced leukocytosis with a total
count of 16 000-30 000/pL accompanied
by a neutrophilia and eosinopenia is usual
although less dramatic changes are
recorded in one series of cases.

Pericardiocentesis

When gross effusion is present the
pericardial fluid may be sampled by
centesis with a 10 cm 18-gauge needle
over the site of maximum audibility of the
heart sound, usually in the fourth or fifth
intercostal space on the left side. In mid-
stage pericarditis the fluid is usually easily
obtained, and is foul-smelling and turbid,
which is diagnostic for pericarditis. In
chronic pericarditis only small amounts
may be present and a sample may not be
obtainable.

NECROPSY FINDINGS

In acute cases there is gross distension of
the pericardial sac with foul- smelling,
grayish fluid containing flakes of fibrin,
and the serous surface of the sac is
covered by heavy deposits of newly
formed fibrin. A cord-like, fibrous sinus
tract usually connects the reticulum with
the pericardium. Additional lesions of
pleurisy and pneumonia are commonly
present. In chronic cases the pericardial
sac is grossly thickened and fused to the
pericardium by strong fibrous adhesions
surrounding loculi of varying size which
contain pus or thin straw-colored fluid.

DIFFERENTIAL DIAGNOSIS

j The typical clinical findings in pericarditis
| are chronic illness, toxemia, fever,
j congestive heart failure and muffled heart
sounds. The major causes of congestive
heart failure in cattle are pericarditis,
endocardial disease, myocardiopathy and
cor pulmonale (pulmonary hypertension
j due to chronic pulmonary disease),

j Endocarditis, lymphomatosis with cardiac

| involvement and congenital cardiac defects
: are all likely to be confused with traumatic

j pericarditis because of the similarity of the
| abnormal heart sounds.

' • Endocarditis is usually associated with

\ a suppurative process in another organ,

1 particularly the uterus or udder, and,
j although the abnormal heart sounds are
j typical bruits rather than pericardial

friction sounds, this may be difficult to
determine when extensive pericardial
1 effusion has occurred

! • Lymphomatosis is usually

accompanied by lesions in other organs
or the presence of a marked
; leukocytosis and lymphocytosis

• Congenital cardiac defects may not

i cause clinical abnormality until the first
! pregnancy but can be diagnosed by the
j presence of loud murmurs, a

pronounced cardiac thrill and an
absence of toxemia

• Less common causes of abnormal heart
sounds include thoracic tumors and
abscesses, diaphragmatic hernia and
chronic bloat, which cause distortion of
the atria and atrioventricular orifices.
They are associated with other
diagnostic signs, particularly
displacement of the heart

• In severely debilitated animals or those
suffering from severe anemia a hemic
murmur which fluctuates with
respiration may be audible

• Occasional cases of hematogenous
pericarditis are encountered, and in
some cases of pasteurellosis a fibrinous
pericarditis may be present, but there is
usually serious involvement of other
organs and the pericarditis is only
secondary

TREATMENT

The results of treatment are usually
unsatisfactory but salvage of up to 50% of
cases can be achieved by long-term
treatment with antimicrobials. Rapid
onset of generalized edema represents a
poor prognosis. Drainage of the pericardial
sac may temporarily relieve the edema
and respiratory embarrassment but relapse
usually occurs within a few days. Selected
cases of traumatic pericarditis have been
treated satisfactorily by pericardiotomy.

PREVENTION

Prevention depends on preventing
traumatic reticuloperitonitis through
management of the environment and the
administration of reticular magnets.

TRAUMATIC SPLENITIS AND
HEPATITIS

Traumatic splenitis and hepatitis occur
relatively uncommonly as sequelae to
traumatic reticuloperitonitis and are mani-
fested either by continuation of the illness
caused by the initial perforation or by
apparent recovery followed by relapse
several weeks later. The prominent clinical
findings include fever (39.5-40.5°C,
103-105°F), tachycardia, gradual decrease
in feed intake and milk yield but ruminal
movements may be present and may be
normal. Percussion of the abdomen over
I the site usually used to detect the pain of
■ traumatic reticuloperitonitis gives a nega-
| tive response although deep, forceful
I palpation may elicit a mild grunt. The
j diagnostic sign is pain on palpation with the
j thumb in the last two intercostal spaces
I halfway down the abdomen on the right
j side when there is hepatic involvement, and
j on the left side when the spleen is affected,
j The total leukocyte count is elevated
j (above 12 000/pL) with a marked neutro-
j philia and a left shift. Rumenotomy is not
usually undertaken except for diagnostic
purposes. Treatment with antibacterial
drugs is effective if commenced sufficiently
early. Oral treatment with sulfadimidine
has been effective in some cases.

IMPACTION OF THE OMASUM

Omasal impaction as a clinical entity
is difficult to define and is usually

Diseases of the abomasum

353

diagnosed at necropsy when the omasum
is enlarged and excessively firm. It seems
unlikely that it could cause death and is
frequently observed in animals dying of
other disease. It is reputed to occur when
feed is tough and fibrous, particularly
alfalfa stalks and loppings from fodder
trees, or under drought feeding con-
ditions in sheep that are fed on the
ground. In the latter, the impaction is due
to the accumulation of soil in the omasum.
Chronic recurrent bouts of indigestion
occur and are manifested by decreased
rumen motility, infrequent and scanty
feces, refusal to eat grain and a negative
ketone test. Pain may be elicited and the
hard distended viscus palpated on deep
pressure under the right costal arch or in
the seventh to ninth intercostal spaces on
the right side. It may also be palpable per
rectum as a large, round, firm mass with a
checkered surface to distinguish it from
the smooth surface of the abomasum.
Repeated dosing with mineral oil is
recommended as treatment.

At necropsy, the omasum is grossly
distended; patches of necrosis may be
present on the leaves and peritonitis may
be evident. Necrosis of the ruminal lining
may also be present. Clinically the disease
is manifested by complete anorexia,
cessation of defecation, an empty rectum
and subacute abdominal pain with
disinclination to move or lie down.

Diseases of the abomasum

Diseases of the abomasum associated
with metabolic disease, lactational
stress and nutritional inadequacies are
common in dairy cattle. The common
diseases of the abomasum are:

° Left-side displacement of the
abomasum (LDA)

' Right-side displacement of the
abomasum (RDA)

Abomasal torsion (volvulus)
Abomasal ulcers
Impaction associated with vagus
indigestion

° Dietary abomasal impaction.

Their recognition is due in part to improved
diagnostic techniques and increased
awareness of their occurrence, but perhaps
there is also an increase in their frequency
because of intensified cattle production.
Dairy cattle are being selected for high
milk production and are being fed large
quantities of grain and kept more com-
monly in total confinement where
exercise is limited - all of which may con-
tribute to abomasal atony, which is the
precursor of abomasal displacements. A
review of abomasal displacement in cattle
is available. 1

A number of general comments are
summarized here that apply to most
diseases of the abomasum.

CLINICAL EXAMINATION OF THE
ABOMASUM

PHYSICAL EXAMINATION

The normal abomasum cannot usually be
examined by the standard techniques of
clinical examination except indirectly by
auscultation and paracentesis. In LDA,
the tympanitic sounds (pings) audible on
auscultation and percussion between the
middle to upper third of the ninth and
13th ribs and over the left paralumbar
fossa are characteristic. In RDA the
tympanitic sounds (pings) audible on
auscultation and percussion between the
lower third of the ninth and 13th ribs and
extending into the right paralumbar fossa,
and the fluid-splashing sounds audible
on auscultation and ballottement of the
right lower to middle third of the
abdomen, are characteristic. An enlarged
abomasum may be palpable on rectal
examination deep in the right lower
quadrant of the abdomen depending on
the size of the animal and the size of the
distended abomasum, and provided the
animal is not in advanced pregnancy.

In abomasal volvulus, the clinical
findings are similar to right-side displace-
ment but much more severe. On rectal
palpation a fluid-filled abomasum feels
tense; an impacted abomasum pits on
digital pressure. (An impacted enlarged
omasum is usually situated slightly to
the right of midline deep in the abdo-
men below the palpable kidney; it feels
firm and does not pit on pressure.) In
abomasal impaction, the enlarged, firm,
doughy viscus can usually be palpated
behind the lower aspect of the right costal
arch but the gravid uterus of later
pregnancy commonly makes this difficult.
Following parturition the abomasum is
more readily detectable by palpation
through the abdominal wall or rectally.

ULTRASONOGRAPHY OF
ABOMASUM

The abomasum can be visualized by ultra-
sonography over the ventral midline caudal
to the xiphoid process and from both left
and right paramedian regions lateral to the
midline site. The abomasum can be clearly
differentiated from adjacent viscera because
of its contents, which appear as a hetero-
geneous, moderately echogenic structure
with echogenic stippling. 2 Abomasal
motility cannot be observed but the relative
size of the abomasum can be detected.
Ultrasonographic examination of the abo-
masum of neonatal lambs provides an
immediate indication of whether or not
the lambs have sucked and maybe useful
in investigations of neonatal mortality, 3

ABOMASOCENTESIS

Centesis of abomasal contents is a safe
procedure if done carefully. 4,5 Percutaneous
ultrasound-guided abomasocentesis can
be done to evaluate the nature and
chemical composition of abomasal
contents. 5 The procedure is done at a site
where the abomasum is large and no
other viscera are located. The optimum
site for abomasocentesis is 10-27 cm
caudal to the xiphoid process and on the
ventral midline, or up to 10 cm caudal and
to the right of it. A spinal needle (0.12 x
9.0 cm) with a stylet is guided by ultra-
sonography through the skin and
abdominal wall and into the abomasum.
Abomasal fluid is assessed for color, smell
and the presence of blood, and pH.
Normally, the color ranges from olive
green to gray, and the fluid has a sour
smell. The pH varies from 1.38-4.50.
Higher values occur with abomasal
hemorrhage, the presence of bile or
chronic abomasitis due to ostertagiasis.

INTUBATION OF ABOMASUM

The abomasum of young calves can be
intubated for experimental purposes. 6

APPLIED ANATOMY AND
PATHOPHYSIOLOGY OF THE
ABOMASUM

In a healthy, non pregnant cow, the abo-
masum is positioned below the rumen in
the ventral part of the abdomen and is
orientated towards the left side of the
animal. During pregnancy, the enlarging
uterus forces the abomasum into a more
cranial position. This change is assumed
to contribute to the development of an
LDA, which generally occurs during the
first 3 weeks after parturition. 7

The anatomical position of the abo-
masum in cows during the last weeks of
pregnancy and through the first 6 weeks
after calving has been examined using
ultrasonography. 5,7 The uterus was always
located on the ventral abdominal wall and
the rumen had no contact with the
ventral abdominal wall. During the last
weeks of pregnancy, the abomasum was
located in a small region of the left ventral
side of the abdominal cavity. At
parturition, the abomasum was positioned
high on the left side and then descended.
The abomasum was furthest from the
midline immediately after calving. The
position of the abomasum changed in a
circadian rhythm. Eating and ruminating
can influence its position. A pocket of the
abomasum, the piriform sac of the fundus,
was detectable on the left side and was
more pronounced when the abomasum
was larger. Its position was related to the
interval after calving, the feed intake and
the pH and osmotic pressure of the
rumen fluid. 7 These findings explain, in

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

part, the high incidence of LDA in the first
weeks after parturition. The pronounced
lateral orientation of the abomasum
predisposes the cow to development of
left-side displacement.

The flow of rumen fluid into the abo-
masum can result in the production of
carbon dioxide and methane gases, which
when their absorption or the motility of the
abomasum is decreased, are unable to
escape from the blind pocket in the
abomasum and may be a major factor in
the pathogenesis of left side displacement.
This may explain why 80% of displaced
abomasums occur towards the left side.

The size of the blind pocket after
calving may determine the development
of a displacement on the left side. Cows
with their abomasum in a high position
would be expected to be at increased risk
of a displacement. There is considerable
variation between individual cows and
having the abomasum in a high position
was negatively associated with the
animal's feed intake after calving. Feed
intake immediately after calving is
negatively associated with body condition
score during the dry period. High feed
intakes were associated with a low posi-
tion of the abomasum, which is probably
a result of increased rumen filling: an
enlarged rumen caused by a high feed
intake forces the abomasum downwards.
Thus inadequate feed intake is associated
with displaced abomasum.

Diseases of the abomasum that cause
stasis and accumulation of ingesta, fluid
and gas in the viscus result in varying
degrees of dehydration, metabolic alkalosis,
hypochloremia and hypokalemia. The
metabolic alkalosis and hypokalemia are
often accompanied by muscular weak-
ness and paradoxic aciduria. When these
changes are severe, as in right-side
dilatation, abomasal torsion and abomasal
impaction, intensive fluid therapy is
necessary for a favorable response. How-
ever, in spite of exhaustive efforts, because
of irreversible abomasal atony the recovery
rate is low.

Abomasal luminal pressure is

increased in left- side displacement and in
volvulus of the abomasum. 8 This may be
associated with the pathogenesis of
ulceration in long-standing cases of LDA
and with the prognosis of survival in
abomasal volvulus. The luminal pressure
is high in abomasal volvulus and higher
in cattle that die or are sold for slaughter
than in cattle that survive and are retained
in the herd. Thus measurement of luminal
pressure during surgery for volvulus may
be of value in formulating prognosis for
survival.

Abomasal hypomotility and a decreased
rate of abomasal emptying are thought to
be important factors in the etiology and

pathogenesis of several diseases of the
abomasum of adult cattle and calves.
Because abomasal hypomotility has been
associated with hypocalcemia, endo-
toxemia, acidosis and alkalosis, hyper-
insulinemia and hyperglycemia, the
approach in treatment of suspected
abomasal hypomotility in adult cattle and
calves has been the correction of acid-
base and electrolyte imbalances, control
of the effects of endotoxemia and
elimination of Gram-negative bacterial
infections. 9 Neostigmine, metoclopramide
or erythromycin have been used in
ruminants for the treatment of abomasal
hypomotility on the basis that these drugs
have a prokinetic effect in other animals.
Prokinetic agents have the ability to
stimulate, coordinate and restore gastric,
pyloric and small-intestinal motility.

Erythromycin is an effective prokinetic
agent in healthy sucking milk-fed calves
similar to its effects in humans, dogs and
horses. 9 Intramuscular administration of
erythromycin at 8.8 mg/kg increased the
frequency of abomasal luminal pressure
waves and the mean abomasal luminal
pressure and decreased the half-time
of abomasal emptying by 3 7%. 9
Metoclopramide, neostigmine and low-
dose (0.88 mg/kg) erythromycin did not
alter abomasal motility, mean luminal
pressure or emptying rate.

Abomasal emptying rate and volume
in calves has been determined using
nuclear scintigraphy and acetaminophen
absorption methods. 10 Ultrasonography
has also been used to evaluate abomasal
volume, location and emptying rate in
sucking calves. 11

ABOMASAL REFLUX

j

| Reflux of abomasal fluid into the omasum
j and reticulorumen occurs when the
; abomasal fluid fails to move normally
j through the pylorus into the small
| intestine. This occurs most commonly in
j diseases of the abomasum, left-side
| displacement, right-side dilatation and
j vagus indigestion. Reflux may also occur
| in peritonitis, compression of the abo-
masum in advanced pregnancy, intus-
j susception and toxemias. The rumen
! chloride levels increase from a normal of
| 10-25 mmol/L to 80-100 mmol/L and the
j buffering capacity of the rumen is
| decreased from 80-110 mmol/L to less
than 50 mmol/L. Hypochloremic, hypo-
kalemic metabolic alkalosis occurs. Treat-
ment consists of removing excessive
quantities of fluid from the rumen and the
administration of large quantities of
balanced electrolytes or simply saline
intravenously. The intravenous adminis-
tration of hypertonic saline solution,
1.8%, is effective for the correction of

experimental hypochloremic metabolic
alkalosis in sheep. 12

Duodenal-abomasal reflux occurs
normally in cattle and may increase
during abomasal displacement; the influx
is lower in LDA than in RDA.The concen-
tration of bile acids in the abomasum is
twice as high in LDA and RDA as in
healthy cattle. 13

A series of abomasal emptying defects
in sheep were characterized by weight
loss, anorexia, variable degrees of abdomi-
nal distension, increased concentrations
of rumen chloride and grossly enlarged
abomasa. 14 No explanation for the
emptying defect was found at necropsy.

The administration of apomorphine to
sheep causes expulsion of acidic abomasal
contents back into the preabomasal
compartments without expulsion of
gastric contents through the mouth -
'internal vomiting'. In sheep, it is esti-
mated that approximately 280 g of sodium
bicarbonate given orally would be necess-
ary to return the ruminal pH to the
neutral range.

REFERENCES

1 . GeishauserT. J Vet Med A 1995; 42:229.

2. Braun U et al. Vet Rec 1997; 140:93.

3. Scott PR et al.Vet Rec 1997; 141:524.

4. Braun U et al.Vet Rec 1997; 140:599.

5. Braun U. Vet J 2003; 166:112.

6. Chapman HW. Can J Vet Resl986; 50:291.

7. Van Winden SCL et al.Vet Rec 2002; 151:446.

8. Constable PD et al. J Am Vet Med Assoc 1992;
201:1564.

9. WitteckT et al. Am J Vet Res 2005; 66:545.

10. Marshall TS et al. Am JVet Res 2005; 66:364.

11. WitteckT et al. Am JVet Res 2005; 66:537.

12. Fubini SL et al. Am J Vet Res 1991; 52:1898.

13. Geishauser T, Seeh C. JVet Med A 1996; 43:445.

14. Rings DM et al. J Am Vet Med Assoc 1985;
185:1520.

LEFT-SIDE DISPLACEMENT OF THE
ABOMASUM

ETIOLOGY

The cause of LDA in cattle is multi-
factorial but is related primarily to feed
intake before and after calving. The
! transition period occurring 2 weeks
prepartum through 2-4 weeks postpartum
is the major risk period in the etiology of
LDA. The prepartum depression of feed
intake and the slow postpartum increase
in intake are risk factors causing decreased
ruminal fill, reduced forage to concentrate
ratio and increased incidence of other
postpartum diseases. Excessive amounts
of concentrate during the prepartum
period increase the risk of left displaced
abomasum, which may occur from the
decreased ruminal fill caused by greater
prepartum intake depression and reduced
forage to concentrate ratio, decreased
ruminal motility from lower ruminal fill
and higher volatile fatty acid con-
centration, and decreased abomasal

Diseases of the abomasum

355

Etiology Gaseous distension and
hypomotility of abomasum possibly due to
feeding high levels of concentrate to dairy
cattle in late pregnancy
Epidemiology High-producing dairy
cows within 6 weeks of calving. Insufficient
crude fiber and roughage in ration.
Concurrent disease such as hypocalcemia
and ketosis may be risk factors but this is
uncertain

Signs Inappetence, ketosis, decreased
milk production, abdomen usually smaller
than normal, reticulorumen movements
not clearly audible or absent, rumen pack
not easily palpable, ping over left
paralumbar fossa and cranial to it. Fatty
liver and abomasal ulcers are possible
complications

Clinical pathology Ketonemia,
ketonuria. Normal hemogram
Lesions Not usually fatal
Diagnostic confirmation Laparotomy
to confirm displacement
Differential diagnosis LDA must be
differentiated from those common diseases
of the forestomach and abomasum that
cause inappetence to anorexia, ketosis,
reduced or abnormal reticulorumen
motility, and abnormal sounds on
percussion and auscultation of the left
abdomen. They are: simple indigestion,
primary ketosis, traumatic
reticuloperitonitis, vagus indigestion, fat
cow syndrome

Treatment Open and dosed surgical
techniques to replace abomasum and
secure in normal position
Control Avoid negative energy balance
prepartum, avoid overconditioning of cows
prepartum, provide optimal feed bunk
management, maximize dry matter intake
in late pregnancy

emptying. 1 The feeding of high levels of
concentrate to dairy cattle results in a
decrease in abomasal motility and
increased accumulation of abomasal gas.

EPIDEMIOLOGY

Occurrence

LDA occurs most commonly in large,
high-producing adult dairy cows immedi-
ately after parturition. Approximately
90% of cases occur within 6 weeks follow-
ing parturition. Occasional cases occur a
few to several weeks before parturition.
The disease is common in the UK and
North America, where daity cattle are fed
grain for high milk production and the
animals are usually housed for part of the
year or kept under confinement (zero
grazing, loose housing). The disease is
uncommon in Australia and New
Zealand, where much less concentrate is
fed to dairy cattle and the animals are
usually on pasture for most of the year.
However, it can occur in pasture-fed dairy
cattle. 2 The importance of exercise in the
etiology of LDA has not been explored.
The incidence of LDA is higher during the

winter months, which may be a reflection
of either a higher frequency of calving or
relative inactivity.

Calves

The disease has been recorded in calves
up to 6 months of age and, rarely, in heifer
calves 4 and 8 weeks of age in which
abomasal ulceration perforation and
peritonitis, and perforation of the abdomi-
nal wall occurred. 3 It was not possible to
determine if the ulceration led to the
atony with subsequent displacement of
the abomasum, or if the displacement
facilitated the ulceration.

Lactational incidence rate
The lactational incidence risk of LDA for
dairy herds in Ontario, Canada is about
2%. 4 In one survey of the prevalence of
disease in dairy herds, during a 3-year
period, 24% of herds reported at least one
caseofLDAandtherewasa prevalence of
1.16% among the affected herds and
0.35% when all herds surveyed were
considered. The mean rate of occurrence
in a cow population over a period of years
in Denmark was 0.62% with a range of
0.2-1. 6%. In Norway 88% of the
abomasal displacements are left-sided
and 12% are right-sided.

Case fatality

In one series of observations, the case
fatality rate was much higher (21%) in
cows with LDA and diarrhea than in cows
with LDA and normal feces (8%).

Risk factors

Dietary risk factors

Prepartum nutrition and management
Based on observations in dairy herds,
significant associations were found
between negative energy balance pre-
partum, as reflected by increased non-
esterified fatty acid concentrations, and
the occurrence of LDA. 5 High body con-
dition scores, suboptimal feed bunk
management, prepartum diets containing
more than 1.65 Meal of NE,/kg of DM,
winter and summer seasons, high genetic
merit and low parity were significant risk
factors. Cows fed these high-energy diets
during the dry period may become obese,
which may result in a decline in dry
matter intake before calving. Calving
during hot summer months also
decreases dry matter intake. It is sug-
gested that hepatic lipidosis may be an
important risk factor for LDA. Herds with
a high mean predicted transmitting ability
(PTA) were associated with a high
occurrence of LDA.

Ketosis diagnosed prior to the occur-
rence of LDA has been implicated as a
risk factor. Ketosis is associated with low
dry matter intake, which would reduce
rumen fill and volume, reducing fore-
stomach motility and, potentially, abomasal

motility. A low rumen volume also offers
less resistance to LDA.

High-level grain feeding
LDA is a disorder of throughput because
of its relationship to diseases associated
with high milk production and con-
centrate feeding. The practice of beginning
to feed concentrates to high-producing
dairy cattle during the last few weeks of
the dry period in preparation for the
transition to lactation after parturition
(lead feeding) may be a high risk factor
for LDA. Cows dried off in high body
condition scores are at increased risk of
LDA because of inadequate dry matter
intake around the time of parturition. 6

High-level grain feeding increases the
flow of ruminal ingesta to the abomasum,
which causes an increase in the con-
centration of volatile fatty acids, which
can inhibit the motility of the abomasum. 5-7
This inhibits the flow of digesta from the
abomasum to the duodenum so that
ingesta accumulates in the abomasum.
The large volume of methane and carbon
dioxide found in the abomasum following
grain feeding may become trapped there,
causing its distension and displacement.
However, the role of an increase in
abomasal volatile fatty acid concentration
as the cause of the abomasal atony is
controversial.

Dietary crude fiber

A crude fiber concentration of less than
16-17% in the diet of dairy cows was
considered a significant risk factor for
LDA. Some initial epidemiological studies
indicated that cows affected with LDA
were higher producers than their herd-
mates, and they were from higher-
producing herds than herds without
LDAs. The affected cows were also older
and heavier than the average for cows
examined in the survey.

The feeding of an experimental com-
pletely pelleted ration to dairy cattle
resulted in an increased incidence of
LDA: 17% compared to 1.6% in cows
receiving loose alfalfa hay, sorghum silage
and an 18% crude protein concentrate.
The pelleted ration was finely ground and
the short length of the dietary fiber may
have been a risk factor by increasing
volatile fatty acid and gas production.

In summary, feeding rations high in
carbohydrates, inadequate levels of
roughage and crude fiber levels below
17 % during the last few weeks of preg-
nancy are probably important dietary
risk factors.

Animal risk factors

A hospital-based case-control study of
LDA and abomasal volvulus in cattle
based on the medical records of 17 North
American veterinary teaching hospitals

;6

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

over a period of 10 years compared risk
factors for the two diseases. 8

Breed and age of cow
LDA occurs predominantly in Holstein-
Friesian, Guernsey and Jersey cows. The
breed disposition for LDA has been
controversial. Some studies have found
higher risk of LDA occurring in Holstein-
Friesian cattle and a lower risk in Brown
Swiss cattle compared with the risk in
Simmental-Red Holstein cross cows in
Switzerland. 9 In other studies, a breed
disposition for displaced abomasum was
found in Ayrshire, Canadienne, Guernsey,
Holstein-Friesian and Jersey cattle. In-
vitro studies of contractile activity of the
abomasal wall of healthy cows of different
breeds did not find any differences
between breeds of cattle. 9

The ratio of LDA to abomasal volvulus
cases was 7.4 to 1. The risk for the two
diseases increased with age with greatest
risk at 4-7 years of age. Dairy cattle were
at higher risk of developing LDA than
beef cattle, with an odds ratio of 95.
Female cattle were at a higher risk of
developing LDA than male cattle, with an
odds ratio of 29.

Season of the year

The odds of both diseases varied con-
siderably throughout the year, with the
lowest number of cases in the autumn.
The odds of abomasal volvulus and
LDA were highest in January and
March, respectively. The greater incidence
of the disease in the spring may also be
related to the depletion of roughage
supplies on farms in the Midwest region
of the USA. In other regions of the world,
the disease occurs throughout the
year independently of the incidence of
parturition.

Influence of weather
The possible effects of weather on the
incidence of abomasal displacement has
been examined. 10 In a study over a period
of 2 years, on 26 farms with a total of 6500
Holstein-Friesian lactating cows, 373 cases
of abomasal displacement occurred. A
change from sunny, warm and dry days to
cool, overcast and humid days was
associated with an increased incidence of
displacement. There were no effect of
either wind velocity or atmospheric
pressure.

Milk production

The relationship between high milk yield
or high milk yield potential and LDA has
been examined in several studies and the
results are inconclusive. In some obser-
vations, a higher incidence of the disease
occurred in high-yielding cows. Later
studies found no difference in herd milk
yield between high- and low-incidence
herds. Genetic correlations between LDA

and production of milk and protein are
very small and should be independent
for selection. In some studies, dairy
herds with a high mean FTA milk index
were associated with a high occurrence
of LDA.

Late pregnancy

Because parturition appears to be the
most common precipitating factor, it has
been postulated that during late preg-
nancy the rumen is lifted from the
abdominal floor by the expanding uterus
and the abomasum is pushed forward
and to the left under the rumen. Follow-
ing parturition, the rumen subsides,
trapping the abomasum, especially if it is
atonic or distended with feed, as it is
likely to be if the cow is fed heavily on
grain.

Proportionately fewer cases of abomasal
volvulus than LDA occurred during the
first 2 weeks after parturition - 28% and
57%, respectively. 8 Because proportionately
fewer cases of abomasal volvulus develop
in the immediate postpartum period it is
suggested that the rumen volume may
directly influence the direction of abo-
masal displacement. On the basis of the
findings, it is suggested that abomasal
atony is a prerequisite for abomasal
volvulus and LDA, and that existence of a
less than full abdomen because of reduced
rumen volume is a major risk and facili-
tates development of abomasal volvulus
and LDA. 8 It is suggested that normal
rumen volume is an effective barrier
against LDA and that the high incidence
of LDA in lactating dairy cattle is the
result of the additive effects of decreased
rumen volume, increased abdominal
void immediately after parturition and
increased exposure to factors that induce
abomasal atony. Additional indirect evi-
dence for the rumen barrier hypothesis is
that feeding a high-roughage diet,
containing at least 17% crude fiber,
| immediately prior to parturition is a
commonly recommended and successful
strategy for minimizing the incidence
of LDA.

Concurrent diseases

Cows with an LDA are more likely to
have had retained placenta, ketosis,
stillborn calf, metritis, twins or parturient
paresis than control cows. 11,12 Concurrent
diseases were present in 30% of abomasal
volvulus cases and 54% of LDA cases. The
greater incidence of concurrent disease in
LDA suggests that inappetence and
anorexia results in decreased rumen
volume, which would predispose to
displacement. Diseases of the wall of the
abomasum (secondary ulcer) and ketosis
and fatty liver are common concurrent
diseases in dairy cows with LDA. 8

Pre-existing subclinical ketosis
Ketosis is one of the most common
complications of LDA but whether or not
pre-existing subclinical ketosis is a risk
factor for LDA has been controversial.
Some clinical studies have reported that
subclinical ketosis is a risk factor for
LDA. 4,13 The serum concentrations of
aspartate transaminase (AST), the serum
and milk beta-hydroxybutyrate and milk
fat to protein ratio may be used in dairy
cows during the first and second weeks
after parturition as tests to predict
the subsequent diagnosis of LDA 13,14
AST values between 100-180 U/L, and
beta-hydroxybutyrate values between
1000-1600 pmol/L were associated with
increased odds ratio and likelihood ratio
of LDA When cutoff values were increased,
sensitivity decreased and specificity
increased. The evaluation of two milk
ketone tests as predictors of LDA in dairy
cows within 2 weeks of parturition
(median of 6 days postpartum and
12 days prior to the diagnosis of LDA)
found high specificity but low sensitivity
for prediction of subsequent occurrence
of LDA. 5 Increased ketone body concen-
tration in milk is claimed to be a
significant risk factor for LDA. This
correlates with an increased fat to protein
ratio in the first milk dairy herd improve-
ment test as a predictor of subsequent
LDA. 15 However, the studies that
conclude that pre-existing subclinical
ketosis occurs before the occurrence of
LDA, and is a risk factor (cause and effect
relationship), do not provide evidence
that the cause of the ketosis was not a
pre-existing LDA. It is possible for the
LDA to develop over a period of several
days to a few weeks in susceptible cows,
which would affect feed intake and
contribute to the pathogenesis of ketosis.
In addition, the sensitivity and specificity
of the clinical diagnostic techniques
(auscultation and percussion) are
unknown and it is plausible that some
cases of LDA are not recognized in their
very early stages when the fundus of the
abomasum has moved only a small
distance up along the left lateral abdomi-
nal wall (see Anterior displacement under
Clinical findings). The studies did not
describe how the diagnosis of LDA was
made. Cows with LDA are also twice as
likely to have another disease than cows
without LDA 4 and the presence of those
diseases could be risk factors for ketosis.

Hypocalcemia

Hypocalcemia, which occurs commonly
in mature dairy cows at the time of
parturition, has been suggested as an
important contributing factor in LDA.
Blood calcium levels affect abomasal
—motility; motility is normal down to a

Diseases of the abomasum

357

threshold value of 1.2 mmol total calcium/L
and below that level abomasal motility is
absent. In a series of 510 dairy cows, those
with hypocalcemia 12 hours before par-
turition (serum ionized calcium concen-
trations < 4.0 mg/dL or total serum
calcium concentration < 7.9 mg/dL) had a
4.8 times greater risk of developing LDA
than did normocalcemic cows. Other
studies concluded that hypocalcemia is
not an important risk factor for LDA. 13 In
cows with LDA, the ionized calcium is not
significantly different from controls.

Metabolic predictors of leftside
displacement of abomasum
There is a predictive association of pre-
partum non-esterified fatty acids (NEFA)
and postpartum beta-hydroxybutyrate
concentrations with LDA. 12 In cows with
subsequent LDA, mean NEFA concen-
trations began to diverge from the means
of cows without LDA 14 days before
calving, whereas mean serum NEFA
concentrations did not diverge until the
day of calving. Prepartum, only NEFA
concentration was associated with the
risk of subsequent LDA. Between 0 and
6 days before calving, cows with NEFA
concentration of 0.5 mEq/L or less were
3.6 times more likely to develop LDA after
calving. Between 1 and 7 days post-
partum, retained placenta, metritis and
increasing serum concentration of beta-
hydroxybutyrate and NEFA were associ-
ated with increased risk of subsequent
LDA. Serum beta-hydroxybutyrate was a
more sensitive and specific test than
NEFA concentration. The odds of LDA
were eight times greater in cows with
serum beta-hydroxybutyrate levels of
1200 pmol/L or higher. Cows with milk
beta-hydroxybutyrate concentration of
200 pmol/L or higher were 3.4 times more
likely to develop LDA. Serum calcium
concentration was not associated with
LDA. In summary, the strategic use of
metabolic tests to monitor transition dairy
cows should focus on NEFA in the last
week prepartum and beta-hydroxybutyrate
in the first week postpartum. 12

Genetic predisposition
An inherited and breed predisposition to
LDA has been suggested and examined
but the results are inconclusive. The data
of 7416 Canadian Holstein cows were
examined to estimate genetic parameters
for the most common diseases of dairy
cows. 7 The heritability of displaced
abomasum across lactations was 0.28
and the estimates between displaced
abomasum and production traits were
small. 7 In the hospital-based study in
North America, the odds of LDA in
Guernsey cattle were higher than in
Holstein cattle. 8

Miscellaneous animal risk factors
Unusual activity, including jumping on
other cows during estrus, is a common
history in cases not associated with
parturition. Occasional cases occur in
calves and bulls but the disease occurs
only rarely in beef cattle. Retained fetal
membranes, metritis and mastitis occur
commonly with LDA but a cause-and-
effect relationship has been difficult to
establish. In one retrospective study the
disease was associated in terms of
increased relative risk with periparturient
factors such as stillbirth, twins, retained
placenta, metritis, aciduria, ketonuria and
low milk yield in the previous lactation.

Economic importance and effects on
production and survivorship

The economic losses from the disease
include lost milk production during the
illness and postoperatively, and the cost
of the surgery. The effects of LDA on test-
day milk yields from 12 572 cows from
parities 1-6 over a 2-year period were
evaluated. 16 From calving to 60 days after
diagnosis, cows with LDA yielded on
average 557 kg less milk than cows
without LDA and 30% of the losses
occurred before diagnosis. 16 Milk loss
increased with parity and productivity
and milk losses were greatest in highest-
yielding cows. Cows with LDA were nearly
twice as likely to have another disease as
were cows without LDA. Cows with LDA
are more likely to be removed from the
herd at any point in time after the
diagnosis than their herdmates. 17 Cows
with LDA survived a median of 18 months,
and control cows survived a median of
27 months. Low milk production is a
common reason for removal of cows with
an LDA and the probability of removal
increased as lactation number increased.

PATHOGENESIS

In the nonpregnant cow, the abomasum
occupies the ventral portion of the
abdomen very nearly on the midline, with
the pylorus extending to the right side
caudal to the omasum. As pregnancy
progresses, the enlarging uterus occupies
an increasing amount of the abdominal
cavity. The uterus begins to slide under
the caudal aspects of the rumen, reducing
rumen volume by one-third at the end of
gestation. This also forces the abomasum
forward and slightly to the left side of the
abdomen, although the pylorus continues
to extend across the abdomen to the right
side. After calving, the uterus retracts
caudally towards the pelvic inlet, which
under normal conditions allows the
abomasum to return to its normal
position. 18

During LDA, the pyloric end of the
abomasum slides completely under the
rumen to the left side of the abdomen.

The relative lack of rumen Jill and
abomasal atony allows the abomasum to
distend and move into the left side of the
abdomen.

A decline in plasma concentration of
calcium around the time of parturition
may contribute to the abomasal atony.'

Normally, the abomasum contains
fluid and is located in the ventral part of
the abdomen. In postpartum cows, the
abomasum may shift to the left without
causing any clinical signs. 19 Abomasal
atony and gaseous distension are con-
sidered to be the primary dysfunctions in
LDA. 20 The existence of abomasal atony
precedes distension and displacement of
the abomasum. The gas accumulated in
the abomasum consists mainly of
methane (70%) and carbon dioxide. 7 In a
normal abomasum, the gas production is
equal to the clearance in an oral or aboral
direction. When motility of the abomasum
is inadequate, accumulation of gas occurs.
The origin of the excess gas is uncertain
but there is evidence that the gas in the
abomasum originates from the rumen in
association with increased concentrate
feeding and an increase in volatile fatty
acid concentrations in the abomasum. A
high-grain, low-forage diet can promote
the appearance of volatile fatty acids in
the abomasum by reducing the depth of
the ruminal mat or raft (consisting
primarily of the long fibers of forages).
Physical reduction of forage particle
length by chopping forages too finely
prior to ensiling or overzealous use of
mixer wagons also can contribute to loss
of rumen raft. 1 The rumen raft captures
grain particles so that they are fermented
at the top of the ruminal fluid. The volatile
fatty acids produced at the top of the
ruminal fluid are generally absorbed from
the rumen with little volatile fatty acid
entering the abomasum. In cows with an
inadequate rumen raft, grain particles fall
to the ventral portion of the rumen and
reticulum, where they are fermented or
pass on to the abomasum. The volatile
fatty acids produced in the ventral rumen
can pass through the rumenoreticular
orifice to enter the abomasum before the
rumen can absorb them. A thick ruminal
raft is generally present during the dry
period, when cows are fed a high forage
diet, but the depth of the raft is rapidly
reduced in early lactation, especially if dry
matter intake decreases. Also, when cows
are fed a higher grain ration, there is less
regurgitation of the cud and mastication,
and less saliva produced, which affects
buffering of the rumen.

The amount of effective fiber determines
the consistency and depth of the rumen raft
and stimulates rumen contractions.

Total mixed rations that are easily
sorted by cows may affect the ratio of

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

forage to concentrate of total feed con-
sumed, which contributes to the develop-
ment of an LDA.

The atonic gas-filled abomasum
becomes displaced under the rumen and
upward along the left abdominal wall,
usually lateral to the spleen and the
dorsal sac of the rumen. It is primarily
the fundus and greater curvature of the
abomasum that becomes displaced,
which in turn causes displacement of the
pylorus and duodenum. Based on
epidemiological observations presented
earlier, it is hypothesized that a reduced
rumen volume in the immediate post-
partum period when there is some
abdominal void allows this displacement
to occur. The omasum, reticulum and liver
are also displaced to varying degrees. The
displacement of the abomasum invariably
results in rupture of the attachment of the
greater omentum to the abomasum. In
some cases, the LDA resolves sponta-
neously; such cases are known as'f loafers'.

Insulin resistance is common in cows
with an LDA. 20 High insulin concen-
trations associated with hyperglycemia
but independent of ketosis are common
in cows with LDA. In-vitro studies of
abomasal motility indicate that the
contractions of the longitudinal muscle
from the pyloric myenteric plexus of cows
with an LDA or RDA are significantly
reduced compared to muscle from normal
cows. In cows with an LDA and high con-
centrations of blood glucose and insulin,
the myoelectrical activity of the abomasum
was reduced, but increased following
surgical correction along with a decrease
in the concentrations of glucose and
insulin. 20

Compression by the rumen of the
impounded part of the abomasum causes
a great decrease in the volume of the
organ and interference with normal
movements. There is probably some
interference with the function of the
esophageal groove due to slight rotation
of all the stomachs in a clockwise
direction, and this impedes forward
passage of digesta. The obstruction of the
displaced segment is incomplete and,
although it contains some gas and fluid, a
certain amount is still able to escape and
the distension rarely becomes severe.
There is no interference with blood
supply to the trapped portion so that
effects of the displacement are entirely
those of interference with digestion and
movement of the ingesta, leading to a
state of chronic inanition. In occasional
cases the abomasum becomes trapped
anteriorly between the reticulum and
diaphragm - anterior displacement of
the abomasum.

A mild metabolic alkalosis with hypo-
chloremia and hypokalemia are common,

probably because of the abomasal atony,
continued secretion of hydrochloric acid
into the abomasum and impairment of
flow into the duodenum. Affected cattle
usually develop secondary ketosis which,
in fat cows may be complicated by the
development of the fatty liver syndrome.
Endotoxemia does not occur in LDA
or RDA. 21

Abomasal luminal gas pressure,
volume and perfusion in cows with
LDA or abomasal volvulus

The luminal pressure in LDA is in-
creased (median 8.7 mmHg; range
3.5-20.7 mmHg), 22 which may contribute
to the pathogenesis of abomasal ulcer-
ation. Abomasal luminal pressure and
volume is higher in cattle with an abo-
masal volvulus than in cattle with an
LDA. 23 Abomasal perfusion decreases as
luminal pressure increases in cattle with
an abomasal volvulus or LDA.

Perforating abomasal ulceration

Perforating abomasal ulceration and acute
local peritonitis with fibrinous adhesions
also occur in some cases of LDA. 24
Abdominal pain and pneumoperitoneum
are common sequelae. The ulcers may
perforate acutely and cause rapid death
due to acute diffuse peritonitis. Duodenal
ulceration has also been associated
with LDA.

CLINICAL FINDINGS

General appearance and ketosis

Usually within a few days or a week
following parturition there will be in-
appetence, sometimes almost complete
anorexia, a marked drop in milk pro-
duction and varying degrees of ketosis,
based on ketonuria and other clinical
findings of ketosis. It is not uncommon to
diagnose an LDA that was treated for
ketosis, improved for a few days and then
relapsed.

On inspection of the abdomen, the left
lateral abdomen appears 'slab-sided'
because the rumen is smaller than normal
and displaced medially. The temperature,
heart rate and respirations are usually
within normal ranges. The feces are
usually reduced in volume and softer than
normal but periods of profuse diarrhea
may occur.

Status of reticulorumen and
spontaneous abomasal sounds

Ruminal movements are commonly
present but decreased in frequency and
intensity, and sometimes inaudible even
though there are movements of the left
paralumbar fossa indicating rumen
motility. In some cases, the rumen pack is
palpable in the left paralumbar fossa, and
the rumen contractions and sounds can
be detected in the fossa as in normal
cows. However, the rumen sounds may

not be audible over an area anterior to the
fossa where they are also audible in normal
cows. The absence of normal ruminal
sounds in the presence of abdominal
ripples suggests the presence of an LDA.

Auscultation of an area below an
imaginary line from the center of the left
paralumbar fossa to just behind the left
elbow reveals the presence of high-
pitched tinkling sounds, which often
have a progressive peristaltic character.
These are abomasal sounds and may
occur several times per minute or
infrequently (as long as 5 min apart). They
are not related in occurrence to ruminal
movements and this can be ascertained
by simultaneous auscultation over an area
between the upper third of the ninth and
12th ribs and palpation of the left para-
lumbar fossa for movements of the dorsal
sac of the rumen. While auscultating over
the same area and ballotting the left lower
abdomen just below the fossa, high-
pitched fluid-splashing sounds of the
LDA are commonly audible.

Pings of the left-side displacement of
the abomasum

Percussion, using a flick of the finger or a
plexor, and simultaneous auscultation
over an area between the upper third
of the ninth and 12th ribs of the
abdominal wall commonly elicits the
high-pitched tympanitic sounds (pings)
that are characteristic of LDA. These pings
may not be present if the cow has just
previously been transported to a clinic for
surgery but they will commonly reappear
in 24-48 hours. Occasionally, careful,
repeated, time-consuming examinations
using percussion and simultaneous
auscultation are necessary to elicit the
pings.

Acute left-side displacement of the
abomasum

In rare cases there is initially a sudden
onset of anorexia accompanied by signs
of moderate abdominal pain and abdomi-
nal distension. These are the acute cases,
which are uncommon. An obvious bulge
caused by the distended abomasum may
develop in the anterior part of the upper
left paralumbar fossa and this may extend
up behind the costal arch almost to the
top of the fossa. The swelling is tympanitic
and gives a resonant note on percussion.
In acute cases the temperature may rise to
39.5°C (I03°F) and the heart rate to
100/min but in the more common
subacute cases the temperature and pulse
rate are normal. The appetite returns but
is intermittent and selective, the animal
eating only certain feeds, particularly hay.
There may be transitory periods of
improvement in appetite and dis-
appearance of these sounds, especially
-after transport or vigorous exercise.

Diseases of the abomasum

359

Concurrent perforating abomasal
ulceration

Perforating abomasal ulceration occurs
concurrently in some cases of LDA,
resulting in localized peritonitis and
pneumoperitoneum. 24 Affected cattle
have the ping over the left abdomen
typical of an LDA, but a ping over both
the right and left paralumbar fossae due
to pneumoperitoneum is also common.
Abdominal pain due to the local peri-
tonitis is characterized by tensing of the
abdominal wall, grunting and arching of
the back on deep palpation over the
abomasal area. The peritonitis is associ-
ated with a fever. The prognosis in these
cases is unfavorable.

Other clinical features

Ultrasound examination
Ultrasound examination can assist in the
diagnosis of abomasal displacements. 25 In
cattle with LDA the abomasum is seen
between the left abdominal wall and the
rumen. It contains fluid ingesta ventrally
and a gas cap of varying size dorsally.
Occasionally, the abomasal folds are
seen in the ingesta. In cattle with RDA,
the liver is displaced medially from the
right abdominal wall by the abomasum,
which has an ultrasonographic appear-
ance similar to that described for left
displacement.

Rectal examination

On rectal examination a sense of
emptiness in the upper right abdomen
may be appreciated. The rumen is usually
smaller than expected and only rarely is
the distended abomasum palpable to the
left of the rumen. Occasionally, there is
chronic ruminal tympany.

Secondary ketosis and fatty liver
Cows in fat body condition at parturition
commonly have severe ketosis and the
fatty liver syndrome secondary to LDA.
The disease is not usually fatal but
affected animals are usually less than
satisfactory production units.

Anterior displacement of abomasum
In anterior displacement, the distended
abomasum moves in a cranial direction
and becomes trapped between the
reticulum and the diaphragm. In one
series of 161 cases of abomasal displace-
ment, anterior displacement accounted
for 12% of all cases. 26 The clinical findings
are similar to those described above
except that the characteristic LDA pings
cannot be elicited over the typical region.
Normal rumen contractions can be heard
in the usual position and gurgling sounds
characteristic of a distended abomasum
may be audible just behind and above the
heart and on both sides of the thorax. 26 It
is necessary to auscultate over the ventral
left abdominal wall, especially over an

area extending from the middle of the
sixth to eighth ribs, above and below an
imaginary line drawn between the point
of the elbow and the tuber coxae. If a
rumenotomy is done the distended
abomasum can be felt between the
reticulum and diaphragm.

Atrial fibrillation

A paroxysmal atrial fibrillation is present
in some cases, which is considered to
be caused by a concurrent metabolic
alkalosis. Following surgical correction
the arrhythmia usually disappears.

Course of left-side displacement of the
abomasum

The course of an LDA is highly variable.
Undiagnosed cases usually reach a certain
level of inanition and may remain at an
equilibrium for several weeks or even a
few months. Milk production decreases to
a small volume and the animal becomes
thin, with the abdomen greatly reduced in
size.

Unusual cases of left-side displacement
Occasional cases occur in cows that are
clinically normal in all other respects. In
one case, a cow had an LDA, which was
confirmed at necropsy, for 1.5 years,
during which time she calved twice and
ate and produced milk normally.

Left-side displacement of the abomasum
in calves

In calves, the clinical findings include
inappetence, reduced weight gain,
recurrent distension of the left para-
lumbar fossa and a metabolic ping and
fluid-splashing sounds on auscultation
and percussion of the left flank.

CLINICAL PATHOLOGY
Hemogram

There are no marked changes in the
hemogram unless there is intercurrent
disease, particularly traumatic reticulo-
peritonitis or abomasal ulcer. A moderate
to severe ketonuria is always present but
the blood glucose level is within the
normal range. There is usually a mild
hemoconcentration evidenced by elev-
ations of the packed cell volume (PCV),
hemoglobin and total serum protein. A
mild metabolic alkalosis with slight hypo-
chloremia and hypokalemia may also be
present.

Serum biochemistry

Ketosis is the most common complication
of LDA and severe cases of ketosis are
commonly accompanied by fatty liver.
The blood levels of AST and beta-
hydroxybutyrate can be measured in
dairy cows during the first and second
weeks after parturition as possible tests to
predict the subsequent diagnosis of
LDA. 14 AST values between 100-180 U/L
and beta-hydroxybutyrate values between

1000-1600 pmol/L were associated with
increased odds ratio and likelihood ratio
of LDA.

In cows with fatty liver, plasmal
lipoprotein concentrations are decreased.
In addition to those of lipoprotein lipids,
concentrations of apolipoprotein B-100
(apo-100), the major apoprotein in very
low-density lipoproteins and low-density
lipoproteins, and apolipoprotein A-l
(apoA-1), the predominant protein
constituent of high-density lipoprotein,
also are reduced in cows with fatty liver.
Decreased serum levels of apo-100 and
apoA-I occur in cows with ketosis and
LDA and may be used during the stages
of nonlactation and early lactation to
predict cows susceptible to ketosis and
LDA. 27 Dairy cows with LDA also have
low plasma and liver a-tocopherol, and
plasma vitamin E values may decrease in
cows with increased liver triglyceride
content. 28

A mild hypocalcemia is usually present
but parturient hypocalcemia is uncommon.

Cowside tests of milk and urinary
ketones

Milk ketone tests can also be used as
predictors of LDA in dairy cows within
2 weeks of parturition. 4 In the first week
of lactation, the Pink test liquid and the
Ketolac test strip were highly sensitive for
the detection of subclinical ketosis when
used in milk. 29 The Ketotest (a milk beta-
hydroxybutyrate test strip) is also highly
sensitive for the detection of subclinical
ketosis. 30

Urine ketones: the Ketostix (urine
nitroprusside strip detecting acetoacetate)
can be used on a regular basis to detect
subclinical ketosis. 30

Metabolic predictors of left side
displacement of abomasum

Metabolic tests to predict the occurrence
of LDA can be used strategically in the
last week prepartum and the first week
postpartum 12 (details under Metabolic
predictors of left side displacement of
abomasum, in Animal risk factors, under
Epidemiology, above).

Liver function

Cows with LDA may have varying
degrees of fatty liver. 31 ' 32 In liver biopsy
samples, more about 55% of cows with
LDA, fatty degeneration may be present. 31
In some cows with LDA, liver biopsies
found 31% fat infiltration and in those
same animals, serum AST and gamma-
glutamyl transferase levels were increased. 32

Abomasocentesis

Centesis of the displaced abomasum
through the 10th or 11th intercostal space
in the middle third of the abdominal wall
may reveal the presence of fluid with no
protozoa and a pH of 2. Ruminal fluid will

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

have protozoa and a pH of between 6 and
7. Fluid is not always present in appreciable
quantity in the abomasum and a negative
result on puncture cannot be interpreted
as eliminating the possibility of abomasal
displacement.

NECROPSY FINDINGS

The disease is not usually fatal but
carcasses of affected animals are some-
times observed at abattoirs. The displaced
abomasum is trapped between the rumen
and the ventral abdominal floor and
contains variable amounts of fluid and
gas. In occasional cases it is fixed in
position by adhesions, which usually arise
from an abomasal ulcer. Fatty liver is
common in cows that died from compli-
cations of LDA within a few days of
parturition or following surgery.

DIFFERENTIAL DIAGNOSIS

Left-side displacement of the abomasum
occurs most commonly in cows within a
few days of parturition and is characterized
by gauntness, a relatively slab-sided left
abdomen and secondary ketosis. The
characteristic pings can usually be elicited
by percussion and auscultation. The
presence of secondary ketosis in a cow
immediately after parturition should arouse
suspicion of the disease. Primary ketosis
usually occurs in high-producing cows
2-6 weeks after parturition. The response
to treatment of primary ketosis is usually
permanent when treated early, while the
response to treatment of the ketosis due
to LDA is temporary and a relapse in a few
days is common.

Left-side displacement of the abomasum
must be differentiated from those common
diseases of the forestomach and
abomasum that cause inappetence to
anorexia, ketosis, reduced or abnormal
reticulorumen motility, and abnormal
sounds on percussion and auscultation of
the left abdomen.

Common differentials

• Simple indigestion is characterized by
normal vital signs, inappetence to
anorexia, history of change of feed,
reduced milk production, a relatively full
rumen with reduced frequency and
intensity of contractions, the absence of
pings and spontaneous recovery in

24 hours

• Primary ketosis is characterized by
inappetence, decline in milk production,
strong ketonuria, normal vital signs, full
rumen with reduced frequency and
intensity of contractions, dry but normal
amount of feces and response to
therapy with dextrose and propylene
glycol in 12-24 hours

• Traumatic reticuloperitonitis in its
acute form is characterized by ruminal
stasis, mild fever, a grunt on deep
palpation over the xiphoid sternum and
a slight neutrophilia with a regenerative
left shift. However, in subacute and
chronic traumatic reticuloperitonitis a

painful grunt may be absent, the
temperature and hemogram may be
normal and on auscultation and
percussion the atonic rumen may be
mistaken for an LDA. The tympanitic
sounds of an atonic rumen occur over a
larger area than with LDA and are not
as high-pitched as those of LDA - they
have been called 'pungs'. An
exploratory laparotomy may be
necessary to distinguish between the
two, although laparoscopy,
ultrasonography and abdominocentesis
are alternatives

• Vagus indigestion is characterized by
progressive abdominal distension due to
a grossly distended rumen with or
without an enlarged abomasum, and is
more common before parturition.
Dehydration is also common

• Fat cow syndrome at parturition is
characterized by excessive body
condition, inappetence to anorexia,
ketonuria, reduced to absent
reticulorumen motility, but usually no
pings over the rumen

TREATMENT

Surgical correction is now commonly
practiced and several techniques have
been devised with emphasis on avoidance
of recurrence of the displacement.

Open surgical techniques

Right paramedian abomasopexy and

right paralumbar fossa omentopexy

are the most widely used means of
correcting left displacement of the
abomasum. The right paralumbar fossa
omentopexy is popular because the
animal is standing and the surgeon can
work alone without assistance. More skill
is required than for the right paramedian
abomasopexy. The right paramedian
abomasopexy requires less manipulation
because the abomasum usually returns to
its normal position when the cow is
placed in dorsal recumbency. The major
disadvantage is the number of people
required to restrain the animal in dorsal
recumbency. There is little difference in
the cost of doing a right paramedian
abomasopexy compared to a right para-
lumbar fossa omentopexy, of which there
are modifications from the original
description. Based on field studies there is
also no difference in either the repro-
ductive performance or incisional compli-
cations following surgery. Based on milk
yield at 1 month after surgery, some
results indicate a slight preference for a
right paramedian abomasopexy.

Closed suture techniques

A few closed suturing abomasopexy
techniques have been advocated because
they are rapid and inexpensive but the
complications that can occur indicate that

laparotomy and omentopexy are desirable.
In the blind suture technique, the precise
location of insertion of the sutures is
unknown. Complications include perito-
nitis, cellulitis, abomasal displacement
or evisceration, complete forestomach
obstruction and thrombophlebitis of the
subcutaneous abdominal vein.

Roll-and-toggle-pin suture procedure
The roll-and-toggle-pin suture, a modifi-
cation of the closed suture technique, is also
available and has been compared with right
paralumbar fossa pyloro-omentopexy. The
roll-and- toggle technique, as with other
closed repositioning and stabilization
techniques, is generally less expensive and
provides results comparable with the open
surgical techniques.

Advantages of the closed suture tech-
nique include confirmation of suture
placement in the abomasum by identifi-
cation of abomasal gas, and deflation of
the abomasum during correction.

Cows with LDA corrected by toggle-
pin suture procedure produced less milk
than control cows, and all the decrease in
production occurred in the first 4 months
of lactation. 33 The occurrence of LDA did
not affect the period from calving to
conception, nor did it affect subsequent
conception rate, but it was associated
with an extended period between calving
and first postpartum artificial insemination.
A higher proportion of LDA cattle were
sold or died. Death and culling were more
pronounced immediately after the diag-
nosis of LDA and the toggle -pin suture
procedure.

Survivorship following surgery to
correct left-side displacement of the
abomasum

In a series of 564 cases of displaced
abomasum (466 LDA, 98 RDA), survival
after surgery was evaluated after 10 days
and 15 months. 34 More LDA than RDA
cows were discharged as cured (82% vs
74%). However, survival after the early
postsurgical period was similar for RDA
and LDA cows. In LDA cows, the factors
associated with a favorable prognosis
were a short duration of disease, an
undisturbed general condition, good
appetite, normal feces, a higher body
weight, lower hematocrit, hemoglobin
and erythrocyte counts, lower urea, AST
and bilirubin, and higher serum sodium,
potassium and chloride concentrations
compared with cows with an unfavorable
prognosis. 34 A thorough clinical and
laboratory examination with special
emphasis on general physical condition,
liver function and dehydration status are
important in determining the prognosis
of abdominal surgery in LDA.

Diseases of the abomasum

361

Treatment of ketosis

Parenteral dextrose and oral propylene
glycol are necessary for treatment of the
ketosis and to avoid fatty liver as a
complication. Postsurgical convalescence
of cows with LDA is clearly related to
disturbances in energy metabolism and
fatty liver. 35 During convalescence, in
cows with no fatty liver or moderate fatty
liver, the feed intake and daily milk
production increases steadily. In cows
with severe fatty liver feed intake remains
low. This emphasizes the need for effec-
tive treatment of excessive lipomobilization,
ketosis and fatty liver along with surgical
correction of the LDA. All cases of LDA
should be corrected as soon as possible to
minimize the incidence of peritoneal
adhesions and abomasal ulcers, which
may perforate and cause sudden death.

Rumen transfaunation following
surgery for left-side displacement of
the abomasum

The administration of 10 L of rumen fluid
via a stomach tube immediately after
surgical correction of an LDA, and on the
next day, resulted in a beneficial effect
characterized by a greater feed intake, less
degree ofketonuria and higher milk yield
compared to control cows given water. 36

CONTROL

The transition period occurring 2-3 weeks
before and after calving is a major risk
period in the etiology of LDA. The pre-
partum depression of dry matter intake
and the slow postpartum increase in dry
matter intake are risk factors causing
lower ruminal fill, reduced forage to
concentrate ratios (in nontotal mixed
ration feeding systems) and increased
incidence of other postpartum diseases. 37
Retained fetal membranes, metritis and
either clinical or subclinical ketosis and
hypocalcemia are probable risk factors for
LDA. Excessive amounts of concentrate,
or too rapid an increase in concentrate
feeding during the peripartum period,
increases the risk of LDA, as higher
volatile fatty acid concentration in the
abomasal contents leads to decreased
abomasal motility and emptying and
excess gas in the abomasum. (See further
details of importance of crude fiber in the
rumen and its effect on the abomasum
under Ftithogenesis, above.)

Prepartum nutrition and
management

Reduction of the incidence of LDA in a
dairy herd can be achieved by optimal
nutrition and management during the dry
period 6 - 38 The following principles are
important:

6 Avoid a negative energy balance
prepartum by avoiding

overconditioning and by providing
optimal feed bunk management to
cows in late gestation
® Feed some concentrates prior to
calving to insure development of
ruminal papillae

0 Maximize dry matter intake in the
immediate postpartum period
° Ensure palatable feed and water
available to periparturient cows at all
times

° Feed bunk management must ensure
that cows have adequate access to
fresh feed at all times to maximize dry
matter intake in late pregnancy and
thus improve energy balance
° Energy density of prepartum diets
should not exceed 1.65 Meal of
NE|/kg of DM.

Every effort should be made to minimize
dietary alterations near parturition that
could result in indigestion. The amount of
grain and com (maize) silage fed prepartum
should be kept at a minimum, while other
forages are fed ad libitum.

Several experiments have shown no
response in production to feeding large
quantities of grain or concentrates (lead
feeding) before parturition when cows
were in good condition at drying-off and
were fed well following parturition. Con-
sequently, there seems little reason to
continue the practice of steaming-up
cows before parturition.

Crude fiber intake

Ensuring an adequate intake of a high-
fiber diet to dairy cows during the 'far- off'
and 'close-up' periods in late pregnancy
and. the immediate 'postfreshening'
period is of critical importance to the
prevention of this disease. 6 The high-fiber
diet will physically expand fhe rumen and
provide a barrier against abomasal
migration. 8 The basic principle is to
maintain adequate ruminal filling before
and after calving. 38 This requires careful
analysis and implementation of the dry
cow feeding program. 6 Readers are
referred to National Research Council,
2001 (see Review literature) for details on
feeding programs for dairy cattle.

The emphasis in the dry cow feeding
program must be on increasing dry
matter intake, increasing particle length
and effective fiber content of the ration.
Feeding a high-roughage diet is con-
sistent with one of the most commonly
recommended and successful manage-
ment strategies for minimizing LDA
during the postparturient period. This
means insuring adequate fiber content of
at least 17%. An adequate level of fiber
will also aid in the control of subacute
ruminal acidosis, which may occur when
dairy cows are fed grain in the latter part

of the dry period in preparation for
lactation.

Monensin in controlled-release
capsule prepartum

Monensin is an ionophore antibiotic that
alters volatile fatty acid production in the
rumen in favor of propionate, which is a
major precursor for glucose in the
ruminant. A monensin controlled-release
capsule is available as an aid in the
prevention of subclinical ketosis in
lactating dairy cattle. The device delivers
335 mg of monensin per day for 95 days.
A monensin controlled-release capsule
has been shown to decrease the incidence
of subclinical ketosis, displaced abomasum
and multiple illnesses when administered
to dairy cows 3 weeks before calving. 39 It is
likely that these effects on clinical health
are mediated by improved energy balance
in monensin-supplemented cows. There
are improvements in energy indicators
such as increased glucose and decreased
beta-hydroxybutyrate after calving.

The administration of a monensin
controlled-release capsule to cows
3 weeks prepartum significantly decreased
NEFA and beta-hydroxybutyrate and
significantly increased concentrations of
serum cholesterol and urea in the week
immediately precalving. 39 No effect of
treatment was observed for calcium,
phosphorus or glucose in the precalving
period. After calving, concentrations of
phosphorus were lower and beta-
hydroxybutyrate tended to be lower, and
cholesterol and urea were higher in
monensin-treated cows. There was no
effect of treatment on NEFA, glucose or
calcium in the first week after calving.
Monensin treatment administered pre-
calving significantly improved indicators
of energy balance in both the immediate
precalving and postcalving periods. The
prevalence of subclinical ketosis as
measured by cowside tests was lower in
monensin-treated cows. These findings
indicate more effective energy meta-
bolism in monensin-treated cows as they
approach calving, which is important for
the prevention of retained placenta,
clinical ketosis and displaced abomasum.
In general, a 40% reduction in both LDA
and clinical ketosis can be expected with
precalving administration of monensin
controlled-release capsules. 40 In addition,
a 25% decrease in retained placenta may
occur.

Genetic selection

There is some evidence that LDA is a
moderately heritable trait and that the
incidence may be lowered by genetic
selection. 41 However, this has not been
explored on a practical basis.

362

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

REVIEW LITERATURE

Geishauser T. Abomasal displacement in the bovine -
a review on character, occurrence, etiology and
pathogenesis. J Vet Med A 1995; 42:229-251.
Shaver RD. Nutritional risk factors in the etiology of
left displaced abomasum in dairy cows: a review.
J Dairy Sci 1997; 80:2449-2453.

Geishauser T, Leslie K, Duffield T. Prevention and
prediction of displaced abomasum in dairy cows.
Bovine Pract 2000; 34:51-55.

Geishauser T, Leslie K, Duffield T. Metabolic aspects
in the etiology of displaced abomasum. Vet Clin
North Am Food Anim Pract 2000; 16:255-265.
National Research Council. Nutrient requirements of
dairy cattle, 7th ed. Washington, DC: National
Academy Press, 2001.

Van Winden SCL, Kuiper R. Left displacement of the
abomasum in dairy cattle: recent developments in
epidemiological and etiological aspects. Vet Res
2003; 34:47-56.

Braun U. Ultrasonography in gastrointestinal disease
in cattle. Vet J 2003; 166:112-124.

REFERENCES

1. Shaver RD. J Dairy Sci 1997; 80:2449.

2. JubbTK et al. AustVet J 1991; 68:140.

3. Mueller K et al. Vet J 1999; 157:95.

4. Geishauser T et al. J Dairy Sci 1997; 80:3188.

5. Vin Winden SCL et al. Vet Rec 2004; 154:501.

6. National Research Council. Nutrient require-
ments of dairy cattle, 7th ed. Washington, DC:
National Academy Press, 2001:196-197.

7. Van Winden SCL, Kuiper R. Vet Res 2003; 34:47.

8. Constable PD et al. Am J Vet Res 1992; 53:1184.

9. Zulaf M et al. Ana J Vet Res 2002; 63:1687.

10. Da Silva C et al. DtschTierarztl Wochenschr 2004;
111:49.

11. Rohrbach BW et al. J Am Vet Med Assoc 1999;
214:1660.

12. LeBland SJ et al. J Dairy Sci 2005; 88:159.

13. GeishauserT et al.Vet Clin North Am Food Anim
Pract 2000; 16:255.

14. Geishauser T et al. Am J Vet Res 1997; 58:1216.

15. Geishauser T et al. Can J Vet Res 1998; 62:144.

16. Detilleux JC et al. J Dairy Sci 1997; 80:121.

17. GeishaserT et al. J Dairy Sci 1998; 81:2346.

18. Van Winden SCL et al. J Dairy Sci 2003; 86:1465.

19. Van Winden SCL et al.Vet Rec 2002; 151:446.

20. Pravettoni D et al. Am J Vet Res 2004; 65:1319.

21. Wittek T et al. J Vet Intern Med 2004; 18:574.

22. Constable PD et al. J Am Vet Med Assoc 1992;
201:1564.

23. Wittek T et al. Am J Vet Res 2004; 65:597.

24. Cable CS et al. J Am Vet Med Assoc 1998;
212:1442.

25. Braun U. Vet J 2003; 166:112.

26. Zadnik T. Vet Rec 2003; 153:24.

27. Oikawa S et al. Am J Vet Res 1997; 58:121.

28. Mudron P et al. JVet Med A 1997; 44:91.

29. Geishauser T et al. J Dairy Sci 2000; 83:296.

30. Carrier J et al. J Dairy Sci 2004; 87:3725.

31. Komatsu Y et al. JVet Med A 2002; 49:482.

32. Sevinc M et al. Rev Med Vet 2002; 153:477.

33. Raizman EA, Santos JEP. J Dairy Sci 2002;
85:1157.

34. Rohn M et al. JVet Med A 2004; 51:294-300.

35. Rehage J et al. Schweiz Arch Tierheilkd 1996;
38:361.

36. Rager KD et al. J Am Vet Med Assoc 2004;
225:915.

37. Barrett SC. Cattle Pract 2003; 11:127.

38. Stengarde LU, Pehrson BG. Am J Vet Res 2002;
63:137.

39. Duffield T et al. J Dairy Sci 2003; 86:1171.

40. Duffield T et al. J Dairy Sci 2002; 85:397.

41. Geishauser T et al. Bovine Pract 2000; 34:51.

RIGHT-SIDE DISPLACEMENT OF
THE ABOMASUM AND
ABOMASAL VOLVULUS

Synojpsis'A&siU V ■rv-.' V’'K"Sv;->,

Etiology Abomasal atony associated with
high-level grain feeding. Cause in calves
unknown

Epidemiology Mature dairy cows within
a few weeks of calving. Abomasal volvulus
usually preceded by right-side displacement
of abomasum but not a necessary
precursor. Occurs in calves spontaneously
Signs Inappetence to anorexia, depression,
absence of rumination, scant abnormal
feces, distension of right abdomen, ping
over right flank, fluid-splashing sounds on
ballottement of right flank, distended
abomasum may be palpable rectally.
Abomasal volvulus manifested by anorexia,
abdominal pain, tachycardia, absence of
feces, ping, fluid-splashing sounds, severe
dehydration and shock, and distended and
tense abomasum rectally. High case fatality
rate unless surgically corrected
Clinical pathology Hypokalemia,
hypochloremia, metabolic alkalosis, severe
dehydration

Lesions Gross distension and/or torsion of
abomasum

Diagnostic confirmation Laparotomy
Differential diagnosis Dilatation and
displacement of abomasum: impaction of
abomasum in vagus indigestion, abomasal
ulceration with dilatation, cecal torsion,
chronic or subacute traumatic
reticuloperitonitis. Abomasal volvulus:
intestinal obstruction, acute diffuse
peritonitis. Pings in right abdomen: Right-
side displacement of abomasum, abomasal
volvulus, cecal dilatation, intestinal
obstruction, dilatation of descending colon
and rectum, pneumoperitoneum
Treatment Medical treatment if detected
early. Deflation of distended abomasum.
Surgical correction. Fluid and electrolyte
therapy. Oral fluid and electrolyte therapy
Control Nothing reliable

ETIOLOGY

The etiology of right-side displacement of
the abomasum (RDA) is not well under-
stood but it is probably similar to LDA.
Abomasal atony is thought to be the
precursor of dilatation and displace-
ment, and consequently abomasal
volvulus. The cause of the abomasal
atony and gaseous distension is thought
to be related to the feeding of grain and
the production of excessive quantities of
gas and volatile fatty acids. 1 The dilatation
is thought to be the result of primary
distension of the abomasum occurring
because of either obstruction of the
pylorus or primary atony of the abomasal
musculature. In adult cattle with RDA,
there is no obstruction of the pylorus and
atony of the abomasum seems to be the
more likely cause. In calves, there may be
an obstruction of the pylorus resulting in
dilatation.

EPIDEMIOLOGY
Occurrence and incidence

Lactating dairy cows

Dilatation, RDA and abomasal volvulus
occurs primarily in adult dairy cows,
usually within the period 3-6 weeks after
calving. 2 The disease is being recognized
with increased frequency because of
improvements in diagnostic techniques
and perhaps because more cows are
being fed intensively for milk production.
Incidence data based on individual dairy
herds are not available but based on cases
of abomasal disease admitted to a
veterinary teaching hospital the ratio of
abomasal volvulus to LDA was 1 to 7 A. 2

Beef cattle

Abomasal displacement and volvulus has
been described in beef cattle breeds from
1 month to 6 years of age with a median
age of 10 months. 3 The typical case was
under 1 year of age.

Calves

Abomasal volvulus occurs in young calves
from a few weeks of age up to 6 months,
usually without a history of previous
illness, which suggests that the cause may
be accidental. Abomasal bloat occurs in
calves with no apparent predisposing
cause.

Mature bulls and pregnant cows
Abomasal volvulus has also occurred in
bulls and pregnant cows but to a much
lesser degree.

Risk factors

There is little information available on the
epidemiology of right-side displacement
of the abomasum and abomasal volvulus.
Most of the risk factors described for LDA
are relevant to RDA and abomasal
volvulus. The feeding of high levels of
grain to high-producing dairy cows in
early lactation is considered to be a major
risk factor. However, there are no good
reliable data to support this cause-and-
effect relationship. Why the disease occurs
in a small percentage of high-producing
dairy cattle being fed high-level grain
rations is unknown.

When this disease was originally
described, the incidence appeared to be
higher in Scandinavian countries than
elsewhere. The risk factors in those
situations were not identified but it was
thought that indoor winter feeding and
the shift of the acid-base balance to an
alkalotic state during the winter months
might be important factors. In Denmark,
the ingestion of large quantities of soil
particles on unwashed root crops used as
feed is considered to be significant. This
may be the reason for the higher inci-
dence of the disease in the later part of
the winter. However, attempts to repro-
duce the condition by feeding large

quantities of sand have been unsuccess-
ful. Because atony is often associated with
vagus indigestion, a relationship between
the two has been suspected but there are
usually no lesions affecting the reticulum
or vagus nerves.

A hospital-based epidemiological study
of the risk factors for abomasal volvulus
and FDA was performed using the
medical record abstracts derived from the
veterinary teaching hospitals of 17 North
American veterinary schools. 2 The risk
for abomasal volvulus increased with
increasing age, with a greater risk in dairy
cows 4-7 years of age. Dairy cattle were at
a much higher risk than beef cattle.
Approximately 28% of cases of abomasal
volvulus occurred within the first 2 weeks
and 52% within 1 month following
parturition. This indicates that propor-
tionately fewer cases of abomasal volvulus
than left displacement occur during the
first 2 weeks following parturition. The
hospital case fatality rate for abomasal
volvulus and LDA was 23.5%, and 5.6%,
respectively. 2

It is suggested that abomasal atony is a
prerequisite for the development of right-
side displacement and abomasal volvulus,
and that following parturition the
abdominal void facilitates such develop-
ment. The direction of the displacement
could be influenced predominantly by the
volume of the forestomach. Immediately
after parturition, displacement occurs to
the left because of a reduction in the size
of the rumen volume. Several weeks later
the dilated abomasum moves caudally
and dorsally in the right abdomen
because the volume of the forestomach is
much larger thereby providing an effec-
tive barrier (rumen barrier).

Abomasal volvulus has also occurred
following correction of LDA by casting
and rolling. 4

PATHOGENESIS

Dilatation and displacement phase

In RDA, abomasal atony occurs initially,
resulting in the accumulation of fluid and
gas in the viscus leading to gradual
distension and displacement in a caudal
direction on the right side (dilatation
phase). During the dilatation phase,
which commonly extends over several
days, there is continuous secretion of
hydrochloric acid, sodium chloride and
potassium into the abomasum, which
becomes gradually distended and does
not evacuate its contents into the duo-
denum. This leads to dehydration and
metabolic alkalosis with hypochloremia
and hypokalemia. These changes are
typical of a functional obstruction of the
upper part of the intestinal tract and occur
in experimental RDA and experimental
obstruction of the duodenum in calves.

Diseases of the abomasum

3

The abomasal luminal pressure in

naturally occurring abomasal volvulus is
increased (median 11.7 mmHg; range
4.1-32.4 mmHg). 5 Increased luminal
pressure in abomasal volvulus could
cause mucosal injury by local vascular
occlusion and affect the prognosis.
Among cattle with abomasal volvulus, the
abomasal luminal pressure was signifi-
cantly higher in those that died or were sold
following surgery (median 20.6 mmHg)
than in cattle that recovered and were
retained in the herd (median 11.0 mmHg).
Calculation of likelihood ratios suggest
that selecting cattle with a value of
16 mmHg for luminal pressure optimized
the distribution of cattle into productive
and nonproductive groups.

The abomasal luminal gas pressure
and volume were higher in cattle with an
abomasal volvulus than in cattle with an
LDA. 6 As luminal gas pressure increases,
abomasal perfusion decreases, resulting
in varying degrees of ischemia to the
abomasal mucosa. In cows with an
abomasal volvulus, lactate concentration
in the gastroepiploic vein was greater
than that in the jugular vein, whereas no
difference in lactate concentrations
was detected in cows with an LDA. This
indicates that cattle with a large and
tensely distended abomasum associated
with a volvulus or LDA should have the
viscus decompressed as soon as possible
to minimize the potential for ischemia-
induced injury to the abomasal mucosa,
which may result in ulcers and
perforations.

An experimental model of hypo-
chloremic metabolic alkalosis by

diversion of abomasal outflow in sheep
has been described. 7,8 A similar model in
adult lactating dairy cows resulted in
weakness and depression in 10-12 hours,
dehydration, hypochloremia, hypokalemia,
hypocalcemia and a milk alkalosis. 9

Up to 35 L of fluid may accumulate in
the dilated abomasum of a mature 450 kg
cow, resulting in dehydration, which will
vary from 5-12% of body weight. In
uncomplicated cases, there is only slight
hemoconcentration and a mild electrolyte
and acid-base imbalance, with moderate
distension of the abomasum. These cases
are reversible with fluid therapy. In
complicated cases there is severe hemo-
concentration, hypovolemia and dehy-
dration 10 and marked metabolic alkalosis
with a severely distended abomasum. The
degree of dehydration is a reliable pre-
operative prognostic aid. The hypovolemia,
compression of the caudal vena cava and
stimulation of the sympathetic nervous
system in response to distension and
twisting of the abomasum results in
tachycardia, which is also a reliable
preoperative prognostic aid. 10 _

In cattle with severe and prolonged
abomasal volvulus, a metabolic acl3osis
may develop and be superimposed on the
metabolic alkalosis, leading to a low base
excess concentration of extracellular fluid.
In the experimental disease in sheep, the
metabolic acidosis observed terminally,
was associated with an increase in plasma
lactate concentration probably due
to hypovolemic shock and anaerobic
metabolism. 7 These severe cases require
surgery and intensive fluid therapy. A
paradoxic aciduria may occur in cattle
affected with metabolic alkalosis associ-
ated with abomasal disease. This may be
due to the excretion of acid by the kidney
in response to severe potassium depletion
or to the excretion of acid metabolites as a
result of starvation, dehydration and
impaired renal function. In the experi-
mental model in sheep, renal net acid
excretion decreases and sodium excretion
increases initially, followed by increased
net acid excretion and decreased sodium
excretion resulting in aciduria and marked
sodium conservation. 8

Volvulus phase

Following the dilatation and displace-
ment phase, the distended abomasum
may twist in a clockwise or anticlockwise
(viewed from the right side) direction in a
vertical plane around a horizontal axis
passing transversely across the body in
the vicinity of the omasoabomasal orifice.
The volvulus will usually be of the order
of 180-270° and causes a syndrome of
acute obstruction with local circulatory
impairment and ischemic necrosis of the
abomasum. Detailed examinations of
necropsy specimens of volvulus of the
abomasum indicate that the displace-
ments can occur in a dual axial system.
One system relates to displacements of
the abomasum on a pendulum model, the
point of suspension being situated on the
visceral surface of the liver and the arms
consisting of parts of the digestive tract
adjacent to the abomasum. The other
system comprises axes centered on the
abomasum, about which this organ is able
to rotate without changing its position in
the abdomen. A theoretical analysis of the
types of displacement of the abomasum
that can occur is described.

In some cases the abomasum and
omasum are greatly distended and form a
loop with the cranial part of the duo-
denum. This loop may twist up to 360° in
a counterclockwise direction as viewed
from the rear or from the right side of the
cow. The reticulum is drawn caudally on
the right side of the rumen by its
attachment to the fundus of the abo-
masum. The probable mode of rotation is
in a sagittal plane. Abomasal volvulus with
involvement of the omasum and reticulum

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

does occur but represents only about 5%
of cases. Pressure and tension damage to
the ventral vagal nerve trunk and to the
blood vessels are in part responsible for
the poor prognosis in severe cases, even
after successful surgical correction.

There is speculation that violent exercise
and transportation may be contributory
factors in the pathogenesis of acute
abomasal volvulus, which occurs occasion-
ally in mature cows and young calves
without a history of immediate previous
illness associated with the dilatation
phase. The metabolic changes that occur
are similar to those described above.

Postsurgical complication in right-
side displacement of the abomasum
or abomasal volvulus

A vagus-indigestion-like syndrome may
occur in cattle treated for RDA or abo-
masal volvulus. 11 Possible mechanisms
include: vagus nerve injury, overstretching
of the abomasal wall during prolonged
distension resulting in neuromuscular
junction alterations and autonomic
motility modification, thrombosis and
abomasal wall necrosis, and peritonitis.

CLINICAL FINDINGS

Dilatation and displacement phase

In right-side dilatation and displacement
there is usually a history of calving within
the last few weeks with inappetence and
decreased milk production; the feces are
reduced in amount and are abnormal. The
cow may have been treated for an
uncertain disorder of the digestive tract
within the last several days. Anorexia is
usually complete when the abomasum is
distended. There is usually depression,
dehydration, no interest in feed, perhaps
increased thirst and sometimes muscular
weakness. Affected cows will commonly
sip water continuously. The temperature
is usually normal, the heart rate will vary
from normal to 100/min, and the respir-
ations are usually within the normal
range. The mucous membranes are
usually pale and dry.The reticulorumen is
atonic and the rumen contents (the
rumen pack) feel excessively doughy. The
distended abomasum may be detectable
as a tense viscus on palpation immediately
behind and below the right costal arch.
Ballottement of the middle third of the
right lateral abdomen immediately
behind the right costal arch along with
simultaneous auscultation will reveal
fluid- splashing sounds suggesting a
fluid-filled viscus. In many cases the
dilatation continues and after 3-4 days
the abdomen is visibly distended on the
right side and the abomasum can be
palpated on rectal examination. It may
completely fill the right lower quadrant of
the abdomen and feel tense and filled
with fluid and gas. Percussion and simul-

taneous auscultation over the right
middle to upper third of the abdomen
commonly elicits a characteristic high-
pitched ping.

Volvulus phase

Abomasal volvulus usually develops
several days after the onset of dilatation of
the abomasum but it is usually not poss-
ible to distinguish precisely the stages of
the disease. However, in abomasal
volvulus, the clinical findings are usually
much more severe than during the
dilatation phase. The abdomen is visibly
distended, depression and weakness are
marked, dehydration is obvious, the heart
rate is 100-120/min and respirations are
increased. Recumbency with a grossly
distended abdomen and grunting may
occur and represents a poor prognosis. A
rectal examination is very important at this
stage. In the dilatation stage the partially
distended abomasum may be palpable
with the tips of the fingers in the right
lower quadrant of the abdomen. It may not
be palpable in large cows. In the volvulus
phase, the distended tense viscus is usually
palpable in the right abdomen anywhere
from the upper to the lower quadrant.

The feces are usually scant, soft and
dark in color. The soft feces must not be
mistaken for diarrhea, as is commonly
done by the owner of the animal. Cattle
with abomasal volvulus usually become
recumbent within 24 hours after the onset
of the volvulus. Death usually occurs in
48-96 hours from shock and dehydration.
Rupture of the abomasum may occur and
cause sudden death.

Acute abomasal volvulus
(adult cattle)

In acute abomasal volvulus in adult cattle
there is a sudden onset of abdominal pain
with kicking at the abdomen, depression
of the back and crouching. The heart rate
is usually increased to 100-120/min, the
temperature is subnormal and there is
peripheral circulatory failure. The animal
feels cool and the mucous membranes are
pale, diy and cool. The abdomen is grossly
distended on the right side and auscul-
tation and percussion reveal the tympanitic
sounds of a gas-filled viscus. Fluid-
splashing sounds are audible on per-
cussion. Fhracentesis of the distended
abomasum will usually reveal large
quantities of blood-tinged fluid with a pH
of 2-4. The distended abomasum can
usually be palpated on rectal examination
but the torsion may have moved it in a
cranial direction and not uncommonly
these are not as readily palpable as when
only dilated. The feces are scant, soft and
dark in color and become blood-stained
or melenic in the ensuing 48 hours if the
cow lives long enough. In some cases
there is profuse watery diarrhea.

Acute abomasal volvulus (calves)

In calves with acute abomasal volvulus, -
there is a sudden onset of anorexia, acute
abdominal pain with kicking at the belly,
depression of the back, bellowing and
straining. The heart rate is usually
120-160/min, the abdomen is distended
and tense, and auscultation and per-
cussion over the right abdomen reveal
distinct high-pitched pings. Palpation
behind the right costal arch reveals a
tense viscus that is painful on even
moderate palpation.

Abomasal displacement and volvulus
in beef cattle

Abdominal distension, anorexia and colic
are common historical findings. 3 Clinically,
there is abdominal distension, tachycardia
and colic, and a high-pitched ping is
audible on percussion over the right side
of the abdomen. A distended gas-filled
viscus is commonly palpable on rectal
examination. The course of the disease in
beef cattle appears to be more protracted
than in dairy cattle.

Postsurgical complication in
abomasal volvulus

The most frequent complication en-
countered following surgical correction of
RDA and abomasal volvulus resembles
vagus indigestion, which occurs in
14-21% of cases. 11 The case fatality rate is
high, with only 12-20% of affected
animals returning to normal production.
In affected cattle, there is ruminal dis-
tension, rumen hypermotility or atony,
and abnormal feces (usually scant and dry).

CLINICAL PATHOLOGY
Serum biochemistry

There are varying degrees of hemo-
concentration (increased PCV and total
serum proteins), metabolic alkalosis,
hypochloremia and hypokalemia.

The severity of volvulus can be
classified, and the prognosis evaluated,
according to the amount of fluid in the
abomasum and the concentration of
serum chloride and the heart rate:

° Group 1 - abomasum distended
principally with gas

° Group 2 - abomasum distended with
gas and fluid, and surgical reduction
possible without removal of fluid
'• Group 3 - abomasum distended with
gas and fluid, 1-29 L of fluid removed
before reduction of abomasum
° Group 4 - abomasum distended with
gas and fluid, more than 30 L of fluid
removed before reduction of torsion.

The serum chloride levels and heart rates
before surgery are also valuable prog-
nostic aids. Cows classified as group 3 or
4 or those having presurgical chloride levels
equal to or below 79 mEq/L (79 mmol/L)

Diseases of the abomasum

3i

or pulse rates of 100/min or more have a
poor prognosis.

The base excess concentration of the
extracellular fluid can be a useful prog-
nostic and diagnostic indicator in cows
with abomasal volvulus or right displace-
ment of the abomasum. In one retro-
spective study cows with a base excess of
± 5.0 mEq/L (5.0 mmol/L) had abomasal
torsion rather than displacement. The
survival rate of cows with abomasal
volvulus was 50% with a base excess
± 0.1 mEq/L (0.1 mmol/L), whereas it was
84% if the base excess was + 10.0 mEq/L
(10.0 mmol/L).

A cross-sectional study of the serum
electrolyte and mineral concentrations in
dairy cows with abomasal displacement
or volvulus at the time of on-farm diag-
nosis found lower serum calcium, phos-
phorus, magnesium, potassium and
chloride levels and an increase in the
anion gap compared to controls. 12

Urinalysis

Paradoxic aciduria may also be present.

Hemogram

The total and differential leukocyte count
may indicate a stress reaction in the early
stages, and in the later stages of volvulus
there may be leukopenia with a neutro-
penia and degenerative left shift due to
ischemic necrosis of the abomasum and
early peritonitis.

Abomasocentesis

Centesis of the distended abomasum will
yield large quantities of fluid without
protozoa and a pH of 2-4. The fluid may
be serosanguineous when volvulus is
present.

PROGNOSTIC INDICATORS

Several clinical and laboratory findings
have been examined as prognostic indi-
cators of cows affected with RDA and
abomasal volvulus. In one series of 458
cows with right displacement or abomasal
volvulus, a decreased temperature and
tachycardia when first examined indi-
cated a poor prognosis. 13 Using multiple
logistic regression of three admission
variables (heart rate, base excess and
plasma chloride) and five surgical variables
(heart rate, base excess, diagnosis,
method of decompression and appear-
ance of abomasal mucosa), it was possible
to predict the outcomes with a high
degree of accuracy. 14 In another series of
80 cattle with abomasal volvulus, the
heart rate, hydration status, period of
inappetence and serum alkaline phos-
phatase were the best preoperative
prognostic indicators. 10 An anion gap of
30 mEq/L was indicative of a poor
prognosis and was more accurate than
either serum chloride or base excess
values. 15 The surgical and postoperative

findings in cattle with abomasal volvulus
are good prognostic indicators of out-
come. 16 Cattle with omasal-abomasal
volvulus have a worse prognosis than
those without omasal involvement. Large
abomasal fluid volume, venous throm
bosis and blue or black abomasal color
before decompression are all indicative of
a poor prognosis.

The evaluation of the degree of circu-
latory insufficiency, dehydration and
levels of base excess and blood lactate are
also used but are less reliable. Post-
operatively decreased gastrointestinal
motility is an unfavorable prognostic sign.

NECROPSY FINDINGS

In abomasal dilatation the abomasum is
grossly distended with fluid and some
gas. The rumen may contain an excessive
amount of fluid. In some cases there may
be impaction of the pylorus with particles
of soil or sand and there may be an
accompanying pyloric ulcer. In abomasal
volvulus the abomasum is grossly
distended with brownish, sanguineous
fluid and is twisted usually in a clockwise
direction (viewed from the right side),
often with displacement of the omasum,
reticulum and abomasum. In complete
volvulus the wall of the abomasum is
grossly hemorrhagic and gangrenous and
may have ruptured.

DIFFERENTIAL DIAGNOSIS

The diagnosis and differential diagnosis of
right-side dilatation, displacement and
volvulus of the abomasum is dependent on
consideration of the presence or absence
of pings in the right abdomen, the findings
on rectal examination and the other clinical
findings, including the history. Detecting a
ping on percussion and auscultation of the
right abdomen must be accompanied by a
rectal examination to determine the
presence and nature of a gas-filled viscus
to account for the ping.

Dilatation and displacement of
abomasum

The characteristic features of dilatation and
right-sided displacement of the abomasum
are: recent calving, a vague indigestion
since calving, soft scant feces, a ping over
the right abdomen and the presence of the
distended tense viscus in the right lower
abdomen. It must be differentiated from
the following:

• Impaction of the abomasum

associated with vagus indigestion is

characterized by an enlarged abomasum
that pits on digital palpation and feels
like a doughy mass behind the lower
aspect of the costal arch, situated on the
floor of the abdomen, whereas most
cases of dilatation are situated more
dorsally adjacent to the right paralumbar
fossa. Pings are not present in abomasal
impaction. A laparotomy may be
required to distinguish between them

• Subacute abomasal ulceration with
moderate dilatation of the abomasum
in a recently calved cow may not be
distinguishable clinically from RDA. The
presence of melena suggests abomasal
ulcers but these may be present as
secondary complications in dilatation
and RDA

• Cecal torsion is characterized by
distension of the right flank, tympanitic
sounds on auscultation and percussion,
and the cecum can usually be palpated
and identified tentatively, on rectal
examination, as a long (60-80 cm),
usually easily movable, cylindrical, tense
tube (10-20 cm in diameter), with a
blind sac

• Fetal hydrops is characterized by
bilateral distension of the lower
abdomen and an enlarged gravid uterus
palpable on rectal examination

• Chronic or subacute traumatic
reticuloperitonitis may resemble
abomasal dilatation but in the former
there may be a grunt on deep palpation,
the feces are usually firm and dry, the
abdomen is gaunt and a mild fever may
be present. However, a laparotomy may
be necessary to make the diagnosis.
Abdominocentesis may be useful

• Abomasal volvulus is characterized by
abdominal distension of the right side,
pings on percussion and auscultation,
dehydration, weakness and shock with
a heart rate up to 120/min. The
distended viscus can usually be palpated
in the right lower quadrant of the
abdomen. It must be differentiated from
the following:

• Intestinal obstruction is characterized
by a history of sudden onset of
anorexia, abdominal pain, scant
feces, which may be blood-tinged,
and the affected portion of the
intestines or loops of distended
intestine may be palpable rectally

• Acute diffuse peritonitis as a sequel
to local peritonitis in a cow soon
after calving may be indistinguishable
from acute abomasal volvulus. There
is severe toxemia, tachycardia,
dehydration, abdominal distension,
grunting, weakness, recumbency and
rapid death. Paracentesis of the
peritoneal cavity will assist in the
diagnosis

Pings over the right abdomen

Diseases resulting in pings over the right
abdomen include dilatation and distension
of the abomasum, cecum, cranial
duodenum, parts of the small intestine,
descending colon and rectum and
pneumoperitoneum.

The evaluation of a ping is dependent
upon the size of the area and location of
the sound elicited by percussion and
simultaneous auscultation. The common
clinical characteristics of these pings are as
follows:

• Dilatation and right-side displacement
of the abomasum: the ping is usually
audible between the ninth and 12th ribs
extending from the costochondral
junction of the ribs to their proximal third
aspects. Rarely will the ping extend into
the paralumbar fossa in right-side
dilatation and displacement

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

• Abomasal volvulus: the area of the
ping is typically larger than that of the
RDA and extends more cranially and
caudally, often extending into the right
paralumbar fossa but not completely
filling the fossa. Also, the ventral border
of the ping area in an abomasal volvulus
is variable, often horizontal because of
the level of fluid within the abomasum

• Cecal dilatation: the ping is usually
confined to the dorsal paralumbar fossa
and caudal one or two intercostal
spaces. In dilatation and torsion of the
cecum the ping usually fills the
paralumbar fossa and extends cranially
and caudally the equivalent of two rib
spaces. The ascending colon is often
involved in a torsion of the cecum,
which will result in an enlarged ping
area extending from the paralumbar
fossa. In dilatation of the ascending
colon the ping may be centered over
the proximal aspects of the 12th and
13th ribs

• Intestinal obstruction: the presence of
multiple, small areas of ping that vary in
pitch and intensity is characteristic of
dilatation of the jejunoileum caused by
intussusception or intestinal volvulus

• Dilatation of descending colon and
rectum: a ping in the right caudal
abdomen just ventral to the transverse
processes of the vertebrae indicates
dilatation of the descending colon and
rectum, which is commonly heard
following rectal examination

• Pneumoperitoneum: pings may be
audible over a wide area of the dorsal
third of the abdomen bilaterally. In one
study, the sensitivity and predictive
values of abomasum as the source of
the ping were 98% and 96%
respectively; for cecum and/or
ascending colon, the sensitivity and
predictive values were both 87%

TREATMENT

The prognosis in right-side dilatation,
displacement and volvulus is favorable if
the diagnosis is made within a few days
after the onset of clinical signs and before
large quantities of fluid accumulate in the
abomasum. Slaughter for salvage may be
the best course of action for cattle of
commercial value. Cows with consider-
able economic worth can be treated as
outlined here. Not all cases require
surgical correction: medical treatment is
possible in mild cases.

Medical therapy for mild cases

In mild cases of dilatation and minimal
displacement with a mild systemic
disturbance, empirical treatment with
500 mL of 25% calcium borogluconate
intravenously may yield good results. The
rationale for the calcium administration is
to improve abomasal motility. Affected
cows are also offered good-quality hay but
no grain for 3-5 days and monitored
daily. Surgical correction may not be
necessary if the appetite and movements

of the alimentary tract return to normal in
a few days. The ping in the right abdomen
may gradually become smaller in 2-3 days
and eventually disappear.

In mild cases of dilatation with only
slight hemoconcentration and metabolic
alkalosis, early treatment with fluids and
electrolytes intravenously and orally will
often yield good results. The fluid therapy
is essential to restore motility of the
gastrointestinal tract, particularly the
abomasum, which is distended with fluid
and must begin evacuating its contents
into the duodenum for absorption of the
electrolytes to occur. The cow will usually
not regain her appetite until the abomasal
atony has been corrected.

A combination of hyoscine-butyl
bromide and dipyrone and fasting has
been recommended based on field
experience. 17 Recovery occurred in about
77% of affected cows within 48 hours.

Deflation of distended abomasum in
calves

Gas can be removed from a grossly
distended (bloated) abomasum of calves
as an emergency measure prior to surgical
correction 18 by laparotomy. The calf is
placed in dorsal recumbency and the
abdomen is punctured with a 16- gauge
12 cm hypodermic needle at the highest
point of the distended abdomen between
the umbilicus and the xiphoid. After the
distension is relieved and fluid therapy is
begun, the need for a laparotomy can be
assessed and performed if necessary.

Surgical correction

In the more advanced cases of dilatation,
displacement and volvulus, a right flank
laparotomy for drainage of the distended
abomasum and correction of the volvulus
j if present is necessary. The surgical tech-
I niques in common use have been
I described. Intensive fluid therapy is usually
i necessary preoperatively and for several
| days postoperatively to correct the dehy-
dration and metabolic alkalosis and to
restore normal abomasal motility. Electro-
myographic studies of the postoperative
abomasal and duodenal motility reveal
loss of motility, some retrograde motility
and loss of spike activity. Cholinergics
have been used to help restore motility
but are not reliable. Rumen transplants to
restore rumen function and appetite will
provide a more effective stimulus to restore
gastrointestinal tract motility.

Postsurgical complications resembling
a vagus-indigestion-like syndrome have
been described 11 (see under Clinical
findings, above) .

Fluid and electrolyte therapy

The composition of the fluids and
electrolyte solutions that are indicated in
RDA and abomasal volvulus has been a

subject of much investigation. There are
varying degrees of dehydration, meta-
bolic alkalosis, hypochloremia and
hypokalemia. With the aid of a labor-
atory it is possible to monitor the serum
biochemistry during administration of the
fluids and electrolytes and to correct
certain electrolyte deficits by adding
('spiking') the appropriate electrolytes to
the fluids. Without a laboratory, the
veterinarian has no choice but to use the
solutions that are considered safe and
judicious. Balanced electrolyte solu-
tions containing sodium, chloride,
potassium, calcium and a source of
glucose will commonly suffice. A mixture
of 2 L of isotonic saline (0.85%), 1 L of
isotonic potassium chloride (1.1%) and
1 L of isotonic dextrose (5%) given at the
rate of 4-6 L/h intravenously is also
recommended and reliable. Experimentally
induced hypochloremic, hypokalemic
metabolic alkalosis in sheep has
been corrected using 0.9 (300 mosmol/L),
3.6 (1200 mosmol/L) and 7.2%

(2400 mosmol/L) of sodium chloride
solutions given intravenously 19 over a 2-
hour period with the administered
volume determined by the estimated total
extracellular fluid chloride deficit. Signifi-
cant difference was not found among
treatments, with all solutions resulting in
return of clinicopathologic variables to
pre-experimental values within 12 hours.
It is suggested that rapid intravenous
replacement of chloride with small
volumes of hypertonic saline solution is
safe and effective for correction of
experimentally induced hypochloremic,
hypokalemic metabolic alkalosis in sheep.
Clinical trials are needed to evaluate the
efficacy of hypertonic saline solution
(7.2%) for the correction of naturally
occurring right-side displacement and
volvulus of the abomasum.

Acidifying solutions

Isotonic solutions of potassium chloride
and ammonium chloride (KC1 108 g,
NH 4 C1 80 g, H 2 0 20 L) will provide a
source of potassium and chloride and will
correct the alkalosis. This solution can be
given intravenously at the rate 20 L over
4 hours to a 450 kg cow. This may be
followed by the use of balanced electro-
lyte solutions at the rate of 100-150 mL/kg
BW over a 24- hour period. However,
acidifying solutions such as potassium
chloride and ammonium chloride must
be used carefully and ideally the serum
biochemistry should be monitored every
hour to insure that acidosis does not
occur. The above solutions are considered
safe when given as described. Normal
saline is also effective and potassium
solutions may not be necessary unless
- there is severe hypokalemia.

Diseases of the abomasum

3

Oral therapy

Oral electrolyte therapy has been
recommended, particularly in the post-
operative period following surgical
drainage of the distended abomasum. A
mixture of sodium chloride (50-100 g),
potassium chloride (50 g) and ammonium
chloride (50-100 g) is given orally daily
postoperatively along with the parenteral
fluids as necessary. Treatment with
potassium chloride (50 g/day) orally can
be continued daily until the cow resumes
her normal appetite.

CONTROL

No reliable information is available on the
control of right-side dilatation, displace-
ment and volvulus of the abomasum.
Because its pathogenetic mechanism is
similar to LDA it would seem rational to
recommend feeding programs that are
used for the control of LDA.

REVIEW LITERATURE

GeishauserT. Abomasal displacement in the bovine -
a review on character, occurrence, etiology and
pathogenesis. J Vet Med A 1995; 42:229-251.

REFERENCES

1. GeishauserT. J Vet Med A 1995; 42:229.

2. Constable PD et al. Am J Vet Res 1992; 53:1184.

3. Roussel AJ et al. J Am Vet Med Assoc 2000;
216:730.

4. St Jean G et al. ComellVet 1989; 79:345.

5. Constable PD et al. J Am Vet Med Assoc 1992;
201:1564.

6. Wittek T et al. Am JVet Res 2004; 65:597.

7. Smith DF et al. Am JVet Res 1990; 51:1715.

8. Lunn DP et al. Am JVet Res 1990; 51:723.

9. Ward JL et al. Can JVet Res 1994; 58:13.

10. Constable PD et al. J Am \fet Med Assoc 1991;
198:2077.

11. Sattier N et al. Can Vfet J 2000; 41:777.

12. Delgardo-Lecaroz R et al. Can Vet J 2000; 41:301.

13. Fubini SL et al. J Am Vet Med Assoc 1991;
198:460.

14. Grohn YT et al. Am JVet Res 1990; 51:1895.

15. Garry FB et al. J Am Vet Med Assoc 1988;
192:1107.

16. Constable PD et al. J Am \fet Med Assoc 1991;
199:892.

17. Buchanan M et al.Vet Rec 1991; 129:111.

18. Kumper H. Bovine Pract 1995; 29:80.

19. Ward JL et al. Am JVet l<es 1993; 54:1160.

DIETARY ABOMASAL IMPACTION
IN CATTLE

Dietary abomasal impaction occurs in
cattle in the prairie provinces of western
Canada during the cold winter months,
and elsewhere with similar circumstances,
when the animals are fed poor-quality
roughage. The disease is most common in
pregnant beef cattle which increase their
feed intake during extremely cold weather
in an attempt to meet the increased needs
of a higher metabolic rate.’ The disease has
also occurred in feedlot cattle fed a variety
of mixed rations containing chopped or
ground roughage (straw, hay) and cereal
grains and in late pregnant dairy cows on
similar feeds.

[.Synopsis

Etiology Ingestion of large quantities of
low-quality roughage during cold weather
Epidemiology Pregnant primiparous
beef cattle during cold weather consuming
low-quality roughage

Signs Anorexia, scant feces, distension of
abdomen, loss of body weight. Normal
vital signs initially. Rumen full and atonic.
Right lower flank distended and may be
able to palpate abomasum through
abdominal wall and recta I ly. Gradually
become weak and recumbent
Clinical pathology Metabolic alkalosis,
hypochloremia, hypokalemia
Lesions Gross enlargement of abomasum
impacted with dry, rumen-like contents
Diagnostic confirmation Laparotomy
Differential diagnosis Impaction of
abomasum associated with vagus
indigestion, impaction of omasum, diffuse
peritonitis, intestinal obstruction
Treatment Slaughter for salvage. Medical
treatment with dioctyl sodium
sulfosuccinate. Abomasotomy
Control Provide nutrient requirements for
pregnant beef cattle during cold weather

ETIOLOGY AND EPIDEMIOLOGY

The consumption of excessive quantities
of poor-quality roughage which are low in
both digestible protein and energy is
the primary cause.’ Impaction of the
abomasum with sand can also occur in
cattle if they are fed hay on sandy soils or
root crops that are sandy or dirty. 2
Outbreaks of impaction with sand have
occurred in which up to 10% of cattle at
risk were affected.

The disease occurs most commonly in
young pregnant beef cows that are kept
outdoors year-round, including during
the cold winter months, when they are
fed roughages consisting of either grass or
legume hay or cereal straw, which may or
may not be supplemented with some
grain. In these circumstances cows com-
monly lose 10-15% of their total body
weight from October to May and even
more during very cold winters. In one
retrospective study of the necropsy
reports of cattle that died with abomasal
impaction, 20% of the animals had
lesions of traumatic reticuloperitonitis,
60% were thought to be due to the
ingestion of too much poor-quality
roughage without a supplement of
concentrate, and 20% did not fit into
either category. 3

When large quantities of long rough-
age without sufficient grain are fed during
very cold weather, the cattle cannot eat
sufficient feed to satisfy energy needs, so
that the roughage is then provided in a
chopped form. The chopped roughage is
commonly mixed with some grain in a
mix mill but usually at an insufficient level
to meet the energy requirements. Cattle

can and do eat more of these chopped
roughage-grain mixtures than of long
roughage because the smaller particles
pass through the forestomachs at a more
rapid rate. But impaction of the abo-
masum, omasum and rumen may occur
because of the relative indigestibility of
the roughage. Outbreaks may occur
affecting up to 15% of all pregnant cattle
on individual farms when the ambient
temperature drops to -5 to -10°C (14 to
-22°F) for several days.

Omasal and abomasal impaction has
occurred in a group of beef suckler cows
in late gestation housed in straw yards
and fed solely on pea haulum. 4 The
disease has also occurred in feedlot cattle
fed similar rations (e.g. 80% roughage,
20% grain) in an attempt to reduce the
high cost of grain feeding and to satisfy
beef grading standards that put the
emphasis on producing a smaller amount
of fat cover. With these constraints and
the increased emphasis on roughage
feeding, it is possible that the incidence of
abomasal impaction may increase in
feedlot cattle. The feeding of almond
shells to dairy replacement heifers has
also resulted in abomasal impaction. 5

The ingestion of gravel (stones) by dairy
cattle kept in dry-lot facilities can result in
complete, nonstrangulating intraluminal
obstruction of the abomasum and duo-
denum. 6 The gravel, consisting of sand
and small stones, may be inadvertently
mixed with the feed when it is being
scraped from bunker silos. It is also
possible that some cows may ingest the
gravel through pica.

PATHOGENESIS

Chopped roughage and finely ground
feeds pass through the forestomachs of
ruminants more quickly than long
roughage and perhaps in this situation
the combination of low digestibility and
excessive intake leads to excessive
accumulation in the forestomachs and
abomasum.

When large quantities of sand are
ingested, the omasum, abomasum, large
intestine and cecum can become impacted.
The sand that accumulates in the abo-
masum causes abomasal atony and
chronic dilatation.

Once impaction of the abomasum
occurs, a state of subacute obstruction of
the upper alimentary tract develops.
The hydrogen and chloride ions are
continually secreted into the abomasum
in spite of the impaction and atony and
an alkalosis with hypochloremia results.
Varying degrees of dehydration occur
because fluids are not moving beyond
the abomasum into the duodenum for
absorption. Potassium ions are also
sequestered in the abomasum, resulting

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases oT the alimentary tract - II

in a hypokalemia. Almost no ingesta
or fluids move beyond the pylorus,
and dehydration, alkalosis, electrolyte
imbalance and progressive starvation
occur. The impaction of the abomasum is
usually severe enough to cause per-
manent abomasal atony.

CLINICAL FINDINGS

Complete anorexia, scant feces and
moderate distension of the abdomen are
the usual presenting complaints given by
the owner. The onset is usually slow and
progressive over a period of several days.
Cattle that have been affected for several
days have lost considerable weight and
are too weak to rise. The body tempera-
ture is usually normal but may be
subnormal during cold weather, which
suggests that the specific dynamic action
of the rumen is not sufficient to meet
the energy needs of basal metabolism.
The heart rate varies from normal to
90-100/min and may increase to 120/min
in advanced cases where alkalosis, hypo-
chloremia and dehydration are marked.
The respiratory rate is commonly increased
and an expiratory grunt due to the
abdominal distension may be audible,
especially in recumbent cattle. A mucoid
nasal discharge usually collects on the
external nares and muzzle, which is
usually dry and cracking because of the
failure of the animal to lick its nostrils and
the effects of the dehydration.

The rumen is usually static and full of
dry rumen contents, or it may contain an
excessive quantity of fluid in those cattle
that have been fed finely ground feed. The
pH of the ruminal fluid is usually within
the normal range (6.5-7.0). The rumen
protozoan activity ranges from normal to
a marked reduction in numbers and
activity as assessed on a low-power field.
The impacted abomasum is usually
situated in the right lower quadrant of the
abdomen on the floor of the abdominal
wall. It usually extends caudally beyond
the right costal arch but may or may not
be easily palpable because of the gravid
uterus, but an impacted omasum may
also be palpable. It may be impossible,
however, to distinguish between an
impacted abomasum and an impacted
omasum. In feedlot steers and non-
pregnant heifers the impacted abomasum
and omasum may be easily palpable on
rectal examination. Deep palpation and
strong percussion of the right flank may
elicit a 'grunt' as is common in acute
traumatic reticuloperitonitis, and this is
probably due to overdistension of the
abomasum and stretching of its serosa.

The course of the disease depends on
the extent of the impaction when the
animal is first examined and the severity
of the acid-base and electrolyte imbalances.

Severely affected cattle will die in 3-6 days
after the onset of signs. Rupture of the
abomasum has occurred in some cases
and death from acute diffuse peritonitis
and shock occurs precipitously in a few
hours. In sand impaction, there is con-
siderable weight loss, chronic diarrhea
with sand in the feces, weakness, recum-
bency and death within a few weeks.

Severe impaction and distension of the
rumen and the abomasum can occur in
cattle given access to large quantities of
finely chopped straw during the cold
winter months. There is gross distension
of the abdomen, anorexia, scant dry feces,
and affected animals will drop large, dry,
fibrous cuds. The rumen is grossly
distended and usually static.

Cows fed solely on pea haulm are dull
and anorexic with grossly distended
abdomens and varying degrees of bloat. 4
Cattle with obstruction of the abomasum
and duodenum with gravel are anorexic,
depressed and weak. 6 The abdomen may
be distended and rumen hypomotility or
atony is present. The feces are scant. The
obstruction cannot usually be felt on
rectal examination and a right flank
laparotomy is necessary to make the
diagnosis. A marked hypochloremic,
hypokalemic metabolic alkalosis is
characteristic.

CLINICAL PATHOLOGY

A metabolic alkalosis, hypochloremia,
hypokalemia, hemoconcentration and a
total and differential leukocyte count
within the normal range are common.

NECROPSY FINDINGS

At necropsy the abomasum is commonly
grossly enlarged to up to twice normal
size and impacted with dry rumen-like
contents. The omasum may be similarly
enlarged and impacted with the same
contents as in the abomasum. The rumen ;
is usually grossly enlarged and filled with \
dry ruminal contents or ruminal fluid. The
intestinal tract beyond the pylorus is ;
characteristically empty and has a dry ;
appearance. Varying degrees of dehy-
dration and emaciation are also present. If ■
rupture of the abomasum occurs, lesions ;
of acute diffuse peritonitis are present. [
Abomasal tears, ulcers, and necrosis of

l

the walls of the rumen, omasum or ;
abomasum may occur. 3 \

TREATMENT
Salvage or treatment?

The challenge in treatment is to be able to ;
recognize the cases that will respond to
treatment and those that will not and
should therefore be slaughtered immedi-
ately for salvage. Those that have a I
severely impacted abomasum and are I
weak with a marked tachycardia ;
(100-120/min) are poor treatment risks

DIFFERENTIAL DIAGNOSIS

The clinical diagnosis of impacted
abomasum depends on the nutritional
history, the clinical evidence of impaction
of the abomasum and the laboratory
results. The disease must be differentiated
from abomasal impaction as a
complication of vagus indigestion, omasal
impaction, diffuse peritonitis and acute
intestinal obstruction due to intestinal
accidents or enteroliths and lipomas.

• Impaction of the abomasum as a
complication of traumatic
reticuloperitonitis usually occurs in
late pregnancy, commonly only in one
animal; a mild fever may or may not be
present and there may be a grunt on
deep palpation of the xiphoid. The
rumen is usually enlarged and may be
atonic or hypermotile. Depending on
the lesion present a neutrophilia may be
present, suggestive of a chronic
infection. A hypochloremia is common,
as in dietary impaction. In many cases it
is impossible to distinguish between the
two causes of impacted abomasum and
a laparotomy may be necessary to
explore the abdomen for evidence of
peritoneal lesions. Cattle with abomasal
impaction as a complication of
traumatic reticuloperitonitis are usually a
single incident and have usually been ill
for several days, whereas those with
dietary impaction have usually been ill
for only a few days and more than one
may be affected 3

• Impaction of the omasum occurs in
advanced pregnancy and is
characterized by anorexia, scant feces,
normal rumen movements, moderate
dehydration and an enlarged omasum
that may be palpable per rectum or
behind the right costal arch. The serum
electrolytes may be within normal limits
if the abomasum is normal

• Diffuse peritonitis is characterized by
anorexia, toxemia, dehydration, scant
feces and a grunt on deep palpation
and percussion. However, in peracute
cases the abdominal pain may be
absent. Fibrinous adhesions may be
palpable on rectal examination, and
paracentesis may yield some diagnostic
peritoneal exudate, but a negative result
cannot rule out peritonitis. The presence
of a marked leukopenia and
neutropenia or a neutrophilia may assist
in the diagnosis, but it is often
necessary to perform an exploratory
laparotomy to confirm the diagnosis

• Intestinal obstructions due to
intestinal accidents or enteroliths result
in anorexia, scant feces, dehydration
and abdominal pain, and the
abnormality may be palpable on rectal
examination. The rumen is usually static
and filled with doughy contents. Fluid
and gas accumulations in the intestines
anterior to the obstruction may be
detectable as fluid-splashing sounds by
using simultaneous auscultation and
succussion of the abdomen

Diseases of the abomasum

369

and should be slaughtered. Rational
treatment would appear to consist of
correcting the metabolic alkalosis, hypo-
chloremia, hypokalemia and dehydration
and attempting to move the impacted
material with lubricants and cathartics, or
surgically emptying the abomasum.
Balanced electrolyte solutions are infused
intravenously on a continuous basis for
up to 72 hours at a rate of 100-150 mL/kg
BW over a 24-hour period. Some cases
will respond remarkably well to this fluid
therapy and begin ruminating and
passing feces in 48 hours. The use of
acidifying isotonic solutions of mixtures
of ammonium chloride and potassium
chloride at a rate of 20 L per 24-hour
period for a 450 kg animal as described
under the treatment for RDA is also
recommended.

Dioctyl sodium sulfosuccinate is

administered into the rumen by stomach
tube at a dose rate of 120-180 mL of a
25% solution for a 450 kg animal repeated
daily for 3-5 days. It is mixed with 10 L
of warm water and 10 L of mineral oil.
The amount of mineral oil can be
increased to 15 L/d after the third day and
for a few days until recovery is apparent.
A beneficial response cannot be expected
in less than 24 hours and most cattle that
do respond will show improvement by
the end of the third day after treatment
begins. Cholinergics such as neostigmine,
physostigmine and carbamylcholine have
been used but appear not to alter the
outcome.

Surgery

Surgical correction consists of an
abomasotomy through a right para-
median approach and removal of the
contents of the abomasum. The results are
often unsuccessful, probably because of
abomasal atony that exists and that
appears to worsen following surgery. 7 An
alternative approach may be to do a
rumenotomy, empty the rumen and
infuse dioctyl sodium sulfosuccinate
directly into the abomasum through the
reticulo-omasal orifice in an attempt to
soften and promote the evacuation of the
contents of the abomasum. The place-
ment of a nasogastric tube into the
omasal groove and into the abomasum
through a rumenotomy procedure is
described. Mineral oil can then be
pumped into the abomasum at the rate of
2 L/day for several days. Recovery should
occur within 5-7 days. A rumenotomy
and emptying of the rumen is necessary
in the case of severe straw impaction of
the rumen.

The induction of parturition using
20 mg of dexamethasone intramuscularly
may be indicated in affected cattle that are
within 2 weeks of term and in which the

response to a few days' treatment has
been unsuccessful. Parturition may assist
recovery as a result of a reduction in intra-
abdominal volume. In sand impaction,
affected cattle should be moved off the
sandy soil and fed good hay and a grass
mixture containing molasses and
minerals. Severely affected cattle should
be treated with large daily doses of
mineral oil - at least 15 L/d.

Gravel obstruction of the abomasum
and duodenum can be corrected surgically
by right flank laparotomy. 6

CONTROL

Provision of nutrient requirements
during cold weather

Prevention of the disease is possible by
providing the necessary nutrient require-
ments for wintering pregnant beef cattle
with added allowances for cold windy
weather when energy needs for main-
tenance are increased. When low-quality
roughage is to be used for wintering preg-
nant beef cattle, it should be analyzed for
crude protein and digestible energy.
Based on the analysis, grain is usually
added to the ration to meet the energy
and protein requirements. 1 Pregnant beef
cows fed a diet of 94% barley straw for 83
days during the cold winter months may
consume only 70% of their energy
requirements. 1 Such straw-based diets
must be supplemented with protein and
energy. 1 During prolonged periods of cold
weather, wintering pregnant beef cattle
should be given additional amounts of
feed to meet the increased feed require-
ment for maintenance, which has been
estimated to be 30-40% greater during
the colder months than during the
warmer months. These increased require-
ments are due almost equally to the
effects of reduced feed digestibility and
the increased maintenance requirements. 8

Nutrient requirements for beef cattle

The published nutrient requirements of
beef cattle are guidelines for the nutrition
of cattle under average conditions and
higher nutrient levels than those indi-
cated may be necessary to provide for
maintenance requirements, particularly
during periods of cold stress. 9 Adequate
amounts of fresh drinking water
should be supplied at all times and the
practice of forcing wintering cows to
obtain their water requirements from
eating snow while on low-quality rough-
age is extremely hazardous. The question
of whether or not low- quality roughages
should be chopped or ground for wintering
pregnant beef cattle is controversial. The
daily voluntary intake of low-quality
roughage can be increased by chopping
or grinding but neither processing
method increases quality or digestibility;
in fact digestibility is usually decreased. If

increased consumption during cold
weather exceeds physical capacity and the
nutrient requirements are still not satisfied,
impaction of the abomasum may occur.
Thus during the coldest period of the
winter low-quality roughages must be
supplemented with concentrated sources
of energy such as cereal grains. 10

Avoid excessive fiber

Omasal and abomasal impaction due to
the provision of excessive poor-quality
roughage is preventable by supple-
mentation with appropriate sources of
energy and protein.

REFERENCES

1. Mathison GW et al. Can J Anim Sci 1981; 61:375.

2. Hunter R. J Am Vet Med Assoc 1975; 166:1179.

3. Ashcroft RA. Can Vet J 1983; 24:375.

4. Simkins KM, Nagele MJ.Vet Rec 1997; 141:466.

5. Mitchell KJ. J Am Vet Med Assoc 1991; 198:1408.

6. Cebra CK et al. J Am Vet Med Assoc 1996;
209:1294.

7. Blikslager AT et al. Compend Contin Educ Pract
Vet 1993; 15:1571.

8. Christopherson RJ. J Anim Sci 1976; 56:201.

9. National Research Council. Nutrient require-
ments of beef cattle, 7th ed. Washington, DC:
National Academy of Sciences, 1996.

10. Christopherson RJ et al. In: Martin J et al, eds.
Animal production in Canada. Edmonton, Alberta:
University of Alberta, Faculty of Extension, 1993.

ABOMASAL IMPACTION IN SHEEP

Abomasal dilatation and impaction in
sheep as a result of an emptying defect
has been reported in Suffolk sheep 1 and
in the Dorset breed. 2 Affected sheep are
ewes, usually 2-6 years of age and in late
| gestation or recently lambed. The duration
i of illness varies from several days to a few
1 months and affected animals may become
| emaciated. The diets fed to affected
; animals consisted of grain and good-
1 quality hay. Rams have also been affected,
j Clinically, they are characterized by
j progressive weight loss, anorexia, variable
; degrees of distension of the right lower
■ abdomen, palpable masses in the right
lower abdomen, increased concentrations
of rumen chloride and a grossly enlarged
and impacted abomasum. 1 Hypo-
chloremia, hypokalemia and metabolic
alkalosis are common 1 and ruminal
chloride levels are increased up to
38.5 mmol/L, suggesting reflux from the
abomasum. 2 Treatment has been ineffective
and the case fatality rate may exceed 90%.
At necropsy, the abomasum is grossly
enlarged and commonly contains rumen-
like contents, which are dry and doughy.
In some cases the abomasum contains an
excessive quantity of fluid.

There is a report of abomasal impac-
tion with anorexia causing high mortality
in young lambs. 3 Affected lambs developed
anorexia, dullness and reluctance to walk.
Sudden death occurred in lambs less than

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases ot the alimentary tract - n

1 month of age, and progressive loss of
body condition and dehydration occurred
in older lambs. Affected animals did not
suck their dams normally. It is suggested
that the ewes had insufficient milk for the
lambs, which consequently forced them
to begin consuming solid feed at an early
age. The impaction was associated with
the presence of phytobezoars, tricho-
phytobezoars and coagulated, rubber-like
milk clots in the abomasum, commonly at
the entrance to the pylorus.

Abdominal enlargement due to abo-
masal dilatation and impaction associated
with multiple adenomata of the abomasal
mucosa has been recorded in an adult
ewe. 4

REFERENCES

1. Smith RM et al. Vet Rec 1992; 130:468.

2. Gabb K et al.Vet Rec 1992; 131:127.

3. Njau BC et al.Vet Res Commun 1988; 12:491.

4. Andrews AH. Vet Rec 1994; 134:605.

ABOMASAL PHYTOBEZOARS
AND TRICHOBEZOARS

A velvety form of abomasal phytobezoar
occurs in goats and sheep in the arid
regions of southern Africa and causes
significant economic loss. 1,2 The compo-
sition of the bezoars resembles that of
pappus hairs and stems of the Karoo
bushes. They have a striking velvety
appearance. Phytobezoars have been
experimentally reproduced in goats and
sheep by feeding the mature flowers or
seeds and pappus hairs of Karoo bushes. 2

Rumenoabomasal lesions have been
reported to occur in steers 20-24 months
of age with a history of inappetence and
weight loss, and licking their own and
other animals' haircoat. 3 Numerous hairs
(0.5-1. 5 cm in length) were found
implanted in the abomasal mucosa,
especially in the region of the torus
pyloricus. Areas of hair implantation were
frequently accompanied by scattered and
severe abomasitis, erosions and ulcers.
Thickening of the rugae and plicae of the
pylorus was present. In the rumen,
rumemtis and hyperkeratosis, characterized
by short, reddish edematous ruminal
papillae containing small numbers of
trapped hairs, were present. The severity
of the lesions increased with the number
of hairs implanted in the mucosa.

REFERENCES

1. Bath GF etal.J S AfrVet Assoc 1992; 63:103.

2. Bath GF et al. J S AfrVet Assoc 1992; 63:108.

3. Tanimcto T.Vet Pathol 1994; 31:280.

ABOMASAL ULCERS OF CATTLE

Abomasal ulceration occurs in mature
cattle and calves and may cause acute
abomasal hemorrhage with indigestion,
melena and sometimes perforation,
resulting in a painful acute local perito-

nitis or acute diffuse peritonitis and rapid
death, or a chronic indigestion with only
minimal abomasal hemorrhage. Some
calves have abomasal ulceration at necropsy
or slaughter that was subclinical.

'Synopsis

: V. ; .. ■-

Etiology Cause of primary ulceration
unknown. Many ulcers occur secondary to
lymphoma, LDA and viral diseases
Epidemiology Mature lactating dairy
cattle, hand-fed calves, nursing beef calves.
Risk factors not understood. Presence of
hair balls not a risk factor in calves
Signs Melena, pallor due to anemia,
abdominal pain, acute local peritonitis due
to perforation

Clinical pathology Melena, occult
blood in feces, anemia
Lesions Ulceration of mucosa, blood in
abomasum. Acute local peritonitis if
perforated

Diagnostic confirmation

Abomasotomy

Differential diagnosis Duodenal
ulceration, acute and chronic traumatic
reticuloperitonitis if ulcer perforated, acute
diffuse peritonitis if perforated, right-side
dilatation of abomasum
Treatment Antacids. Blood transfusions.
Kaolin and pectin. Surgical excision
Control Nothing reliable

ETIOLOGY
Primary ulceration

While many different causes of primary
abomasal ulceration have been suggested
the cause is unknown. Possible causes
that have been considered but for which
there is no reliable evidence of a cause
and effect relationship include:

• Abomasal hyperacidity in adult
cattle - but there is no direct evidence
to support the hypothesis

° Mechanical abrasion of the pyloric
antrum due to the ingestion of coarse
roughage, such as straw, or the
presence of trichobezoars
° Bacterial infections such as
Clostridium perfringens type A or
unidentified fungi

° Trace mineral deficiencies such as
copper deficiency

• Concurrent stress as in cattle with
severe inflammatory processes or in
severe pain

° Abomasal hyperacidity in calves
nursing their dams or calves hand-fed
milk or milk-replacers has also been
proposed as a cause of primary
ulceration 1 but there is no direct
evidence.

Secondary ulceration

Abomasal ulceration secondary to
other diseases occurs. Examples include
lymphoma of the abomasum and erosions
of the abomasal mucosa in viral diseases

such as bovine virus diarrhea, rinderpest
and bovine malignant catarrh.

EPIDEMIOLOGY
Primary abomasal ulcers

Primary abomasal ulcers occur in lactating
dairy cows, mature bulls, hand-fed calves,
veal calves and sucking beef calves. The
epidemiological circumstances for each of
these groups are presented here.

Lactating dairy cows

Some observations have found that acute
hemorrhagic abomasal ulcers occur in
high-producing mature dairy cows in
early lactation, while others have found
that most acute bleeding ulcers occurred
in cows 3-6 months after parturition. The
close relationship of the disease to
parturition suggests that a combination of
the stress of parturition, the onset of
lactation and high-level grain feeding is
associated with acute ulceration in dairy
cows.

However, epidemiological observations
of acute hemorrhagic abomasal ulceration
in cattle have found no association with
the stress of calving. The incidence was
highest in dairy cows during the summer
months when the animals were grazing
on pasture. There was also a direct
association between amount of rainfall,
amount of fertilizer used, and stocking
rate, and the amount of milk produced by
affected cows. This suggests that some
factor in grass may be a risk factor in the
acute disease in mature dairy cattle.

Mature high-producing dairy cows in
early lactation may develop acute
hemorrhagic ulceration of the abomasum
following a prolonged illness such as
pneumonia or after having been to a
cattle show and sale. This suggests that
stress may be an important contributing
cause.

The prevalence of abomasal ulcers in
mature cattle varies depending on the
population of animals surveyed. Of cattle
admitted to a veterinary teaching hospital
over a 4-year period, 2.17% had confirmed
abomasal ulcers. In surveys at abattoirs
the prevalence may reach 6%. The case
fatality rate for mature cattle with
confirmed abomasal ulcers is about 50%,
for those with severe blood loss or diffuse
peritonitis the case fatality rate is usually
100%. Type I nonperforating abomasal
ulcers were found in 21% of cows
examined at the abattoir and there was no
clinical evidence of the ulcers before
slaughter, but 32% of the animals were
anemic and 44% were hyperproteinemic,
which could be expected in cattle with
chronic blood loss. 2

Mature bulls and feedlot cattle
Acute bleeding ulcers occur occasionally
in mature dairy and beef bulls, particularly

Diseases of the abomasum

3

following long transportation, prolonged
surgical procedures and in painful
conditions such as a fractured limb or
rupture of the cruciate ligaments of the
stifle joint. Abomasal ulcers have also
been the cause of sudden death in
yearling feedlot cattle. Examination of a
random sample of the abomasa of feedlot
cattle revealed that erosions were present
in up to 33% of the animals, depending
on their origin. 3 It is hypothesized that
the feeding of high levels of grain in feed-
lot cattle may be a risk factor associated
with abomasal erosions.

Hand-fed calves

Ulcers of the abomasum are common in
hand-fed calves when they are weaned
from milk or milk replacer and begin
consuming roughage. The causes of the
acute ulceration are unknown but by
association it appears that some calves
are susceptible when they are changing
from a diet of low dry matter content
(milk or milk replacer) to one of a higher
dry matter content (grass, hay, grain).
Most of these ulcers are subclinical and
nonhemorrhagic. The incidence of abo-
masal ulcers in milk-fed veal calves is
higher when the animals have access to
roughage than when roughage is not
provided. 4 The type of roughage may also
be a factor: pellets produced from corn
silage were associated with more lesions
than pellets produced from barley straw
or alfalfa hay. 4 Occasionally, milk-fed
calves under 2 weeks of age are affected
by acute hemorrhagic abomasal ulcers,
which may perforate and cause rapid
death.

Perforating abomasal ulcers have
occurred in calves up to 6 months of age,
with the majority between 6 and 12 weeks
of age. 5,6 Left-side displacement of the
abomasum was present in 70% of the
cases.

Veal calves

Abomasal ulceration is a common finding
in veal calves slaughtered at 3-5 months
of age. The incidence and severity of
lesions are greatest in loose-housed
calves with access to straw and fed milk
substitute ad libitum. There was no
evidence that erosions and ulcers found
in the majority of veal calves affected their
growth rate or welfare. No relationship
was found between the presence of
abomasal erosions and ulcers and the
behavior of crated veal calves fed milk for
22-24 weeks.

Sucking beef calves

Well -nourished sucking beef calves,
2-4 months of age, may be affected by
acute hemorrhagic and perforating
abomasal ulcers while they are on
summer pasture. Abomasal trichobezoars

are commonly present in these calves, but
whether the hair balls initiated the ulcers
or developed after the ulcers is uncertain.

Abomasal ulcers and abomasal tympany
occurs in range beef calves from 3-12 weeks
of age in beef herds in the north central
region of the USA, along the eastern
slopes of the Rocky Mountains and in
Alberta. 7

In a retrospective study of 46 abo-
masotomies in young beef calves in
western Canada, in affected herds the
average incidence was 1.0% with a range
among herds from 0.2-5. 7%. 8 In 80% of
surgeries of the abomasum, abomasal
ulcers were found, and hairballs were
present in the abomasum of 76%, but this
does not necessarily mean that hairballs
are a causative agent (see below) . Calves
housed in pens or on stubble fields were
nearly three times as likely to receive
surgery for abomasal disease than those
kept on pasture.

On-farm investigations of western
Canadian beef herds that had reported
abomasal ulcers in calves found that the
average number of suspected and con-
firmed cases of fatal abomasal ulcers were
2.4 and 1.9 per farm, respectively. 9 Most
producers reported that the affected
calves had died without exhibiting any
clinical signs and that the affected calves
were average or above average in growth
performance. Most (85.6%) of the ulcers
occurred in calves under 2 months of age.
Most (93.3%) of the fatal ulcers were
perforating, the remainder (6.7%) were
hemorrhagic ulcers. 10 The peak number of
cases occurred in April and May but
this seasonal incidence reflects the age
structure of the calf population in
Canada, where most beef calves are born
during the late winter and early spring
months. There was no sex predilection
and no evidence of breed predisposition.
There was no evidence to suggest that
j C. perfringens type A, Helicobacter pylori or
Campylobacter spp. were involved in ulcer
formation. 11

The relationship between the abomasal
hairballs and perforating abomasal
ulcers in unweaned beef calves under
4 months of age has been examined. 12 For
many years it was thought that the
presence of hairballs in the abomasum
abraded the mucosa, initiating an ulcer-
ogenic process, eventually culminating in
a perforating ulcer. However, finding
hairballs in the abomasum of nursing
beef calves with perforating ulcers does
not necessarily mean that the hairballs
caused the ulcer. Hairballs are present in
the abomasum of the same class of calves
that die from other diseases unrelated to
the abomasum. Calves under 1 month of
age dying of an ulcer were almost four
times more likely to have an abomasal-

hairball than were calves dying of. all
other diseases. But this relationship did
not exist in older calves over 30 days of
age, in which about 60% of all calves,
regardless of the cause of death, had an
abomasal hairball. The prevalence of
hairballs in the young and old ulcer calves
was 57.7% and 56.7%, respectively; in the
old nonulcer calves it was 63.3%. The
prevalence of hairballs in the young
nonulcer calves was 20.1%.

Two factors may account for the lower
prevalence in young nonulcer calves.
First, more than half (55%) of the
nonulcer calves died in the first few weeks
of life, compared with only 12.5% of the
ulcer calves. Thus calves in the ulcer
group had more time to develop an
abomasal hairball. Second, the majority
(68%) of the calves died of enteritis and
sepsis, making them less likely to engage
in normal nursing behavior, which
involves muzzling and licking the udder,
resulting in the ingestion of hair. Only
57% of calves dying of perforating ulcer
had a hairball, indicating that the hair-
balls are not necessary for an ulcer to
develop. This is supported by field obser-
vations of pathologists, who report that
only 25% of calves with a perforating
ulcer had an abomasal hairball. 12 Another
argument against the hairball theory is
that 89% of perforations occurred in the
body of the abomasum, a region that has
a poorly developed musculature and is
incapable of producing strong peristaltic
contractions. It is suggested that the weak
frictional forces generated in this region
could exert an abrasive action upon the
mucosal surfaces. In summary, it is
suggested that abomasal hairballs are not
necessary for abomasal ulcers to develop
in nursing beef calves. 12

Dietary factors in calves fed milk or milk
replacer

The cause of the high prevalence of
abomasal ulceration in nursing beef
calves is unknown. A low abomasal
luminal pH due to the diet has been
proposed as a possible factor. Experi-
mentally, feeding dairy calves (17 days of
age) cow's whole milk, resulted in lower
abomasal luminal pH compared to the
feeding of two different milk replacers (an
all milk protein or combined milk and soy
protein milk replacer). 1 It has been
hypothesized that the sucking of cow's
whole milk results in a lower mean abo-
masal luminal pH and, because fasting or
infrequent sucking of milk replacer results
in a sustained period of low abomasal
luminal pH, this may provide evidence for
primary abomasal ulceration in nursing
beef calves. 13 This may be related to the
occurrence of abomasal ulceration in
nursing beef calves after a period of

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

inclement weather, during which time the
frequency of nursing may be decreased.

Captive white-tailed deer
Abomasal ulceration has been described
in 32 of 200 captive white-tailed deer
examined by necropsy over a period of
3.5 years. 14 Ulceration was most common
in the abomasal pylorus and at the
abomasal-duodenal junction. All deer
had intercurrent disease, including bacterial
pneumonia, enterocolitis, intussusception,
chronic diarrhea, capture myopathy and
experimentally induced tuberculosis. The
anatomical distribution of abomasal
ulcers resembled that seen in veal calves.

Secondary abomasal ulcers

Abomasal ulcers occur secondary to left-
and right-side abomasal displace-
ments, abomasal impaction or volvulus,
lymphomatosis and vagus indigestion, or
unrelated to other diseases.

PATHOGENESIS

Any injury to the gastric mucosa allows
diffusion of hydrogen ions from the lumen
into the tissues of the mucosa and also
permits diffusion of pepsin into the differ-
ent layers of the mucosa, resulting in further
damage. There may be only one large ulcer
but more commonly there is evidence of
numerous acute and chronic ulcers.

A classification of abomasal ulcers in
cattle is as follows.

Type 1: Nonperforating ulcer

There is incomplete penetration of the
abomasal wall resulting in a minimal
degree of intraluminal hemorrhage, focal
abomasal thickening, or local serositis.
Nonbleeding chronic ulcers commonly
cause a chronic gastritis.

Type 2: Ulcer causing severe blood
loss

There is penetration of the wall of a major
abomasal vessel, usually in the submucosa,
resulting in severe intraluminal
hemorrhage and anemia. In acute ulcer-
ation with erosion of a blood vessel there is
acute gastric hemorrhage with reflex spasm
of the pylorus and accumulation of fluid in
the abomasum, resulting in distension,
metabolic alkalosis, hypochloremia,
hypokalemia and hemorrhagic anemia.
Usually within 24 hours there is release of
some of the abomasal contents into the
intestine, resulting in melena. The ruminal
chloride level may increase in about 40% of
cows with bleeding ulcers, which suggests
abomasal reflux of acid into the rumen. 15

Plasma gastrin activity increases signifi- j
cantly in cattle with bleeding abomasal
ulcers. 16

Type 3: Perforating ulcer with acute,
local peritonitis

There is penetration of the full thickness
of the abomasal wall, resulting in leakage

of abomasal contents. Resulting perito-
nitis is localized to the region of the
perforation by adhesion of the involved
portion of abomasum to adjacent viscera,
omentum or the peritoneal surface.
Omental bursitis and empyema may
develop, with the accumulation of a large
quantity of exudate and necrotic debris in
the omental cavity.

Abomasal-pleural fistula associated
with cranial displacement of the abo-
masum and abomasal ulceration has been
described in a 11-month-old bull. 17

Type 4: Perforating ulcer with diffuse
peritonitis

There is penetration of the full thickness
of the abomasal wall, resulting in leakage
of abomasal contents. Resulting perito-
nitis is not localized to the region of
the perforation; thus digesta is spread
throughout the peritoneal cavity.

In nursing beef calves, about 90% of
perforated abomasal ulcers occur in the
body of the abomasum, with a propensity
for the greater curvature. 12

In some calves the ulcers are sub-
clinical and the factors that determine
how large or how deep an ulcer will
become are unknown. Based on abattoir
studies it is evident that abomasal ulcers
will heal by scar formation.

CLINICAL FINDINGS

The clinical syndrome varies depending
on whether ulceration is complicated by
hemorrhage or perforation. The import-
ant clinical findings of hemorrhagic
abomasal ulcers in cattle are abdominal
pain, melena and pale mucous mem-
branes. At least one of these clinical
findings is present in about 70% of cattle
with abomasal ulcers. The case fatality j
j rates for cattle with types 1, 2, 3 or 4 are
j 25, 100, 50 and 100%, respectively. In the
j common clinical form of bleeding
abomasal ulcers there is a sudden onset
of anorexia, mild abdominal pain,
tachycardia (90-100/min), severely
depressed milk production and melena
Acute hemorrhage may be severe enough
to cause death in less than 24 hours. More
commonly there is subacute blood loss
over a period of a few days with the
development of hemorrhagic anemia. The
feces are usually scant, black and tarry.
There are occasional bouts of diarrhea.
Melena may be present for 4-6 days, after
which time the cow usually begins to
recover or lapses into a stage of chronic
ulceration without evidence of hemorrhage.

Melena is almost a pathognomonic
sign of an acute bleeding ulcer of the
abomasum. However, the presence of
normal-colored feces does not preclude
the presence of chronic nonbleeding
| ulcers, which may be the cause of an i
j intractable indigestion. The use of an—j

occult blood test on the feces will aid in
differentiating those that are equivocal.
Abomasal ulceration secondary to
lymphoma of the abomasum is charac-
terized by chronic diarrhea and melena.
The ulcer does not heal.

In some cases the abomasum is
grossly distended and fluid-splashing
sounds are audible on succussion similar
to those in RDA. Moderate dehydration is
common and affected cows commonly
sip water continuously and grind their
teeth frequently. 15 The prognosis in
chronic ulceration is poor because of the
presence of several ulcers and the
development of chronic abomasal atony.
Some cows improve temporarily but
relapse several days later and fail to
recover permanently. Duodenal ulceration
and abdominal abscesses have also been
described. 18

Perforation of ulcer

Perforation of an ulcer is usually followed
by acute local peritonitis unless the
abomasum is full and ruptures, when
acute diffuse peritonitis and shock
result in death in a few hours. With the
development of local peritonitis, with or
without omental adhesions, there is a
chronic illness accompanied by a fluctu-
ating fever, anorexia and intermittent
diarrhea. This is common in dairy cows in
the immediate postpartum period. Pain
may be detectable on deep palpation of
the abdomen and the distended, fluid-
filled abomasum may be palpable behind
the right costal arch. Periabomasal
abscess formation from a perforated
ulcer also occurs and is similar to local
peritonitis.

In calves with a perforated abomasal
ulcer, abdominal distension and abdomi-
nal pain are common. 3

Perforation of an abomasal ulcer and
the development of an abomasal-pleural
j fistula has been described in an 11-month-
j old bull. 17 Pleuritis, pericarditis, unilateral
pneumothorax and pulmonary abscessation
were present.

j Nursing beef calves

j Calves with abomasal ulceration may
have a distended gas-filled and fluid-
filled abomasum that is palpable behind
the right costal arch. Deep palpation may
j reveal abdominal pain associated with
local peritonitis due to a perforated ulcer.
I Unless an abomasal ulcer has extended to
the serosa it is unlikely that it can be
detected by deep palpation. Many cases
of abomasal ulcers, particularly in calves,
cause no apparent illness.

CLINICAL PATHOLOGY

Melena

The dark brown to black color of the feces
is usually sufficient indication of gastric

Diseases of the abomasum

3

hemorrhage but tests for occult blood
may be necessary. Results from experi-
ments simulating abomasal hemorrhage
indicate that the transit time for blood to
move from the abomasum to the rectum
ranges from 7-19 hours. The available
fecal occult blood tests may not detect
slow abomasal hemorrhage at any one
sampling. This can be overcome by testing
several fecal samples over a 2-4-day
period and reading multiple smears per
specimen. The sensitivity of the occult
blood tests increases after the fecal
samples have been stored at room tem-
perature for 2 days. The predictive value of
the occult blood test may be a more
reliable diagnostic indicator of abomasal
disease than abdominal pain or the
presence of anemia. When perforation
has occurred, with acute local peritonitis,
there is neutrophilia with a regenerative
left shift for a few days, after which time
the total leukocyte and differential count
may be normal.

Hemogram

In acute gastric hemorrhage there is acute
hemorrhagic anemia.

Plasma gastrin activity

Plasma gastrin concentration increases
significantly in cattle with bleeding
abomasal ulcers. The mean plasma gastrin
concentration in healthy cattle was
103.2 pg/mL; in cattle with bleed-
ing abomasal ulcers the mean was
1213 pg/mL. 16

NECROPSY FINDINGS

Ulceration is most common along the
greater curvature of the abomasum. There
is a distinct preference for most of the
ulcers to occur on the most ventral part of
the fundic region with a few on the
border between the fundic and pyloric
regions. The ulcers are usually deep and
well defined but may be filled with blood
clot or necrotic material and often contain
fungal mycelia, which may be of etiological
significance in calves. The ulcers will
measure from a few millimeters to 5 cm in
diameter and are either round or oval
with the longest dimension usually
parallel to the long axis of the abomasum.
In bleeding ulcers the affected artery is
usually visible after the ulcer is cleaned
out.

Most cases of perforation in cattle are
walled off by omentum, with the for-
mation of a large cavity 12-15 cm in
diameter in the peritoneal cavity that
contains degenerated blood and necrotic
debris. Material from this cavity may
infiltrate widely through the omental fat.
Adhesions may form between the ulcer
and surrounding organs or the abdominal
wall (omental bursitis and omental
emphysema). Multiple phytobezoars are

commonly present in the abomasum of
beef calves with abomasal ulcers. The
mucosal changes associated with abomasal
ulceration in veal calves reveal an increase
in the depth of the mucosa with a loss of
mucins in the region of erosions and ulcers.

Abomasal ulcers in captive white-
tailed deer were characterized by focal to
multifocal, sharply demarcated areas of
coagulation necrosis and hemorrhage
extending through the mucosa, with
fibrin thrombi in mucosal blood vessels of
small diameter. Visible bacteria were not
associated with ulcerative lesions. 14

DIFFERENTIAL DIAGNOSIS

• Acute abomasal ulceration in mature
cattle is characterized by abdominal
pain, melena and pallor. The melena
may not be evident for 1 8-24 hours
after the onset of hemorrhage.
Examination of the right abdomen may
reveal a distended abomasum and a
grunt on deep palpation over the
abomasum, caudal to the xiphoid
sternum on the right side. Tachycardia is
common

• Duodenal ulceration may cause
melena and a syndrome
indistinguishable from hemorrhagic
abomasal ulceration

• Chronic abomasal ulceration in
mature cattle is difficult to diagnose
clinically if the hemorrhage is
insufficient to result in melena. The
clinical findings of chronic ulceration are
similar to several other diseases of the
forestomach and abomasum of mature
cattle. An illness of several days
duration with inappetence, ruminal
hypotonicity, scant feces and
dehydration are common to many of
those diseases. The presence of occult
blood in the feces of hemorrhagic
anemia suggests ulceration. The
hemorrhage may be intermittent and
repeated fecal tests for occult blood
may be necessary. A positive result for
occult blood may also be due to
abomasal volvulus, intestinal obstruction
or blood-sucking helminths

• Abomasal ulceration with
perforation and local peritonitis is
indistinguishable from acute traumatic
reticuloperitonitis unless hemorrhage
and melena occur. However, the
abdominal pain elicited on deep
palpation is most intense over the right
lower abdomen and lateral aspect of
right lower thoracic wall

• Abomasal ulceration with
perforation in sucking beef calves is
characterized by sudden onset of
weakness, collapse, moderate
abdominal distension shock and rapid
death. It must be differentiated from
other causes of diffuse peritonitis and
intestinal obstruction

• Chronic abomasal ulceration in
sucking beef calves associated with
hair balls and chronic abomasitis from
eating sand and dirt cannot usually be
diagnosed as a separate entity

TREATMENT

The conservative medical approach is
usually used for the treatment of abo-
masal ulcers in cattle.

Blood transfusions

Blood transfusions and fluid therapy may
be necessary for acute hemorrhagic
ulceration. The most reliable indication
for a blood transfusion is the clinical state
of the animal. 15 Weakness, tachycardia
and dyspnea are indications for a blood
transfusion. A hematocrit below 12%
warrants a transfusion. In the case of
severe blood loss, a dose of 20 mL/kg BW
may be necessary.

Coagulants

Parenteral coagulants are used but are of
doubtful value.

Antacids

The goal of antacid treatment is to create
an environment that is favorable to ulcer
healing. This can be done by decreasing
acid secretion (oral or parenteral adminis-
tration of histamine type-2 receptor
antagonists [H 2 antagonists] and proton
pump inhibitors) or neutralizing secreted
acid (oral administration of magnesium
hydroxide and aluminum hyroxide)! 9 The
elevation of the pH of the abomasal
contents would abolish the proteo-
lytic activity of pepsin and reduce the
damaging effect of the acidity on the
mucosa.

Histamine type-2 receptor
antagonists

These compounds increase gastric pH
through selective and competitive antag-
onism of histamine at the H 2 -receptor on
the basolateral membrane of parietal
cells, thereby reducing acid secretion. H 2 -
receptor antagonists are characterized
pharmacologically by their ability to inhibit
gastric acid secretion and kinetically by
their similarity in absorption, distribution
and elimination.

Cimetidine and ranitidine are syn-
thetic H 2 antagonists that inhibit basal as
well as pentagastrin- and cholinergic-
stimulated gastric acid secretion. Both
have been used extensively to treat gastric
ulcers in many species, including horses,
dogs and humans. Oral and parenteral
administration of cimetidine and ranitidine
increases abomasal pH in sheep and
cattle. High doses of cimetidine (20 mg/kg
BW intravenously, or 50-100 mg/kg orally)
increase abomasal pH in weaned lambs
for more than 2 hours. Daily oral adminis-
tration of cimetidine (10 mg/kg BW for
30 d) to veal calves may facilitate healing
of abomasal ulcers. Because ranitidine is
three to four times more potent than
cimetidine, results of studies in ruminants
suggest that oral administration of
cimetidine (50-100 mg/kg) and ranitidine

374

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

(10-50 mg/kg) should increase abomasal
pH in milk-fed calves.

Experimentally, the oral administration
of cimetidine (50 or 100 mg/kg every 8 h)
and ranitidine (10 or 50 mg/kg every 8 h)
to normal calves fed milk-replacer caused
a significant dose- dependent increase in
mean 24-hour abomasal luminal pH. 19
However, the effects of these agents have
not been examined in calves with known
abomasal ulcers.

Alkalinizing agents

Compounds such as magnesium hydroxide
and aluminum hydroxide are weak bases
that have a direct effect on gastric acidity
by neutralizing secreted acids. Aluminum
hydroxide directly absorbs pepsin, there-
by decreasing the proteolytic activity of
pepsin in the stomach. Both compounds
bind bile acids, thereby protecting against
ulceration induced by bile reflux.

Experimentally, the oral administration
of commercially available preparations
containing aluminum hydroxide and
magnesium hydroxide to calves being fed
milk-replacer resulted in a short-term
increase in abomasal luminal pH. 20 How-
ever, as with the synthetic H 2 antagonists,
the efficacy of these weak bases to aid in
the treatment of calves with abomasal
ulcers has not been determined.

Magnesium oxide (500-800 g/450 kg
BW weight daily for 2-4 d) has been
successful empirically in some cases of
abomasal ulceration in mature cattle. The
injection or infusion of the antacid directly
into the abomasum would probably be
much more effective but injections of the
abomasum through the abdominal wall
are not completely reliable. An abomasal
cannula placed through the abdominal
wall may provide a means of ensuring the
infusion of antacids directly into the
abomasum.

Kaolin and pectin

Large doses of liquid mixtures of kaolin
and pectin (2-3 L twice daily for a mature
cow) to coat the ulcer and minimize
further ulcerogenesis have been suggested,
and used with limited success.

Surgical excision

Surgical excision of abomasal ulcers has
been attempted, with some limited success.
The presence of multiple ulcers may
require the radical excision of a large por-
tion of the abomasal mucosa and hemor-
rhage is usually considerable. A laparotomy
and exploratory abomasotomy are required
to determine the presence and location of
the ulcer. The diagnostic criteria for
deciding to do surgery have not been
described, which makes it difficult to
select cases with a favorable prognosis.
Valuable animals with clinical evidence of
chronic ulceration or those that relapse

should be considered for surgical correc-
tion. Surgical correction of perforated
abomasal ulcers in calves is possible and
may be successful.

PREVENTION

Recommendations for the prevention of
abomasal ulceration in cattle cannot be
given because the etiology is so poorly
understood.

REFERENCES

1. Constable PD et al. J Vet Intern Med 2005; 19:97.

2. Braun U et al. JVet Med A 1991; 38:357.

3. Jensen R et al. Am J Vet Res 1992; 53:110.

4. WensingT et al. Vet Res Commun 1986; 10:1985.

5. Von Rademacher G, Lorch A. Tierarztl Umsch
2001; 56:563.

6. Lorch A, von Rademacher G. Tierarztl Umsch
2001; 56:572.

7. Mills KW et al. JVet Diagn Invest 1990; 2:208.

8. Katchnik R. Can Vet J 1992; 33:459.

9. Jeiinski MD et al. Agri-Practice 1995; 16:16.

10. Jeiinski MD et al. PrevVet Med 1996; 26:9.

11. Jeiinski MD et al. Can Vet J 1995; 36:379.

12. Jeiinski MD et al. Can Vet J 1996; 37:23.

13. Ahmed AF et al. J Dairy Sci 2002; 85:1502.

14. Palmer MV et al. J Comp Pathol 2001; 125:224.

15. Braun U et al.Vet Rec 1991; 129:279.

16. Ok Metal. JVet Med A 2001; 48:563.

17. Costa LRR et al. Can V?t J 2002; 43:217.

i 18. Weaver AD. J Am V?t Med Assoc 1989; 195:1603.

19. Ahmed AF et al. Am J Vet Res 2001; 62:1531.

20. Ahmed AF et al. J Am Vet Med Assoc 2002;
220:74.

ABOMASAL BLOAT (DISTENSION)
IN LAMBS AND CALVES

Abomasal bloat or severe distension
] occurs in lambs and calves fed milk-
replacer diets. Feeding systems that allow
lambs to drink large quantities of milk
[ replacer at infrequent intervals predispose
them to abomasal bloat. This situation can
occur under ad libitum feeding when the
supply of milk replacer is kept at about
15°C (59°F) or higher, and particularly if it
is not available for several hours. Lambs
fed warm milk replacer to appetite twice
daily appear to be very susceptible to
i abomasal bloat. Ad libitum feeding of
cold milk replacers containing few or no
insoluble ingredients, and adequately
. refrigerated, results in little or no bloating.

; The pathogenesis of the abomasal
! tympany is thought to be associated with
I a sudden overfilling of the abomasum
: followed by the proliferation of gas-
I forming organisms, which release an
excessive quantity of gas that cannot
escape from the abomasum. The severe
distension causes compression of the
thoracic and abdominal viscera and blood
vessels leading to them. This results in
asphyxia and acute heart failure. Affected
lambs and calves will become grossly
distended within 1 hour after feeding and
die in a few minutes after the distension
of the abdomen is clinically obvious.
At necropsy, the abomasum is grossly

distended with gas, fluid and milk
replacer, which is usually not clotted. Tire
abomasal mucosa is hyperemic.

Abomasal bloat also occurs in Norway
in lambs 15-30 days of age just prior to
being turned on to pasture. 1 Housing
these lambs on floors with built-up litter
when silage is used as a roughage is a
predisposing epidemiological factor.
It is postulated that affected lambs eat
bedding contaminated with feces, which
may result in the growth of an abnor-
mal gas-producing microflora in the
abomasum.

Abomasal bloat, hemorrhage and ulcers
occur in young lambs in Norway. 1 Affected
lambs are 3-4 weeks of age. The major
clinical findings are tympany and colic.
There is severe abdominal pain, such as
stretching of the hind legs, lifted tails,
repeated attempts to defecate and anorexia.
Untreated lambs die within a few hours
but some lambs are found dead without
having shown any clinical signs. Some
lambs are anemic and have melena.

Affected lambs, approximately 1 week
before developing abomasal bloat, had
significantly lower serum iron levels than
unaffected lambs. 2 The administration of
iron dextran to lambs during their first
week of life reduced the incidence of
abomasal bloat, suggesting that iron
deficiency may be a predisposing factor.

At necropsy, there is abomasal tympany,
abomasal hemorrhage and ulceration. 1
Lambs with ulcers had a higher frequency
of trichophytobezoars than the cases
without ulcers or the controls. Sarcinia-
like bacteria were found in sections of and
smears from the abomasum in 79% of
cases. 3 Clostridium fallax and Clostridium
sordelli were also cultured from some
cases, but their causative significance is
uncertain.

REFERENCES

1. Vatn S, Ulvund MJ. Vet Rec 2000; 146:35.

2. Vatn S, Torsteinbo WO. Vet Rec 2000; 146:462.

3. Vatn S et al. J Comp Pathol 1999; 122:193.

OMENTAL BURSITIS

Inflammation of the omental bursa occurs
rarely, usually in dairy cattle. Tire causes
include perforated abomasal ulcers of the
medial wall of the abomasum, pene-
tration of the ventral wall of the blind sac
of the rumen, penetration of the reticulum
by a foreign body, spread of an umbilical
infection to the greater omentum, exten-
sion of an abdominal abscess and
localized peritonitis, with subsequent
spread to the omental bursa secondary to
postpartum parametritis. Inflammation of
the bursa results in the accumulation of
inflammatory exudate in the bursal cavity,
which enlarges beyond its normal
capacity. There may also be rupture of the

leaves of the greater omentum, resulting
in diffuse peritonitis, ileus or functional
obstruction of the intestines.

Clinical findings include anorexia of
several days' duration, chronic toxemia,
dehydration and abdominal distension,
particularly of the right lower flank. Fluid-
splashing sounds may be audible on
auscultation and percussion of the
right flank. On rectal examination a large,
amorphous, spongy mass may be pal-
pable anterior to the pelvic brim in the
right upper quadrant of the abdomen. The
peritoneal fluid may reveal evidence of a
chronic suppurative inflammation. A
neutrophilia and an increase in the serum
fibrinogen are common. There may also
be a metabolic alkalosis with hypo-
chloremia and hypokalemia.

Treatment consists of surgical drainage
and long-tenn therapy with antimicrobials.
At necropsy there is diffuse fibrinous and
necrotizing peritonitis and a large accu-
mulation of purulent exudate in the
omental bursa.

Diseases of the intestines
of ruminants

CECAL DILATATION AND
VOLVULUS IN CATTLE

Cecal dilatation occurs primarily in dairy
cattle in the first few months of lactation.
The cecum may be dilated with gas or
distended with ingesta, and volvulus may
occur. Clinically it is characterized by
inappetence, drop in milk production,
decreased amount of feces, a ping over
the right upper flank and a distended,
easily recognizable viscus on rectal
palpation. The prognosis is usually good if
the diagnosis is made early.

ETIOLOGY

The etiology is uncertain. Experimentally,
a rise in the concentration of volatile fatty
acids in the cecum can result in cecal
atony. Dietary carbohydrates not com-
pletely fermented in the rumen are
fermented in the cecum, resulting in an
increase in the concentration of volatile
fatty acids, a drop in pH and cecal atony.
Butyric acid has the greatest depressant
effect on cecal motility while acetic has
the least. Inhibition of cecal motility may
lead to accumulation of ingesta and gas in
the organ and consequently dilatation,
displacement and possible volvulus.

The concentrations of absolute and
undissociated acetic, propionic, butyric, i-
valerianic and n-valerianic acids, and total
volatile fatty acids are significantly higher
in samples collected from the cecum and
proximal loop of the ascending colon of
cows with cecal dilatation or dislocation

Diseases of the intestines of ruminants

375

compared with concentrations in control
cows. 1 However, the role of increased
concentrations of volatile fatty acids in
the etiology and pathogenesis of cecal
dilatation or dislocation is uncertain.

EPIDEMIOLOGY

Dilatation and volvulus of the cecum
occurs in well-fed, high-producing dairy
cows 3-5 years of age during the first
12 weeks after parturition. 2 The disease
occurs throughout the year but most
commonly during the calving season in
North America and Europe. There is a
record of five cases occurring in lactating
dairy cows on one farm within 9 days. 3
The cows were pastured day and night on
grass dominated by white clover and
received a 22% crude protein concentrate
in the milk parlor twice daily in addition
to silage. Cecal volvulus has also been
described in sheep. 4

Atony or hypotonicity affecting the
cecum and proximal loop of the ascend-
ing colon is thought to initiate the disease,
leading to dilatation and displacement,
including volvulus. The feeding of grain
increases the concentration of volatile
fatty acids in the cecum, lowering the
pH of cecal contents and inhibiting cecal
motility.

PATHOGENESIS

The pathogenesis of cecal dilatation,
displacement and volvulus is thought to
be similar to that which occurs in
dilatation and displacement of the abo-
masum. The combination of intestinal gas
and decreased cecal motility results in
accumulation of fluid and gas in the
cecum followed by dilatation and dis-
placement of the cecum into the pelvic
inlet. This results in a mild indigestion, or
the dilatation may be subclinical and may
be detected incidentally when the cow is
examined for other purposes. There may
be volvulus or torsion of the cecum but
the outcome is probably the same.

In cecal volvulus, the apex of the
cecum is rotated cranially and the cecal
body becomes distended. 2,5 The viscus
and the first few segments of the proximal
loop of the ascending colon twist about
the mesentery, causing incarceration and
eventually strangulation obstruction of
the affected portions of the intestine.
Torsion is a condition in which the cecum
is twisted on its longitudinal axis; it may
occur cranial to the ileocecocolic junction,
at the ileocecocolic junction, or caudal to
the junction. Torsion of the cecum may
occur to the left or right and in each case
involves the proximal loop of the ascend-
ing colon. 6 The net effect is partial or total
obstruction of the intestinal tract,
accumulation of gas and/or ingesta in the
cecum, varying degrees of paralytic ileus,
reduced amount of feces and necrosis-of

the cecum because of ischemia- Cecal
impaction is characterized by gross
distension of the viscus with dry ingesta and
in a mature cow the cecum may measure
90 cm in length by 20 cm in diameter. 7 The
severity of the disease depends primarily on
the degree of twisting of the cecum and Its
adjacent spiral colon, which results in
ischemic necrosis. Rarely, a prolapse of the
small intestine through a tear in the
mesentery of the small intestine near its
root may also pull the cecum cranially by
the ileocecal fold and cause an anti-
clockwise volvulus as viewed from the right
side of the animal. 8

It has been postulated that hypo-
motility of the cecum and proximal loop
of the ascending colon may be responsible
for the delayed recovery from and recur-
rence of cecal dilatation and displacement
that occur following surgical evacuation
of the cecum. However, the myoelectric
activity of the cecum and proximal loop of
the ascending colon in cows after spon-
taneous dilatation and displacement of
the cecum indicates that delayed recovery
is not caused by hypomotility. 9 The
myoelectrical activity of the cecum is well
coordinated with the ileum and the
proximal loop of the ascending colon. 10

CLINICAL FINDINGS

In cecal dilatation without volvulus,

there are varying degrees of anorexia,
mild abdominal discomfort, a decline of
milk production over a period of a few
days and a decreased amount of feces. 2,5
In some cases there are no clinical signs
and the dilated cecum is found co-
incidentally on rectal examination. In
simple dilatation, the temperature, heart
rate and respirations are usually within
normal ranges. A distinct ping is detect-
able on percussion and simultaneous
auscultation in the right paralumbar
fossa, extending forward to the 10th
intercostal space. 5 Simultaneous ballotte-
ment and auscultation of the right flank
may elicit fluid-splashing sounds. There
may be slight distension of the upper
right flank but in some cases the contour
of the flank is normal.

In cecal volvulus, anorexia, ruminal
stasis, reduced amount or complete
absence of feces, distension of the right
flank, dehydration and tachycardia are
evident, depending on the severity of the
volvulus and the degree of ischemic
necrosis. There may be some evidence of
mild abdominal pain characterized by
treading of the pelvic limbs and kicking at
the abdomen. The ping is centered over
the right paralumbar fossa and may
extend to the 10th and 12th intercostal
spaces. Fluid-splashing sounds are usually
audible on ballottement and auscultation
of the right flank.

6

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

On rectal examination the distended
cecum can usually be palpated as a long,
cylindrical, movable organ measuring up
to 20 cm in diameter and 90 cm in length.
Palpation and identification of the blind
end of the cecum directed towards the
pelvic cavity is diagnostic. In simple
dilatation, with minimal quantities of
ingesta, the cecum is enlarged and easily
compressible on rectal palpation. In cecal
volvulus, the viscus is usually distended
with ingesta and feels enlarged and tense
on rectal palpation. The blind end of the
cecum may be displaced cranially and
laterally or medially, and the body of the
cecum is then felt in the pelvic cavity.
Varying degrees of distension of the colon
and ileum may occur, depending on the
degree of displacement or volvulus present.
Rupture of the distended cecum may
occur following rectal palpation or trans-
portation of the animal. This is followed
by shock and death within a few hours.

Ultrasonographic examination of the
cecum

The cecum and proximal and spiral ansa
of the colon can be visualized ultra-
sonographically using a 3.5 MHz linear
transducer in mature cows. 11 The cecum
can be visualized from the middle region
of the abdominal wall. It extends
caudocranially, varies in diameter from
5.2-18.0 cm and is situated immediately
adjacent to the abdominal wall. The
lateral wall of the cecum appears as a
thick, echogenic, crescent-shaped line. It
can be visualized as far cranially as the
12th intercostal space. Although its
junction cannot be identified, the proximal
ansa of the colon is recognizable on the
basis of its anatomical position and its
diameter, which is smaller than that of the
cecum. The spiral ansa of the colon and
the descending colon are situated dorsal
to the cecum and can be identified by
moving the transducer horizontally along
the abdominal wall to the last rib. The
spiral ansa of the colon is situated ventral
to the descending colon, and its walls
appear as thick echogenic lines. In a
contracted state, the spiral colon has the
appearance of a garland.

The ultrasonographic findings in cows
with dilatation, torsion and retroflexion of
the cecum have been described and com-
pared with the findings on laparotomy. 12
The wall of the proximal ansa of the colon
and of the dilated cecum closest to the
abdominal wall is visible in all cows and
appears as an echogenic semicircular line
immediately adjacent to the peritoneum.
The contents of the cecum and of the
proximal and spiral ansa of the colon are
not always visible because of gas. In some
cows, the contents are hypoechogenic to
echogenic in appearance. The dilated

cecum can be imaged from the right
abdominal wall at the level of the tuber
coxae. The cecum can be imaged from the
12th, 11th and 10th intercostal spaces in
some cows, and in other cows the cecum
and proximal ansa of the colon are
situated immediately adjacent to the right
abdominal wall by the liver and/or gall
bladder. The diameter of the cecum,
measured at various sites, varies from
7.0-25.0 cm. Cecal dilatation can be
diagnosed on the basis of the results of
rectal examination in most cows but in all
cows ultrasonographically. Dilatation and
caudal displacement of the cecum and
dilatation and craniodorsal retroflexion of
the cecum can be visualized. In some
cows, the direction of the retroflexed
cecum cannot be determined.

CLINICAL PATHOLOGY

A mild degree of dehydration may
be present and a compensated hypo-
chloremia and hypokalemia occur. 13
Hematological values are normal in most
affected cattle unless there is necrosis of
the cecum accompanied by peritonitis. 13

DIFFERENTIAL DIAGNOSIS

• Cecal dilatation and volvulus must
be differentiated from right-side
dilatation and volvulus of the
abomasum. The ping in cecal dilatation
and volvulus is usually centered in the
paralumbar fossa; in abomasal dilatation
and volvulus it is usually centered over
the last few ribs and lower in the
middle third of the right abdomen. The
distended cecum is usually easily
palpable rectally in the upper part of the
abdomen and is readily identified as the
cecum because it is movable. In
dilatation and volvulus of the
abomasum, the distended viscus is -
usually palpable in the right lower
quadrant of the abdomen much further
forward than a dilated cecum and not
movable. In many cases, the distended
abomasum can barely be touched with
the tips of the fingers, while the
distended cecum can be palpated easily

• Intestinal obstruction of the small
intestines or other parts of the large
intestine are characterized by subacute
abdominal pain, absence of feces, more
marked systemic signs such as
dehydration and tachycardia, and
perhaps the presence of distended loops
of intestine on rectal examination

TREATMENT

The method of treatment depends on the
severity of the case and whether there is
uncomplicated dilatation and displacement
caudally or if volvulus is present.

Medical therapy

Mild cases of uncomplicated gaseous
dilatation may be treated conservatively
by feeding good-quality hay and recovery

can occur in 2-4 days. The use of
parasympathomimetic drugs such as
neostigmine given subcutaneously every
hour for 2-3 days has been recommended 14
but controlled trials were not done.
Xylazine is contraindicated for the
abdominal pain associated with cecal
dilatation because it reduces myo-
electrical activity of the cecum and
proximal loop of the ascending colon. 15
Cisapride at 0.08 mg/kg BW shows some
promise. 15 Bethanechol at 0.07 mg/kg BW
and neostigmine at 0.02 mg/kg BW
increased the frequency of cecocolic spike
activity, the duration of cecocolic spike
activity and the number of cecocolic
propagated spike sequences every
10 minutes. 16 Bethanechol is considered
superior to neostigmine because it
induces more pronounced coordinated
and aborally propagated spike activity. 16

Surgical correction

For torsion and volvulus with the
accumulation of ingesta and the poss-
ibility of necrosis of the cecum, the
treatment of choice is surgical correction
and the prognosis is usually good. 5,14 The
recurrence rate of cecal dilatation and
displacement ranges from 11-13% within
the first week after surgery, whereas the
long-term recurrence rate is about 25%. 9
In severe cases with necrosis of
the cecum, partial resection or total
typhlectomy may be necessary. Extensive
cecal necrosis requires total typhlectomy,
which can be successful and lactating
dairy cows may thrive and their milk
production may be excellent in the
current lactation. 17

REFERENCES

1. Abegg R et a 1. Am J Vet Res 1999; 60:1540.

2. Braun U et al. Vet Rec 1989; 125:265.

3. Leonard D.Vet Rec 1996; 139:576.

4. Modransky PD et al. J Am Vet Med Assoc 1989;
194:1726.

5. Fubini SL et al. J Am Vet Med Assoc 1986; 189:96.

6. Geishauser T, Pfander C. Dtsch Tierarztl
Wochenschr 1996; 103:205.

7. Desrochers A, St-Jean G. Can Vet J 1995; 36:430.

8. Kemble T ctal.VetRec 1994; 134:521.

9. Stocker S et al. Am J Vet Res 1997; 58:961.

10. Meylan M et al. Am JVet Res 2002; 63: 78.

11. Braun U, Amrein E. Vet Rec 2001; 149:45.

12. Braun U et al. Vet Rec 2002; 150:75.

13. Braun U et al. Vet Rec 1989; 125:396.

14. Braun U et al.Vet Rec 1989; 125:430.

15. Steiner A etal. Am JVet Res 1995; 56:623.

16. Steiner A et al. Am JVet Res 1995; 56:1081.

17. Green MJ, Husband JA.VetRec 1996; 139:233.

INTESTINAL OBSTRUCTION IN
CATTLE

Intestinal obstructions in cattle include
volvulus, intussusception and strangulation.
The characteristic clinical findings are
anorexia, abdominal pain, absence of feces,
the passage of dark fecal blood and mucus,
dehydration and acid-base imbalance

Diseases of the intestines of ruminants

377

and death if physical obstructions are
untreated.

Etiology Physical obstruction of intestine
due to intussusception, volvulus,
strangulation, mesenteric torsion, luminal
blockages

Epidemiology Uncommon, but do occur
Signs Abdominal pain (treading of
hindlegs, stretching, kicking at abdomen),
scant or absence of feces, feces may be
bloodstained, rumen stasis, distension of
abdomen (later stages), distended loops of
intestine, progressive dehydration and
toxemia leading to shock and recumbency
Clinical pathology Hypochloremic,
hypokalemic, metabolic alkalosis,
hemoconcentration
Lesions Intussusception, volvulus,
strangulation, peritonitis
Diagnostic confirmation Laparotomy
Differential diagnosis Adult cattle:
diffuse peritonitis, acute local peritonitis,
abomasal ulcers, right-side displacement
and volvulus of abomasum, grain overload,
duodenal ileus, urethral obstruction in
male ruminants. Calves under 2 months of
age: abomasal dilatation - dietary in origin,
abomasal volvulus, perforated abomasal
ulcers, intussusception, torsion of root of
mesentery, acute diffuse peritonitis,
peracute to acute enteritis
Treatment Surgical correction
Control Nothing reliable

ETIOLOGY AND EPIDEMIOLOGY

The commonest causes are the intestinal
accidents - volvulus, intussusception and
strangulation - in which there is physical
occlusion of the intestinal lumen. A
functional obstruction occurs with local
or general paralytic ileus - the lumen
remains physically patent but there is no
passage of ingesta along it.

There are three common groups of
causes:

° Physical obstruction of the intestinal
lumen along with infarction of the
affected section of intestine -
intestinal accidents
° Physical obstruction of the intestinal
lumen - luminal blockages
0 Functional obstructions with no
passage of intestinal contents but with
the lumen still patent - paralytic ileus.

Intestinal accidents

Volvulus

Volvulus of the small intestine is rare and
sporadic in cattle and occurs more
commonly in dairy cattle than beef cattle. 1,2
It is not more common in calves than in
adults but there may be a decreased risk in
cattle over 7 years of age compared to
calves under 2 months of age. 1

Mesenteric torsion

This is most common in calves and young
cattle, e.g. coiled colon on its mesentery.

As in cecal torsion, the colon may be
dilated before torsion develops. A case
has been described in a mature cow,
which recovered following surgery. 3

Intussusception

Intussusceptions are rare in cattle and
most common in calves under 2 months
of age. 4 The high prevalence of diarrhea
due to enteritis in calves suggests that
enteritis may be a risk factor in this age
group.

Four types of intussusception are

recognized in cattle: 5

° The enteric type involves one

segment of the small intestine, usually
the distal jejunum or ileum,
invaginating into another. The enteric
type is most common in adults, with
the distal jejunum most commonly
affected due to the length and
mobility of its mesenteric
attachments. The high incidence of
jejunojejunal intussusception in
cattle has been attributed to the
length and mobility of the jejunal
mesenteric attachments, especially the
distal third

0 In the ileocecocolic type, the ileum
invaginates into the cecum or into the
proximal colon at the cecocolic
junction

3 The cecocolic type occurs with

invagination of the cecal apex into the
proximal colon

° In the colonic type, invagination of
the proximal colon, or sometimes the
spiral colon, occurs into a more distal
segment.

The latter three do not occur commonly
in adult cattle, presumably because the
mesenteric fat deposits and the ileo-
cecocolic ligament stabilize the intestine.
In calves, the incidence of intussusception
is more uniformly distributed among the
four types, presumably because of the
thin, fragile nature of the mesentery,
which may be more susceptible to tearing
under tension and allowing increased
movement of adjacent segments of
intestine. A series is recorded in cows
with intestinal polyposis: polyps in the
mucosa dragged a section of intestine
into an invagination in the next section.
There is also intussusception of colon into
spiral colon; and intussusception of the
spiral colon has been described in an
adult bull. 6 One recorded intussusception
has been associated with a transmural
adenocarcinoma in an aged cow.

Strangulation

Strangulation may occur through a
mesenteric tear or behind a persistent
vitelloumbilical band, the ventral liga-
ment of the bladder, through the lateral
ligament of a bull's bladder, or via ~an

adhesion, especially one between the
omentum and an abscess of the umbilical
artery in a young animal. Rupture of the
small intestinal mesentery and strangu-
lation of the intestine has been described
in adult postparturient cows. 7 A persistent
urachus can also cause intestinal strangu-
lation in mature cattle. Herniation of
distal jejunum into a partially everted
urinary bladder of a mature cow has been
reported. 8 Strangulation of the duodenum
by the uterus during late pregnancy in
cows has been described. 9 The whole of
the uterus had passed through a gap
between the mesoduodenum and duo-
denum and with increasing weight had
led to strangulation of the duodenum.
The mesoduodenum and both walls of
the greater omentum adjacent to its
caudal edge were not connected with the
duodenum, probably as a result of a
congenital inhibitory malformation.

Gut tie has been described in male
cattle that have recently been castrated
using the open method and traction of
the spermatic cord. 10 When the spermatic
cord is pulled and broken during
castration, it may recoil through the
inguinal ring and become entangled
around small intestine, causing a physical
obstruction. It is also possible that
traction of the spermatic cord may tear
the peritoneal fold of the ductus deferens
that attaches the ductus to the abdominal
wall, permitting loops of intestine to pass
through this hiatus and resulting in
incarceration.

Compression stenosis
This may arise from a blood clot from an
expressed corpus luteum site on an ovary,
or traumatic duodenitis caused by migra-
tion of a metallic foreign body.

Cecal dilatation

This can be followed by cecal volvulus
(see Cecal dilatation and volvulus, above).

Incarceration of small intestine
Incarceration by remnants of the ductus
deferens is recorded. 8

Luminal blockages

External pressure

External pressure by fat necrosis of
mesenteries and omenta, and also
lipomas may occur.

Ileal impaction in cows
Ileal impaction in Swiss Braunvieh cows
in Switzerland has been described. 11 The
cause is uncertain but may be related to
seasonal influences and winter feeding
with a hay-based ration.

Fiber-balls or phytobezoars
These may be common in areas where
fibrous feeds, e.g. Romulea bulbocodium or
tree loppings, form a large part of the diet.
The ability of R. bulbocodium to survive dry

'8

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

autumns and dominate the pasture
insures that many fiber balls develop in
the abomasum in autumn. Obstructions
do not occur until the next spring when
pasture is lush. The disease is common in
late pregnancy or the first 2 weeks of
lactation or after a period of activity such
as estrus. Bezoars pass at this time from
the abomasum into the first part of the
duodenum, where they stick fast.

Trichobezoars (hairballs)

In cold climates a more common obstruc-
tion is by trichobezoars. Cattle confined
outside have long shaggy hair coats and
licking themselves and others probably
leads to ingestion of the hair. Hairballs
causing obstruction of the small intestine
of young beef calves has been described. 12

'Rectal paralysis'

In cows near parturition, an apparent
rectal paralysis leading to constipation
may occur. The cause is unknown but is
considered to be the result of pressure by
the fetus or fetuses on pelvic nerves.

Duodenal ileus

Duodenal ileus caused by obstruction or
compression of the duodenum has been
described in mature cows. 13 The lumen
may be obstructed by phytobezoars,
blood clots, or compression from or
adhesion to a liver abscess.

Functional obstructions

Peritonitis and hypocalcemia are two
common causes of functional obstruction
in cattle.

PATHOGENESIS
Physical obstruction
Physical obstruction of the small
intestines of cattle results in an absence
of feces, distension of the intestine cranial
to the obstruction with fluid and gas,
acute abdominal pain and a hypo-
chloremic, hypokalemic metabolic alkalosis
and dehydration. The alkalosis results
from small -intestinal and abomasal reflux
into the rumen, with chloride and hydrogen
ion sequestration in the abomasum. Ileus
of the small intestines is one of the most
common consequences of obstruction,
resulting in distension and hypomotility
cranial to the obstruction . The myoelectric
activity patterns occurring during small
intestinal obstruction are disorganized in
the segment orad to the obstruction,
characterized by rapidly migrating, pro-
longed, high- amplitude spikes that
sometimes occur in clusters. 14 This
probably accounts for the intermittent
abdominal pain.

Ileal impaction in Swiss Braunvieh
cows in Switzerland is characterized
clinically by anorexia, sudden drop in milk
production and some evidence of colic,
including shifting of weight from leg to

leg and occasional kicking at the
abdomen. The ventral aspect of abdomen
was enlarged and pear-shaped, and a
tense abdominal wall was present in
some cows. A ping could be elicited over
the right abdomen in most cows. The
feces in the rectum may be reduced in
amount or there may be none. On rectal
palpation, dilated loops of both small and
large intestine are usually palpable. On
laparotomy, the impaction was situated at
the ileocecal valve, and the ileum proximal
to ileocecal junction was impacted with
ingesta for up to 15 cm in length. The
color of the serosa of the ileum and distal
part of the jejunum was normal.

Volvulus and intussusception
Volvulus of the small intestine is a

rotation of the entire small intestine, with
or without the cecum and spiral colon, or
of only the distal third of the jejunum and
the proximal portion of the ileum about
its mesenteric axis. The volvulus results in
intestinal distension, vascular compromise,
intestinal necrosis and eventually death
unless surgically corrected. 1

Intussusception is the invagination of
one portion of the intestine into the
lumen of an adjacent segment of intestine.
Jejunojejunal intussusception is the most
common form in cattle, although isolated
cases of ileocecal, ileocecocolic, cecocolic
and colocolic intussusception also occur.
In most cases the intussusception is
single, but doubles do occur. There are
reports of cattle surviving after sloughing
of an intussusceptum but these are rare
and death usually occurs 5-8 days after
the onset of clinical findings if surgical
correction is not carried out.

In general, the effects of intestinal
accidents in cattle are not as remarkable
as in the horse. Neither the abdominal
pain nor the cardiovascular collapse is as
severe in adult cattle as in horses with
similar lesions. The exception is in calves,
in which the effects are more marked and
more rapid. Distension of the abdomen
occurs much more frequently in calves
than in adult cattle. 15 Involvement of large
segments of intestine as in torsion of the
root of the mesentery may result in
metabolic acidosis because of the rapid
onset of shock. Ischemic necrosis of the
intestinal wall results in various degrees
of severity of peritonitis and abnormal
peritoneal fluid containing erythrocytes,
leukocytes and increased serum proteins.

Hemorrhage into the intestinal tract at
the level of the obstruction results in the
passage of small quantities of dark blood,
which may be almost black if the
obstruction is high up in the small
intestinal tract. Distension of intestines
with fluid and gas cranial to the obstruc-
tion may cause some mild distension _of

the abdomen but primarily if the large
intestine is obstructed as in torsion of the
coiled colon. The longer duration of the
disease and the profound depression that
develops suggest that endotoxemia, as in
horses, may be the lethal agent, but the
course is much slower than in the horse.

The effect of myoelectric activity of the
cecum and proximal loop of the ascend-
ing colon on motility of this segment of
intestine in experimental obstruction of
the large intestine in cattle has been
examined. 14 Obstruction of the colon
results in prestenotic hypermotility (colic
motor complex) or prolonged propulsive
peristaltic waves directed toward the
obstruction site. This may represent an
effort of the intestine to overcome the
obstruction in order to re-establish
the continuity of the passage of ingesta.

Patterns of myoelectric activity in the
small and large intestine of cows orad and
aborad to an obstruction site have been
measured. 16 Myoelectric activity in the
ileum immediately orad to the occlusion
was characterized by abolition of the
migrating myoelectric complex and a
constant pattern of strong bursts of long
duration. Organized cyclic activity occurred
in the large intestine despite complete
disruption of the small-intestinal migrating
myoelectric complexes, indicating the
presence of mechanisms able to initiate
and regulate coordinated myoelectric
patterns in the large intestine indepen-
dently of the small intestine. 16

Duodenal ileus

In duodenal ileus caused by obstruction
of the lumen by phytobezoars or com-
pression of the duodenum by a liver
abscess associated with traumatic reticulo-
peritonitis in mature cows, there is
abomasal and duodenal reflux into the
rumen resulting in metabolic alkalosis
with hypochloremia and increased
ruminal chloride. 13 The obstruction caused
by phytobezoars and liver abscesses may
occur at almost any segment of the
duodenum. 13 The ileus results in a
marked reduction in gastrointestinal
motility and distension of the fore-
stomach and abomasum due to the
accumulation of excessive quantities of
fluid, which results in dehydration.
Abdominal pain is associated with the
distension of the duodenum. The ileus
results in marked decrease in movement
of ingesta and the feces are markedly
reduced in quantity. Duodenal obstruc-
tion caused by malposition of the gall-
bladder in a heifer has been described. 17

Functional obstruction
In functional obstruction, there is
paralytic ileus and an increase in the
transit time of ingesta and feces. The feces
are scant and do not contain blood.

Diseases of the intestines of ruminants

379

Sequestration of fluids in the intestines
may result in varying degrees of dehy-
dration and a metabolic alkalosis with
hypochloremia and hypokalemia.

CLINICAL FINDINGS
General findings

There is an initial attack of acute
abdominal pain in which the animal kicks
at its abdomen, treads uneasily with the
hindlegs, depresses the back and may
groan or bellow from pain. The pain
occurs spasmodically and at short, regular
intervals and may occasionally be
accompanied by rolling. This stage of
acute pain usually passes off within a few
(8-12) hours and during this time there is
anorexia and little or no feces are passed.
The temperature and respiratory rates are
relatively unaffected and the heart rate
may be normal or elevated, depending on
whether or not blood vessels are
occluded. If there is infarction of a section
of intestine there will be signs of endo-
toxic shock, including low blood pressure,
very rapid heart rate, and muscle
weakness and recumbency. These signs
are absent in cases where the blood
supply of the intestine is not com-
promised. For example, in cecal torsion
the heart rate may be normal. In all cases,
as the disease progresses and dehydration
becomes serious the heart rate rises and
may reach as high as 100/min just before
death.

When the acute pain has subsided, the
cow remains depressed, does not eat nor
ruminate and passes no feces. The
circulation, temperature and respirations
are usually within normal limits and
ruminal activity varies. In most cases
there is complete ruminal stasis but, in
exceptional cases, movements will
continue, though they are usually greatly
reduced. The rumen pack feels dry and
firm on palpation through the abdominal
wall.

Abdomen

The abdomen is slightly distended in all
cases. Where there is distension of loops
of intestine, as in ileus due to dietary
error, there may be some distension of the
right abdomen. Fluid-splashing sounds
can be elicited by ballottement and
simultaneous auscultation over the right
abdomen in most cases and in a minority
of cases over the left abdomen. With
obstruction of the pylorus the splashing
sounds can be elicited only on the right
side, just behind the costal arch and
approximately halfway down its length.
Regurgitation of fluid ingesta through the
nose is common.

Feces

The character of the feces is highly
variable. In the early stages they will be

normal but passed frequently and in
small amounts. It may be necessary to
carry out a rectal examination because the
feces may not be passed from the anus. In
some cases they will be hard, turd-like
lumps, usually covered with mucus. Blood
is often present, not as melena but as
altered red blood, in the form of a thick
red slurry, leaving dried flakes of it around
the anus, especially in intussusception.
The last fecal material is more mucoid
and may consist entirely of a plug of
mucus. In some cases of obstruction
caused by fiber balls the fecal material is
pasty, evil-smelling and yellow-gray in
color.

Rectal examination

When there is intussusception or volvulus
of the small intestine, the affected
segment is usually felt in the lower right
abdomen but the site varies with the
nature of the obstruction. It is important
to appreciate that not all intestinal
obstructions can be palpated on rectal
examination. It depends on the location
of the affected segment of intestine: those
in the anterior part of the abdomen are
not palpable, those in the caudal part of
the abdomen may be palpable. In
addition, the affected segment may or
may not be palpable, and the adjacent
segments cranial to the obstruction may
be palpable as distended segments of
intestine.

In intussusception the affected seg-
ment may be palpable, usually as an
oblong, sausage-shaped mass of firm
consistency, but if a long length of
intestine is involved a spiral develops and
is palpable as such. In volvulus the
intestinal loop may be small, soft and
mobile. In many cases, it is possible to
follow tightly stretched mesenteric bands
coursing dorsoventrally in the middle part
of the abdomen. 1 Palpation of distended
j loops of intestine may cause distress,
j especially in the early stages, and dis-
j tension of a number of loops may
j increase intra-abdominal pressure to the
| point where entry of the hand beyond the
j pelvis is difficult. Within a few days, the
j rectum is empty except for tarry mucus
j and exudate and insertion of the arm
; usually causes pain and vigorous strain-
: ing. Distension of loops of intestine is not
I nearly as obvious as in horses with
j intestinal obstruction and may not occur
i unless the colon or cecum is involved.

i Duodenal ileus

Duodenal ileus in mature cows is
j characterized by anorexia, depression,
j dehydration, abdominal pain (treading,
j kicking and stretching, frequent lying
j down and standing up), rumen distension
i and hypotonicity, moderate bloat in some
s cases, scant feces and the presence of

fluid-splashing sounds on auscultation
and ballottement of the right abdomen. 13
Rectal examination may reveal no abnormal
findings or an enlarged L-shaped rumen
and distended loops of small intestine.
Ultrasonography can be used to visualize
the distended duodenum in the 10th to
12th intercostal spaces. 18 If only one loop
of intestine is visible, it indicates
distension of the duodenum; when several
loops of intestine are visible it indicates
ileus of the jejunum or ileum. Duodenal
obstruction caused by malposition of the
gallbladder in cattle can be diagnosed
using abdominal ultrasonography and
laparotomy. 17

Torsion of the coiled colon (mesenteric
root torsion)

This can cause death in less than 24 hours.
It is characterized by distension of the
right abdomen and a number of dis-
tended loops of intestine can be palpated.
When there is torsion or dilatation of the
cecum, there is usually one grossly
distended intestinal loop extending
horizontally across the abdomen just
cranial to the pelvis and caudally or
medially to the rumen. It may be possible
to palpate the blind end of the cecum, and
in cases which have been affected for
several days the organ may be so
distended with fluid andgasthatitcanbe
seen through the right flank, or fluid
sounds can be produced by ballottement
or simultaneous percussion and auscul-
tation. Rarely, the distended cecum may
be located in the left paralumbar fossa
between the rumen and the abdominal
wall, in a position reminiscent of an LDA.
The disease is likely to recur in the same
cow in subsequent years, and a case of
chronic dilatation that persisted for
10 months is recorded.

Lipomas and fat necrosis
These abnormalities are usually easily
palpable as firm, lobulated masses that
can be moved manually. They may encircle
the rectum. An obstructing phytobezoar
may be palpable on rectal examination in
the right anterior abdomen. It is usually
5-15 cm in diameter and so mobile that
when touched it may immediately pass
out of reach. Affected cattle may remain
in this state for 6-8 days but during this
time there is a gradual development of a
moderate, pendulous, abdominal enlarge-
ment, profound toxemia and an increase in
heart rate. The animal becomes recumbent
and dies at the end of 3-8 days.

CLINICAL PATHOLOGY

Clinicopathologic findings are generally
nonspecific and of limited assistance in
making a diagnosis or assessing prog-
nosis preoperatively.

380

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

Serum biochemistry

Hypochioremia, hyponatremia, azotemia,
and hyperglycemia are common. 1

Hemogram

Hemoconcentration, a mild left shift and
an inverted neutrophil-to-lymphocyte ratio
are common in cases of intussusception. 4

NECROPSY FINDINGS

In small-intestinal volvulus, gross changes
are consistent with vascular thrombosis
and intestinal necrosis. 1 Serosal, omental
and mesenteric hemorrhages of varying
degrees of transmural necrosis are com-
mon. Intestinal contents include gas,
ingesta and various amounts of blood. In
both intussusception and volvulus
extensive intestinal necrosis and diffuse
peritonitis are common.

TREATMENT

Slaughter for salvage may be the most
economical option for the disposition of
animals which are of commercial value. If
the diagnosis of intestinal obstruction
requiring surgery can be made early in the
course of the disease, the animal will
usually pass premortem and postmortem
inspection at a slaughter house. When
diffuse peritonitis secondary to vascular
thrombosis and intestinal necrosis has
developed, the animal should be destroyed
and disposed of accordingly.

Surgical correction

Surgical correction of physical obstruc-
tions of the intestine is the only method
of treatment for animals in which survival
and recovery are desirable. Right side
paralumbar fossa celiotomy is the most
common approach. The methods for
surgical correction are presented in
textbooks dealing with large-animal
surgery. Survival rates for correction of
volvulus of the entire small intestine have
been 44%; 86% for volvulus of the distal
jejunum and ileum. 1 Survival rates were
much higher in dairy cattle (63%) than
beef cattle (22%). 1 Survival rates for
intussusception in cattle were about
50%. 4 In ileal impaction in cattle, the
postoperative outcome following lapar-
otomy and massage of the contents of the
impacted ileum into the cecum is
excellent. 11

Fluid therapy

Fluid and electrolyte therapy given
intravenously may be necessary pre-
operatively and always postoperatively
(see Ch. 2). Multiple electrolyte solutions
or normal saline are effective even though
metabolic alkalosis with hypochioremia
and hypokalemia may be present.

Antimicrobials

Antimicrobials pre- and postoperatively
are recommended for the control of
peritonitis, which is inevitable.

DIFFERENTIAL DIAGNOSIS

• Acute intestinal obstruction in
mature cattle is characterized by
sudden onset of anorexia, reticulorumen
atony, usually moderate abdominal pain,
scant feces, fluid-splashing sounds over
the right abdomen, possibly distended
loops of intestine on rectal palpation,
and a progressively worsening course. It
must be differentiated from other
diseases of the forestomach and
abomasum that result in scant feces,
reduced reticulorumen activity,
abdominal pain, and distended loops of
intestine on rectal examination (see
Table 6.2). Those diseases include: vagus
indigestion with or without abomasal
impaction, diffuse peritonitis, RDA,
abomasal ulcers, duodenal ileus (see
Table 6.2)

• Hemorrhagic jejunitis syndrome of

dairy cattle is a sporadic disease
characterized by sudden anorexia and
loss of milk production, moderate
abdominal distension, weakness leading
to recumbency, bloody to dark feces
(melena), fluid-splashing sounds on
ballottement over the right abdomen,
tachycardia and distended firm loops of
small intestine palpable on rectal
examination. The case fatality rate is
high. At necropsy there is severe
necrohemorrhagic enteritis or jejunitis
with intraluminal hemorrhage or blood
clots

• Cecal dilatation and volvulus is

characterized by gastrointestinal atony
with inappetence, possibly distension of
the right abdomen, a high-pitched ping
on auscultation and percussion of the
right paralumbar fossa, and the cecum
is easily identifiable by rectal
examination

• Renal and ureteric colic may simulate
intestinal obstruction but occur rarely.
Acute involvement of individual renal
papillae in pyelonephritis in cattle is also
thought to cause some of these attacks
of colic

• Urethral obstruction in male
ruminants causes abdominal pain but
there are additional signs of grunting,
straining, distension of the urinary
bladder and tenderness of the urethra.
Defecation is not affected

• Photosensitive dermatitis in cattle is
also accompanied by kicking at the belly
but the skin lesions are obvious and
there are no other alimentary tract signs

• Acute intestinal obstruction in
calves under 2 months of age must be
differentiated from abomasal dilatation
- dietary in origin, abomasal volvulus,
perforated abomasal ulcers,
intussusception, torsion of the root of
mesentery, acute diffuse peritonitis,
peracute to acute enteritis and
gastrointestinal tympany - dietary in
origin. The salient features of each of
these diseases is summarized in

Table 6.4

Nonsteroidal anti-inflammatory
drugs

NSAIDs have also been used for their
anti-inflammatory and antiendotoxic
effects.

REFERENCES

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5. Horne MM. Can Vet J 1991; 32:493.

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HEMORRHAGIC BOWEL
SYNDROME IN CATTLE (JEJUNAL
HEMORRHAGE SYNDROME)

Hemorrhagic bowel syndrome, also
known as jejunal hemorrhage syndrome,
is a recently recognized disease of cattle
characterized clinically by a syndrome
similar to obstruction of the small
intestine causing abdominal distension,
dehydration and shock due to necro-
hemorrhagic enteritis affecting primarily
the small intestine. At necropsy there is
segmental necrohemorrhagic enteritis of
the small intestine and large intraluminal
blood clots. In spite of intensive medical
and surgical therapy, the prognosis is
unsatisfactory and the case fatality rate is
almost 100%.

ETIOLOGY

The etiology is unknown. C. perfringens
type A has been isolated from the
intestines of naturally occurring cases but
its significance is uncertain. Because
C. perfringens type A can be found in the
intestinal tracts of healthy cattle and is
able to proliferate quickly after death, the
role of the organism in the pathogenesis
of hemorrhagic jejunitis is uncertain.

EPIDEMIOLOGY

The disease occurs sporadically, primarily
in mature lactating dairy cows in North
America. 1,2 Individual cases have occurred
in beef cows. 3 In Germany, the disease
occurs in Simmental cattle. 4

The morbidity is low but the case
fatality rate is almost 100%. 3

Investigations of herds with cases have
failed to identify any reliable possible risk
factors. 2 Most cases occur in lactating
dairy cows in the first 3 months of lactation.
In a single dairy herd, 22 cases occurred in
a period of 4 years. Affected cows ranged
from 2-8 years of age and the time since
parturition ranged from 9-319 days.

A mail and conference survey of dairy
cattle veterinarians in Minnesota found
that the disease occurred with greatest
frequency in lactating dairy cows in early
lactation under a wide variety of manage-
ment systems, in varying herd sizes and in
both free-stall and tie-stall housing
systems. 1 The incidence appeared to be
higher in herds of more than 100 cows
and in herds using total mixed rations.

As part of the National Animal Health
Monitoring System's Dairy 2002, infor-
mation was collected about hemorrhagic
jejunitis in dairy cattle in the USA. 5 The
disease was observed in 9.1% of herds
within the previous 5 years and in 5.1% of
herds during the preceding 12 months.
Risk factors found to be associated with
the disease during the preceding 12
months were large herd size, adminis-
tration of bovine somatotrophin and
routine use of milk urea nitrogen con-
centration to determine ration composition.
Use of pasture as part of the lactating cow
ration during the growing season was
associated with decreased odds of the
disease in herds with a rolling herd
average milk production of 20 000 lb or
less, whereas in herds with higher milk
production, use of pasture was not associ-
ated with the occurrence of the disease.
For individual cows with signs consistent
with the disease, the third lactation was
the median of the parity distribution and
the medial time between parturition and
the onset of clinical signs was 104 days. In
summary, management practices imple-
mented to achieve high milk production
may increase the risk of developing the
disease in dairy cattle. Increased con-
sumption of high-energy diet seems to be
the most plausible common pathway of
all the risk factors that have been
described. 5

Feeding rations high in soluble carbo-
hydrates has been suggested as a possible
risk factor by providing the intestinal
environment for C. perfringens type A to
proliferate and produce enterotoxins,
similar to the situation that may cause
hemorrhagic enteritis, abomasitis and
abomasal ulceration in calves. 6

PATHOGENESIS

The primary lesion is an acute localized
necrotizing hemorrhagic enteritis of the
small intestine leading to the develop-
ment of an intraluminal blood clot, which
causes a physical obstruction of the

Diseases of the intestines of ruminants

381

intestine, and ischemia and devitalization
of the wall of the affected segment of the
intestine. 6 The lesion is similar to
hemorrhagic enterotoxemia associated
with C. perfringens in young rapidly
growing calves, lambs or piglets.

There is gastrointestinal stasis with
accumulation of intestinal gas and fluids
proximal to the obstructed intestine,
resulting in distended loops of intestine,
hypochloremia, hypokalemia, dehydration
and varying degrees of anemia. The serum
biochemistry changes are those of an
obstruction of the upper small intestine
and sequestration of abomasal secretions,
with resultant hypokalemia and hypo-
chloremia. The hemorrhagic enteritis is
progressive, with the ischemia and
necrosis extending through the intestinal
wall, and within 24-48 hours there is
marked fibrinous peritonitis, dehydration,
continued electrolyte imbalance, marked
toxemia and death.

CLINICAL FINDINGS

Common historical findings include
sudden anorexia and depression, marked
reduction in milk production, abdominal
distension, weakness progressing to
recumbency, bloody to dark-red feces or
dry scant feces, dehydration and abdomi-
nal pain, including bruxism, vocalization,
treading and kicking at the abdomen. 6
Sudden death without prior clinical
findings has been reported. 6

On clinical examination there is
depression, dehydration, the body tem-
perature may be normal to slightly
elevated, the heart rate is increased to
90-120 beats/min, the mucous membranes
are pale and the respiratory rate is
increased. The abdomen is usually dis-
tended moderately over the right side.
The rumen is usually atonic. Fluid-
splashing sounds are commonly audible
| by succussion over the right abdomen. In
some cases, a ping can be elicited over the
right abdomen.

On rectal examination, the feces are
black-red, jelly-like and sticky, and smell
like digested blood. 4 On deep palpation
of the right abdomen, distended loops of
intestine may be palpable, some of which
are firm (those loops containing the blood
clot) while others may be resilient, repre-
senting loops of intestine proximal to the
blood clot obstruction that contain
excessive fluid and gas and in which the
intestine is in a state of ileus.

The course of the disease in most cases
is 2-4 days. Even with intensive fluid and
electrolyte therapy, affected animals
continue to worsen progressively, become
weak, recumbent and die, or euthanasia is
chosen.

On laparotomy, the abomasum is
commonly distended with fluid. Up. to

60-100 cm of small intestine may be
distended and firm to touch, with a
markedly dark red to purplish hemorrhagic
serosal surface covered with fibrin tags.
The mesenteric band may be too tense to
allow exteriorization of the affected intes-
tine. Manipulation of the affected intestine
may lead to its rupture because of its thin
and fragile intestinal wall due to ischemia
and devitalization. The small intestine
proximal to the affected segment is
usually distended with fluid and gas and
compressible; that distal to the affected
segment is usually relatively empty.

CLINICAL PATHOLOGY
Hematology

The hemogram is variable and not diag-
nostic. Leukocytosis and mature neutro-
philia with increased band neutrophils
and increased fibrinogen concentrations
are common but neutropenia with a left
shift may also occur. 7 The PCV and plasma
protein concentrations are variable.

Serum biochemistry

Metabolic alkalosis with compensatory
respiratory acidosis, hypokalemia and
hypochloremia are common, which is
consistent with abomasal outflow obstruc-
tion due to the obstruction caused by the
clotted blood or ileus. 7

NECROPSY FINDINGS

The abdomen is moderately distended as
a result of marked dilatation of the small
intestine, which is dark red, hemorrhagic
and commonly covered by fibrinous
exudate. The affected segment of intestine,
especially the jejunum and ileum, may be
1 m or more in length and contains a firm
blood clot, adherent to the mucosa, which
is necrotic and hemorrhagic over the
entire length of the affected portion.

Histologically, there is multifocal sub-
mucosal edema and neutrophil infiltration,
segmental necrosis, ulceration, and
mucosal and transmural hemorrhage
(hematoma) of the jejunum. Frequently,
the epithelium is completely sloughed
and, in the area of attachment of the
blood clot, the mucosa is absent. 7 Exten-
sive fibrin and neutrophil infiltration
occur on the serosal surface and fibrinous
peritonitis is common.

C. perfringens type A has been isolated
from the intestinal contents of typical
cases but its significance is unknown.

TREATMENT

No specific treatment is available. For
valuable animals, intensive fluid and
electrolyte therapy is indicated. Because
of the possibility of clostridial infection,
penicillin is indicated if treatment is
attempted. Laparotomy and resection of
the affected segment of the intestine and
anastomosis is indicated but has been
unsuccessful to date.

182

PART 1 GENERAL MEDICINE ■ Chapter 6: Diseases of the alimentary tract - II

DIFFERENTIAL DIAGNOSIS

The disease must be differentiated from
other causes of acute physical or functional
obstruction of the small intestine causing
distended loops of intestine, fluid-splashing
sounds on ballottement of the abdomen
and dehydration and electrolyte
imbalances. These include intussusception,
cecal dilatation and volvulus and diffuse
peritonitis (causing ileus). In ileal impaction
in mature cows, distended loops of
intestine are palpable on rectal
examination but on laparotomy the
abnormalities consist of ileal impaction and
distended loops of intestine which are
amenable to treatment.

Diseases causing melena and dysentery
include bleeding abomasal ulcers, acute
salmonellosis and coccidiosis.

Transabdominal ultrasonography
(Fig. 6.8) can be used to detect ileus of the
small intestine and distension of loops of
small intestine with homogeneous
echogenic intraluminal material compatible
with intraluminal hemorrhage and clot
formation. 2

CONTROL

No control or prevention strategies have
been developed.

REFERENCES

1. Godden S et al. Bovine Pract 2001; 35.97.

2. Dennison AC et al. J Am Vet Med Assoc 2002;
221 : 686 .

3. Abutarbush SM et al. CanVetJ 2004; 45:48.

4. Von Rademacher G et al. Tierarztl Umsch 2002;
57:399.

5. Berghans RD et al. J Am Vet Med Assoc 2005;
226:1700.

6. Kirkpatrick MA et al. Bovine Pract 2001; 35:104.

7. Abutarbush SM, Radostits OM. Can Vet J 2005;
46:711.

INTESTINAL OBSTRUCTION IN
SHEEP

Intestinal obstructions are not commonly
observed in sheep unless a series of them
causes a noticeable mortality. Some notable
occurrences have been:

Heavy infestation with nodular worm
(i Oesophagastomum columbianum)
leading to high prevalence of
intussusception occlusion by adhesion

Fig. 6.8 Ultrasonogram and schematic of the abdomen in a cow with ileus due
to obstruction of the jejunum with coagulated blood (hemorrhagic bowel
syndrome). The jejunal loops are dilated and there is anechoic fluid
(transudate) between the dilated loops. The ultrasonogram was obtained from
the right abdominal wall caudal to the last rib using a 5.0 MHz-linear scanner.

1 = Lateral abdominal wall; 2 = Dilated jejunal loops; 3 = Anechoic fluid
between the jejunal loops. Ds, Dorsal; Vt, Ventral. (Reproduced with kind
permission of U. Braun.)

° High incidence of intussusception in
traveling sheep for no apparent
reason

° Cecal torsion (red-gut) in sheep
grazing lush pastures of alfalfa or
clover in New Zealand. Affected
lambs survive only a few hours and
up to 20% of a flock are affected. The
outstanding postmortem lesion is a
distended, reddened cecum and/or
colon that has undergone torsion. The
rumen is smaller and the large •
intestine larger than normal because
of the high digestibility of the diet. All
ages, except sucking lambs, are
affected and the mortality rate may be
as high as 20%. Sheep that are seen
alive have a distended abdomen,
show abdominal pain and have
tinkling sounds on auscultation of the
right flank.

TER MINA L ILEITIS OF LAMBS

This disease causes poor growth in lambs
4-6 months old. The circumstances
usually suggest parasitism or coccidiosis.
The terminal 50-75 cm of the ileum is
thickened and resembles the classical
lesion of Johne's disease. Chronic inflam-
mation is evident and there are some
shallow ulcers in the epithelium. The
terminal mesenteric lymph node is
enlarged. Histopathological examination
of affected ileal wall shows mucosa
thickened by epithelial hyperplasia,
leukocytic infiltration and connective
tissue infiltration. The cause is unknown,
and the course of the disease has not
been identified because most affected
lambs are likely to be culled for ill-thrift.

rAKI I GENERAL MEDICINE

Diseases of the liver and pancreas

DISEASES OF THE LIVER -
INTRODUCTION 383

PRINCIPLES OF HEPATIC
DYSFUNCTION 383

Diffuse and focal hepatic disease 383
Hepatic dysfunction 383
Portal circulation 383

MANIFESTATIONS OF LIVER AND
BILIARY DISEASE 384

Jaundice 384
Nervous signs (hepatic
encephalopathy) 385
Edema and emaciation 386
Diarrhea and constipation 386
Photosensitization 386

Diseases of the liver -
introduction

Primary diseases of the liver, with the
exception of the fat cow syndrome of
cows in early lactation, seldom occur in
farm animals except as a result of poison-
ing. Liver metabolism in late pregnancy
and early lactation in dairy cows is under
a great deal of stress. The metabolic
demands at these times are much
increased and require that the liver
synthesize more glucose from non-
carbohydrate precursors, metabolize
butyrate and, because the cow is so often
in negative energy balance, mobilize body
fat, resulting in an increase in deposition
of fat in the liver; a fatty liver and
the fat cow syndrome may result (see
Ch. 28).

Secondary disease of the liver, arising
as part of a generalized disease process or
by spread from another organ, occurs
more commonly. In primary hepatic
disease the clinical manifestations are
caused solely by the lesions in the liver
while in secondary involvement the
syndrome may include clinical signs
unrelated to the hepatic lesions. This
chapter is devoted to a consideration of
primary diseases of the liver and to
those aspects of other diseases in which
manifestations of hepatic involvement
occur.

Diseases of the liver are in general
neglected by agricultural animal clinicians
and clinical descriptions of them are
meager.

Hemorrhagic diathesis 386
Abdominal pain 386
Alteration in size of the liver 386
Displacement of the liver 386
Rupture of the liver 386
Black livers of sheep 386

SPECIAL EXAMINATION OF THE
LIVER 387

Palpation and percussion 387
Biopsy 387

Medical imaging of the liver 387
Laboratory tests for hepatic disease and
function 388

PRINCIPLES OF TREATMENT IN
DISEASES OF THE LIVER 391

Principles of hepatic
dysfunction

DIFFUSE AND FOCAL HEPATIC
DISEASE

The liver has a large reserve of function
and approximately three-quarters of its
parenchyma must be rendered inactive
before clinical signs of hepatic dys-
function appear. Diffuse diseases of the
liver are more commonly accompanied
by signs of insufficiency than are focal
diseases, which produce their effects
either by the toxins formed in the lesions
or by pressure on other organs, including
the biliary system. The origin of a toxemia
is often difficult to localize to the liver
because of the physical difficulty of
examining the organ.

Diffuse diseases of the liver can be
classified as hepatitis and hepatosis
according to the pathological change that
occurs, and the classification also corre-
sponds roughly with the type of causative
agent. Clinically the differences between
these two diseases are not marked,
although some assistance can be obtained
from clinicopathological examination.

HEPATIC DYSFUNCTION

There are no specific modes of hepatic
dysfunction. The liver has several import-
ant functions and any diffuse disease of
the organ interferes with most or all of the
functions to the same degree. Variations
occur in the acuteness and severity of the
damage but the effects are the same and

1 -

DIFFUSE DISEASES OF THE
LIVER 391

Hepatitis 391

FOCAL DISEASES OF THE LIVER 395

Hepatic abscess 395
Telangiectasis of the bovine liver
('sawdust liver') 395
Tumors of the liver 395
Diseases of the biliary system 396

DISEASES OF THE PANCREAS 396

Diabetes mellitus 396
Pancreatic adenocarcinoma 397
Pancreatic adenoma 397
Pancreatitis 397

the clinical manifestations vary in degree
only. The major hepatic functions that,
when disordered, are responsible for
clinical signs include:

° The maintenance of normal blood
glucose levels by providing the source
as glycogen

° The formation of some of the plasma
proteins

° The formation and excretion of bile
salts and the excretion of bile
pigments

° The formation of prothrombin
° The detoxification and excretion of
many toxic substances, including
photodynamic agents.

The clinical signs produced by inter-
ference with each of these functions are
dealt with under manifestations of hepatic
dysfunction. A rather special aspect is the
role of the liver in the genesis of primary
ketosis of cattle.

PORTAL CIRCULATION

The portal circulation and the liver are
mutually interdependent, the liver
depending upon the portal vein for its
supply of nutrients and the portal flow
depending upon the patency of the
hepatic sinusoids. The portal flow is
unusual in that blood from the gastro-
splenic area and the lower part of the
large intestine passes to the left half of the
liver and the blood from the two intes-
tines to the right half, without mixing of
the two streams in the portal vein. The
restriction of toxipathic hepatitis to one

384

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

half of the liver and the localization of
metastatic abscesses and neoplasms in
specific lobes results from the failure of
portal vein blood from different gut
segments to mix. The localization of
toxipathic hepatitis may be because
of selective distribution of the toxin or of
protective metabolites. The passage
of blood from the portal circuit through
the liver to the caudal vena cava is
dependent upon the patency of the
hepatic vascular bed, and obstruction
results in damming back of blood in the
portal system, portal hypertension, inter-
ference with digestion and absorption,
and in the final stages the development of
ascites.

Manifestations of liver and
biliary disease

JAUNDICE

Jaundice is a clinical sign that often arises
in diseases of the liver and biliary system
but also in diseases in which there are no
lesions of these organs. It does not always
occur and may be conspicuously absent in
acute hepatitis. Although jaundice is a
result of the accumulation of bilirubin, the
staining is much more pronounced with
conjugated (direct) bilirubin than with
unconjugated (indirect) bilirubin. Thus
the jaundice is more intense in cases of
obstructive and hepatocellular jaundice
than in hemolytic jaundice. The levels of
bilirubin in blood also affect the intensity
of the jaundice, the obstructive form often
being associated with levels of bilirubin

that are ten times higher than those
commonly seen in hemolytic anemia. The
staining of jaundice is due to staining of
tissues, especially elastic tissue, and not to
accumulation in tissue fluids, so that it is
best detected clinically in the sclera, and
jaundice that may be detectable easily at
necropsy may not be visible on clinical
examination. Many classifications have
been suggested but the simplest is that
proposed by Popper and Schaffner,
illustrated in Figure 7.1.

The primary differentiation has to be
made between jaundice with and without
impairment of bile flow. Some indication
of the type of jaundice can be derived
from clinical examination. Thus jaundice
is usually much more severe when
impairment of flow occurs and when bile
pigments are absent from the feces. How-
ever, obstructive jaundice can occur with
only partial occlusion of hepatic flow
provided at least half the bile flow is
obstructed. In such cases jaundice may
occur even though bile pigments are still
present in the feces. With lesser obstruc-
tion the portion of the liver and biliary
tract that is functioning normally excretes
the extra load of bile pigments. The only
accurate basis for the differentiation
between jaundice with impaired bile flow
and jaundice without impaired flow is the
examination of the urine for the presence
of bilirubin and urobilinogen and the
determination of the relative amounts of
conjugated and unconjugated bilirubin
present in the serum. Unconjugated
(indirect) bilirubin that has not passed
through hepatic cells is not excreted by
the kidney, so that in hemolytic jaundice

the indirect bilirubin content of serum is
increased markedly and, although the -
urine contains an increased amount of
urobilinogen, no bilirubin is present. In
those cases in which jaundice is caused by
impairment of bile flow there is a marked
increase in the serum level of conjugated
(direct) bilirubin, and the bilirubin content
of the urine is greatly increased. The
amount of urobilinogen varies depending
on whether any bilirubin reaches the
intestine to be metabolized to urobilinogen
and reabsorbed. In complete extrahepatic
biliary obstruction urobilinogen is not
present in the urine.

OVERPRODUCTION OR HEMOLYTIC
JAUNDICE

Hemolytic jaundice is common in animals
and may be associated with bacterial
toxins, invasion of erythrocytes by protozoa
or viruses, inorganic and organic poisons
and immunological reactions. Diseases in
which bacterial toxins cause intravascular
hemolysis are bacillary hemoglobinuria of
cattle and leptospirosis, although the
mechanism by which hemolysis is pro-
duced in the latter disease does not seem
to have been accurately determined. Tire
common protozoan and viral diseases in
which hemolysis occurs include babesiosis,
anaplasmosis, eperythrozoonosis and
equine infectious anemia. Chronic copper
poisoning, selenium poisoning in sheep,
phenothiazine poisoning in horses,
pasturing on rape and other cruciferous
plants and bites by some snakes are other
common causes. Postparturient hemo-
globinuria has an uncertain etiology but
is usually attributed to a deficiency of

Fig. 7.1 Classification of jaundice.

phosphorus in the diet and the feeding of
cruciferous plants. Isoimmunization hemo-
lytic anemia of the newborn is caused by
an immunological reaction between the
sensitized cells of the newborn and
antibodies in the colostrum of the dam.
The occurrence of acute hemolytic anemia
and jaundice in calves that drink large
quantities of cold water may also be of the
nature of an immunological response.

Neonataljaundice is relatively common
in babies and is regarded as a benign
condition. It is rarely, if ever, observed
clinically in newborn animals but may be
noticeable at necropsy. Although it is
generally stated that the jaundice is
hemolytic and results from the destruc-
tion of excess erythrocytes when postnatal
life begins, it appears more probable that
it is due to retention of bile pigments
because of the immaturity of the hepatic
excretion mechanism. It does occur in
foals and is an important differential
diagnosis from isoerythrolysis.

Hemolytic jaundice is characterized
clinically by a moderate degree of yellow-
ing of the mucosae, and by the presence
of hemoglobinuria in severe cases.
Clinicopathological findings indicate the
presence of anemia, an increase in
urobilinogen and an absence of bilirubin
in the urine, and a preponderance of
indirect bilirubin in the serum.

JAUNDICE DUE TO HEPATIC CELL
DEGENERATION

The cause may be any of those diffuse
diseases of the liver that cause degener-
ation of hepatic cells, which are listed
under hepatitis. Because there is only
partial obstruction of biliary excretion, the
changes in serum and urine lie between
those of hemolytic jaundice and extra-
hepatic biliary obstruction. Serum levels
of total bilirubin are increased because of
retention of direct bilirubin, which also
passes out in the urine, causing an
elevation of urine levels. The urobilinogen
levels in the urine also rise.

EXTRAHEPATIC BILIARY
OBSTRUCTION

Obstruction of the bile ducts or common
bile duct by biliary calculi or compression
by tumor masses is a rare occurrence in
farm animals. Commonly listed causes
are obstruction of the common duct by
nematodes and inflammation of the bile
ducts by extension from an enteritis or by
infestation with trematodes.

A significant number of pigs die with
biliary obstruction and purulent cholangitis
secondary to invasion of the ducts by
Ascaris lumbricoides. Parasitic cholangitis
and cholecystitis also occur due to fascio-
liasis and infestation with Dicrocoelium
dentriticum. In horses an ascending
cholangitis may develop from a parasitic

Manifestations of liver and biliary disease

435

duodenal catarrh and cause signs of
biliary obstruction.

Obstruction is usually complete and
results in the disappearance of bile
pigments from the feces. Serum levels of
conjugated bilirubin rise, causing a
marked elevation of total bilirubin in the
serum. Excretion of the conjugated
bilirubin in urine occurs on a large scale
but there is no urobilinogen because of
the failure of excretion into the alimentary
tract. Partial obstruction of the common
bile duct or occlusion of a number of
major bile ducts may cause variations in
serum and urine similar to those observed
in complete obstruction, except that the
feces do contain bile pigments and
urobilinogen appears in the urine. In this
circumstance it is difficult to differentiate
between partial extrahepatic biliary
obstruction and jaundice caused by
hepatic cell degeneration (see above).

JAUNDICE DUE TO INTRAHEPATIC
PRIMARY CHOLESTASIS

The mechanical stasis of biliary flow
caused by fibrous tissue constriction and
obliteration of the small biliary canaliculi
may occur after hepatitis and in many
forms of fibrosis. Cholelithiasis, the
formation of biliary calculi, is frequently
reported as a cause of cholestasis in
humans and has been reported in horses 1
and cattle. 2 Functional stasis is a major
problem in hepatic disease in humans but
has not been defined in animals. In both
instances the defect is the same as in
extrahepatic biliary obstruction and the
two diseases cannot be differentiated by
laboratory tests.

NERVOUS SIGNS (HEPATIC
ENCEPHALOPATHY) -

Nervous signs include:

° Hyperexcitability
° Convulsions

0 Muscle tremor and weakness
° Dullness
° Yawning

0 Compulsive walking
° Head-pressing
° Failure to respond to signals
° Mania in some cases.

These are common with any severe
hepatocellular insufficiency or major
circulatory bypass of the liver. Terminally,
hepatic coma may occur. The biochemical
and anatomical basis for these signs is not
well understood. Many factors, including
hypoglycemia and failure of normal
hepatic detoxification mechanisms, lead-
ing to the accumulation of excess amino
acids and ammonia, or of acetylcholine,
and the liberation of toxic breakdown
products of liver parenchyma, have all
been suggested as causes and -it is

probable that more than one^factor is
involved .

One of the primary effects of severe,
acute liver damage is a precipitate fall in
blood glucose accompanied by nervous
signs, including hyperexcitability,
convulsions and terminal coma. If the
hepatic damage occurs more slowly the
hypoglycemia is less marked and less
precipitous and is accompanied by:
inability to perform work, drowsiness,
yawning and lethargy. With persistent
hypoglycemia, structural changes may
occur in the brain (hypoglycemic
encephalopathy) and these may be the
basis for the chronically drowsy animals
or dummies.

However, hypoglycemia does not
always' occur in acute hepatitis and
cannot be considered to be the only or
even the most important factor in
producing the cerebral signs.

High blood levels of ammonia occur
in pyrrolizidine poisoning in sheep, and
are reflected in the development of
spongy degeneration in the brain and the
clinical signs of hepatic encephalopathy.

Status spongiosa has also been
reproduced experimentally in sheep and
calves by the intravenous infusion of
ammonia. This role of ammonia as a
cerebrotoxicant can be important in
hepatopathies in which the detoxicating
function of the liver is lost, and also in
congenital defects of hepatic vasculature
in which blood is bypassed around the
liver. In the latter case ammonia and
similar toxic byproducts of protein
degradation in the large intestine avoid
the detoxication filter of the liver.
Blood ammonia levels are increased and
sulfobromophthalein sodium (BSP) dye
clearance is delayed.

The most common cause of hyper-
ammonemia and encephalopathy in the
horse is a depression of hepatic function
due to acute or chronic liver disease. The
severity of encephalopathy clinically
correlates well with the degree of hepatic
functional compromise but only poorly
with the degree of hyperammonemia.
Other factors, such as hypokalemia,
alkalosis, short-chain volatile fatty acids,
and false and true neurotransmitters, may
be important in the pathogenesis of
hepatic coma in cattle and horses. 3,4

Neurological disease was reported in a
13-year-old horse with hyperammonemia
and no gross or histological evidence
of disease. 5 The ammonia level was
475 pmol/L (normal 7-60pmol/L).
Neurological signs included apparent
blindness, ataxia, falling, dysphagia,
bruxism, circling, head pressing, muscle
fasciculations, yawning and depression.

Plasma ammonia levels are also
significantly elevated in cattle with

6

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

hepatic disease. Clinical signs of hepatic
encephalopathy such as blindness, head
pressing, excitability, ataxia and weak-
ness, together with fever and jaundice, are
grave prognostic signs. 4

An intrahepatic porto-systemic shunt
causing hepatoencephalopathy has been
reported in a 3-month-old goat. 6

EDEMA AND EMACIATION

Failure of the liver to anabolize amino
acids and protein during hepatic
insufficiency is manifested by tissue
wasting and a fall in plasma protein. This
may be sufficiently severe to cause edema
because of the lowered osmotic pressure
of the plasma. Hepatic edema is not
usually very marked and is manifested
most commonly in the intermandibular
space (bottle jaw). If there is obstruction
to the portal circulation, as may occur
in hepatic fibrosis, the edema is much
more severe but is largely limited to the
abdominal cavity.

DIARRHEA AND CONSTIPATION

In hepatitis, hepatic fibrosis and obstruc-
tion or stasis of the biliary system, the
partial or complete absence of bile salts
from the alimentary tract deprives it of the
laxative and mildly disinfectant qualities
of these salts. This, together with the
reflex effects from the distended liver in
acute hepatitis, produces an alimentary
tract syndrome comprising anorexia,
vomition in some species and consti-
pation punctuated by attacks of diarrhea.
The feces are pale in color and, if there is
an appreciable amount of fat in the diet,
there is steatorrhea.

PHOT OSENSITIZATIO N

Most photosensitizing substances, includ-
ing phylloerythrin, the normal breakdown
product of chlorophyll in the alimentary
tract, are excreted in the bile. In hepatic
or biliary insufficiency excretion of these
substances is retarded and photo-
sensitization occurs.

HEMORRHA GIC DIATH ESIS

In severe diffuse diseases of the liver there
is a deficiency in prothrombin formation
and a consequent prolongation of the
clotting time of the blood. Abnormality of
the prothrombin complex is not the only
defect, deficiencies of fibrinogen and
thromboplast also occurring. Prothrombin
and other factors in the prothrombin
complex depend upon the presence of
vitamin K for their formation and an
absence of bile salts from the intestine
retards the absorption of this fat-soluble
vitamin. Parenteral administration of
vitamin K is advisable before surgery is

undertaken in patients with severe
hepatic dysfunction.

ABDOMINAL PAIN

Two mechanisms cause the pain in
diseases of the liver: distension of the
organ with increased tension of the
capsule, and lesions of the capsule. Acute
swelling of the liver occurs as a result of
engorgement with blood in congestive
heart failure and in acute inflammation.
Inflammatory and neoplastic lesions of
the capsule, or of the liver parenchyma
just beneath the capsule, cause local
irritation to its pain end organs. The pain
is usually subacute, causing abnormal
posture, particularly arching the back, and
disinclination to move. Tenseness of the
abdominal wall and pain on deep pal-
pation over the liver area may also be
detected in the majority of cases.

ALTERATION IN SIZE OF THE
LIVER

Great variation in the size of the liver is
often seen at necropsy but clinical detec-
tion is not easy unless the liver is grossly
enlarged. This is most likely to occur in
advanced congestion of the liver due to
congestive heart failure, in some plant
poisonings in horses and when multiple
abscesses or neoplastic metastases occur.
In acute hepatitis the swelling is not
sufficiently large to be detected clinically
and in terminal fibrosis the liver is much
smaller than normal.

Atrophy of the right lobe of the liver
occurs in the horse and may be related to
chronic distension of adjacent segments
of the intestinal tract. 7 The normal equine
liver is anatomically bisected into two
approximately equal halves by the
umbilical interlobar fissure; and additional
interlobular fissures divide the liver into
four distinct lobes in the foal: right, left,
quadrate and caudate. In horses with
right lobe atrophy, the capsule of the right
lobe is wrinkled and thick when atrophy
is severe. In clinically normal horses, the
right lobe constitutes half of the total liver
weight while the right lobe in horses with
atrophy ranges from 11.0-38.8% of the
total liver weight. 7 This is thought to be
due to long-term, insidious compression
of this portion of the liver by abnormal
distension of the right dorsal colon and
base of the cecum.

DISPLACEMENT OF THE LIVER

The liver may be displaced from its
normal position and protrude into the
thoracic cavity through a diaphragmatic
hernia, causing respiratory distress and
abnormal findings on percussion of the
chest. Torsion of a lobe of the liver has

been recorded in aged sows in the early -
part of lactation. 8 Inappetence, uneasiness
and unwillingness to suckle the young
were followed by severe, prolonged
vomiting, acute abdominal pain and
dyspnea. The twisted lobe was greatly
increased in size and in one case the
capsule was ruptured, leading to severe
internal hemorrhage.

RUPTURE OF THE LIVER

Rupture of the liver is an occasional
accident in animals, occurring usually as a
result of trauma. In most instances
rupture results in death from hemor-
rhage, although small breaks in the
capsule may heal. Horses used for the
production of serum frequently develop
hepatic amyloidosis, presumably as a
reaction to repeated injection of foreign
protein, and the death rate from rupture
of the liver is relatively high in this group. 9
Amyloidosis is essentially a space-
occupying lesion, which results in a liver
with a friable texture. The amyloid masses
exert pressure on liver cell cords and
sinusoids, gradually causing pressure
atrophy, ischemic degeneration and
necrosis of hepatic parenchyma.

A high prevalence of liver rupture is
recorded in newborn lambs of the North
Country Cheviot breed. Losses resulting
from the condition were 12.5% of all neo-
natal deaths in purebred lambs, and
varied from 6.4-24.7% on individual
farms. The lambs are stillborn, or are born
alive but become anemic and weak and
die within 12 hours of birth from internal
hemorrhage. It is thought that the cause
of the fatal anemia is an inherited short
sternum, which exposes the liver to
compression and rupture of its capsule.
Vitamin E deficiency in the ewes and
lambs may also be a factor. 10

BLAC K LIVERS OF SHEEP

Dark brown to black pigmentation of the
liver and kidneys occurs commonly in
sheep in certain parts of Australia. No
illness is associated with the condition
but the livers are not used for human
consumption for esthetic reasons and
extensive financial loss may result. Com-
monly referred to as 'melanosis', the
pigmentation has been determined to be
the result of deposition of the pigment
lipofuscin at various stages of oxidation.
Areas in which the disease occurs carry
many mulga trees (Acacia aneura), the
leaves of which are fed to sheep in
drought times.

The above condition should not be
confused with the black livers found in a
mutant strain of Corriedales in California.
In these mutant sheep there is photo-
sensitization following retention of

phylloerythrin. The darkening of the liver
is due to melanin.

Special examination of the
liver

When disease of the liver is suspected
after a general clinical examination,
special techniques of palpation, biopsy
and biochemical tests of function can be
used to determine further the status of
the liver.

PALPATION A ND PERCUSSIO N

In cattle, the liver is well concealed by the
rib cage on the right-hand side and its
edge cannot be palpated. A general
impression of the size of the liver can be
obtained by percussion of the area of liver
dullness but accurate definition is not
usually attempted. Deep percussion or
palpation to detect the presence of
hepatic pain can be carried out over the
area of liver dullness in the posterior
thoracic region on the right-hand side.
Percussion over the entire area is necess-
ary, as the pain of a discrete lesion may be
quite localized.

If the liver is grossly enlarged in cattle,
its edge can be felt on deep palpation
behind the costal arch and the edge is
usually rounded and thickened compared
to the more defined edge of the normal
liver. In cattle, the liver may be enlarged
and palpable in advanced right-sided
congestive heart failure, multiple liver
abscesses and diffuse hepatitis. This type
of palpation is relatively easy in ruminants
but is unrewarding in horses and pigs
because of the thickness of the abdominal
wall and the shortness of the flank.

BIOPSY

Biopsy of the liver has been used exten-
sively as a diagnostic procedure in infec-
tious equine anemia, poisoning by
Crotalaria spp. and other species of plants,
and experimental work on copper and
vitamin A deficiency. The technique requires
some skill and anatomical knowledge.

The most satisfactory instrument is a
long, small-caliber trocar and cannula to
which is screwed a syringe capable of
producing good negative pressure. The
sharp point of the instrument is intro-
duced in an intercostal space on the right-
hand side (the number depending on the
species) and advanced across the pleural
cavity so that it will reach the diaphragm
and diaphragmatic surface of the liver at
an approximately vertical position. The
point of insertion is made high up in the
intercostal space so that the liver is
punctured at the thickest part of its edge.

Special examination of the liver

3

For example, in cattle the biopsy is made
in the 11th intercostal space at a point on
an imaginary line between the right
elbow and tuber coxa. The instrument is
rotated until the edge of the cannula
approximates the liver capsule; the trocar
is then withdrawn, the syringe is attached
and strong suction is applied; the cannula
is twisted vigorously and advanced until it
reaches the visceral surface of the liver. If
its edge is sufficiently sharp the cannula
will now contain a core of liver parenchyma
and if the instrument is withdrawn with
the suction still applied a sample suffi-
cient for histological examination and
microassay of vitamin A, glycogen or
other nutrient is obtained.

Details of the technique for cattle, 11,12
sheep 13 and horses 14 are available. A
disposable biopsy needle suitable for use
in animals is available and a needle has
also been designed that includes a device
that ensures that the core of tissue in
the cannula is in fact detached from the
parenchyma of the organ. 14

A system to score liver biopsies as a
prognostic aid in horses with suspected
liver disease is highly reliable. 13 Horses
with scores of 0 or 1 were equally likely to
survive up to 6 months with a combined
mortality of 4%. Horses with biopsy
scores between 2 and 6 had a combined
mortality of 33% and were at a 12-fold
increased risk of nonsurvival within
6 months compared to horses with a
biopsy score of 0. Horses with biopsy
scores between 7 and 14 had a combined
mortality of 86% and were at a 46-fold
increased risk of nonsurvival compared to
horses with a biopsy score of 0. The
evidence indicates that liver biopsy is the
one antemortem test of greatest value in
the absence of noninvasive tests that are
able to reliably distinguish horses with
significant liver disease from those with-
out. Examination of liver biopsies may
establish the presence of liver disease,
provide a specific diagnosis, guide
therapeutic choice and also help deter-
mine prognosis in cases of suspected liver
disease.

Multiple liver biopsies can be done
safely in neonatal calves from 4-28 days
of age. 16

The major deficiency of the method
lies in the small sample that is obtained,
and unless the liver change is diffuse the
sample may not be representative. The
procedure has been repeated many times
on one animal without injury. The
principal danger is that if the direction of
the instrument is at fault it may approach
the hilus and damage the large blood
vessels or bile ducts. If the liver is
shrunken or the approach too caudal
no sample is obtained. Fatal hemo-
peritoneum may result if a hemorrhagic

tendency is present and peritonitis may
occur if the liver lesion is an abscess
containing viable bacteria. Biliary
peritonitis results if a large bile duct is
perforated. It seems possible that the
technique could precipitate a fatal attack
of 'black disease', but many thousands of
biopsies are performed without such an
incident.

Compared to the human patient, who
can voluntarily restrain respiratory move-
ments, the animal patient will traumatize
its diaphragm and liver if the needle is not
withdrawn quickly.

MEDICAL IMAGING OF THE LIVER

ULTRASONOGRAPHY

Ultrasonography of the liver is now being
used as an aid to diagnosis of diseases of
the liver of large animals. A complete
ultrasonographic assessment of the liver
can provide detailed information about
the size, position and parenchymal
pattern of the liver. Ultrasonographic
examinations of the liver of normal
cattle 17 and sheep 18 have now been
described and represent the basis for use
of the technique in diagnosis of liver
disease. In cattle, the liver, caudal vena
cava, portal vein and gallbladder can be
visualized. 1 ' Ultrasonography is the only
practical method for the diagnosis of
thrombosis of the caudal vena cava. 19

Ultrasonographic technique

Examination of the liver of cattle is done
with a 3.5 MHz linear transducer on the
right side of the abdomen while the cows
are standing. The hair is clipped and the
skin shaved between the sixth intercostal
space and a hand's breadth behind the
last rib. After application of transmission
gel to the transducer the cows are
examined, beginning caudal to the last rib
and ending at the sixth intercostal space.
Each intercostal space is examined
dorsally to ventrally, with the transducer
held parallel to the ribs. The texture and
the visceral and diaphragmatic surface of
the liver are scanned, and the hepatic and
portal veins, caudal vena cava and biliary
system are examined. 20 Breed and age of
cow does not influence the ultra-
sonographic appearance of the liver,
particularly position, size, and vasculature
of the liver and gallbladder. 21 During
pregnancy, the diameter of the caudal
vena cava increases slightly and that of
the portal vein decreases. Ultrasonography
has been used to detect thrombosis of the
caudal vena cava in a cow with ascites 22
and cholelithiasis in horses. 23

Percutaneous ultrasound-guided
cholecystocentesis in cows is an excellent
method of obtaining samples of bile for
demonstration of Fasciola hepatica and
Dicrocodium dendriticum eggs and for

:88

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

determination of bile acids. The procedure
is done on the right side in the ninth, 10th
or 11th intercostal space. 24

Percutaneous ultrasound-guided
portocentesis in cows is an excellent
method for measuring the composition of
hepatic portal blood and comparing it
with peripheral blood. 25

Ultrasonography and digital analysis
can be used for the diagnosis of hydropic
degeneration of the liver of cows instead
of biochemical analysis. 8 Diffuse hepato-
cellular disease such as fatty liver in dairy
cows can also be detected and evaluated. 26
Ultrasonography has been used to
evaluate the liver-kidney contrast in the
diagnosis of fatty liver infiltration in dairy
cattle. 27

Cholestasis

Cholestasis in cows can be diagnosed
using ultrasonography (Fig. 7.2) to visualize
dilatation of the extrahepatic and intra-
hepatic bile ducts, and dilatation of the
gallbladder. 28 The presence of jaundice
and bilirubinuria combined with the
ultrasonographic findings supports the
diagnosis of jaundice due to obstruction. 20

Hepatic abscesses

Hepatic abscesses in cows and feedlot
cattle can be visualized using ultra-
sonography. 20-30 The abscesses may vary
in location from the caudodorsal aspect of

the liver in the 11th and 12th intercostal
spaces to the cranioventral aspect of the
liver in the sixth, seventh and eighth
intercostal spaces. 20 Those on the left side
of the liver cannot be detected. The medical
imaging of the abscesses was more
diagnostic than laboratory evaluation of
liver tests, which was not useful. 30 Tire
diameter of the abscesses in cows may
vary in size from 5-15 cm and the presence
of the abscesses can be confirmed by
centesis and aspiration of the contents.

RADIOGRAPHY

Lateral abdominal radiography can be
used to determine the size and location of
tire liver in foals. 27 Fluoroscopy and con-
trast media injected into the mesenteric
vein have been used to detect the
presence of portosystemic shunts in foals
and calves. 26-27

LABORATORY TESTS FOR HEPATIC
DISEASE AND FUNCTION

Hepatic disease is difficult to diagnose
based on clinical findings alone and the
use of laboratory tests is necessary. The
results and interpretation of such tests,
however, depend on the nature of the
lesion, the duration and severity of the
disease, and species variations. Specific
tests that identify the exact nature of the
lesion are not available, and a combi-

Fig. 7.2 Ultrasonogram and schematic of the liver in a cow with obstructive
cholestasis due to fasciolosis. The intrahepatic bile ducts are dilated. Normally,
they are not visible. The ultrasonogram was obtained from the 11th intercostal
space of the right side using a 5.0 MHz linear transducer. 1 = Lateral
abdominal wall; 2 = Liver; 3 = Dilated intrahepatic bile ducts. Ds, Dorsal;

Vt, Ventral. (Reproduced with kind permission of U. Braun.)

nation of tests is usually necessary to
make a diagnosis. For example, it is
suggested that testing for serum bile
acids, arginase and gamma-glutamyl
transferase (GGT) gives a sensitive
indicator of cholestasis and/or hepato-
cellular necrosis, and a liver biopsy would
form the minimum combination of tests
for the diagnosis and prognosis of hepatic
disease in the horse. 31-32 Total serum bile
acids, plasma glutamate dehydrogenase,
GGT and liver biopsy are useful in the
horse with liver disease. 33 Based on
experimentally induced liver disease in
cattle, it is suggested that the serum acti-
vities of sorbitol dehydrogenase (SDH),
GGT and aspartate aminotransferase
(AST, formerly known as SGOT), and the
BSP clearance test, provide sensitive
indicators of hepatocellular injury in
cattle.

All laboratory tests are aids to diag-
nosis and must be carefully interpreted in
conjunction with clinical and other
available data. This is particularly import-
ant in the laboratory investigation of liver
disease in the horse. 34 No one test will
provide sufficient information, and a
combination of tests is necessary. Depend-
ing on the time of sampling in relation to
the pathological processes developing
and the presence of complicating or
secondary pathology, there may be
elevations in alkaline phosphatase (ALP)
and GGT. A horse with chronic hepatic
lesions may have a leukocytosis and
neutrophilia, hypoalbuminemia, hyper-
betaglobulinemia, increased ALP and
GGT and, depending on other factors,
there may be increases in AST, SDH, total
lactate dehydrogenase and others. None
of these individual tests are specific for
hepatic disease and there is no direct
relationship between the magnitude of the
serum enzyme level and the degree of
liver injury. For these reasons, it is often
necessary to take a liver biopsy.

The laboratory tests for the diagnosis
of hepatic disease and to evaluate hepatic
function in farm animals can be divided
into those that measure:

° Excretory rate of parenterally
administered substances such as
BSP

0 Ability of the liver to remove
substances from the serum and
detoxify them

° Serum levels of liver enzymes that
increase following hepatic injury
n Indirect assessment of hepatic
function such as blood glucose,
serum proteins, clotting factors and
urinalysis.

HEPATIC FUNCTION

The sulfobromoplithalein sodium clear-
" ance test has been used in cattle, sheep

Special examination of the liver

389

and horses, and although little infor-
mation is available the test appears to
have diagnostic value. The single injection
technique has the advantage of being
noninvasive, repeatable and suitable for
conscious animals. 35 The time required by
the normal liver to reduce the plasma
concentration of BSP to half the initial
concentration is taken as the standard
BSP half-life and in cattle is 2.5-5.5
minutes, in sheep 2.0 minutes 36 and in
normal horses about 2.0 minutes. 35 All
horses with confirmed liver disease
have a reduction in plasma BSP clearance
against time. 35 The results are modified by
the ability of the liver to excrete BSP via
the biliary system and to store it in
hepatocytes. Factors other than liver
disease that increase the half-life signifi-
cantly are starvation in horses, competition
with bilirubin for excretory capacity, and
youth, foals less than 6 months of age
having a significantly slower clearance
time. Precise timing of samples is needed
because of the rapid excretion rate.

In sheep, where severe hepatic dys-
function is accompanied by a steep rise in
blood ammonia levels, and where this is
reflected in the development of spongy
degeneration in the brain, the level of
glutamine in the cerebrospinal fluid is
also elevated. Glutamine is a byproduct of
the metabolism of ammonia in brain cells.
Acute ammonia toxicity is manifested by
tetany, ataxia and pulmonary edema, and
affected animals are likely to die before
the effects of subacute poisoning, hepatic
encephalopathy, are seen.

ICTERIC INDEX

Measurement of the icteric index of
plasma, by comparing its color with a
standard solution of potassium dichromate,
cannot be considered to be a liver func-
tion test but it is used commonly as a
measure of the degree of jaundice present.
The color of normal plasma varies widely
between species depending upon the
concentration of carotene. Horse, and to a
less extent cattle, plasma is quite deeply
colored, but sheep plasma is normally
veiy pale. The color index needs to be
corrected for this factor before the icteric
index is computed. Hyperbilirubinemia
occurs in many diseases of cattle and in
most cases is related to a failure of the
liver to remove unconjugated bilirubin
from the serum rather than to a failure of
the liver to excrete conjugated bilirubin. 37
The cause may be associated with anorexia,
which resembles the hyperbilirubinemia
associated with fasting in sick horses.

Adult cattle with hepatic disease do
not consistently have high serum
bilirubin concentrations and visible
jaundice does not occur frequently in
cattle with hyperbilirubinemia. Total

bilirubin concentrations in adult cattle
should be 0.4 mg/dL but young healthy
calves may have mean concentrations
0.87 mg/dL and even higher, up to
1.7mg/dL. 38 The use of high bilirubin
concentrations as an indicator of liver
disease in calves is unreliable because the
sensitivity is only about 66%. This is
similar to results in adult cattle in which
serum bilirubin concentrations are neither
a specific nor a sensitive test for chronic
liver disease.

Persistent hyperbilirubinemia has

been reported in a healthy Thoroughbred
horse that was not related to feed intake
and not associated with increased
hemolysis or acquired hepatic disease. 39
Inappropriate conjugation of bilirubin
rather than any abnormality in bilirubin
uptake or excretion is considered a
possibility similar to the human syndrome
associated with a familial deficiency of
bilirubin-uridine diphosphate glucuronyl
transferase.

SERUM HEPATIC ENZYMES

The determination of serum levels of
hepatic enzymes is used commonly for the
detection and evaluation of hepatic disease.
The interpretation of elevated values of
enzymes in plasma is dependent not only
on the tissue and site of origin but also on
the half-time of clearance of the enzyme.

* Sorbitol dehydrogenase (also called
L-iditol dehydrogenase (ID)) is

almost completely selective as an
indicator of liver damage and is the
preferred test for hepatic damage in
sheep and cattle

° Lactate dehydrogenase (LDH) is

abundant in liver, kidney, muscle and
myocardium

8 Aspartate aminotransferase or
L-alanine aminotransferase (ALT,
previously known as SGPT) are of

some value as an indicator of liver
damage because of their high content
in liver but are generally considered to
be too nonspecific to be of great
diagnostic value

0 Arginase is a specific indicator of
hepatic disease because it is not found
in appreciable quantities in other
organs. Arginase has a short blood
half-life, which makes it useful for the
diagnosis of acute hepatic disease but
not for less severe forms 31
° Gamma-glutamyl transferase is an
enzyme widely distributed in a variety
of equine tissues. Specific activity of
GGT in the horse is highest in the
kidney, pancreas and liver. Serum
GGT activity is used as a diagnostic
criterion for hepatobiliary diseases in
cattle, sheep and horses. In the horse,
increases in serum GGT may be
associated with hepatocellular -

damage and liver necrosis in„a variety
of natural and experimentally induced
liver diseases. These include bile duct
ligation, carbon disulfide toxicity,
carbon tetrachloride toxicoses
cholestasis, iron hepatoxicosis, Senecio
poisoning 40 and hyperlipidemia in
ponies. GGT is a sensitive indicator of
liver damage in horses affected with
pyrrolizidine alkaloids in the early
stages of the disease but values do
not correlate with the increase in the
severity of the lesions observed on
liver biopsy samples collected later in
the chronic phase of the disease. 40
GGT has sufficient sensitivity (75 %)
and specificity (90%) to function as a
primary screening test for subclinical
liver disease in horses exposed to
pyrrolizidine alkaloids. In horses that
had consumed hay contaminated with
Senecio vulgaris, the GGT values
fluctuated widely: some horses with
high levels did not die, whereas
others had values slightly above
reference values at the initial sample
collection and died. GGT is a practical
routine test for the evaluation of liver
amyloidosis status in serum -
producing horses. 41 In foals during
the first month of life values were
1.5-3 times higher than the upper
physiological reference values for
healthy adult horses. 42 In neonatal
foals, the serum ALP, GGT and SDH
activities were increased during the
first 2 weeks of life 43
8 Glutamate dehydrogenase (GD)
occurs in high concentration in the
serum of ruminants and horses with
liver disease

8 Ornithine carbamoyl-transferase
(OCT) levels are also elevated even in
chronic diseases, but only when there
is active liver necrosis and not when
the lesions are healing
° Alkaline phosphatase levels are
used as a test of hepatic excretory
function in the horse and are of value
in that species but variations in
normal cattle have such a wide range
that results are difficult to interpret.

Of the tests available for testing of
biliary obstruction the serum ALP test
is preferred. However, there is a
similar response to damage in other
tissues.

Hepatic enzyme profile according to
species

The serum hepatic enzymes considered to
be most useful as an aid in the diagnosis
of liver disease in the different species are
as follows.

Cattle

In adult cattle, GGT, ALP, SDH, AST
an d GD are most useful in identifying

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

animals with chronic hepatic disease. 38
The dehydrogenases (SDH and GD) have
the shortest half-lives in serum and may
not increase in cattle with chronic liver
disease.

In the early stages of hepatic dys-
function in cattle, SDH is the most effi-
cient and sensitive test. In the later stages
when tests of biliary excretion are more
applicable, estimations of serum bilirubin
and BSP test are indicated.

Calves

In neonatal calves under 6 weeks of age,
none of the common tests for assessment
of liver damage or function in adult cattle
are useful for detection of hepatic
disease. 38 The serum activity of most
enzymes, total bilirubin concentration
and sulfobromophthalein sodium clearance
half-time are significantly higher in new-
born calves than in 2-week-old calves. 38
In calves less than 6 weeks of age with
suspected liver disease, several tests should
be used to assess liver damage, which
includes GD activity and total serum bile
acid concentration. The concentrations of
direct bilirubin may be of more value than
determination of total bilirubin for
assessing liver damage. It is suggested
that percutaneous liver biopsy may pro-
vide the most information.

Horses

The clinicopathological features of
primary liver disease in the horse
have been examined in several case
studies. 15,33 ' 34,44 " 46 Total serum bile acids,
GD, GGT and liver biopsy are helpful in
studying different types of hepatic disease
in the horse. 3 In one series of primary
hepatic disease all horses had high
activities of serum GGT and most had
high activities of serum GD and high
concentrations of bile acids. 44 Horses that
were euthanized or died had significantly
higher concentrations of GGT, GD and
bile acids than survivors. Horses with
signs of hepatic encephalopathy had
plasma ammonia levels greater than
90 pmol/L but this was not correlated
with the clinical severity of the disease.
Half of the cases with hepatic encepha-
lopathy were hyperglycemic, none was
hypoglycemic, and none had abnormally
low levels of plasma urea. 44

In a series of 82 cases in horses, 61
were confirmed to have significant liver
disease and 12 were not. 46 Only serum
concentrations of GGT, globulins and
ALP were found to be significantly differ-
ent between the two groups of horses.

Clinical and ultrasonographic data
were found, when present, to be good
indicators of the presence of liver disease.

The single positive test results of greatest
diagnostic value were the presence of
hepatic encephalopathy, increased GGT,

hypoalbuminemia, increased ALP,
increased total bile acids and increased
total bilirubin. Increased AST and
increased GD were also good diagnostic
value but only when used in combination
with the above tests. No single combi-
nation or sequential test was able to fully
discriminate between horses with and
without biopsy-confirmed liver disease
and reliance on the use of noninvasive
tests for the prediction of the presence or
absence of significant liver disease may
lead to frequent diagnostic errors. Certain
positive results did reliably predict the
presence of liver disease but negative test
results were invariably unsatisfactory
predictors of absence of liver disease.

In the early stages of hepatic dys-
function, SDH is preferred. Plasma
ammonia concentrations may be signifi-
cantly elevated compared to clinically
normal horses but are not always
accompanied by a decline in plasma urea
concentration. A fall in plasma glucose
concentration represents a poor prognosis.

The most useful noninvasive prognostic
test in cases of suspected liver disease in
adult horses is the severity of clinical

34

signs.

SERUM BILE ACIDS

The concentration of total serum bile
acids has been reported as a sensitive and
specific indicator of hepatobiliary disease
in humans and animals. 47 Abnormalities
of bile acid metabolism may be detectable
in animals with liver disease that have
little evidence of hepatic dysfunction as
determined by other common liver func-
tion tests. Bile acids are the end-products
of the metabolism of cholesterol by the
liver. They are excreted in the bile and
reabsorbed from the intestine either
unchanged or after further transformation
by bacterial action. In experimental chronic
copper poisoning in sheep, the total bile
acid concentration in the plasma is a more
sensitive indicator of hepatic damage than
the concentration of plasma bilirubin or
the activity of transaminases. The rise
in total serum bile acid concentration
usually correlates well with the severity of
liver disease. In cattle, there is extreme
variability among all types and ages of
animals and the variation is even greater
in beef cattle than in dairy cattle. 48 Values
for calves 6 weeks of age and for
6-month-old heifers are significantly
lower than values for lactating dairy cows.

The 5th-95th percentile range of values
(pmol/L) were:

° For beef cattle, 9-126
? For lactating dairy cattle, 15-88
° For 6-month-old daily heifers, 11-64.

In order to be specific for liver damage in
cattle, the value determined for a single

sample would have to be more than
126 pmol/L in beef cattle, or more than
88 pmol/L in lactating dairy cattle. There
are hour-to-hour fluctuations in serum
bile acid concentrations in cattle, which
makes interpretation difficult. 49 Feeding
practices and stage of lactation can also
affect the serum bile acid concentrations.

The serum bile acid concentrations in
dairy cattle with hepatic lipidosis were
compared with liver fat content and
sulfobromophthalein (BST) half-life. 47
Because of the large variability in serum
bile acid concentrations in fed cows and
the lack of correlation of measured values
with liver fat content, bile acid determi-
nations are not reliable as an indicator of
subclinical hepatic lipidosis. 47

In cattle, total serum bile acids are
more specific and sensitive indicators of a
wide variety of hepatic disease and are
significantly correlated with the degree of
illness compared to other tests of hepatic
function. Some diurnal variations in total
serum bile acids occur in normal cattle. In
horses, total serum bile acid concen-
trations are also a sensitive indicator of
several hepatic diseases and are most
useful when combined with other tests of
hepatic disease 41

Blood ammonia levels

The microbial deamination of amino
acids in the intestinal tract is the major
source of ammonia which is absorbed by
the intestine into portal venous blood and
converted into urea by the liver. The
concentration of blood ammonia can be
an indication of functional hepatic mass.
Generally, plasma ammonia concentration
is a sensitive and specific indicator of
hepatic disease in the horse, although it
may fluctuate widely even on the same
day and the concomitant low plasma urea
concentration anticipated because of the
liver's reduced synthetic ability is often
not apparent. 3

In cattle with hepatic disease, plasma
ammonia levels are significantly elevated
compared to normal animals but not
always accompanied by a decline in plasma
urea concentrations. In healthy cattle, the
plasma ammonia :urea concentration ratio
is 9:1 and the plasma ammonia:glucose
concentration 11:1. In hepatic disease, a
plasma ammonia:glucose ratio 40:1 or
plasma ammonia:urea ratio 30:1, parti-
cularly with a rising total ketone body
concentration and a declining glucose
concentration, represents a guarded
prognosis. 4

Most cases of portosystemic shunts are
accompanied by marked increases in
blood ammonia levels. 50

Careful handling of the blood samples
is critical to obtain reliable results. Blood
_ samples with species and preferably

Principles of treatment in diseases of the liver

391

age- matched controls should be collected,
transported on ice, and evaluated
immediately.

REVIEW LITERATURE

West HJ. The evaluation of hepatobiliary disease in
horses and cattle. FRCVS thesis, London, 1994.
McGorum BC, Murphy D, Love S, Milne EM.
Clinicopathological features of equine primary
hepatic disease: a review of 50 cases. Vet Rec 1999;
145:134-139.

Pearson EG. Liver disease in the mature horse. Equine
Vet Educ 1999; 11:87-96.

REFERENCES

1. Johnston JK et al. J Am Vet Med Assoc 1989;
194:405.

2. West HJ, Hogg R. Vet Rec 1988; 122:251.

3. West HJ. EquineVet J 1996; 28:146.

4. West HJ. Vet Res Commun 1997; 21:169.

5. Mair TS, Jones RD. Vet Rec 1995; 137:642.

6. Humann-Ziehank E et al. Small Rumin Res 2001;
42:157.

7. Jakowski RM. J Am Vet Med Assoc 1994;
204:1057.

8. Acorda JA et al.Vet Radiol Ultrasound 1995; 36:322.

9. Abdelkader SV et al. J Comp Pathol 1991;
105:203.

10. Smart ME. Compend Contin Educ PractVet 1985;
7:5327.

11. Green LE et al.Vet Rec 1995; 136:197.

12. Buckley WT et al. Can J Anim Sci 1986; 66:1137.

13. Harvey RB et al. Cornell Vet 1984; 74:322.

14. Simpson JW. Vet Rec 1985; 117:639.

15. Durham AE et al. EquineVet J 2003; 35:534.

16. Swanson KS et al. J Anim Sci 2000; 78:2459.

17. Braun U. Am J Vet Res 1990; 51:1522.

18. Braun U, Hausammann K. Am J Vet Res 1992;
53:198.

19. Braun U et al.Vet Rec 2002; 150:209.

20. Braun U et al.Vet Rec 1995; 137:284.

21. Braun U, Gerber D. Am J Vet Res 1994; 55:1201.

22. Braun U et al. Schweiz Arch Tierheilkd 1992;
134:235.

23. ReefVB et al. J Am Vet Med Assoc 1990; 196:1836.

24. Braun U, Gerber D. Am J Vet Res 1992; 53:1079.

25. Braun U et al.Vet Rec 2000; 147:623.

26. Acorda JA et al. Vet Radiol Ultrasound 1994;
35:196.

27. Acorda JA et al. Vet Radiol Ultrasound 1994;
35:400.

28. Braun U et al.Vet Rec 1995; 137:537.

29. Braun LI et al. Schweiz Arch Tierheilkd 1994;
136:275.

30. Liberg P, Jonsson G. Acta Vet Scand 1993; 34:21.

31. Hoffmann WE et al. Am J Vet Res 1987; 48:1343.

32. rtearson EG. EquineVet Educ 11:1999; 87.

33. West HJ. EquineVet J 1996; 28:146.

34. Durham AE et al. EquineVet J, 2003; 35:542.

35. West HJ. Res Vet Sci 1988; 44:343.

36. West HJ. Res Vet Sci 1989; 46:258.

37. McSherry BJ et al. Can J Comp Med 1984; 48:237.

38. Ffearson EG et al. J Am Vet Med Assoc 1995;
207:1466.

39. Divers Tf et al. Cornell Vet 1993; 83:237.

40. Curran JM et al. AustVet J 1996; 74:236.

41. West HJ. Res Vet Sci 1989; 46:264.

42. Fbtterson WH, Brown CM. Am J Vet Res 1986;
47:2461.

43. Bauer JE et al. Am JVet Res 1989; 50:2037.

44. McGorum BC et al.Vet Rec 145:1999; 134.

45. Smith MRW et al. EquineVet J 2003; 35:549.

46. Durham AE et al. EquineVet J 2003; 35:554.

47. Garry FB et al. JVet Intern Med 1994; 8:432.

48. Craig AM et al. Am J Vet Res 1992; 53:1784.

49. Pearson EG et al. Am JVet Res 1992; 53:1780.

50. Fortier LA et al. Vet Surg 1996; 25:154.

Principles of treatment in
diseases of the liver

In diffuse diseases of the liver no general
treatment is satisfactory and the main aim
should be to remove the source of the
damaging agent. The most that can be
attempted in acute hepatitis is to tide the
animal over the danger period of acute
hepatic insufficiency until the subsidence
of the acute change and the normal
regeneration of the liver restores its func-
tion. Death may occur during this stage
because of hypoglycemia, and the blood
glucose level must be maintained by oral
or intravenous injections of glucose.
Because of the danger of guanidine
intoxication an adequate calcium intake
should be insured by oral or parenteral
administration of calcium salts.

There is some doubt as to whether
protein intake should be maintained at a
high level, as incomplete metabolism of
the protein may result in toxic effects,
particularly in the kidney. However, amino
acid mixtures, especially those containing
methionine, are used with apparently
good results. The same general recommen-
dations apply in prevention as in the
treatment of acute diffuse liver disease.
Diets high in carbohydrate, calcium and
protein of high biological value and a
number of specific substances are known
to have a protective effect against hepato-
toxic agents.

In chronic, diffuse hepatic disease
fibrous tissue replacement causes com-
pression of the sinusoids and is irreversible
except in the very early stages, when
removal of fat from the liver by the
administration of lipotrophic factors
including choline and maintenance on a
diet low in fat and protein may reduce the
compressive effects of fibrous tissue cont-
raction. A high-protein diet at this stage
causes stimulation of the metabolic activity
of the liver and an increased deposit of fat,
further retarding hepatic function.

Local diseases of the liver require
surgical or medical treatment depending
upon the cause, and specific treatments
are discussed under the respective diseases.

Diffuse diseases of the liver

HE PATITIS

The differentiation of hepatic diseases
into two groups of hepatitis and hepatosis
has not achieved general acceptance and
nonspecific terms such as hepatic injury
have been suggested to avoid the conno-
tation of inflammation associated with
the word hepatitis. To facilitate ease of
reading, the word hepatitis is used

throughout this chapter to indude all
diffuse, degenerative and inflammatory
diseases that affect the liver. It is used here
also to include the common pathological
classification of cirrhosis. Clinically the
syndrome caused by fibrosis of the liver is
the same as that caused by hepatitis and
the etiology is the same, the only difference
being that the onset of the disease is slower
and less acute than in hepatitis.

ETIOLOGY AND EPIDEMIOLOGY

Although there is an extensive list of
causes of hepatitis there are still a number
of unknown factors. At least there
are many sporadic cases of hepatic
insufficiency, especially in horses, in
which the cause is not determined. In
most cases the clinical disease has an
acute onset and a fatal outcome but the
lesion is of a much longer duration.

In a case-control study of cases of
equine hepatic disease admitted to the
Liphook Equine Hospital in the UK,
ponies were more likely to develop
hepatic disease than light riding horses
but neither age nor gender were signifi-
cant factors. 1 Overall the case fatality was
low (25.9%); horses with unclassified
hepatopathies had the lowest fatality rate
and horses with cholangiohepatitis,
pyrrolizidine alkaloid toxicity and chronic
active hepatitis had significantly higher
fatality rates by comparison. None of age,
breed or gender had any detectable effect
on outcome.

In a series of 50 cases of equine
primary hepatic disease in England,
37 cases were in ponies; 2 25 cases were
caused by pyrrolizidine alkaloid toxicity
and 11 cases classified as undifferentiated
nonmegalocytic cirrhosis on the basis of
histopathological findings.

The literature on primary liver disease
in the horse has been reviewed. 3

Toxic hepatitis

The common causes of toxic hepatitis in
farm animals are:

° Inorganic poisons - copper,
phosphorus, arsenic, possibly
selenium

° Organic poisons - carbon

tetrachloride, hexachloroethane,
Gossypol, creosols and coal tar pitch,
chloroform and copper diethylamine
quinoline sulfonate.

Ferrous fumarate administered in a diges-
tive inoculate to newborn foals is also
recorded as a cause. 4

Poisonous plants

These include the following:

0 Weeds, including Senecio, Crotalaria,
Heliotropium, Amsinckia and Tribulus
spp., Encephalartos lanatus and
Tmchyandra spp.

392

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

° Fhsture and cultivated plants -

Panicum effusum, lupins, alsike clover, 5
water-damaged alfalfa hay 6
® Trees and shrubs - lantana ( Lantana
camara); yellow wood (Tmninalia
oblongata); ngaio tree ( Myoporum
laetum); Australian boobialla
(. Myoporum tetrandrun); seeds of
cycads ( Zamia spp.)

° Fungi - Pithomyces chartarum,
Aspergillus flavus, Penicillium rubrum,
Phomopsis leptostromiformis, Fusarium
spp., Myrothecium spp., Periconia spp.

0 Algae - the slow death factor
° Insects - ingestion of sawfly larvae
(Lophyrotoma interrupta).

Miscellaneous farm chemicals
These include dried poultry waste, cotton-
seed cake, herring meal.

Toxemia perfusion hepatitis

Moderate degrees of hepatitis occur in
many bacterial infections regardless of
their location in the body and the hepatitis
is usually classified as toxic; whether the
lesions are caused by bacterial toxins or by
shock, anoxia or vascular insufficiency is
unknown. Hepatic failure may occur in
dairy cattle following mastitis or metritis;
it is thought that the hepatic dysfunction
may have been the result of endotoxemia. 7
The same position applies in hepatitis
associated with extensive tissue damage
occurring after bums, injury and infarction.

Infectious hepatitis

Diffuse hepatic lesions in animals are
rarely associated with infectious agents.
The significant ones are:

3 The virus of Rift Valley fever
° Bacillus piliformis, associated with
Tyzzer's disease in foals
° The equid herpesvirus 1 of viral
rhinopneumonitis as a cause of
abortion in horses

0 Deltaproteobacterium associated with
epizootic abortion of cattle in
California

3 Postvaccinal hepatitis of horses, also
known as serum hepatitis,
idiopathic acute hepatic disease,
Theiler's disease and acute liver
atrophy, is the most common cause
of acute hepatic failure in the horse. 8
The disease is commonly associated
with the administration of biologies of
equine origin, usually tetanus
antitoxin. 9

A series of four fatal cases of serum
hepatitis associated with the adminis-
tration of commercial plasma in the horse
has been reported. 10 The prevalence in
one veterinary teaching hospital has been
recorded as 0.4%. 10

A large number of cases of equine
hepatic encephalopathy occurred in France

between 1992 and 1997 11 and the cause
remains unknown.

° Severe cases of equine viral arteritis
manifest signs of hepatitis
° Systemic mycoses, e.g. histoplasmosis,
may be accompanied by multiple
granulomatous lesions of the liver
0 Other diseases in which hepatic
lesions may be common at necropsy,
but in which there are no overt signs
of clinical disease during life. Some of
these are infectious equine anemia,
salmonellosis, septicemic listeriosis,
leptospirosis in aborted foals 12
° Infectious necrotic hepatitis associated
with Clostridium novyi has been
described in a 9-year-old mare. 13

Parasitic hepatitis

3 Acute and chronic liver fluke
infestation

0 Migrating larvae of Ascaris sp.

3 Fibrosing granulomas of liver in
horses with chronic shistosomiasis 14
3 Hepatic sarcocystosis in a horse. 15

Nutritional hepatitis (trophopathic
hepatitis)

Selenium and vitamin E deficiency are
factors in dietary hepatic necrosis in pigs.
A multiple dietary deficiency has also
been suggested as the cause of a massive
hepatic necrosis observed in lambs and
adult sheep on trefoil pasture in California.
Hepatic lipidosis and hyperlipemia occurs
most commonly in pregnant Shetland
pony mares on a falling plane of nutrition. 16
The fat cow syndrome occurs in beef and
dairy cattle in late pregnancy or within
days after parturition and is associated
with excess energy intake in pregnancy
followed by a sudden mobilization of
body depot fat in late pregnancy or at the
onset of lactation. 17 The fatty infiltration
of the liver that occurs in most dairy cattle
in late pregnancy and early lactation is
functional and reversible and related to
the metabolic demands of those periods
in the production cycle. 17

White liver disease is a well -identified
clinical entity occurring in young sheep in
the warmer parts of New Zealand. The
cause is unknown but the disease affects
only cobalt-deficient sheep. The disease
occurs on leafy pastures with lots of leaf
litter, and in spring and early summer.
Affected sheep show photosensitivity,
anorexia, weight loss, sometimes jaundice
and blindness. At necropsy there is a very
much enlarged, light- colored, fatty liver.
Most deaths occur in a chronic phase after
the acute signs have passed. A similar
disease, suspected to be caused by a
mycotoxin, has been observed in Norway.

Idiopathic hepatosis and cirrhosis
Hepatic cirrhosis and hemochromatosis
in horses has been recorded. 18 There is

cirrhosis with increased iron stores in the
parenchymal cells of the liver. Hepatic
fatty cirrhosis (hard yellow liver) in
sheep and cattle has occurred in isolated
areas of western and southern Texas
during years of maximal rainfall. 19 The
cause is unknown but the high incidence
during periods of heavy rainfall suggests
the possibility of either a mycotoxin or
nutritional deficiency. 20

Congestive hepatopathy

Increased pressure in the sinusoids of the
liver causes anoxia and compression of
surrounding hepatic parenchyma. Con-
gestive heart failure is the common cause
and leads to centrilobular degeneration.

Inherited hepatic insufficiency occurs
in Southdown and Corriedale sheep (see
Ch. 34, Inherited photosensitization).

Portosystemic vascular anomaly

Portosystemic shunts in large animals
have been recorded occasionally in foals
and calves. 12,21 There is altered blood flow
through the liver and hepatic insufficiency
secondary to hepatic atrophy.

PATHOGENESIS

Hepatitis may be associated with a num-
ber of agents but the clinical effects are
approximately the same in all instances as
described under clinical manifestations
earlier in the chapter. The usual lesion in
toxipathic hepatitis is centrilobular and
varies from cloudy swelling to acute
necrosis with a terminal veno-occlusive
lesion in some plant poisonings. If the
necrosis is severe enough or repeated a
sufficient number of times, fibrosis
develops. The effects of endotoxin on the
liver include multifocal hepatocellular
necrosis, decreased hepatic gluconeo-
genesis and decreased hepatic blood
flow. 7 It is possible that endotoxin may
cause the Kupffer cells to release lysosomal
enzymes, prostaglandins and collagenase,
which can damage hepatocytes. Endotoxin
not detoxified by the Kupffer cells may
interact directly with the hepatocytes,
causing lysosomal damage and decreased
mitochondrial function, leading to necrosis.
In infectious hepatitis the lesions vaiy
from necrosis of isolated cells to diffuse
necrosis affecting all or most of the
hepatic parenchyma.

Serum hepatitis in the horse is
characterized by severe central lobular
necrosis following the administration of
biologies of equine origin such as tetanus
antitoxin, commercial equine plasma and
other products. 10

In parasitic hepatitis the changes
depend upon the number and type of
migrating parasites. In massive fluke
infestations sufficient damage may occur
to cause acute hepatic insufficiency,
manifested particularly by submandibular

Diffuse diseases ofthe liver

edema. In more chronic cases extension
from a cholangitis may also cause chronic
insufficiency.

Trophopathic hepatitis is characterized
by massive or submassive necrosis.
Hepatic lipidosis is characterized by fatty
infiltration of hepatocytes progressing to
development of fatty cysts.

Congestive hepatitis is characterized
by dilatation of central veins and sinusoids
with compression of the parenchymal
cells. Hepatic fibrosis develops parti-
cularly if there is massive hepatic necrosis
that destroys entire lobules. Degeneration
is not possible, as it is when the necrosis
is zonal, and fibrous tissue replacement
occurs. Thus fibrosis is a terminal stage of
hepatitis that may have developed acutely
or chronically and is manifested by the
same clinical syndrome as that of hepatitis
except that the signs develop more
slowly. Fibrosis may also develop from a
cholangitis.

The term cirrhosis has been avoided
because it carries connotations from
human medicine that may be misleading
when applied to animals. Hepatic fatty
cirrhosis occurs in sheep and cattle and is
characterized at necropsy by ascites,
hydropericardium and acquired hepatic
vascular shunts. 20 There is progressive
fatty change of the liver leading to
cirrhosis. Fibrosis begins in the periacinar
zone associated with ruptured fatty cysts
and continues until there is widespread
bridging periacinar fibrosis. No lesions of
hepatic encephalopathy occur. 20

In portosystemic vascular anomalies
the increased levels of ammonia, short-
chain fatty acids and amino acids in the
peripheral circulation are the cause of
the depression and neurological abnor-
malities that are typical of hepatic
encephalopathy. 22 These high levels of
metabolites are the result of failure of the
hepatic metabolism and detoxification of
substances absorbed from the intestines,
which are normally delivered to the liver
via the portal vein before they enter the
peripheral circulation.

Liver disease and liver failure

The liver has vast reserves of function, an
almost embryonic capacity to regenerate
itself, and it can perform adequately
despite often extensive pathological
damage to its integrity. This is best
exemplified in liver abscesses in cattle,
where rarely is clinical disease evident in
the presence of large abscesses.

Liver disease is usually diagnosed by
identifying clinical signs produced by
failure of some of its functions. 23 There is
often liver disease prior to failure of
function and laboratory tests may detect
disease before there is actual failure. The
liver has a reserve of about 70-80% and

this must be compromised before some of
its functions fail. Some functions fail
before others, which explains the pro-
gression of clinical signs.

Intravascular hemolysis in equine
liver disease

Intravascular hemolysis with prominent
hemoglobinuria has occurred in horses
with severe and advanced liver disease 24
Neutrophil hypersegmentation of undeter-
mined cause was present in one horse
with liver disease and intravascular
hemolysis.

CLINICAL FINDINGS

The cardinal signs of hepatitis are
anorexia, mental depression - with excite-
ment in some cases, muscular weakness,
jaundice and in the terminal stages
somnolence, recumbency and coma with
intermittent convulsion. Hemoglobinuria
is also a variable sign in horses. The
hemolytic crisis with which it is associ-
ated is always a precursor to a fatal out-
come. Animals that survive the early acute
stages may show photosensitization, a
break in the wool or hair leading to
shedding of the coat and susceptibility to
metabolic strain for up to a year.

The clinical findings of hepatic disease
in the horse are generally nonspecific but
the most useful noninvasive prognostic
test in cases of suspected liver disease in
adult horses is the severity of clinical
signs. 25 Regardless of the cause, consistent
clinical findings include weight loss,
anorexia, dullness and depression. Other
findings include jaundice, tachycardia,
intennittent fever, abdominal pain, ventral
body wall edema, clotting deficiency,
muscle fasciculations and diarrhea or
constipation. 16 Jaundice is a constant
feature in acute hepatic necrosis.
Dysphagia, photosensitization, encepha-
lopathy and hemorrhages tend to occur
terminally, particularly in horses with
cirrhosis. In chronic liver disease, the
course is several months.

The initial anorexia is often accompanied
by constipation and punctuated by attacks
of diarrhea. The feces are lighter in color
than normal and if the diet contains much
fat there may be steatorrhea.

In a series of 50 cases of primary
hepatic disease in horses, the following
occurrence of clinical signs was observed
(%): dull demeanor (68); anorexia (56);
abdominal pain (50); encephalopathy
(50); weight loss (50); jaundice (42); abnor-
mal intestinal motility (42); abnormal
fecal consistency (28): dehydration (18);
photosensitization (16); bilateral laryngeal
paralysis (14); clinical coagulopathy (10);
dermatitis and pruritus (8); peripheral
edema (6); oral ulceration (6); tenesmus
(4); penile prolapse (2); and rectal
impaction (2). 2 -

The nervous signs are often pro-
nounced and vary from ataxia and lethargy
with yawning, or coma, to hyper-
excitability with muscle tremor, mania,
including aggressive behavior, and con-
vulsions. A characteristic syndrome is the
dummy syndrome, in which affected
animals push with the head, do not
respond to normal stimuli and may be
blind. There may be subacute abdominal
pain, usually manifested by arching of the
back, and pain on palpation of the liver.
The enlargement of the liver is usually not
palpable.

Jaundice and edema may or may not
be present and are more commonly
associated with the less acute stages of
the disease. Photosensitization may also
occur but only when the animals are on a
diet containing green feed and are
exposed to sunlight. A tendency to bleed
more freely than usual may be observed.
In chronic hepatic fibrosis the signs are
similar to those of hepatitis but develop
more slowly and persist for longer periods,
often months. Ascites and the dummy
syndrome are more common than in
hepatitis.

Serum hepatitis (Thelier's disease)

is the most common cause of acute
hepatic failure in the horse. 9 Typically,
clinical findings become apparent several
weeks after administration of tetanus
antitoxin. Lactating mares appear to be at
a higher risk than other horses but this
may be due to the administration of
the antitoxin to mares at the time of
parturition. In a group of affected horses,
the illness may begin with an unexplained
death in a horse after a short illness.
Clinical findings include sudden anorexia,
marked lethargy, stiff gait, subcutaneous
edema of the distal aspects of all four
limbs and body wall, blindness, head-
pressing, circling, bruxism, abdominal
pain, tachycardia, icterus and a marked
reduction in gastrointestinal sounds.
Death in a few days is common. 9

Serum hepatitis following the trans-
fusion of commercial plasma into horses
may cause severe unresponsive colic,
lethargy and sudden death 41-60 days
later. 10 Severe encephalopathy has also
been described.

Hepatic disease in cattle is charac-
terized by weight loss, dullness and
depression. 26 Signs of hepatic encepha-
lopathy include blindness, head pressing,
excitability, ataxia and weakness. The
presence of fever and jaundice represents
a poor prognosis.

Hepatic fatty cirrhosis in ruminants
in Texas is characterized by failure to gain
weight, progressive emaciation, loss of
wool crimp, ascites, depression, head-
pressing, and walking with the head held
high. In the terminal stages, animals

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

become immobile and die in a state of
coma. 7 Morbidity may reach 80-100%
and mortality varies from 10-60%.
Mortality increases during each succeed-
ing month following October, climaxes in
January and February, and then decreases
in the months thereafter.

Portosystemic shunts

In young animals with portosystemic
shunts the clinical findings include
stunted growth, ascites and variable
neurological abnormalities resulting from
hepatic encephalopathy. Calves and foals
may be a few weeks to a few months of
age before they are presented for
examination. Apparent cortical blindness,
circling and dementia are common.
Ftersistent tenesmus is common in calves. 13
Recurrent episodes of unexplained neuro-
logical clinical findings in a young foal
suggest the presence of a portosystemic
shunt. A tentative diagnosis may be made
using clinicopathological results but a
definitive diagnosis requires porto-
venography. 22 Blood ammonia levels are
markedly increased and serum bile acids
are also increased but the serum levels
of hepatic derived enzymes may be
normal. 21

CLINICAL PATHOLOGY

The clinicopathological features of pri-
mary liver disease have been examined 2,27
and are summarized in the section deal-
ingwith laboratory tests for hepatic disease
and function.

Scoring liver biopsies of the horse with
suspected liver disease is highly predictive
of the severity of the lesion and of
prognosis 28

In a series of 82 cases in horses,
61 were confirmed to have significant liver
disease and 12 were not. 29 Only serum
concentrations of GGT, globulins and ALP
were found to be significantly different
between the two groups of horses.

Clinical and ultrasonographic data
were found, when present, to be good
indicators of the presence of liver disease.

The single positive test results of
greatest diagnostic value were the presence
of hepatic encephalopathy, increased
GGT, hypoalbuminemia, increased ALP,
increased total bile acids and increased
total bilirubin. Increased AST and
increased GD were also good diagnostic
value but only when used in combination
with the above tests. No single combi-
nation or sequential test was able to fully
discriminate between horses with and
without biopsy-confirmed liver disease
and reliance on the use of noninvasive
tests for the prediction of the presence or
absence of significant liver disease may
lead to frequent diagnostic errors. Certain
positive results did reliably predict the
presence of liver disease but negative test

results were invariably unsatisfactory
predictors of absence of liver disease.

The most useful noninvasive prognostic
test in cases of suspected liver disease in
adult horses is the severity of clinical
signs. 25 A significantly poorer prognosis
was found in association with clinical
signs suggestive of liver disease, presence
of hepatic encephalopathy, ultrasonographic
abnormalities, increased globulins, in-
creased total bile acids, increased ALP,
increased GGT, erythrocytosis, leukocytosis,
low serum albumin and low serum urea.
The literature on liver disease in the
mature horse has been reviewed. 23

NECROPSY FINDINGS

The liver in hepatitis is usually enlarged
and the edges swollen but the appearance
of the hepatic surface and cross-section
varies with the cause. In acute toxic and
trophopathic hepatitis the lobulation is
more pronounced and the liver is paler
and redder in color. The accentuation of
the lobular appearance is caused by
engorgement of the centrilobular vessels
or centrilobular necrosis. There may be
accompanying lesions of jaundice, edema
and photosensitization. In infectious
hepatitis the lesions are inclined to be
patchy and even focal in their distri-
bution. Parasitic hepatitis is obviously
traumatic, with focal hemorrhages under
the capsule and the necrosis and
traumatic injury definable as tracks.
Congestive hepatitis is marked by severe
enlargement of the liver, a greatly
increased content of blood and marked
accentuation of the lobular pattern
caused by vascular engorgement and fatty
infiltration of the parenchyma. In hepatic
fibrosis the necropsy findings vary widely
depending on the causative agent, the
duration of its action and on its severity.
The liver may be grossly enlarged or be
much reduced in size with marked
lobulation of the surface.

Hepatic encephalopathy associated
with portosystemic shunt is characterized
by spongiform changes and gliosis of
white matter in all levels of the brain. 30
The liver may be of normal size or small
and firm, with a prominent reticular
pattern visible on the capsular and cut
surfaces, 22 and the portal veins may be
absent.

TREATMENT

The principles of treatment of hepatitis
have already been outlined. Results are
seldom good. Protein and protein hydro-
lysates are probably best avoided because
of the danger of ammonia intoxication.
The diet should be high in carbohydrate
and calcium and low in protein and fat,
but affected animals are usually completely
anorectic. Because of the failure of
detoxification of ammonia and other

DIFFERENTIAL DIAGNOSIS

Hepatitis is easily misdiagnosed as an
encephalopathy unless jaundice or
photosensitization is present. The nervous
signs are suggestive of:

• Encephalomyelitis

• Encephalomalacia

• Cerebral edema.

Congestive hepatitis is usually not
manifested by nervous signs and, being a
secondary lesion in congestive heart
failure, is usually accompanied by ascites
and edema in other regions and by signs
of cardiac involvement. Hepatic fibrosis
may produce ascites without evidence of
cardiac disease.

Acute diseases affecting the alimentary
tract, particularly engorgement on grain in
cattle and horses, may be manifested by
signs of nervous derangement resembling
those of acute hepatic dysfunction but the
history and clinical examination usually
suggest a primary involvement with the
alimentary tract. Anorexic hepatic
insufficiency may be mirrored by an
adenocarcinoma of the pancreas, which is
unlikely to be diagnosed during life.

nitrogenous substances by the damaged
liver and their importance in the pro-
duction of nervous signs, the oral adminis-
tration of broad-spectrum antibiotics has
been introduced in humans to control
protein digestion and putrefaction. The
results have been excellent with neomycin
and chlortetracycline, the disappearance
of hepatic coma coinciding with depression
of blood ammonia levels. Purgation and
enemas have also been used in combi-
nation with oral administration of anti-
biotics but mild purgation is recommended
to avoid unnecessary fluid loss. Supple-
mentation of the feed or periodic injec-
tions of the water-soluble vitamins are
desirable. Hepatic fibrosis is considered to
be a final stage in hepatitis and treatment
is not usually undertaken.

REVIEW LITERATURE

Ross MA. The relationship of hepatic drug meta-
bolism to hepato toxicity with some examples in
sheep. Vet Annu 1982; 22:129-134.

McGorum BC, Murphy D, Love S, Milne EM-
Clinicopathological features of equine primary
hepatic disease: a review of 50 cases. Vet Rec 1999;
145:134-139.

Pearson EG. Liver disease in the mature horse. Equine
Vet Educ 1999; 11:87-96.

Olsman AF, Sloet van Oldruitenborgh-Oosterbaan
MM. Primary liver disease in the horse. Tijdschr
Diergeneeskd 2004; 129:510-522.

REFERENCES

1. Smith MRW et al. Equine Vet J 2003; 35:549.

2. McGorum BC et al.Vet Rec 1999; 145:134-139.

3. Olsman AF, Sloet van Oldruitenborgh-Oosterbaan
MM. Tijdschr Diergeneeskd 2004; 129:510.

4. MullaneyTP, Brown CM. Equine Vet J 1988; 20:119.

5. Nation PN. Can Vet J 1991; 32:602.

6. Putnam MR et al. J Am Vet Med Assoc 1986;
189:77.

Focal diseases of the liver

395

7. Sweeney RW et al. J Vet Intern Med 1988; 2:80.

8. Messer NT, Johnson PJ. J Am Vet Med Assoc 1994;
204:1934.

9. Messer NT, Johnson PJ. J AmVet Med Assoc 1994;
204:1790.

10. Aleman M et al. J Vet Intern Med 2005; 19:120.

11. Zentara S et al.Vet Rec 1994; 134:18.

12. Wilkie IW et al. Can Vet J 1988; 29:1003.

13. Sweeney HJ, Greig A. Equine Vet J 1986; 18:150.

14. BuergeltCD, Greener EC. JVetDiagn Invest 1995;
7:102.

15. Davis CR et al. J Parasitol 1999; 85:965.

16. West HJ. Equine Vet J 1996; 28:148.

17. West HJ. Bovine Pract 1990; 25:127.

18. Pearson EG et al. J Am Vet Med Assoc 1994;
204:1053.

19. Helman RG et al. J Am Vet Med Assoc 1993;
202:129.

20. Helman RG et al.Vet Pathol 1995; 32:635.

21. Fortier LA et al.Vet Surg 1996; 25:154.

22. Hillyer MH et al.Vet Rec 1993; 132:457.

23. Pearson EG. Equine Vet Educ 11:1999; 87-96.

24. Ramaiah SK et al. JVet Intern Med 2003; 17:360.

25. Durham AE et al. EquineVet J,2003; 35:542.

26. West HJ.VetRes Commun 1997; 21:169.

27. West HJ. EquineVet J 1996; 28:146.

28. Durham AE et al. EquineVet J 2003; 35:534.

29. Durham AE et al. EquineVet J 2003; 35:554.

30. Gill PA, Townsend WL. Aust Vet J 1993; 70:69.

Focal diseases of the liver

HEPATIC ABSC ESS

Local suppurative infections of the liver
do not cause clinical signs of hepatic
dysfunction unless they are particularly
massive or extensively metastatic. They do
cause significant losses in feedlot and
grain-fed cattle because of the frequency
of rumenitis in those cattle leading to
hepatic abscess formation and the rejection
of the affected livers at the abattoir. In
feedlot cattle in North America the
incidence of liver abscesses averages about
16% but ranges from about 8% to 40% or
even higher, up to 78%. 1

In a 2-year study of bovine hepatic
abscessation in 10 abattoirs in Ireland, the
livers of 6337 12-16-month-old heifers
were examined. 2 The frequency of gross
lesions was 5.8%, of which 1.9% had
abscesses. Only 1.17 had scarring, and
0.7% telangiectasis. Of the livers with
abscesses, 44% had a single large abscess,
35% had a single small abscess and 19%
had more than two abscesses; in 16% the
abscesses were resolving and in 8.3% the
abscesses were ruptured. A total of 43% of
the livers with abscesses had adhesions to
the diaphragm and diaphragmatic lung
lobes, 2.5% had adhesions to other
abdominal organs, 10% also had scarring
and 1.7% also had lesions attributable to
the liver fluke. Clinical signs attributable
to the abscesses were observed in only
one animal.

Cattle started on feed in November
and January in North America, and cattle
housed in confinement or outside with-

out overhead shelter, had higher incidences
of liver abscesses. 1 Virginiamycin at
16.5-19.3 mg/kg DM in the diet reduced
the incidence of liver abscesses in feedlot
cattle. 3 Occasional cases occur in dairy
cows and cause severe illness. 4 The
toxemia of traumatic hepatitis is usually
due to toxins from Arcanobacterium
pyogenes, Streptococcus and Staphylococcus
spp. and Fusobacterium necrophorum,
which are implanted in the lesions by the
perforating foreign body; of the F.
necrophorum isolates most will be of the A
biotype, although the B biotype does
occur usually in combination with other
bacteria. 5

Hepatic abscesses in goats have been
described. 6 Out of 658 necropsies of
goats, 2.5% had hepatic abscesses. The
abscesses occurred most commonly in
adults. All the affected animals were in
poor bodily condition. The organisms
isolated included Corynebacterium pseudo-
tuberculosis (58.9%), Escherichia coli
(11.8%), Corynebacterium spp. (11.8%),
Mannheimia haemolytica (5.0%), Proteus sp.
(5.9%) and Staphylococcus aureus (5.9%).

Omphalophlebitis, ruminal para-
keratosis or rumenitis may also lead to
hepatic invasions by F. necrophorum or
other organisms and abscessed livers are
common in cattle fed heavily on concen-
trates. Black disease is a profound toxemia
caused by the liberation of potent
exotoxin from C. novyi. Clostridium sordellii
is associated with hepatic abscesses in
neonatal lambs and bacillary hemo-
globinuria by a toxin from Clostridium
haemolyticum with focal hepatic necroses.
A focal bacterial hepatitis, identified as
Tyzzer's disease' and associated with
Bacillus piliformis, and yersiniosis associ-
ated with Yersinia pseudotuberculosis are
listed elsewhere. Occasional cases of
strangles that develop bacteremic spread
may also develop hepatic abscesses, as
may septicemia in lambs associated with
Histophilus somni.

The fungus Mortierella wolfii has been
isolated from a liver abscess in a cow in
Australia. 7 The liver abscess was grossly
indistinguishable from other common
bacterial abscesses, such as those associ-
ated with A. pyogenes or F. necrophorum.

The clinical signs of these specific
diseases are included under the discussion
of each disease and the only finding com-
mon to all is local pain on palpation or
percussion over the liver.

A most important relationship is that
between liver abscess and caudal vena
caval syndrome. Sudden death, or any
death, of cattle due to pulmonary hemor-
rhage should be examined with this
possibility in mind. Liver abscesses have
been produced experimentally in cattle by
injecting F. necrophorum into the hepatic

portal vein. They are characterized ^y an
elevation of blood levels of sialic acid and
mucoprotein. High concentration of
alpha-1 acid glycoprotein (cq-AG) present
in naturally occurring cases is correlated
with sialic acid concentration. 8

Hepatic abscesses in horses

Hepatic abscesses in horses are charac-
terized clinically by a history of weight
loss, fever, inappetence and depression.
The etiology and pathogenesis are
unknown. Clinicopathological abnor-
malities are consistent with a diagnosis of
chronic bacterial infection such as leuko-
cytosis with a mature neutrophilia,
thrombocytosis, hyperglobulinemia, hypo-
albuminemia and a markedly decreased
albumin-to-globulin concentrations ratio. 9
Ultrasonography is a useful diagnostic
aid. Secondary immune-mediated com-
plications may develop in young adult
horses with hepatic abscesses. The prog-
nosis is very unsatisfactory, in spite of
intensive antibiotic and supportive therapy,
and euthanasia is recommended.

TELANGIECTASIS OF THE BOVINE
LIVE R ('SAWDUST LIVER')

Telangiectasis of the bovine liver accounts
for about 10% of all bovine liver condem-
nations in federally inspected slaughter
facilities in the USA. 10 Condemnation is
based on aesthetics. The lesion is usually
easily diagnosed by inspectors but its
biological significance is undetermined.
Affected livers contain more bacteria than
normal livers but telangiectasis cannot be
linked to an infectious process. In some
affected livers, E. coli 0157 was present,
which is a potential zoonotic risk. 10 It is
believed that E. coli 0157 in meat at
slaughter is an external contaminant and,
experimentally in cattle, there is no
evidence that the organism translocates
from the alimentary tract to deeper
tissues. The morphological, immuno-
histochemical and ultrastructural studies
of pretelangiectasis and telangiectasis of
the bovine liver have been examined. 11

TUMORS OF THE LIVER

Metastatic lesions of lymphomatosis in
calves are the commonest neoplasms
encountered in the liver of animals,
although primary adenoma, adeno-
carcinoma and metastases of other
neoplasms in the area drained by the
portal tract are not uncommon, especially
in ruminants. For the most part, they
produce no signs of hepatic dysfunction
but they may cause sufficient swelling to
be palpable, and some abdominal pain by
stretching of the liver capsule. Primary
tumors of the gallbladder and bile ducts
also occur rarely and do not generally

6

PART 1 GENERAL MEDICINE ■ Chapter 7: Diseases of the liver and pancreas

cause clinical signs. A primary hepatic
fibrosarcoma in a goat has caused loss of
body weight, although appetite was
maintained, anemia and jaundice. 12
Hepatic biliary cystadenoma has been
described in a 10 -year-old horse. 13 It is
regarded as a morphological variant of
biliary cystadenoma of domestic animals.

A series of 66 primary hepatic tumors
of cattle has been examined and classified
using modem criteria. 14 Fifty hepatocellular
tumors (10 adenomas and 40 carcinomas),
10 cholangiocellular tumors, two cavernous
hemangiomas, two hemangioendothelial
sarcomas, one fibroma and one
Schwannoma were diagnosed. An associ-
ation with cirrhosis was not found. A bile
duct hamartoma in a calf has been
reported. 15

REFERENCES

1. Harman BR et al. J Anim Sci 1989; 67:311.

2. O'Sullivan EN.Vet Rec 1999; 145:389.

3. Rogers JA et al. J Anim Sci 1995; 73:9.

4. Cahill LW. Bovine Pract 1993; 27:171.

5. Scanlan CM, Hathcock CL. Cornell Vet 1983;
73:288.

6. Rosa JS et al. BrVet J 1989; 145:73.

7. Uzal FA et al.Vet Rec 1999; 145:260.

8. MotoiY et al. Am J Vet Res 1992; 53:574.

9. Sellon DC et al. J Am Vet Med Assoc 2000;
216:882.

10. Stotland EL et al. J Am Vet Med Assoc 2001;
219:36.

11. Marcato PS et al. J Comp Fcithol 1998; 119:95.

12. Higgins RJ et al.Vet Rec 1985; 116:444.

13. Salvaggio A et al.Vet Pathol 2003; 40:114.

14. Bettini G, Marcato PS. J Comp Pathol 1992;
107:19.

15. De Bosschere H, Ducatelle R. Vet Rec 1999;
144:210.

DISEASES OF THE BILIARY
SYSTEM

Cases of biliary tract disease with clinical
manifestations are uncommon in food
animals and horses. Occasional cases of
cholangitis occur in cattle and horses.
Associated clinical signs include fever,
pain over the liver, jaundice and photo-
sensitization. There is usually an
accompanying leukocytosis and a left
shift. In horses a sequel to cholangitis
may be a diffuse bacterial hepatitis with
signs of hepatic insufficiency. Septic
cholangiohepatitis and cholangiocarcinoma
have been recorded in a horse. 1

Concretions in the biliary system of
cattle are usually a sequel to fascioliasis. 2
Mild cases show anorexia and pain over
the liver. Severe cases show recurrent
attacks of severe abdominal pain, alimen-
tary tract stasis and pain on percussion
over the liver. Jaundice occurs only in the
terminal stages of fatal cases and is
accompanied by recumbency, depression
and coma. 3 The frequency of pigment
gallstones is high in sheep and associated
with high total bilirubin concentration in

the bile. 4 Other causes of biliary tract
disease include gallbladder empyema and
a bile duct carcinoma. In the latter case
there was severe loss of body weight and
signs referable to metastases in other
organs but there were no clinical or post-
mortem signs of biliary malfunction.
Biliary atresia in young foals is manifested
by an early period of normality for
2-3 weeks after birth followed by the
development of listlessness, anorexia, the
passage of gray, pasty feces and jaundice.
Death occurs about a week later.

Obstructive cholelithiasis in horses
may cause intermittent colic or continuous
pain and sometimes jaundice. A series of
10 cases in horses is reported. 5 Clinical
findings included fever, icterus, mild
intermittent colic and weight loss.
Laboratory findings included leukocytosis,
hyperproteinemia and hyperfibrino-
genemia. GGT and lactate dehydrogenase
were also elevated.

Cholangiohepatitis in horses

A series of nine cases was reported of
cholangiohepatitis and cholelithiasis in
mature horses with a median age of 13
and a range of 4-18 years. 6 Clinical signs
that prompted referral of each horse to a
veterinary teaching hospital included
anorexia, depression, weight loss, colic,
intermittent fever and icterus. In all
horses, the GGT and ALP were elevated,
and there was hyperbilirubinemia. Trans-
abdominal ultrasonography was used to
evaluate the size and nature of the liver
and to obtain liver biopsy for histo-
pathology and culture. The ultra-
sonographic findings included increased
hepatic echogenicity, hepatomegaly,
enlarged distended bile ducts and
occasional calculi as the salient features.
Neutrophilic cholangiohepatitis consistent
with an infectious cause was a feature of
biopsy material from each horse.

The etiology and pathogenesis of
cholangiohepatitis and cholelithiasis in
horses is uncertain. Retrograde bacterial
infection from the small intestine is
considered probable. Culture of liver
biopsy material yielded E. coli and
Bacteroides vulgatus from only a small
number of affected animals. Long-term
parenteral Gram-negative antibiotics
daily for a median of 51 days (range
17-124) was associated with survival in
7/9 horses. Supportive intravenous fluid
therapy is also necessary. Progress can be
monitored by evidence of clinical improve-
ment and declining levels of GGT.

Cholangiohepatitis in a 2-month-old
calf was characterized clinically by
depression, fever and diarrhea. 7 There was
marked leukocytosis and neutrophilia. The
GGT and ALP were markedly elevated
and total bilirubin was elevated. Ultra-

sonographic examination of the liver
revealed gross abnormality and liver
biopsy results indicated neutrophilic
hepatitis and multifocal hyperplasia of the
biliary epithelium suggesting cholangio-
hepatitis. Culture of liver tissue yielded
E. coli sensitive to amikacin, cefazolin and
ceftiofur. Supportive fluid therapy and
antibiotics may be successful.

Suppurative cholangiohepatitis and
cholelithiasis associated with enteritis has
been described occurring in adult horses. 8
Clinical findings included nonresponsive
colic, fever, depression, severe abdominal
pain, tachycardia, dehydration, gastric
fluid accumulation and absence of
abdominal sounds over all four quadrants.
Distended loops of small intestine were
palpable on rectal examination and the
peritoneal fluid was serosanguinous.
Azotemia, hyperbilirubinemia, increased
ALP and GGT were present and persisted
for several days. Cases were associated
with severe inflammation of the small
intestine and hypotensive shock.

Cholangiohepatitis and pancreatitis
secondary to gastroduodenal ulceration in
a 2-month-old foal was characterized
clinically by colic unresponsive to surgical
treatment. 9 At necropsy, gastric ulcer-
ation, segmental duodenal stenosis and
severe chronic cholangiohepatitis and
pancreatitis were present.

Choledocholithiasis attributable to a
foreign body in a horse is recorded. 10
Clinical signs suggestive of biliary disease
in adult horses may be due to neoplasia of
the pancreas (see below). A case of
congenital hepatic fibrosis in a newborn
calf is recorded. 11

REFERENCES

1. Durando MM et al. J Am Vet Med Assoc 1995;

206:1018.

2. West HJ, Hogg R. Vet Rec 1988; 122:251.

3. Lechtenberg KF et al. Am J Vet Res 1988; 49:58.

4. Catallini A et al. Am JVet Res 1991; 52:2043.

5. Johnston JK et al. J Am Vet Med Assoc 1989;

194:405.

6. Peek SF, Divers TJ. Equine Vet J 2000; 32:301.

7. Coombs DK et al.Vet Rec 2002; 150:551.

8. Davis JL, Jones SL. J Vet Intern Med 2003; 17:583.

9. Buate M. Can Vet J 2003; 44:746.

10. Gerros TC et al. J Am Vet Med Assoc 1993;

202:301.

11. Yoshikawa H et al.Vet Pathol 2002; 39:1.

Diseases of the pancreas

Pancreatic disease in large animals is rare
and only a few comments are presented
here.

DIABETES MELLITUS

Lesions of the pancreas causing diabetes
mellitus are recorded in cows 1 and horses
and donkeys. 2 The clinical syndrome in
horses includes weight loss, polydipsia,

Diseases of the pancreas

397

polyuria, intense hyperlipidemia and high
blood levels of cholesterol, triglycerides
and glucose. Clinical observations suggest
that the disease is most likely to occur in
old horses and may be due to pancreatic
injury related to migration of strongyle
larvae . 3 Diabetes mellitus resulting from
pancreatic beta -cell failure is rare in the
horse but has been reported in a
domesticated Spanish Mustang . 4 In cows
there is afebrile emaciation, polydipsia,
ketonuria, glucosuria and hyperglycemia.

PANCREATIC ADENOCARCINOMA

The pancreatic duct of the horse is
anatomically close to the common bile
duct and it is not unexpected that a tumor
mass should cause a syndrome of biliary

duct pathology , 5,6 although there is a
surprising absence of jaundice at some
stages of the disease. There is emaciation,
concomitant moderate abdominal pain
and variable fecal texture up to diarrhea.
GGT and blood ammonia levels are
greatly increased.

PANCREATIC ADENOMA

Convulsions due to hypoglycemia have
been recorded in a pony with a pancreatic
adenoma . 7 It is assumed that the hypo-
glycemia resulted from hyperinsulinism
generated by the beta-cell adenoma.

PANCREATITIS

Pancreatitis is rare in farm animals.
Inflammatory and degenerative changes

are detected post mortem in scfrne cattle
but are rarely diagnosed clinically because
of a lack of clinical and laboratory
findings. Ultrasonographic imaging of
experimentally induced pancreatitis in
cattle has been described . 8

REFERENCES

1. Mostaghni K, Ivoghli B. Cornell Vet 1977; 67:24.

2. Moore JN et al. Endocrinology 1979; 104:576.

3. Bulgin MS, Anderson BC. Compend Contin Educ
PractVet 1983; 5:S482.

4. Johnson PJ et al. J Am Vet Med Assoc 2005;
226:584.

5. KerrOM et al. Equine Vet J 1982; 14:338.

6. Church S et al. Equine Vet J 1987; 19:77.

7. Ross MW et al. Cornell Vet 1983; 73:151.

8. MohamedT et al.Vet J 2003; 165:314.

PART 1 GENERAL MEDICINE

Diseases of the cardiovascular system

PRINCIPLES OF CIRCULATORY
FAILURE 399

Heart failure 399
Circuit failure 399
Cardiac reserve and compensatory
mechanisms in heart failure 399
Cardiac enlargement 401

MANIFESTATIONS OF CIRCULATORY
FAILURE 401

Chronic (congestive) heart failure 401
Acute heart failure 404

SPECIAL EXAMINATION OF THE
CARDIOVASCULAR SYSTEM 405

Physical examination 405
Measurement of jugular venous
pressure 407
Exercise tolerance 407
Electrocardiography 407

Principles of circulatory
failure

The primary function of the cardiovas-
cular system is to ensure an adequate
circulation of blood so that nutrients are
delivered, waste products are removed
and a homeostatic milieu is maintained at
the organ and cellular level. An inade-
quate circulation interferes with nutrient
delivery and waste product removal, and
ultimately leads to circulatory failure, the
primary concept in diseases of the
cardiovascular system.

The two functional units of the
cardiovascular system are the heart and
the blood vessels; these two units are best
characterized as a pump (the heart) and a
circuit (the blood vessels and blood). The
pump and circuit may fail independently
of each other, giving rise to two forms of
circulatory failure - heart failure and
circuit failure. In heart failure the primary
problem is inadequate pump perform-
ance, whereas in circuit failure the
deficiency is in the vascular system, which
fails to return an adequate volume of
blood to the heart. Circuit failure can also
result from decreased circulating blood
volume.

HEART FAILURE

The failure of the heart as a pump can
result from a defect in filling of the heart,
an abnormality in the generation or con-
duction of the electrical wave of depolari-
zation, an abnormality in contractile
function, excessive workload or a combi-
nation of one or more abnormalities.

Serum cardiac troponin I
concentration 409
Phonocardiography 409
Cardiac output 410
Measurement of arterial blood
pressure 410
Echocardiography 41 1
Cardiac catheterization 41 1
Radiographic and angiocardiographic
examination 412

ARRHYTHMIAS 412

Sinus tachycardia, sinus bradycardia
and physiological dysrhythmias 413
Arrhythmias with normal heart rates or
bradycardia 414

Arrhythmias with tachycardia 41 6

DISEASES OF THE HEART 420

Myocardial disease and

Causes of cardiovascular dysfunction

• Cardiac arrhythmia

• Obstructed flow

• Regurgitant flow

• Contractile dysfunction (systolic failure)

• Inadequate filling (diastolic filling)

• Loss of blood

It is usual to divide heart failure into
two types, acute heart failure and chronic
(congestive) heart failure. However, a
complete range of syndromes occurs and
some of them do not fit neatly into one or
other category. Circulatory equilibrium is
not maintained when cardiac output is
deficient. If this develops sufficiently
slowly, compensatory mechanisms, plus
the failure of the heart itself as a pump,
result in an increase in venous pressure
and congestive heart failure. If on the
other hand there is an acute reduction of
cardiac output, as is caused by sudden
cessation of the heart beat, the effect is to
deprive tissues of their oxygen supplies
and the syndrome of acute heart failure
develops.

Heart failure can be left-sided, right-
sided or both left- and right-sided. Left-
sided heart failure causes an increase in
left ventricular end diastolic pressure,
mean left atrial pressure and pulmonary
venous pressure. Depending upon the
magnitude and rate of the increase in
pressure, left-sided heart failure results
in interstitial edema in the lungs and,
if severe enough, pulmonary edema,
dyspnea and death. Right-sided heart
failure causes an increase in -right
ventricular end-diastolic pressure, mean

cardiomyopathy 420
Rupture of the heart and acute
cardiovascular accidents 422
Cor pulmonale 422
Valvular disease and murmurs 423
Endocarditis 427

DISEASES OF THE
PERICARDIUM 429

Pericarditis 429
Congenital cardiac defects 431

CARDIAC NEOPLASIA 433

DISEASES OF THE BLOOD
VESSELS 433

Arterial thrombosis and embolism 433
Venous thrombosis 435
Hemangioma and
hemangiosarcoma 436

right atrial pressure and jugular venous
pressure. Depending upon the magnitude
and rate of the increase in pressure, right-
sided heart failure results in symmetric
venous distension (most readily detected
in the jugular veins), an increase in
pleural, pericardial and abdominal fluid
(ascites), and hepatomegaly.

a RCU IT FAILURE

In circuit failure the effective blood
volume is decreased because of loss of
fluid from the vascular system (hypo-
volemic shock) or by pooling of blood in
peripheral vessels and increased capillary
permeability (maldistributive shock).
The failure of venous return results in
incomplete filling of the heart and a
reduction in cardiac output, although
there is no primary defect in pump
performance. The effects of circuit failure
are the same as those of chronic
(congestive) heart failure in that the sup-
ply of nutrients to the tissues and the
removal of waste products from the
tissues are reduced.

CARDIAC RESERVE AND
COMPENSATORY MECHANISMS
IN HEART FAILURE

The normal heart has the capacity to
increase its output severalfold in response
to normal physiological demands created
by exercise and to a lesser extent by
pregnancy, lactation, digestion and hot
ambient temperatures. Collectively, these
compensatory responses comprise the
cardiac reserve. Similar compensatory
responses are utilized by the failing heart
in an attempt to maintain cardiac output.

400

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

Cardiac reserve and its response in heart
failure have not been studied extensively
in large domestic animals and conse-
quently its description must rely heavily
on studies on cardiac failure in small
domestic animals and studies of the effect
of exercise on cardiovascular performance
in the horse. 1 " 6 Clinical observations on
cardiac insufficiency and cardiac failure in
large animals suggest that the processes
are very similar to those in small animals
and humans.

The major mechanisms whereby the
blood flow to an organ can be increased
are:

o Increase in heart rate
o Increase in stroke volume
o Redistribution of blood flow to vital
organs, or organs with particularly
high metabolic requirements.

All of these mechanisms act synergisti-
cally and are interrelated. Heart rate and
stroke volume are the determinants of
cardiac output (cardiac output is the
product of heart rate and stroke volume).

CARDIAC RESERVE AND HEART RATE

There is a great deal of cardiac reserve in
the heart rate, and an elevation of heart
rate alone is a significant factor in
increasing cardiac output in the exercising
horse. There is a limitation to heart rate
reserve because with increasing heart
rates there is a decrease in diastolic filling
time, and stroke volume falls at excessive
heart rates. Effective heart rate reserve can
be increased with exercise training, and
maximum heart rate in trained exercising
horses is six to seven times resting
values. 7 This large increase in heart
rate reflects the metabolic scope of
trained horses. In contrast, cattle can only
increase their heart rate to two to four
times their resting values. An increase in
heart rate is also used to maintain cardiac
output by the failing heart. With cardiac
insufficiency in the horse and the cow it is
rare for the heart rate to exceed 120/min,
and rates higher than this are frequently
due to tachyarrhythmias that require
immediate treatment.

CARDIAC RESERVE AND STROKE
VOLUME

Stroke volume is variable and depends
upon the amount of shortening that the
myocardial fibers can attain when
working against arterial pressure. It is
determined by an interplay of four
factors:

Ventricular distending or filling
pressure (preload)

° Contractility of the myocardium
(inotropic state)

® The tension that the ventricular
myocardium must develop during

contraction and early ejection
(afterload)

o The sequence of atrial and ventricular
depolarization.

An increase in ventricular distending
pressure (end -diastolic pressure orvolume)
will increase ventricular end-diastolic
fiber length, which, by the Frank-Starling
mechanism and stretch-dependent calcium
sensitization, will result in increased stroke
work and a larger stroke volume. Ven-
tricular distending pressure is influenced by
atrial contraction and is greatly augmented
by increased venous return associated
with exercise and increased sympathetic
activity. Contractility is most influenced
by adrenergic activity and circulating
catecholamines. An increase in stroke
volume is achieved primarily by an
increase in the ejection fraction and a
reduction in the end-systolic volume but
can also be achieved by a decrease in
afterload, which is primarily a function of
aortic or pulmonary impedance (the resist-
ance and reactance of the vasculature to
ejection).

CARDIAC RESERVE AND MIXED
VENOUS OXYGEN TENSION

In normal animals at rest, the oxygen
tension of mixed venous blood is above
40 mmHg (5.3 kPa), which represents a
considerable reserve. Increased extraction
of oxygen from the blood by various
tissues, with a subsequent decrease in
mixed venous oxygen tension and a
corresponding increase in arterial venous
oxygen difference, occurs during exercise
and in pump and circuit failure. 4 In
uncompensated heart failure, where
stroke volume is reduced, the mixed
venous oxygen tension falls below
40 mmHg, reaching 15-25 mmHg in
severe shock states, and the arterial
venous oxygen difference is large.There is
also a redistribution of blood flow to vital
organs. In the horse the splenic storage
capacity for erythrocytes is large and the
spleen may contain one-third of the total
red cell volume. Maximal emptying of
the spleen under adrenergic activity
can significantly influence the oxygen-
transporting capacity of the blood and, in
the horse, the splenic reservoir contributes
significantly to cardiovascular reserve.

CARDIAC RESERVE AND AUTONOMIC
NERVE ACTIVITY

It is evident that increased sympathetic
nerve activity also plays a significant role
in compensating for the failing ventricle,
but one that is not readily determined
clinically. An increase in sympathetic
activity acts to augment cardiac output by
increasing the heart rate, by improving
the contractility of the myocardium
and by augmenting venous return to the

heart. Autonomic nerve activity also
regulates blood flow to more essential
organs even when faced with insufficient
cardiac output.

CARDIAC RESERVE IN CARDIAC
INSUFFICIENCY

In cardiac insufficiency the principal
defect is in the contractile state of the
myocardium, and ventricular performance
at any given end-diastolic volume or
pressure is diminished. In early failure,
cardiac output may still be maintained in
the normal range by an increase in filling
pressure and, through utilization of
stretch-dependent calcium sensitization
and the Frank-Starling principle, the ven-
tricles can eject a normal stroke volume
despite the depression in contractility.
Thus, early in the course of cardiac failure,
the end-diastolic pressure may be
elevated only during periods with heavy
demands on the heart, such as during
exercise. However, as myocardial function
becomes increasingly impaired, this
mechanism is increasingly utilized for
lesser work demands until end-diastolic
pressure is elevated even at rest or with
normal activity.

Ventricular filling pressure is augmented
by increased venous return associated
with contraction of the venous capaci-
tance vessels under increased sympathetic
tone, and by an increase in blood volume
as the result of salt and water retention by
the kidney. Decreased renal perfusion
results in the release of renin by the
juxtaglomerular cells in the kidney and
the activation of the renin-angiotensin-
aldosterone system. Renin causes the
conversion of angiotensinogen to angio-
tensin I and angiotensin I in turn is
converted to angiotensin II in the lungs.
Angiotensin II is a powerful vasocons-
trictor and promotes the effect of
norepinephrine. Angiotensin II also
stimulates the release of aldosterone from
the adrenal cortex, which acts to increase
sodium retention by the kidney with
consequent expansion of the interstitial
fluid and blood volumes.

Although the increase in ventricular
end -diastolic pressure acts to maintain
cardiac output, it is associated with a
marked increase in systemic or pulmon-
ary venous pressure, producing secondary
effects that result in many of the clinical
abnormalities associated with congestive
heart failure. Where the contractile state
of the heart is markedly reduced, the
increased end-diastolic pressure is unable
to maintain normal stroke volume,
even at normal activity, and cardiac
output is reduced even at rest - the
state of uncompensated heart failure,
which is clinically manifest . as pump
_ failure.

Manifestations of circulatory failure

401

MEASUREMENT OF CARDIAC
RESERVE

From a clinical standpoint it would be
desirable to be able to detect incipient
cardiac insufficiency at a very early
stage.

A clinical estimation of cardiac reserve
based on physical examination is import-
ant when a prognosis is to be made for an
animal with heart disease. Some of the
important criteria used in making this
assessment include the heart rate, the
intensity of the heart sounds, the size of
the heart, the characteristics of the pulse
and the tolerance of the animal to
exercise. A resting heart rate above
normal indicates loss of cardiac reserve.
The absolute intensity of the heart sounds
suggests the strength of the ventricular
contraction, soft sounds suggesting
weak contractions and sounds that are
louder than normal suggesting cardiac
dilatation and possibly hypertrophy,
although this is a very crude and
insensitive measure. The interpretation of
variation in intensity must be modified by
recognition of other factors, such as
pleural and pericardial effusion, that
interfere with audibility of the heart
sounds.

Pulse characteristics are of value in
determining the cardiac reserve but they
are greatly affected by factors other than
cardiac activity. An increased amplitude
of the pulse occurs when the cardiac
stroke volume is increased, but a
decreased amplitude may result from
reduced venous return as well as from
reduced contractile power of cardiac
muscle.

Exercise tolerance is an excellent guide
to cardiac reserve and the least expensive
and most practical method for quanti-
fying cardiovascular reserve. Exercise
tolerance is best assessed by measuring
the maximum heart rate attained after a
standard exercise test, and the speed
with which the heart rate returns to
normal. 1,3-4

REFERENCES

1. Flaminio MJBF et al. Vet Clin North Am Equine
Pract 1996; 12:565.

2. ElAguera El et al. J Equine Vet Sci 1995; 15:532.

3. Physick-Sheard PW. Vet Clin North Am Equine
Pract 1 1985; 2;:383.

4. Evans DL, Rose RJ. Pflugers Arch 1988; 411:316.

5. Hinchcliff KW et al. Am J Physiol 1990;
258:R1177.

6. Seeherman HJ, Morris EA. Equine Vet J Suppl
1990; 9:20.

7. HarkinsJD, Kamerling SG. J Equine Vet Sci 1991;
11:237.

CARDIAC ENLARGEMENT

The ratio of heart weight to body weight
is greater in athletic animals than in

nonathletic animals, and the heartrweight
ratio in horses can be modestly increased
during training as a result of physiological
hypertrophy. Cardiac enlargement is also
a compensatory response to persistent
increased workloads that are associated
with cardiovascular disease. The heart
may respond by dilatation, hypertrophy
or a combination of both.

Cardiac hypertrophy (concentric
hypertrophy) is the usual response to an
increased pressure load, and there is
hypertrophy of individual fibers with an
increase in the number of contractile units
(sarcomeres) and an increase in total
muscle mass. However, cardiac hyper-
trophy is usually accompanied by
decreased capillary density and increased
intercapillary distance and, in states of
cardiac insufficiency, coronary blood
flow reserve places limitations on this
compensatory mechanism.

Cardiac dilatation (eccentric hyper-
trophy) is the usual response to an
increased volume load and probably
results from fiber rearrangement. Con-
tractions occurring in a dilated chamber
can eject a larger volume of blood per
unit of myocardial shortening. However,
the limitation to this compensatory
mechanism is evident in the law of
Laplace, which shows that in the dilated
chamber greater myocardial wall tension
is required to produce an equivalent
elevation of intrachamber pressure during
ejection.

The significance of finding cardiac
enlargement on clinical examination is
that it indicates the presence of a
significant volume or flow load on the
heart, or the presence of myocardial
disease and a reduction of cardiac reserve.
The detection of cardiac enlargement on
physical examination is aided by careful
auscultation of the heart, palpation of
the apex beat and rarely by thoracic
percussion. A palpable and audible
increase in the apex beat and area of
audibility, backward displacement of the
apex beat, increased visibility of the
cardiac impulse at the base of the neck
and behind the elbow and increased
area for the cardiac shadow during
thoracic percussion are all suggestive
of cardiac enlargement. Care must be
taken that the abnormalities observed
are not due to displacement of the heart
by a space-occupying lesion of the thorax
such as thymic lymphosarcoma, or to
collapse of the ventral part of the lung
and withdrawal of lung tissue from
the costal aspects of the heart. Echo-
cardiography should be used to quantify
the magnitude of the enlargement when-
ever the results of physical examin-
ation suspect the presence of cardiac
enlargement.

Manifestations of
circulatory failure

The manifestations of circulatory failure
depend on the rapidity of its onset, the
magnitude of its severity, and on its
duration. Chronic (congestive) heart failure
and acute heart failure are discussed
below.

CHRONIC (CONGESTIVE) HEART
FAILURE

Etiology Diseases of the endocardium,
myocardium and pericardium that interfere
with the flow of blood into or away from
the heart, or that impair myocardial
function, may result in congestive heart
failure

Clinical findings Generalized venous
distension and edema in right-sided failure.
Pulmonary edema and respiratory distress
in left-sided failure

Clinical pathology Increased serum
concentration of cardiac troponin I, a
cardiac-specific enzyme
Necropsy findings Subcutaneous
edema, ascites, hydrothorax and
hydropericardium; enlargement and
engorgement of the liver with right-sided
failure. Pulmonary edema with left-sided
failure

Diagnostic confirmation Clinical
Treatment Treatment of specific cause,
often unsuccessful. Diuretics, salt
restriction, minimize activity, possibly
digoxin

ETIOLOGY

Causes of chronic (congestive) heart
failure can be broadly characterized as
follows.

Valvular disease

° Endocarditis resulting in either
valvular stenosis or valvular
insufficiency

° Congenital valvular defects - most
commonly valvular stenosis
° Rupture of valve or valve chordae.

Myocardial disease

° Myocarditis - bacterial, viral, parasitic
or toxic

° Myocardial degeneration - nutritional
or toxic

° Congenital or hereditary
cardiomyopathy

° Toxins affecting cardiac conduction.

Congenital anatomical defects
producing shunts

° Cardiac defects, such as ventricular or
atrial septal defects, tetralogy of Fallot
° Vascular abnormalities producing
shunts, such as patent ductus
arteriosis.

402

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

Hypertension

0 Pulmonary hypertension - high
altitude disease, cor pulmonale
° Systemic hypertension -

undocumented cause of congestive
heart failure in large animals.

Pressure load

Pressure loads occur with lesions that
produce an obstruction to outflow such as
aortic or pulmonary valve stenosis, where
the heart is required to perform more
work to eject an equivalent amount of
blood. Pressure loads are not necessarily
associated with lesions in the heart. For
example, pulmonary hypertension, such
as occurs in high altitude disease of cattle
due to an increase in pulmonary vascular
resistance, may result in cardiac insuffi-
ciency. In general, the left ventricle can
tolerate a pressure load to a much greater
extent without overt signs of cardiac
insufficiency than the right ventricle.

Volume load

Volume loads (flow loads) occur com-
monly with both acquired and congenital
heart defects. In aortic valve insufficiency
and mitral valve insufficiency the volume
of blood delivered to the tissues does not
differ significantly from normal. However,
in order to achieve a normal cardiac
output, the forward stroke volume of the
ventricle is markedly increased and the
heart is much more inefficient for the
same amount of effective work. In a
similar manner a patent ductus arteriosus
or an interventricular septal defect with a
large left-to-right shunt of blood can
place a considerable flow load on the left
ventricle. In general, the right ventricle is
more capable of sustaining a flow load
than the left ventricle.

Pumping defects (systolic failure)

Cardiac insufficiency may occur without
any increase in workload if there is a
primary weakness in the myocardium or
defect in its rhythmic and coordinated
contraction. Myocarditis, cardiomyopathy
and neoplasms of the heart, especially
bovine viral leukosis lesions of the right
atrium, are the common causes. Arrhyth-
mias are a rare cause of congestive heart
failure but a common cause of acute heart
failure.

Filling defects (diastolic failure)

Pericardial diseases such as pericarditis
and pericardial tamponade can result in
cardiac insufficiency by interfering with
diastolic filling. Filling of the ventricle is
determined by the complex interaction of
a number of factors, including mean
circulatory filling pressure, mean right
atrial pressure, stiffness of the ventricular
chamber (which is determined, in part, by

mean arterial blood pressure) and the
pressure gradient across the ventricular
wall. The latter is markedly affected by
increases in pericardial fluid pressure that
are present in pericarditis and pericardial
tamponade.

PATHOGENESIS

Cardiac reserve and compensatory mech-
anisms in heart failure are described in
the preceding section. In the early stages
of cardiac disease circulatory equilibrium
may be maintained. However, cardiac
reserve is reduced and the animal is not
able to cope with circulatory emergencies
as well as a normal animal. This is the
stage of waning cardiac reserve in which
the animal iscomparativelynormal at rest
but is incapable of performing exercise -
the phase of poor exercise tolerance - or
responding appropriately to a physiological
stressor such as late gestation or being
housed in hot ambient temperatures.
Congestive heart failure develops when
these compensatory mechanisms reach
their physiological limit and the heart is
unable to cope with the circulatory
requirement at rest.

Failure may manifest as primarily
being right-sided, left-sided or both left-
and right-sided. Many of the clinical signs
that appear during the development of
cardiac insufficiency, as well as those
associated with decompensated heart
failure, are the consequence of congestion
or edema due to increased venous
hydrostatic pressure. A decreased cardiac
output also contributes to the clinical
signs by the production of tissue hypoxia.

Right-sided congestive heart failure

Venous congestion is manifest in the
systemic circulation. The increase in mean
right atrial pressure increases the mean
capillary pressure and the net force for
| filtration of fluid across the capillary bed
is therefore greatly increased. This results
; in the production of edema in dependent
subcutaneous body areas and in body
j cavities. In the kidneys the increase in
hydrostatic pressure is offset by the
reduced flow of blood and urine output
is reduced. The increased back pressure
! to the glomerulus causes increased per-
meability and escape of plasma protein
| into the urine. Venous congestion in the
| portal system is an inevitable sequel of
hepatic congestion and is accompanied
i by impaired digestion and absorption and
terminally by diarrhea.

Left-sided congestive heart failure

Increased pulmonary venous pressure
results in venous congestion, decreased
compliance of the lung and an increase in
respiratory rate, an increase in the work of
breathing, and exercise intolerance.
Similarly, bronchial capillary congestion

and edema result in encroachment on
airways and a decrease in ventilatory
efficiency. Where venous hydrostatic
pressure is exceptionally high, the net
force for filtration of fluid across the
pulmonary capillary bed is greatly
increased. This can result in pulmonary
edema, with the presence of fluid around
the septal vessels and in the alveolar
spaces accompanied by marked impair-
ment of gas exchange. The development
of clinically detectable pulmonary edema
depends to some extent on the rapidity
of the onset of cardiac failure. In chronic
failure syndromes, the development of
a capacious lymphatic drainage system
limits the occurrence of clinical pulmon-
ary edema and, iir large animals, pulmonary
edema is usually limited to acute heart
failure where there is a relatively sudden
onset of a volume load on the left
ventricle.

CLINICAL FINDINGS

The specific findings on auscultation and
other examinations are described under
the specific causes of congestive cardiac
failure.

In the very early stages when cardiac
reserve is reduced but decompensation
has not yet occurred there is respiratory
distress on light exertion. The time required
for return to the normal respiratory and
pulse rates is prolonged. In affected
animals there may be evidence of cardiac
enlargement and the resting heart rate is
moderately increased. There maybe a loss
of body weight.

Right-sided congestive heart failure
The heart rate is increased and there is
venous distension and subcutaneous
edema. The superficial veins are

engorged. In ruminants there is sub-
cutaneous edema occurring in the
brisket region, under the jaw and along
the ventral midline, and ascites as indi-
cated by the presence of an abdominal
fluid wave on ballottement with palpation
and less frequently by the presence of
abdominal distension with a pear-shaped
abdomen. Ascites needs to be differ-
entiated from other causes of abdominal
distension, and the detection by palpation
per rectum of viscera floating in a fluid
medium and the presence of a fluid wave
on abdominal ballottement are highly
suggestive of ascites. Care must be taken
to differentiate ascites from uroabdomen
and hydrops conditions of the uterus.
Hydrothorax and hydropericardium may
also be clinically detected in animals with
ascites. In horses, edema is initially more
prominent in the pectoral region between
the front limbs, the ventral abdominal
wall, the prepuce and the limbs. Ruminants
and camelids do not get edema in their
legs in right-sided heart failure because

Manifestations of circulatory failure

their comparatively thicker skin acts as an
antigravity suit ('G' suit), minimizing the
extent of hydrostatic pooling of blood in
the limbs.

The liver is enlarged and, in cattle,
may be palpable, protruding beyond the
right costal arch with a thickened and
rounded edge. In both horses and cattle
liver enlargement may be detected by
ultrasound examination. The respiration
is deeper than normal and the rate may
be slightly increased. Urine flow is usually
reduced and the urine is concentrated
and contains a small amount of protein.
The feces are usually normal at first but in
the late stages diarrhea may be evident.
Body weight may increase because of
edema but the appetite is poor and
condition is lost rapidly. Epistaxis may
occur in the horse but is rare in
other species. The attitude and behavior
of the animal is one of listlessness
and depression; exercise is undertaken
reluctantly and the gait is shuffling and
staggery through weakness.

Left-sided congestive heart failure
The heart rate is increased and there is
an increase in the rate and depth of
respiration at rest, with cough, the
presence of crackles (discontinuous
sounds) at the base of the lungs and
increased dullness on percussion of the
ventral borders of the lungs. Terminally
there is severe dyspnea and cyanosis.

The prognosis in congestive heart
failure varies to a certain extent with the
cause but in most cases in large animals it
is poor to grave. The possibility of
recovery exists with an arrhythmia,
pericardial tamponade or pericarditis, but
when the epicardium, myocardium or
endocardium are involved complete
recovery rarely if ever occurs, although
the animal may survive with a per-
manently reduced cardiac reserve.
Uncomplicated defects of rhythm occur
commonly in the horse and these defects
are more compatible with life than are
extensive anatomical lesions.

CLINICAL PATHOLOGY

Clinicopathological examinations are
usually of value only in differentiating the
causes of congestive heart failure and
in differentiating from other diseases.
Aspiration of fluid from accumulations in
any of the cavities may be thought
necessary if the origin of the fluid is
in doubt. 1 The fluid is an edematous
transudate except in pericardial tamponade
(serosanguinous) or pericarditis (effusion)
when it may be septic or nonseptic. 2 In
most cases protein is present in large
amounts because of leakage of plasma
from damaged capillary walls. Proteinuria
is often present because of pressure-
induced damage to the glomerulus. The

serum concentration of cardiac tropinin
I provides an excellent cardiac biomarker
in large animals, providing a sensitive and
persistent indicator of cardiac injury. 3

NECROPSY FINDINGS

Lesions characteristic of the specific cause
are present and may comprise abnor-
malities of the endocardium, myocardium,
pericardium, lungs or large vessels. Space-
occupying lesions of the thorax may
constrict the cranial vena cava and inter-
fere with venous return. The lesions that
occur in all cases of congestive heart
failure, irrespective of cause, are: pulmon-
ary congestion and edema if the failure is
left-sided; anasarca, ascites, hydrothorax
and hydropericardium and enlargement
and engorgement of the liver, with a
'nutmeg 1 pattern of congested red centers
of liver lobules surrounded by paler fatty
peripheral regions, if the failure is right-
sided. It is important to characterize the
heart failure as being left-sided, right-
sided or both left- and right-sided at
necropsy, because this information will
help in prioritizing the likely cause.

DIFFERENTIAL DIAGNOSIS

• Causes of edema

• Causes of dyspnea

TREATMENT

The treatment of animals with clinical
signs of congestive heart failure due to
pericarditis or pericardial tamponade
focuses on removing the pericardial fluid
and preventing its return. In animals with
pump failure, the treatment of congestive
heart failure initially focuses on the
reduction of the effects of increased
preload by administering diuretic agents
and restricting sodium intake, reducing
the demands on cardiac output by
restricting activity, and improving con-
tractility by the administration of positive
inotropic agents such as cardiac glycosides.

Diuretics

Diuretic treatment, furosemide, aceta-
zolamide or chlorothiazide, is an import-
ant component of treatment in that it
mobilizes and eliminates excess body
fluids. Furosemide is most commonly
used because it is the most potent diuretic
available, is inexpensive and pharma-
cokinetic parameters have been determined
for large animals. Furosemide should be
administered at an initial intravenous
dose of 0.25-1.0 mg/kg for horses and
2.5-5.0 mg/kg for cattle for the treatment
of congestive heart failure, 4 ' 5 Multiple
doses of furosemide will induce a
hypokalemic, hypochloremic metabolic
alkalosis, so it is important to monitor

serum potassium and chloride concen-
trations during treatment. Access" to free
salt should be stopped, although it is
usually impractical to formulate a salt-
restricted diet.

Stall rest

Stall rest in a thermoneutral environment
is also an important treatment require-
ment. Parturition may be electively induced
in late gestation in order to prevent in-
utero fetal hypoxia and abortion, and to
decrease the additional demand placed by
placental blood flow on the cardiac output.

Cardiac glycosides

Digoxin is the most commonly used
cardiac glycoside. In horses it can be
administered either intravenously or
orally but in ruminants it must be given
intravenously or after induction of
esophageal groove closure because digoxin
is destroyed in the rumen. Digoxin should
not be given intramuscularly in any
species as it causes severe muscular
necrosis and this is also reflected in erratic
plasma digoxin concentrations following
intramuscular administration. Treatment
with digoxin results in an increase in
cardiac contractility and a decrease in heart
rate with increased myocardial oxygen
consumption, increased cardiac output
and a decrease in cardiac size. 4 The
improvement in cardiac output promotes
diuresis and the reduction and elimi-
nation of edema.

The half-life of digoxin in the horse is
17-23 hours. 6,7 and a plasma therapeutic
range for digoxin of 0.5-2.0ng/mL has
been suggested. 6 Pharmacokinetic studies
suggest that therapeutic but nontoxic
plasma concentrations of digoxin in the
horse will be achieved by an initial
intravenous loading dose of 1. 0-1.5 mg/
100 kg followed by a maintenance dose
of 0.5-0.75 mg/100 kg every 24 hours. 7
In the horse the bioavailability of
powdered digoxin given orally is low,
being less than 20% of the administered
dose. An oral loading dose of 7 mg /
100 kg, followed by a daily oral main-
tenance dose of 3.5 mg/100 kg is suggested
by pharmacokinetic studies. 6

The half-life of digoxin in cattle is
5.5-7.2 hours, 8 ' 9 requiring more frequent
dosing than in horses, and an initial
intravenous loading dose of 2.2 mg/
100 kg followed by 0.34 mg/100 kg every
4 hours has been suggested. 8 An alter-
native is to give digoxin as a continual
infusion at 0.086 mg/100 kg. 5 There is no
established dose for digoxin administration
in sheep but the half-life is similar to that
in cattle. 10

No dosing regimen is absolute and
the dose may need adjustment based
on clinical response, evidence of toxicity,
or by measuring the plasma digoxin

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

concentration. Dose rates other than those
above have been used successfully. 11,12
Toxicity with digoxin treatment is reported
and may occur because the clearance of
digoxin in some animals with congestive
heart failure differs from that of normal
animals on which the suggested doses
have been based. 13

If treated animals are not eating, the
daily oral administration of KC1 (cattle
100 g, horses 30 g) is recommended 5 and
it is recommended that serum potassium
concentrations be monitored because the
toxic effects of digoxin are impacted by the
serum potassium concentration. Because of
the necessity for frequent dosing in cattle
and the ineffectiveness of oral treatment,
digoxin therapy has major limitations in
ruminants, especially since the primary
pathology that leads to congestive heart
failure in cattle is commonly not correct-
able. Unless myocardial damage is
transient, administration of the digoxin in
all species will probably have to be
continued for life, and this is rarely practical.

REVIEW LITERATURE

Muir MW, McGuirk SM. Pharmacology and pharma-
cokinetics of drugs to treat cardiac disease in
horses. Vet Clin North Am Equine Pract 1985;
1:335-352.

Muir MW, McGuirk S. Cardiovascular drugs. Their
pharmacology and use in horses. Vet Clin North
Am Equine Pract 1987; 3:37-57.

McGuirk SM. Treatment of cardiovascular disease in
cattle. Vet Clin North Am Food Anim Pract 1991;
7:729-746.

REFERENCES

1. Milne MH et al. Vet Rec 2001; 148:341.

2. Jesty SA et al. J Am Vet Med Assoc 2005; 226:1555.

3. Phillips W et al. J Vet Intern Med 2003; 17:597.

4. Muir MW, McGuirk S.Vet Clin North Am Equine
Pract 1987; 3:37.

5. McGuirk SM.VetClin NorthArn Food Anim Pract
1991; 7:729.

6. Button C et al. Am JVet Res 1980; 41:1388.

7. Brumbaugh GW et al. JVet Pharmacol Ther 1983;
6:163.

8. Koritz GD et al. JVet Pharmacol Ther 1983; 6:141.

9. Gany FB, Klee W.Tierarztl Umsch 1990; 45:750.

10. Dix LP et al. Am JVet Res 1985; 46:470.

11. Staudacher G. Berl Munch Tierarztl Wochenschr
1989; 102:1.

12. Stewart GA ct al.AustVet J 1990; 67:187.

13. Peardon EG et al. Compend Contin Educ PractVet
2(1987; 1):1.

ACUTE HEART FAILURE

ETIOLOGY

Acute heart failure can occur when there
is a severe defect in filling, when there is
failure of the heart as a pump, either due
to severe tachycardia, bradycardia or
arrhythmia, and where there is a sudden
increase in workload. The sudden occur-
rence of tachyarrhythmias in association
with excitement and severe enough to
cause acute heart failure presumably
results from the exacerbating influence of
catecholamines. 1,2 These are released in

Etiology Sudden onset of a severe
arrhythmia, rupture of a heart valve or
vessel, pericardial tamponade
Clinical findings Sudden loss of
consciousness, falling with or without
convulsions, severe pallor of the mucosae
and either death or complete recovery
from the episode

Clinical pathology Increased serum
cardiac troponin I concentrations, but
clinical course usually too short for
examination

Diagnostic confirmation Clinical
Necropsy findings Pulmonary
congestion and edema. Findings related to
specific cause

Treatment Treatment of specific cause,
often unsuccessful

association with episodes of excitement
and act to heighten the discharge poten-
tial of ectopic excitatory foci associated
with myocardial disease.

Acute heart failure can also occur in
the absence of primary cardiac disease
under the influence of pharmacological
agents that affect cardiac conduction.
These are associated with the ingestion of
certain poisonous plants.

The many causes of acute heart failure
are listed in greater detail under myo-
cardial diseases. Some examples are as
follows:

• Disorders of filling

0 Pericardial tamponade - atrial and
ventricular rupture

• Aortic and pulmonary arteiy rupture
8 Tachyarrhythmia

• Myocarditis, e.g.
encephalomyocarditis virus, foot-
and-mouth disease

° Nutritional deficiency myopathy,
e.g. copper or selenium deficiency
0 Plant poisoning, e.g. Phalaris spp.,
white snake root

° Electrocution and lightning strike

• Bradycardia

0 Iatrogenic, e.g. intravenous calcium
gluconate or borogluconate
administration, xylazine, tolazoline,
concentrated solutions of
potassium chloride
° Plant poisoning, e.g. Taxus spp.

0 Increase in workload
° Rupture of aortic valve
® Acute anaphylaxis.

Arrhythmias and cardiac arrest may occur
during the induction of anesthesia with
barbiturates in the horse and may also
occur without premonitory signs in
horses under halothane anesthesia.

PATHOGENESIS

With excessive tachycardia the diastolic
period is so short that filling of the ven-

tricles is impaired and cardiac output is -
grossly reduced. In ventricular fibrillation
no coordinated contractions occur and no
blood is ejected from the heart. The
cardiac output is also seriously reduced
when the heart rate slows to beyond a
critical point because cardiac output is the
product of heart rate and stroke volume,
and stroke volume cannot be markedly
increased. In all these circumstances there
is a precipitate fall in cardiac output and
a severe degree of tissue ischemia. In
peracute cases the most sensitive organ,
the brain, is affected first and the clinical
signs are principally neurological. Pallor is
also a prominent sign in acute heart failure
because of the reduction in blood flow.

In less acute cases respiratory distress
is more obvious because of pulmonary
edema and although these can be classified
as acute heart failure they are more
accurately described as acute congestive
heart failure.

CLINICAL FINDINGS

The acute syndrome may occur while the
animal is at rest but commonly occurs
during periods of excitement or activity.
The animal usually shows dyspnea,
staggering and falling, and death often
follows within seconds or minutes of the
first appearance of signs. There is marked
pallor of the mucosae. Although clonic
convulsions may occur they are never
severe and consist mainly of sporadic
incoordinate movements of the limbs.
Death is usually preceded by deep,
asphyxial gasps. If there is time for
physical examination, weakness or absence
of a palpable pulse and bradycardia,
tachycardia or absence of heart sounds
are observed. The specific findings in the
heart and vascular system depend upon
the arrhythmia and are detailed in
the section on arrhythmias later in this
chapter.

Horses with sudden onset of tachy-
arrhythmias due to atrial fibrillation or
multiple ventricular extrasystoles, or with
rupture of the aortic or mitral valve
chordae show a syndrome where sudden
onset of respiratory distress is the pro-
minent manifestation. However, examin-
ation of the heart will allow a diagnosis of
the underlying cause.

Acute heart failure is the cause of
death in a significant proportion of horses
that die suddenly and unexpectedly
during training or racing. 3 The diagnosis
is based primarily on the findings of
significant pulmonary hemorrhage and
edema, although myocardial pathology is
absent in most cases. Severe arrhythmic
disturbances secondary to pre-existing
myocardial injury and the concurrent
presence of catecholamines, hyperkalemia
and metabolic acidosis are likely causes.

CLINICAL PATHOLOGY

In general, there is insufficient time avail-
able in which to conduct laboratory tests
before the animal dies. The demonstra-
tion of elevated serum troponin I concen-
trations, a sensitive and specific marker
of myocardial damage, strongly supports
the presence of myocardial disease.
Laboratory tests may also be used to
elucidate the specific etiology.

NECROPSY FINDINGS

In typical acute cases engorgement of
visceral veins may be present if the attack
has lasted for a few minutes but there
may be no gross lesions characteristic of
acute heart failure. Microscopic examina-
tion may show evidence of pulmonary
congestion and early pulmonary edema.
In more prolonged cases, venous engorge-
ment with pulmonary congestion and
edema are evident along with hydrothorax
but these are more accurately described as
acute congestive heart failure. The pri-
mary cause may be evidenced by macro-
scopic or microscopic lesions of the
myocardium.

DIFFERENTIAL DIAGNOSIS

Acute heart failure should always be a
major consideration as a cause of sudden
and unexpected death in large animals,
especially when death is associated with
exertion or excitement. Acute heart failure
may be mistaken for primary disease of the
nervous system but is characterized by
excessive bradycardia or tachycardia, pallor
of mucosae, weakness or absence of the
pulse and the mildness of the convulsions.
Epilepsy and narcolepsy are usually
transient and repetitive and have a
characteristic pattern of development.

TREATMENT

Treatment of acute heart failure is not
usually possible or practical in large
animals because of the short course of the
disease. Deaths due to sudden cardiac
arrest or ventricular fibrillation while
under anesthesia can be avoided to a
limited extent in animals by external or
internal cardiac compression or electrical
conversion-stimulation but these tech-
niques are generally restricted to sophisti-
cated institutional surgical units. Also, the
electrical energy required for defibrillation
of animals larger than a sheep or goat is
beyond the capabilities of conventional
defibrillators unless the paddles are
placed directly across the pericardium or
transvenous electrodes are used. Intra-
cardiac injections of very small doses of
epinephrine in conjunction with external
cardiac compression by jumping up and
down on the thorax with the knees can be
tried, with occasional success.

Special examination of the cardiovascular system

405

REFERENCES

1. VanVleet JF et al. Am J Vet Res 1977; 38:991.

2. Rona G. J Mol Cell Cardiol 1985; 17:291.

3. Gelberg HB et al. J Am Vet Med Assoc 1985;
187:1354.

Special examination of the
cardiovascular system

The more commonly used techniques of
examination of the heart and pulse are
described in Chapter 1. A more detailed
clinical examination of the system that
gives greater attention to nuances of
location and intensity of heart sounds and
arterial and venous pulse characteristics
is conducted whenever cardiovascular
disease is suspect.

Special techniques of examination are
also available which may be of value in
some cases. With the exception of jugular
venous pressure measurement, assess-
ment of exercise intolerance, electrocar-
diography and indirect methods for
measuring arterial blood pressure, many
of these techniques have limited applica-
tion in general practice as they require
sophisticated and expensive equipment.
The use of specialized diagnostic equip-
ment is generally confined to teaching
hospitals and investigative units.

PHYSICAL EXAMINATION

In the examination of animals suspected
to have heart disease, it is important to
determine the rate, rhythm and intensity
of the individual heart sounds and the
rate, rhythm and amplitude of the arterial
pulse, examine for the presence of venous
pulsation at the jugular inlet, and identify
the point of maximal intensity and timing
of murmurs within the cardiac cycle.

HEART SOUNDS

In the horse it is not uncommon to hear
four heart sounds on auscultation,
whereas two to three heart sounds are
heard in ruminants and camelids.

First heart sound

The first heart sound (SI) signals the
onset of ventricular systole, is synchro-
nous with the apex beat and is temporally
associated with closure of the mitral and
tricuspid valves. The area for maximal
audibility of the mitral valve in the horse
is on the left fifth intercostal space, at a
level midway between a horizontal line
drawn through the point of the shoulder
and one drawn at the sternum at the
caudal edge of the triceps muscle. With
cattle, sheep, goats and swine the sound
is located at a similar level but at the
fourth intercostal space. The area for
maximal audibility of the tricuspid valve
is on the right side of the chest slightly

ventral to the equivalent leveLfor the
mitral valve and at the fourth intercostal
space in the horse; and at the level of
the costochondral junction at the third
intercostal space for the other species.

Second heart sound

The second heart sound (S2) is associated
with aortic and pulmonic valve closure
and is synchronous with the end of
systole and the beginning of cardiac
diastole. The aortic component is most
audible just ventral to a horizontal line
drawn through the point of the shoulder
and in the left fourth intercostal space in
horses and the left third in the other
species. The pulmonic component is
most audible ventral and anterior to the
aortic valve area in the left third
intercostal space in horses and the left
second or third intercostal space close to
the costochondral junction in the other
species. These two components of the
second heart sound have the same
temporal occurrence on auscultation but
tonal differences can frequently be
detected at the two areas of maximal
audibility. Splitting of the second sound
in the horse can be detected on phono-
cardiographic examination but cannot be
detected on auscultation and there is no
respiratory-associated splitting, as occurs
with some other species.

Third heart sound

The third heart sound (S3) is associated
with rapid filling of the ventricle in early
diastole and is heard as a dull thudding
sound occurring immediately after the
second sound. It is usually most audible
on the left side just posterior to the area
of maximal audibility of the first heart
sound. However it is frequently heard
over the base and also over the area of
cardiac auscultation on the right side.
Phonocardiographically there are two
components to this heart sound but these
are not usually detectable on clinical
auscultation.

The third heart sound is very common
in horses and can be detected in the
majority of fit racing animals. It is more
audible at heart rates slightly elevated
above resting normal. The third heart
sound is very common in slightly excited
cattle (heart rates 80-100 beats/min) but
becomes more difficult to hear when the
heart rate exceeds 100 beats/min.

Fourth heart sound

The fourth heart sound (S4) is associated
with atrial contraction. It is also called the
'a' sound. It occurs immediately before the
first heart sound and is a soft sound most
audible over the base of the heart on the
left- and right-hand side. It is also com-
mon in horses but its clear separation
from the first heart sound is dependent

406

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

upon the length of the P-R interval,
which varies between horses. At resting
heart rates the S4 sound is detectable on
clinical examination in at least 60% of
horses.

The interval between the S4 and SI
frequently varies in the same horse at rest
in association with variation in the P-Q
interval and results in a clear separation in
some beats with slurring of the two
sounds together in other beats. The fourth
heart sound or a split SI is also commonly
heard in young cattle, but phonocardio-
graphic studies have not been undertaken.

Sequence of heart sounds

The sequence of heart sound occurrence
is thus 4-l-2-3.The intensity of the third
and fourth sounds is less than that of the
first and second and the complex can be
described as du LUBB DUP boo. In some
horses, the third or fourth sound may be
inaudible so that 1-2, 4-1-2 and 1-2-3
variations occur. The name gallop
rhythm is frequently applied when these
extra sounds occur. Gallop rhythms also
occur in cattle and may be due to the
occurrence of a fourth or third sound or to
true splitting of the components of the
first heart sound. In sheep, goats and pigs
only two heart sounds are normally
heard. The occurrence of a third or fourth
heart sound in horses and cattle is not an
indication of cardiovascular abnormality,
as it is in other species.

Variation in heart sound intensity

Change in the intensity of the generation
of sound by the heart or change in the
transmission of the sounds between the
heart and the stethoscope can result in
variation in the intensity of heart sounds
normally heard on auscultation.

° A decrease in the intensity of heart
sound generation occurs in disease
where there is poor venous return
and decreased strength of cardiac
contractility, such as in terminal heart
failure, in hypocalcemia in cattle or in
circulatory failure in all species
3 Conversely the intensity of the heart
sounds may increase with anemia,
cardiac hypertrophy and metabolic
diseases such as hypomagnesemia.
However, the intensity of the heart
sounds is most often increased by
sympathetic activation as a result of
exercise, fear and excitement.

Muffling of the heart sounds suggests an
increase in tissue and tissue interfaces
between the heart and the stethoscope.
This can be due to a shift in the heart due
to displacement by a mass, changes in the
pericardium (increased fluid or fibrous
tissue), changes in the pleural space or
increased subcutaneous fat. Heart sounds
are detectable by auscultation on the left

side in animals of all condition scores but
heart sounds may become inaudible on
the right side where the condition score
approaches 5/5.

Heart rate

The relative temporal occurrence and
the intensity of the third and fourth heart
sounds changes with heart rate. At
moderately elevated heart rates the third
heart sound becomes more audible. At
faster heart rates the third sound may
merge and sum with the fourth sound or
the fourth sound may merge with the first
sound if the P-R interval decreases.
During periods of a rapid change in heart
rate, such as during the increase in rate
that occurs following sudden noise or
similar stimuli in excitable horses or the
subsequent decrease in rate, the variation
in the occurrence and the intensity of the
third and fourth sound coupled with the
variation in intensity of the first and
second sound during this change can give
the impression of a gross arrhythmia.
Such impressions should be ignored if
they occur only at times of rapid change
of rate that is obviously induced by
external influences and if there is no
arrhythmia at the resting rate or the
intervening stable elevated rate. Examina-
tion of the pulse during these periods of
rapid change is also of value.

Variations in the intensity of the
individual heart sounds or complete
absence of some of them can occur in
conduction disturbances and arrhyth-
mic heart disease and can provide
valuable clinical information. In several of
these disturbances there is variation in
the intensity of the first and third heart
sounds associated with variation in the
time of the preceding diastolic period and
variations in diastolic filling. The intensity
of the first heart sound may also vary with
variations in the P-R interval or where
there is complete atrioventricular disso-
ciation. In several of the arrhythmias
there is absence of one or more of the
heart sounds. These findings are detailed
| below under the specific abnormalities.

i EXAMINATION OF THE ARTERIAL
PULSE

In arrhythmic heart disease the arterial
pulse should be examined in more detail
than that applied during routine clinical
examination.

Pulse rate

The pulse rate should be examined over a
period to determine if there is any sudden
| change in rate such as can occur with a
j shift in pacemaker to an irritable myo-
cardial focus. At some stage during the
examination of animals with tachy-
arrhythmias the heart rate and pulse rate
should be taken synchronously to

determine the presence of a pulse deficit
(auscultation of SI but a weak or absent
S2 accompanied by a weak or absent
pulse). A convenient artery for this
purpose is located on the posterior medial
aspect of the radius and carpus in the
horse and cow. However, the best arteiy
to determine the pulse rate, rhythm and
amplitude is the descending aorta; this
artery should be palpated during rectal
examination in horses and cattle.

Pulse rhythm

Pulse rhythm is carefully examined. When
a 'dropped pulse' or arrhythmia is detect-
able in the pulse the basic underlying
rhythm should be established in order to
determine if the heart is under regular
pacemaker influence. This is best done by
mentally or physically tapping out the
basic rhythm of the heart and continuing
this rhythm when irregularity occurs.
With conditions such as second-degree
heart block where there is a basic under-
lying rhythm initiated by the sinoatrial
node, it is possible to tap through the
irregularity and re-establish synchrony
with the pulse. However, in conditions
such as atrial fibrillation where there is no
regular pacemaker it is not possible to
establish any basic rhythm. This examin-
ation of rhythm can alternatively be
conducted by auscultation and allows
an immediate categorization of the arrhy-
thmia into one of the two basic group,
those superimposed on a regular pace-
maker influence (occasionally irregular)
and those in which there is no regular
pacemaker (irregularly irregular) .

Amplitude

The amplitude of the pulse should also be
carefully examined. Variations in pulse
amplitude are associated with those
arrhythmias that produce a variation in
diastolic filling period within the heart.
The extreme of this is a pulse deficit
(decrease in intensity or absence of a pulse
associated with heart sounds).

EXAMINATION OF THE JUGULAR
VEIN

In the normal adult horse and cow, the
jugular vein will be distended with blood
some 5-8 cm above the level of the base
of the heart when the animal is standing
with its head in a normal, nonfeeding,
alert position. There is a rapid but minor
fall in the level of jugular distension
associated with the fall of blood into the
ventricle during the period of rapid filling
during ventricular diastole followed by a
slower rise in the level of jugular filling to
its original point. Superimposed on this,
and immediately preceding the fall, is a
small wave or retrograde distension
associated with atrial contraction ('a'
wave) and a second smaller retrograde

Special examination of the cardiovascular system

wave ('c'wave) associated with bulging of
the atrial ventricular valves into the
atrium during ventricular systole. These
pulsations can be observed in most horses
and cattle by careful observation of the
jugular vein at its entrance into the thorax
and can be timed in conjunction with
auscultation of the heart.

Observation of the presence or
absence of the atrial 'a' wave is an aid in
the clinical differentiation of first- and
second-degree heart block. Cannon atrial
waves occur periodically in complete
heartblock when atrial contractions occur
against a closed atrioventricular valve. An
accentuated'c'wave occurs with tricuspid
valve insufficiency.

MEASUREMENT OF JUGULAR
VENOUS PRESSURE

The jugular veins are symmetrically
distended in chronic (congestive) right-
sided heart failure. This distension is
accompanied by an increased jugular
venous pressure that can be subjectively
assessed by palpation or objectively
determined by measuring jugular venous
pressure.

This underutilized technique can be
easily and rapidly performed. The equip-
ment required is a 14-16-gauge needle
attached to a three-way stopcock. A
20 mL syringe containing heparinized

0. 9. NaCl is attached directly opposite
the needle, and a flexible rigid wall fluid
administration line is attached to the
remaining port on the three-way stop-
cock. The stopcock is turned so that the
needle is in the off position, the needle is
threaded down the jugular vein towards
the heart, the syringe is pushed to fill the
first 10 cm of the flexible fluid line with
heparinized 0.9% NaCl, and the stopcock
is turned so that the syringe is in the off
position. 1 Blood will flow into the flexible
tube and the vertical distance (in cm)
between the top of the column of 0.9%
NaCl supported by the jugular venous
pressure and the point of the shoulder
(scapulohumeral joint), which approxi-
mates the position of the right atrium, 2 is
a direct measure of jugular venous pressure.

REFERENCES

1. Sellers AF, Hemingway A. Am J Vet Res 1951;

12:90.

2. Amory H et al. Vet Res Commun 1992; 16:391.

EXE RC ISE T OLE R, ANCE

Dyspnea, fatigue and a prolonged eleva-
tion in heart rate following exercise are
signs suggestive of cardiac insufficiency.
Frequently, animals with suspect cardiac
disease are exercised in an attempt to
elicit these signs and to get an estimate of
exercise tolerance. 1,2 In most practice
situations the assessment of exercise

tolerance is subjective. There is obviously
a considerable difference in the amount
of exercise that a beef bull and a trained
racehorse can tolerate under normal
conditions, and the amount of exercise
given to any one animal is determined by
the clinician's judgment. The rate of fall in
heart rate following exercise and the time
required to reach resting levels depend
upon the severity of the exercise, even in
fit horses. Heart rate falls rapidly over the
first minute and then more slowly over
the ensuing 10-15-minute period.

More objective tests have been
developed for the horse, which include
evaluation by means of telemetry from
horses timed over a measured distance on
race tracks 3 or the use of a treadmill 1,4 to
provide a defined amount of exercise. The
amount and intensity of exercise can
be varied by the speed and incline of
the treadmill and by the duration of the
exercise period. The treadmill allows
the recording of a variety of cardiorespi-
ratory measurements in the exercising
horse 5,6 and can be used for evaluating
the significance of cardiopulmonary
disease and for establishing the cause of
poor racing performance.

There are many noncardiac causes of
exercise intolerance and, in a report on
the evaluation of 275 horses, 84% were
found to have more than one problem
leading to poor athletic performance 7
Criteria for cardiovascular performance
in endurance rides are described and the
rapidity of heart rate decline following
completion of each section of the ride can
be used for field assessment of this
function. 1,8,9

REFERENCES

1. Rirente EJ. Vet Clin North Am Equine Pract 1996;
12:421.

2. Mitten LA. Vet Clin North Am Equine Pract 1996;
12:473.

3. Gati L, Holmes JR. Equine Vet Educ 1990; 2:28.

4. Scheffer CWJ et al. Vet Rec 1995; 137:371.

5. Seeherman HJ, Morris EA. Equine Vet J Suppl
1990; 9:20.

6. Evans DL, Rose RJ. Equine Vet J 1988; 20:94.

7. Morris EA, Seeherman HJ. Equine Vet J 1991;
23:169.

8. Fbggenpoel RG. Equine Vet J 1988; 20:224.

9. Rose RJ et al. Equine Vet J 1979; 11:56.

ELECTROCAR DIOGRAPH Y

The electrocardiogram (ECG) provides a
record and measure of the time varying
potential difference that occurs over the
surface of the body as the result of
electrical activity within the heart. This is
associated with depolarization and
repolarization of the myocardium. At any
one instant during depolarization and
repolarization there are generally several
fronts of electrical activity within the
heart. However, at the body surface the
potential difference is generally the sum

of this activity and at any one instant the
electrical activity in the heart registers as a
single dipole vector that has polarity,
magnitude and direction.

The polarity is determined by the
charge on the surface of the cells while
the magnitude and direction is determined
by the mass of muscle being depolarized
or repolarized and the sum of the
instantaneous vectors. Thus a wave of
depolarization or repolarization over a
muscle mass such as the atria or the ven-
tricles is presented at the body surface as
a sequence of instantaneous vectors with
changing magnitude and direction.

THE ELECTROCARDIOGRAPH

The electrocardiograph is used to detect
these characters. In simple terms it can
be considered as a voltmeter consisting
of two input terminals, an amplifier to
allow the recording of low input signals
and a galvanometer with an attached
recording device such as a heated stylus
on heat sensitive paper or an ink pen or
ink squirter. When a potential difference
exists across the input terminals
(electrodes), current flows through the
coils of the electromagnet suspended
between the poles of the permanent
magnet to cause a deflection of the
recording pen. The electrocardiograph can
therefore detect the polarity of the cardiac
electrical vectors and by calibration of the
machine and appropriate placement of
electrodes on the body surface it can
detect their magnitude and direction.

Calibration of most electrocardio-
graphs is such that an input of 1 mV
produces a 1 cm deflection of the record-
ing pen. Recording speeds are generally
25 or 50 mm/s. In recording an ECG,
certain standard electrode positions are
used for recording.

° A lead is the recording or circuit
between two recording points.
Depending upon the wiring within
the electrocardiograph the same
potential difference across a lead
could result in an upward or
downward deflection of the recording
pen

° In order to allow standard recording
and comparison between recordings
the polarity of the electrodes for
standard leads has been established
by convention and the leads are
always recorded at these polarities
0 The electrodes of a lead are

commonly called positive or negative
° A positive electrode in a lead is one
that, when electrically positive relative
to the other, due to a potential
difference between them, yields an
upward or positive deflection of the
recording pen.

408

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

DEPOLARIZATION AND
REPOLARIZATION

In the normal heart, depolarization and
repolarization of the myocardium occurs
in a definite pattern and sequence and
the electrocardiography can be used to
measure and time these events. Thus
discharge of the sinoatrial node results in
a wave of depolarization over the atria to
produce a P wave in the ECG. The delay
in conduction at the AV node is registered
by no electrical activity at the body surface
and an isoelectric P-R interval on the
ECG (isoelectric means zero voltage
difference between the two leads).
Depolarization of the ventricles occurs
with several sequential fronts to produce
the QRS complex, which is followed
by another isoelectric period before
repolarization represented by the T wave.

In dogs, cats and humans the electro-
cardiogram can be used to assess the
cardiac rhythm and the size of the cardiac
chambers. However, the order of ven-
tricular activation in horses, cattle,
sheep and swine differs from that of
humans and dogs in that ventricular
depolarization is represented by only two
fronts of activity. Depolarization of a large
proportion of the myocardial mass in
large animals is not recognized by the
surface electrocardiogram because the
Purkinje fibers penetrate much more
deeply in these species and depolari-
zation occurs over multiple minor fronts
that tend to cancel out, rather than over
a large single front as in dogs. For this
reason, the detection of chamber enlarge-
ment by vector analysis of the electro-
cardiogram is, in general, not possible in
large animals. Consequently, electrocar-
diography is confined to a simple base-
apex lead system to examine for con-
duction disturbances and arrhythmias,
which are detected by measurement of
the various waveforms and intervals in
the ECG that represent depolarization
and repolarization in the heart, and
by observation of their absence or
abnormality.

LEAD SYSTEMS

The base-apex lead system provides the
best method for electrocardiography in
large animals, with the only exception
being fetal electrocardiography. All other
lead systems are clinically superfluous
or inferior, or have only a research
application.

Traditional lead systems are based
on Einthoven's triangle as used in humans,
and the standard bipolar limb leads (I, II
and III) and the augmented unipolar limb
leads (aVR, aVL, aVF) are commonly used
in conjunction with an exploring unipolar
chest lead. Variations in the position of the
feet may produce changes in ECG

waveforms with this lead system and
recordings should be taken with the
animal standing square or with the left
front foot set slightly in advance of the
right front foot. This lead system is quite
satisfactory for the detection of conduc-
tion disturbances and arrhythmic heart
disease but is subject to movement
artefact. There are, however, deficiencies
associated with its use for the detection of
change in the magnitude and direction of
electrical vectors in the heart of large
animals. 1,2 Nevertheless, traditional lead
systems have been used extensively for
this purpose.

Vector-based lead systems. There
have been several studies to determine if
it is possible to detect changes in cardiac
chamber size in large animals. Many of
these have examined alternative lead
systems, recognizing that the standard
limb leads are not particularly suited for
detection of vector changes associated
with changes in chamber dimensions. The
standard limb leads are primarily
influenced by vectors in the frontal plane
(longitudinal and transverse) whereas
early and late forces in the myocardium
are significantly directed in the vertical
direction. Furthermore, the heart is not
electrically equidistant from the electrodes
of each lead and distortion of recorded
vector loops can result. 1,3 A partial
correction of these deficiencies can be
made by recording a lead using an
exploring electrode at the V10 position
over the dorsal spinous processes in
addition to the standard limb leads.
However, for proper representation of the
vector changes associated with electrical
activity within the heart, completely
different electrode placement is required.
A number of systems have been
proposed. The electrode placement varies
and is quite complicated but electro-
cardiographic studies using these methods
are available for horses, 3 ' 5 cattle, 6,7 pigs 5
and sheep. 9 In general, a three lead
system consisting of leads I, aVf and V10
provides semiorthogonal axes suitable for
three-dimensional reconstruction of
depolarization and repolarization.

The base-apex lead system is most
commonly used as it records the major
electrical forces in the heart of large
animals with consistently clear and large-
amplitude waveforms. Animal movement
also has minimal effect on the quality of
the ECG. The most commonly used
bipolar lead placement in horses and
cattle consists of two electrodes, one
positive and one negative, in a format
called the base-apex lead. The positive
electrode of lead I (left arm) is attached to
the skin of the left thorax at the fifth
intercostal space immediately caudal to
the olecranon, and the negative electrode

(right arm) is placed on the jugular furrow
in the caudal third of the right neck. This
is the most common lead placement,
although some investigators place the
negative electrode on the left side of the
neck instead of the right side. With sheep,
where wool interferes with placement on
the neck, the negative electrode can be
placed on the midline of the poll. When
using the base-apex lead system, the
ground electrode is placed remote from
the heart, and the location of the ground
is not important. The electrodes are
usually placed using alligator clips and a
70% isopropyl alcohol or gel contact,
although disposable human stick-on type
electrodes can be used in horses after
clipping of the skin and cleaning with
alcohol before application of the gel. In
order to ensure good adherence to the
skin, the skin should be shaved and
cleaned with alcohol prior to the applica-
tion of the gel. The ECG is recorded with
the animal in a standing position with
minimal restraint. Normal values for
cattle, horses, and pigs are summarized
in Table 8.1.

FETAL ELECTROCARDIOGRAPHY

The fetal ECG may be recorded, and can
be of value in determining if the fetus is
alive, the presence of a singleton or
twins, and as a monitor for fetal distress
during difficult or prolonged parturition.
A modified bipolar lead system is
required, with the RA electrode being
placed on the right ventral abdomen and
the LA electrode below placed on the
ventral midline in front of the udder. The
ground lead can be situated anywhere.
The bipolar lead should be recorded using
increased sensitivity with meticulous
attention to obtaining the best electrical
connection to the skin. The animal needs
to be electrically isolated (standing on a
rubber mat) and muscular activity must
be minimized.

Duration (ms)

Cattle Horses Sows

p

80 ± 10

100 ±32

82 ± 0

P-R

200 ± 20

136 ± 7

QRS

60 ± 10

91 ± 10

75 ± 6

Q-T

370 ± 30

485 ± 52

276 ±6

T

90 ± 10

Values are obtained from 600 healthy
Holstein-Friesian female cattle aged 1 or more
years (Rezakhani A et al. Vet Arch 2004; 74:351),
1 7 healthy male and female horses aged
6 months to 8 years (P Constable, personal
communication) and 467 healthy sows (Takemura
N et al. JJpn Med Assoc 1988; 41:398).

Fetal electrocardiography has been
used in cattle to monitor fetal viability,
but the fetal ECG signal is very weak and
suffers from interference from the
maternal ECG, the electromyogram and
motion artifacts caused by gastro-
intestinal movement. 10 For these reasons,
the position of the bipolar recording leads
on the abdomen should be moved to
provide the optimal recording site for
each cow. Digital processing of the fetal
ECG signal can assist in detection of
fetal heart rate 10,11 at more than 157 days
of gestation. Fetal heart rates for calves
tend to decrease with advancing gesta-
tion, approximating 140 beats/min from
160-190 days of gestation and 120 beats/
minute at 250-280 days of gestation. 10

The foal fetal heart rate decreases
logarithmically from approximately
110 beats/min at 150 days before term to
75 beats/min near to term. 12 Continued
monitoring traces may be needed to
assess fetal distress. Fetal heart rate and
heart rate variability has also been
measured as an indicant of hypoxia and
fetal distress during parturition in
cattle . 13,14 Cardiac arrhythmia is common
at the time of birth and is believed to
result from the transient physiological
hypoxemia that occurs during the birth
process. 15 Following birth and during
early growth of the foal there are age-
dependent increases in the electrocardio-
graphic intervals and changes in the
orientation of the mean electrical axis. 16

OTHER USES OF THE
ELECTROCARDIOGRAM

0 Changes in the electrocardiogram
occur with some electrolyte
imbalances in large animal species
0 There is an approximately linear
correlation between the heart-rate-
corrected Q-T interval and plasma
ionized calcium concentration in
cattle, with elongation of the interval
in hypocalcemic and shortening in
hypercalcemic states

■ Decreased amplitude and flattening of
the P wave, widening of the QRS
complex and an increased symmetry
and amplitude of the T wave are seen
with hyperkalemia 18
° Estimates of heart size of the horse
have been made from measurements
of the QRS duration on the
electrocardiogram and the resultant
heart score is used to assess potential
racing performance 19
- Exercise and postexercise

electrocardiograms frequently deliver
information additional to that of the
resting ECG, and can be recorded by
radiotelemetry or Holter monitor
systems 20-22

Special examination of the cardiovascular system

409

• Heart rate variability has received
recent interest as a research method
to evaluate the relative contributions
of sympathetic and parasympathetic
tone to the cardiovascular system.
Heart rate variability has been
assessed in cattle using time domain 23
and frequency domain procedures. 24

REVIEW LITERATURE

Hamlin RL, Smith CR. Categorization of common
domestic mammals based upon their ventricular
activation process. Ann NY Acad Sci 1965;
12:195-203.

Kanagawa H, Too K, Kawata K, Ono H. Fetal electro-
cardiogram in dairy cattle II. Diagnosis for twin
pregnancy. Jpn JVet Res 1965; 13:111-119.

Too K, Kanagawa H, Kawata K. Fetal electrocardio-
gram in dairy cattle. I Fundamental studies. Jpn J
Vet Res 1965; 13:71-83.

Robertson SA. Practical use of the ECG in the horse.
In Pract 1990; 12:59-67.

Amory H et al. Bovine vector cardiography: a com-
parative study relative to the validity of four
tridimensional systems. J Vet Med A 1992;
39:453-469.

REFERENCES

1. Nielsen K,Vibe Petersen G. Equine Vet J 1980;
12:81.

2. Fregin GF. Vet Clin North Am Equine Pract 1985;
1:419.

3. Miller PJ, Holmes JR. ResVet Sci 1984; 36:370.

4. Miller PJ, Holmes JR. ResVet Sci 1984; 37:334.

5. Deegen E, Reinhard HJ. Dtsch Tierarztl
Wochenschr 1974; 81:257.

6. Schultz RA, Pretorius PJ. Onderstepoort J Vet Res
1972; 39:209.

7. Amory H et al. JVet Med A 1993; 40:81.

8. Thielscher HH. Zentralbl Vet Med 1969; 16A:370.

9. Torio R. Small Rumin Res 1997; 24:239.

10. Chen W et al. Anim Sci J 2002; 73:545.

11. Chen W et al. Anim Sci J 2004; 75:471.

12. Matsui K et al. Jpn JVet Sci 1985; 47:597.

13. Jonker FH et al. Am JVet Res 1996; 57:1373.

14. Steffen S et al. Schweiz Arch Tierheilkd 1995;
137:432.

15. Yamamoto K et al. EquineVet J 1992; 23:169.

16. Lombard CW et al. EquineVet J 1984; 16:342.

17. Stewart JH et al. EquineVet J 1984; 16:332.

18. Spier SJ et al. J Am Vet Med Assoc 1990; 197:1009.

19. Blakely JA, Blakely A A. N Z Vet J 1995; 43:57.

20. Jacobson LH, Cook CJ. Vet J 1998; 155:205.

21. Scheffer CJW, Sloet van Oldruitenborgh-
Oosterbaan MM. Vet Q 1996; 18:2.

22. Scheffer CJW et al. Vet Rec 1995; 137:37 1 .

23. Mincro M et al. Vet 2001; Rec 149 772.

24. Fbmfrett CJD et al. Vet Rec 2004; 154:687.

SERUM CARDIAC TROPONIN I
CONCENTRATION

The serum concentration of cardiac
tropinin I provides an excellent cardiac
biomarker in large animals, providing
a sensitive and persistent indicator of
cardiac injury. 1 Troponin I, T and C
are components of the tropomyosin-
troponin complex in cardiac and skeletal
muscle, with cardiac troponin I and T
having different amino-acid sequences at
the N-terminal end compared to skeletal
muscle tropinin I and T. This means
that an immunoassay directed at the

N-terminal end will be able to differen-
tiate between cardiac and skeletal muscle
isoforms and therefore the site of injury. 2
Myocardial tissue from horses, cattle,
sheep and pigs has high reactivity for
cardiac troponin I when tested using a
human immunoassay, and this reactivity
is selective for the myocardium, being
more than 1000-fold higher in cardiac
tissue than in skeletal muscle. 1 Cardiac
troponin I has greater myocardial selec-
tivity than cardiac troponin T, and is
therefore preferred as a biomarker of
cardiac injury. 1,2 3-8% of cardiac troponin
I and T are found in the myocardial
cytosol; damage to the myocardial cell
membrane causes cytosolic tropinin I and
T to escape into the interstitial fluid,
thereby increasing serum cardiac troponin I
concentrations.

Serum activities of cardiac isoenzymes
of creatine kinase (creatine kinase
isoenzyme MB (CK-MB)) and lactate
dehydrogenase (isoenzymes 1 and 2)
have been used in the past as indices of
cardiac disease in horses. However, only
1.5% of the total CK activity in the equine
heart is attributable to CK-MB (compared
to 20% in the human heart); 3 therefore
CK-MB is an insensitive indicator of
cardiac disease in the horse. Isoenzymes
of lactate dehydrogenase suffer from a
similar lack of specificity for cardiac
disease. Cardiac troponin I is the preferred
biomarker for detecting and quantifying
cardiac disease in animals, 4 and healthy
horses have cardiac troponin I concen-
trations below 0.11 ng/mL using the
human immunoassay. 1,3,6 Healthy neonatal
foals have cardiac troponin I concen-
trations of less than 0.49 ng/mL. 7 Healthy
cattle have cardiac troponin I concen-
trations below 0.04 ng/mL. 8

REFERENCES

1. O'Brien PJ et til. ClinChem 1997; 43:12.

2. Cornelisse CJ et al. J Am Vet Med Assoc 2000;
217:231.

3. Argiroudis SA et al. EquineVet J 1982; 14:317.

4. Wallace KB et al. Toxicol Pathol 2004; 32:106.

5. Smith G W et al. Am JVet Res 2002; 63:538.

6. Phillips W et al. JVet Intern Med 2003; 17, 597.

7. Slack JA et al. JVet Intern Med 2005; 19:577.

8. Jesty SA et al. J Am Vet Med Assoc 2005; 226:1555.

PHONOCARDIOGRAPHY

Phonocardiography allows the recording
and measurement of heart sounds. A
special microphone is placed directly over
the various areas of the thorax used for
heart auscultation and the heart sounds
are recorded graphically on moving paper
or on an oscilloscope. Prior to recording,
the heart sounds are usually passed
through high-pass, low-pass or band-
pass filters to allow better discrimination
of the individual sounds and to allow a
crude frequency examination. Phono-

410

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

cardiograms are usually recorded in
conjunction with an electrocardiogram
and chamber pressure measurements,
which permits timing of their occurrence
in relationship to the electrical activity
within the heart.

Phonocardiograms can provide consi-
derable information on heart sounds
additional to that acquired by stetho-
scopic examination. In the horse, up to 11
sound events can be detected in each
cardiac cycle and figures of the occurrence
and duration of normal heart sounds in
large animals are available. 1 ' 3 In con-
junction with an electrocardiogram, the
phonocardiogram can be used to measure
systolic time intervals, which may be
altered in congenital and acquired cardio-
vascular abnormalities. 4

Phonocardiograms have been infre-
quently used for the characterization and
timing of murmurs in animals with
cardiovascular disease, especially at fast
heart rates where simple stethoscopic
examination may not allow this. However,
phonocardiography has been rarely used
as a clinical diagnostic tool, and the wide-
spread availability of echocardiographs
make the clinical application of phono-
cardiography less likely in the future.

REFERENCES

1. Vanselow B et al. AustVet J 1978; 54:161.

2. Welker FH, Muir WW. Equine Vet J 1990; 22:403.

3. Leurada AA et al. Am J Vet Res 1970; 31:1695.

4. Miller PJ, Holmes JR. EquineVet J 1985; 17:181.

CARDIAC OUTPUT

There are several techniques available for
the measurement of cardiac output but
the one almost universally applied in large
animals is the indicator dilution technique
using thermodilution (injection of iced
5% dextrose) or indicator dyes such as
Evans blue, indocyanine green or lithium
chloride. 1,2 With dye dilution, an exact
amount of dye is injected into the jugular
vein or pulmonary artery via a catheter
and the serial collection of blood samples
is performed from a suitable proximally
located artery that has been catheterized.
Cardiac output is most commonly
measured using thermodilution 3 but can
also be calculated from a dye dilution
curve by determining the mean con-
centration of the dye and the time taken
for one circulation through the heart. 1
Automated cardiodensitometers are also
available for this estimation. Cardiac
output is expressed as liters per minute
and is usually corrected to cardiac
index on the basis of weight or body
surface area.

Most domestic animals have a cardiac
index of 100 (mL/kg body weight (BW))/
min at rest. The cardiac index for horses,
sheep and cattle at rest has been deter-

mined as 86 ± 13, 131 ± 39 and 113 ±
11 (mL/kg)/min, respectively. Stroke
volume can also be calculated from the
measured cardiac output and simulta-
neously determined heart rate, whereby
stroke volume = cardiac output/heart rate.
In general the normal variation between
animals in indexes of cardiac output is too
great to allow it to be used as a diagnostic
measure in individual animals suspected
to have cardiac disease. Measures of cardiac
output are used in experimental studies,
where the effects of certain procedures
can be followed within the same animal.
Indicator dilution curves using dyes or
thermodilution methodology can be used
to detect the presence of intracardiac
defects such as septal defects and to
quantify their significance.

Doppler echocardiography can be
used to estimate cardiac output and gives
values equivalent to those obtained by
thermodilution techniques 4,5

REFERENCES

1. Fisher EW, Dalton RG. BrVet J 1961; 118:143.

2. Corley KTT et al. EquineVet J 2002; 34:598.

3. Muir WW. Am J Vet Res 1976; 37:697.

4. Young LE et al. Br J Anaesth 1996; 77:773.

5. Blissitt KJ et al. EquineVet J 1997; 29:18.

MEASUREMENT OF ARTERIAL
BLOOD PRESSURE

Blood pressure may be determined
directly by arterial puncture and pressure
measurement but this is impractical in
clinical cases. The development of simple
methods for the indirect determination
of arterial blood pressure has proved
difficult in large animals because of the
paucity of suitably located arteries where
a pressure cuff can be applied and
because there are problems in detecting
pulse return by simple auscultatory or
palpatory methods.

In the horse a simple and relatively
inexpensive method uses oscillometric
j sphygmomanometry to detect arterial
j pulsations and therefore simultaneously
j determine heart rate and mean arterial
1 pressure. 1-4 For adult horses, the optimal
j cuff width for the oscillometric method is
j approximately 20-35% of the tail
. circumference, 1,2 when the cuff is applied
) snugly to the base of the tail and the
| ventral coccygeal artery pressure is
monitored. The mean tail circumference
of an adult horse is 22 cm, therefore the
optimal cuff width for horses is 5-8 cm for
oscillometric pressure measurement.
Because the oscillometric units were
designed for use in humans, the software
programs often have difficulty in measuring
arterial pressure when the heart rate is
less than 40 beats/min 2 and when
arrhythmias or arterial hypotension are
present 3 , which minimizes the clinical

utility of these units in trained or sick
horses. The units are also susceptible to -
motion of the tail and it is therefore
preferable to keep the tail still during
recording. Other methods of indirect
pressure measurement in the horse
(modified auscultatory technique, ultra-
sonic Doppler methodology) appear less
accurate than the oscillometric sphygmo-
manometry. Moreover, oscillometric tech-
niques offer the advantage of providing
systolic, diastolic and mean arterial blood
pressures, whereas other indirect methods
do not provide mean arterial pressure. 3

Systolic and diastolic blood pressure of
a large series of trained Thoroughbred
horses were 112 ± 16mmHg (14.9 ±
2.1 kPa) and 77 ± 14 mmHg (10.2 ±
1.9 kPa) respectively. 1 Equivalent values
have been recorded in other breeds. These
values are coccygeal uncorrected values
and can be corrected to the correct
reference level (scapulohumeral joint,
which is equivalent to the right atrium) by
adding 0.7mmHg (0.09 kPa) for every
centimeter in height between the
scapulohumeral joint and the tail if the
coccygeal artery was the recording site for
indirect pressure measurement. Posture
of the horse is important, as lowering the
head significantly lowers systolic, diastolic
and pulse pressure.

Hypertension has been found in
association with epistaxis, laminitis in
horses and painful fractures of the distal
bones of the limb. Systolic blood pressure
is often also elevated in obstruction of the
large intestine in horses. Blood pressure
measurements are of value in the assess-
ment of the degree of shock and possibly
may prove of value in the differential
diagnosis of conditions such as acute
salmonellosis and in assessing the
prognosis of colic. Mean arterial pressure
is considered the true driving pressure for
blood flow and organ perfusion, therefore
determination of mean arterial pressure
provides one index of perfusion. How-
ever, its is important to recognize that
mean arterial pressure is poorly correlated
with cardiac output.

Blood pressure readings can be obtained
by equivalent techniques from the tails of
cattle. However, because of anatomical
differences these do not always correlate
well with true blood pressure. Pressures
have been observed to be 100-140 mmHg
(13.3-18.6 kPa) systolic and 50-85 mmHg
(6.7-11.3 kPa) diastolic.

j REFERENCES

1. Wagner AE, Brodbelt DC. J Am Vet Med Assoc

1997; 210:1279-1285.

2. Latshaw H et al. EquineVet J 1979; 11:191-194.

3. Muir WW et al. J Am Vet Med Assoc 1983;

182:1230.

4. Parry BW et al. EquineVet J 1984; 16:53.

5. Giguere S et al. J Vet Intern Med 2005; 19:571.

Special examination of the cardiovascular system

ECHOCARDIOGRAPHY

Echocardiography has provided a relatively
simple and noninvasive method for the
examination of the heart that can give
considerable information on its function.
In echocardiography, high-frequency
sound waves are pulsed through tissues
at known velocities. When the sound
waves encounter an acoustic tissue inter-
face, echoes are reflected back to a
transducer and recorded in a number of
different modalities. The modalities have
become increasingly sophisticated and
they have largely replaced traditional
invasive evaluations of cardiac function
such as cardiac catheterization. The newer
technologies are expensive and are
currently limited to teaching hospitals
and referral clinics.

Echocardiography will allow the
measurement of cardiac chamber size,
wall thickness, global and regional wall
movement and valve structure and
function. 1 ' 3 Functional indices can be
calculated that will allow the determina-
tion of the presence of hypertrophy or
dilatation of areas of the heart and the
percentage of wall thickening. 4 The
fractional shortening of the left ventricle
can be used as a sensitive index of left
ventricular contraction. Quantitative studies
are available for the horse, 3,5 " 11 sheep, 12
pigs 2,13 and cattle. 1,4,14 " 16 The measurement
of the ratio of cardiopulmonary blood
volume to stroke volume, determined
from a radiocardiogram following the
injection of technetium-99m pertechnetate,
has proved a more sensitive test for
cardiac insufficiency in horses than
measurements of cardiac output. 17
Measurements of cardiac and individual
chamber dimensions, vessel diameters
and flow rates can be used to assess
normality, indexes of contractility and
effects of cardiac lesions on cardiac
response and function. 5,18 " 21 They can also
be used to predict the type of lesion likely
to result in these changes. 19

Valvular defects and endocarditis may
be diagnosed by imaging abnormal valve
motion, incompetent valve orifices or
vegetative masses associated with the
valves 22 and tumor masses in the heart
can be detected. 23 Similarly, the severity
of valvular regurgitation can be
quantified. 24 Echocardiography can be of
considerable value in the diagnosis of
congenital cardiovascular defects 1 and the
injection of echogenic materials such as
microbubble-laden saline may aid in the
detection of shunts. 2,19 Echocardiography
can also be used to determine the
presence and extent of pleural and
pericardial effusion. In the examination of
the vascular system, ultrasound is capable
of the early detection of iliac thrombosis

in horses and is more sensitive than
manual palpation per rectum. 3

There is a long-held belief that horses
with a large heart relative to their body size
have greater athletic capacity. 25 An accurate
and noninvasive method for determining
heart weight therefore has potential utility
as one method for predicting racing success.
Echocardiography provides a useful esti-
mate of heart weight that may compliment
electrocardiographically determined heart
score (calculated from the QRS duration) in
the prediction of athletic performance. The
thickness of the interventricular septum in
diastole provides an accurate prediction of
heart weight ; 26 the predictive accuracy was
such that echocardiography using this
measurement has utility as an index of
subsequent athletic performance 27 and has
been used in North America, Europe and
Australia in such a manner.

REVIEW LITERATURE

Reef VB. Advances in echocardiography. Vet Clin
North Am Equine Pract 1991; 7:435-450.

Bonagura JD. Echocardiography. J AmVet Med Assoc
1994; 204:516-522.

Marr CM. Equine echocardiography - sound advice at
the heart of the matter. BrVet J 1994; 150:527-545.
\foros K. Quantitative two-dimensional echocardio-
graphy in the horse: a review. ActaVet Hung 1997;
45:127.

Braun U et al. Echocardiography of the normal bovine
heart: technique and ultrasonographic appearance.
Vet Rec 2001; 148:47- 41.

REFERENCES

1. Reef VB. Equine Vet J Suppl 1996; 19:97.

2. Kvart C et al. Equine Vet J 1985; 17:361.

3. Reef VB. J Am Vet Med Assoc 1987; 190:286.

4. Braun U et al. Am JVet Res 2005; 66:962.

5. Tucker RL et al. J Equine Vet Sci 1995; 15:404.

6. Reef VB. Vet Clin North Am Equine Pract 1991;
7:435.

7. Young LE, Scott GR. Equine Vet J 1998; 30:117.

8. BlissittKJ. Equine Vet J 1997; 29:18.

9. Seeherman HJ, Morris EA. Equine Vet J Suppl
1990; 9:20.

10. Harkins JD, Kamerling SG. J EquineVetSci 1991;
11:237.

11. \foros K et al. Equine Vet J 1991; 233:461.

12. Moses BL, Ross JN. Am JVet Res 1987; 48:1313.

13. Gwathmey JD et al. Am JVet Res 1989; 50:192.

14. Amory H et al. Am JVet Res 1992; 53:1540.

15. Pipers FS et al. Bovine Pract 1978; 13:114.

16. Amory H, Lekeux P. Vet Rec 1991; 128:349.

17. Guthrie AJ et al. J S AfrVet Med Assoc 1991; 62:43.

18. Young LE, Scott GR. Equine Vet J 1998; 30:117.

19. Bonagura JD. J Am Vet Med Assoc 1994; 204:516.

20. Marr CM. BrVet J 1994; 150:527.

21. Slater JD, Herrtage ME. Equine Vet J Suppl 1996;
19:28.

22. ReefVB et al. Equine Vet J 1998; 30:18.

23. Braun U et al. Schweiz Arch Tierheilkd 1995;
137:187.

24. HagioM, Otsuka H. Jpn JVet Sci 1987; 49:1113.

25. Buhl R et al. J Am Vet Med Assoc 2005; 226:1881.

26. O'Callaghan MW. Equine Vet J 1985; 17:361.

27. Seder JA et al. J Equine Vet Sci 2003; 23:149.

CARD IAC CATHE TERIZATION

The measurement of pressure within the
various chambers of the heart and in

the inflow and outflow vessels _can
provide diagnostic information in both
acquired and congenital heart disease in
large animals. Generally, pressure is
determined by means of fluid -filled
catheters introduced into these areas and
connected to an external pressure 1
transducer. These systems are generally
satisfactory for the measurement of
pressure and the detection of changes
with abnormality. However, because of
their transmission characteristics, they are
less suitable for the precise timing of
pressure events, and high-fidelity catheter
tip manometers should be used for this
purpose.

Catheterization of the right side of the
heart is a comparatively simple procedure
in large animals but is not without risk to
the animal. Catheterization is done in the
standing position, and descriptions are
available for horses 1,2 and cattle. 3 " 7 Flow-
directed catheters are used and can be
introduced through a needle inserted into
the jugular vein. Balloon-tipped catheters
aid the flow of the catheter into the pul-
monary artery. Catheterization of the left
side of the heart is more complicated and
less commonly performed. Left heart
catheterization is usually performed
under general anesthesia and requires the
use of a stiffcatheterthatis introduced into
the carotid or femoral artery by surgical
methods and subsequently manipulated
to the left ventricle.

The systematic determination of the
pressure within each area of the heart and
in the inflow and outflow vessels can
allow a determination of the type of
abnormality that is present. Valvular
stenosis or incompetence is associated
with abnormal pressure differences across
the affected valve during systole or
diastole. Cardiac hypertrophy is generally
accompanied by an increase in pressure
during systole of the affected chamber.
With high-fidelity equipment, pressure
waveforms can also have diagnostic value.

The right atrium is usually used as the
reference point for pressure comparison
and is arbitrarily assigned a reference
pressure of zero when recording using a
fluid-filled catheter system. The scapulo-
humeral joint (point of the shoulder) is
taken as the anatomical equivalent
reference height in the standing animal. 4
A simultaneously recorded base-apex
electrocardiogram assists in interpretation
of the pressure tracings. Numerous
publications have reported cardiovascular
values for conscious awake horses, adult
cattle and calves, and representative
values are presented in Table 8.2.

During catheterization blood may be
withdrawn through the catheter and
subjected to blood gas analysis. In right-
sided catheterization an increase in

2

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

fable 8 2 r 1e n (± SD) cardiopulmonary values tor adult horses cattle and Ca \.ts and pigs

Measured value

Adult horses 9

Adult cattle 7

Calves 6

Pigs

m

10

’

Body weight (kg)

560

540

40

43

Mean arterial pressure (mmHg)

120 ± 14

150

±

27

92 ± 15

130

±

12

Mean pulmonary artery pressure (mmHg)

21 ± 5

36

±

9

18 ± 6

16

±

2

Mean central venous pressure (mmHg)

6.9 ± 2.7

NS

2.4 ± 1.2

4.8

±

1.2

Heart rate (beats/min)

44.4 ± 7.8

73

±

14

1 14 ± 9

134

±

10

Cardiac index ((mlVkg)/min)

93 ± 23

64

±

14

20 ± 48

150

±

10

Respiratory rate (breaths/min)

18 ± 7

45

±

12

NS

19

±

2

Arterial pH

7.41 ±0.02

7.42

±

0.03

7.37 ±0.03

7.42

±

o

o

Arterial Pco 2 (mmHg)

40 ± 3

38

±

3

50 ± 6

43

±

2

Arterial Po 2 (mmHg)

93 ± 14

109

±

12

92 ± 10

105

±

4

Animals are unsedated and standing with their head in a normal, nonfeedirig position. Pressures are referenced to the scapulohumeral joint.
NS, not stated.

oxygen saturation in the right ventricle or
pulmonary artery can be diagnostic for
the presence of a left-to-right shunt due
to an atrial septal defect, a ventricular
septal defect or a patent ductus arteriosus.
The normal maximum increase in venous
oxygen content between the right heart
chambers and pulmonary artery in
humans is 0.9 mL 0 2 /dL from the right
atrium to right ventricle and 0.5 mL
0 2 /dL blood from the right ventricle to
the pulmonary artery. 3 It is a reasonable
assumption that similar changes in
oxygen content (due to streaming of
blood flow and variability in sampling site
within the right atrium and ventricle)
exist in large animals. Not only can blood
gas analysis indicate the presence of a
left-to-right to shunt; sequential blood
gas analysis can be used to quantify the
magnitude of the shunt by calculating the
pulmonary-to-systemic flow ratio and
therefore assist in prognosis.

The pulmonary blood flow and systemic
blood flow are approximately equivalent
in healthy individuals, with the exception
of a small amount of right-to-left shunt
(physiological shunt) caused by venous
blood from coronary and bronchial blood
flow draining into the left ventricle,
left atrium or pulmonary veins. The
pulmonary-to-systemic flow ratio should
therefore approximate l.O. 8 In animals
with a left-to-right shunt, the pulmonary
to systemic flow ratio (Q p /Q s ) quantifies
the magnitude of the left-to-right shunt
across the defect. The pulmonary-to-
systemic flow ratio is calculated using the
Fick method from measurements of S a o 2
(oxygen content of arterial blood), MV0 2
(oxygen content of mixed venous blood,
which is the pulmonary artery in animals
without a shunt, the right ventricle in
animals with a patent ductus arteriosis,
the right atrium in animals with a ven-
tricular septal defect, and the vena cava in
animals with an atrial septal defect), P v 0 2
(oxygen content of pulmonary venous
blood), and P a 0 2 (oxygen content of
pulmonary artery blood), such that:

(Qp/Qs) = (S a o 2 - MV0 2 )/(P v o 2 - P a o 2 ). 8
This method assumes the animal is in
steady state and that cardiac output does
not change during blood sampling. 8
Oxygen content (in mL 0 2 /dL blood) is
calculated from the measured values for
blood hemoglobin concentration ([Hb], in
g/dL), oxygen tension and percentage 0 2
saturation, such that 0 2 content = [Hb] x
1.39 x 0 2 saturation/100 + 0.003 x Po 2 . 8 In
clinical cases at sea level, it is assumed
that that saturation of pulmonary venous
blood and arterial blood = 97.5% and
that Po 2 = 90 mmHg. Application of this
equation and assumptions to data from
a 2-year-old Holstein-Friesian cow with a
ventricular septal defect, atrial fibrillation
and pulmonary hypertension (mean
pressure 67 mmHg) indicated that
(Qp/Qs) = (8.67 - 5.89)/(8.67 - 8.04) = 4.4,
using the right atrial content as the mixed
venous sample because the right ventricle
contained a large volume of oxygenated
blood from the left ventricle. This cal-
culation indicated the presence of an
extremely large left-to-right shunt (shunt
= Qp - Qs = Qp(l - 1/4.4) = 0.77 x Q p ); in
other words, 77% of the blood flowing
through the lungs was from the left heart.
Such a large shunt into the right ventricle
was suspected based on the large step up
in 0 2 content from the right atrium to
right ventricle (2.1 mL 0,/dL; Table 8.3)
which exceeded the maximal normal

value of 0.9 mL 0 2 /dL. A 2 cm diameter
ventricular septal defect was confirmed at
necropsy.

Shunts can also be demonstrated by
dye or thermodilution techniques,. 8 but
these are much more complicated to
analyze than blood gas analysis of
sequential blood samples obtained from a
fluid-filled catheter during a pullback
from the pulmonary artery through the
right ventricle into the right atrium.

Echocardiography can provide infor-
mation that, while different, may be of
equivalent diagnostic value to that
obtained by cardiac catheterization and,
because it is noninvasive and technically
a much easier procedure, echocardio-
graphy has largely supplanted cardiac
catheterization in the examination of
cardiac disease in large animals.

REFERENCES

1. Brown CM, Holmes JR. Equine Vet J 10:1978; 188.

2. Brown CM, Holmes JR. Equine Vet J 10:1978; 207.

3. Manohar M et al. J Am Vet Med Assoc 1973;
163:351.

4. Amory H et al.Vet Res Common 1992; 16:391.

5. Amory H et al.Vet Rec 1993; 132:426.

6. Constable PD. Shock 1999; 12:391.

7. Wagner AE et al. Am J Vet Res 1990; 51:7.

8. Yang SS et al. From cardiac catheterization data to
hemodynamic parameters, 2nd ed. Philadelphia,
PA: FA Davis, 1978:209-231.

9. Muir WW et al. Am J Vet Res 1977; 38:195.

10. Smith GW et al. Am J Vet 1999; Res 60:1292.

Measured value

Right atrium

Right ventricle

Pulmonary artery

pH

7.42

7.47

7.48

Pco 2 (mm Hg)

42.9

36.4

35.3

Po 2 (mm Hg)

33.0

48.6

48.8

0 2 saturation (%)

64,1

87.7

91.6

Hemoglobin concentration (g/dL)

Calculated value

6.5

6.4

6.2

Blood 0 2 content (mL O z /dL blood)

5.89

7.95

8.04

RADIOGRAPHIC AND

ANGIOCARDIOGRAPHIC

EXAMINATION

Because of the size of horses and cattle
these methods of examination are largely
confined to neonates of these species
except in teaching hospitals. Angiocardio-
graphy can be a diagnostic method of
examination in congenital cardiac defects
where the passage of contrast media
through abnormal routes can be detected.

Arrhythmias (dysrhythmias)

Variations in cardiac rate and rhythm
include tachycardia (increased rate),
bradycardia (decreased rate), arrhythmia
or dysrhythmia (irregularity in rate and
rhythm) and gallop rhythms. The rate and
rhythm of the heart is influenced pri-
marily by the integrity of the pacemaker,
the conducting system and the myo-
cardium, and also by the influence of the
autonomic nervous system. Variation in
the rate and rhythm can occur in normal
animals due to strong or varying
autonomic influence but can also be a
reflection of primary myocardial disease.
Other factors such as acid-base and
electrolyte imbalance can influence rate
and rhythm. These factors must be taken
into consideration in the assessment of
apparent abnormalities detected on
clinical examination of the cardiovascular
system.

The majority of arrhythmias and
conduction disturbances can be detected
on clinical examination. However, some
may be unsuspected on clinical examin-
ation and be found only on electro-
cardiographic examination. The occurrence
of conduction and myocardial disturb-
ances is probably more common than
generally recognized, because an electro-
cardiogram is usually only taken from
animals in which there have been prior
clinical indications of conduction abnor-
malities. Because of the importance of
electrocardiography in the diagnosis of
arrhythmias the salient electrocardio-
graphic findings are given in the sections
below.

The common conduction disturbances
and arrhythmias in large animals are
listed in Table 8.4. A large scale cross
sectional study of 952 healthy dairy cattle
aged 1 or more years produced the
following prevalence of arrhythmias: 1
sinus arrhythmia, 8.5%; first-degree
atrioventricular block, 1.6%; ventricular
premature complexes, 0.6%; atrial pre-
mature complexes, 0.4%; sinus bradycardia,
0.2% and ventricular escape beats, 0.1%.
Atrial fibrillation was not observed in
healthy cattle in this study. 1

Arrhythmias (dysrhythmias)

403

Table 8.4 Common arrhythmias and. conduction disturbances in the horse and cow -

Horses

Cattle

Second-degree atrioventricular block

First-degree atrioventricular block

Atrial fibrillation

Atrial premature complexes

Atrial premature complexes

Ventricular premature complexes

Ventricular premature complexes

Atrial fibrillation

First degree atrioventricular block

Sinoatrial block

The treatment of arrhythmic heart
disease generally relies on the treatment
of the underlying clinical condition
causing the problem. This may vary from
electrolyte and acid-base disturbance and
toxicities to primary myocardial disease
resulting from myocarditis, myocardial
ischemia and changes resulting from
heart failure or myopathies resulting from
nutritional deficiency. These are detailed
in later sections in this text. Racing and
work horses should be rested for periods
up to 3 months following evidence of
myocardial disease. Frequently a course of
corticosteroids, or a nonsteroidal anti-
inflammatory drug (NSAID) such as
flunixin meglumine, is given to attempt to
reduce the severity of myocarditis if this is
not contraindicated by the initiating
cause. Specific antiarrhythmic therapy
may be applied in certain conditions and
is detailed below.

It is important to be able to recognize
those forms of arrhythmia that are not
indicative of pathological heart disease
but are normal physiological variations.
These occur commonly in the horse and
most can be differentiated on physical
examination. It is also important to
understand the difference between a
premature beat or contraction and a
premature complex. A beat or contrac-
tion is a mechanical event that can be
clinically detected by auscultation,
palpation of an artery or visual examin-
ation of the jugular venous pulse, or
recorded by pressure measurements. A
complex is an electrical event that is
detected by an electrocardiograph. A beat
is always associated with a complex; how-
ever, a complex can be unaccompanied by
a beat, particularly in electromechanical
dissociation. The terms beat or contrac-
tion should therefore be used to describe
an arrhythmia that is detected by auscul-
tation, palpation or recording of the
arterial pulse, whereas the term complex
should be used when the arrhythmia is
detected electrocardiographically.

REVIEW LITERATURE

Hilwig RW. Cardiac arrhythmias in the horse. J Am Vet

Med Assoc 1977; 170:153-163.

McQuirk SM, Muir WW. Diagnosis and treatment of

cardiac arrhythmias. Symposium on Cardiology.

Vet Clin North Am Equine Pract 1985;.

1:353-370.

Fregin GF. Medical evaluation of the cardiovascular
system. Vet Clin North Am Equine Pract 1992;
8:329.

Mitten LA. Cardiovascular causes of exercise in-
tolerance. Vet Clin North Am Equine Pract 1996;
12:729-746.

REFERENCE

1. Rezakhani A et al. Rev Med Vet 2004; 155:159.

SINUS TACHYCARDIA, SINUS
BRADYCARDIA AND
PHYSIOLOGICAL DYSRHYTHMIAS

The heart rate results from the discharge
of impulses from the sinoatrial node,
which has its own intrinsic rate of dis-
charge but which is also modified by
external influences, particularly the vagus
nerve.

SINUS TACHYCARDIA

The term sinus tachycardia or simply
tachycardia is used to describe an
increase in heart rate caused by detect-
able influences such as pain, excitement,
exercise, hyperthermia, a fall in arterial
blood pressure or the administration of
adrenergic drugs. The heart rate returns to
normal when the influence is removed or
relieved.

It needs to be stated that sinus
tachycardia indicates an increase in heart
rate that is initiated by the sinoatrial node
in the right atrium (hence the sinus
modifier). This means that the term sinus
tachycardia should be reserved for use
when electrocardiography has been per-
formed and the sinus node has been
determined to be the dominant pace-
maker. For comparison, the term tachy-
cardia should be used when an increased
heart rate is detected by auscultation or
palpation of the pulse and the origin of
the pacemaker has not been determined.
In resting horses and cattle that are used
to being handled heart rates are not
usually elevated above 48 and 80 beats/
min respectively and rates above this
are usually classified as tachycardia
(Figure 8.1). In the cow and horse it is rare
for the causes of sinus tachycardia to
elevate the heart rate above 120 beats/
min in the resting animal, and at heart
rates above this an intrinsic pathological
tachycardia should be sought.

414

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

A. Normal sinus rhythm in a horse (heart rate = 33 beats/m in).

B. Normal sinus rhythm in a cow (heart rate = 68 beats/min).

C. Atrial premature complexes in a cow (4 & 5 P waves from

F. Atrial fibrillation in a cow (increased ventricular rate).

G. Atrial fibrillation in a cow (ventricular rate = 186 beats/min) with chronic
(congestive) heart failure and pleural fluid accumulation leading to decreased
QRS amplitude

Fig. 8.1 Base-apex electrocardiograms of large animals with normal sinus
rhythm (panels A & B), supraventricular arrhythmias (panels C, D, E, F, G, & H),
hyperkalemia (panels H & I) or ventricular arrhythmias (panels J, K, & L). All
electrocardiograms were recorded at 25 mm/sec and 10 mm = 1 mV.

SINUS BRADYCARDIA

Sinus bradycardia or simple bradycardia is
used to describe a decrease in heart rate
due to a decreased rate of discharge from
the sinoatrial node. Sinus bradycardia is
most commonly associated with highly
trained, fit animals and can be differen-
tiated from the pathological bradycardias
by its abolition by exercise or the adminis-
tration of atropine. Obviously sinus brady-
cardia, like sinus tachycardia, requires
electrocardiographic confirmation that the
sinus node is the dominant pacemaker.

Bradycardia may also occur in asso-
ciation with an increase in arterial blood
pressure, space-occupying lesions of the
cranium and increased intracranial press-
ure, pituitary abscess, hyperkalemia
(Figure 8.1) hypothermia and hypoglycemia
and following the administration of
alpha-2-adrenergic agonists such as
xylazine or detomidine. Bradycardia is
sometimes associated with vagus indiges-
tion and diaphragmatic hernia in cattle
and also occurs in cattle deprived of
food. 1 Bradycardia has also been reported
in cattle with bovine spongiform
encephalopathy, 2 although this probably
reflects inappetence rather than damage
to the vagal nucleus in the brain stem; the
latter would be expected to increase,
rather than decrease, heart rate. Brady-
cardia can be induced in young ruminants
by forceful elevation of the tail. Sinus
arrhythmia is usually present in animals
with sinus bradycardia.

The resting heart rate seldom falls
below 22 beats/min in adult horses and
44 beats/min in adult cattle. Rates below
this are suggestive of pathological brady-
cardias, and hypothermia, hypothy-
roidism or an intrinsic cardiac problem
should be suspected. However, a general
rule is that resting heart rates are
inversely proportional to body weight,
and large, fit horses and cattle have
apparently low heart rates.

PHYSIOLOGICAL ARRHYTHMIAS

There are several dysrhythmias that can
occur in the absence of heart disease and
that appear to result from excess vagal
tone. These occur especially in the horse
and include:

° Sinus arrhythmia

° Wandering pacemaker
° Sinoatrial block

0 First-degree and second-degree

atrioventricular block.

These physiological arrhythmias occur in
animals at rest and can frequently be
induced by the application of a nose
twitch in horses or by forceful elevation of
the tail in young ruminants. There is some
debate as to the significance of these
arrhythmias in animals but it is generally

believed that if they are abolished by
exercise or excitement and if there is no
evidence of cardiac insufficiency they are
not of pathological significance and do
not require further investigation.

Perinodal myocardial fibrosis and
microvascular abnormality have been
reported in horses with sinoatrial and
atrioventricular block, and considered as
the excitatory cause. 3 However, because
myocardial fibrosis is common in horses,
being present in 79% of horse hearts
examined at random, 4 it remains likely
that these arrhythmias are physiological
in horses. All animals with evidence of
arrhythmic heart disease should be

examined following exercise, as should
any animal in which cardiac disease is
suspected.

The occurrence of cardiac irregu-
larities following exercise is highly
indicative of serious cardiac disease.

A high frequency of arrhythmia has
been recorded in newborn foals imme-
diately following birth. 5 48 of 50 foals had
some form of arrhythmia; atrial premature
complexes were recorded in 30 foals,
atrial fibrillation in 15 foals and ven-
tricular premature complexes in 10 foals.
Other arrhythmias were recorded with
less frequency. It was concluded that the
arrhythmias resulted from transient

Arrhythmias (dysrhythmias)

5

H. Second degree AV block in a 3-month-old calf. The 3 rd P wave is not followed

absence of P waves, and prolonged QRS duration in a 7-day-old calf with

J. Sinus tachycardia in a heifer (heart rate = 148 beats/min) with a premature
ventricular complex.

1

4

1

I

|T: ::

j|

1

i

H

-1

.14

'4?

•rrr

i

: :

l

mm

f

r- :

nr

1

K. Ventricular premature complex in a cow. Note the markedly abnormal QRS
complex that has opposite polarity to the normal complex, increased QRS
duration, and a large T wave amplitude.

L. Ventricular arrhythmia in a cow (normal P, QRS, & T wave in 3 complex)

Fig. 8.1 ( Cont'd ) Base-apex electrocardiograms of large animals with normal
sinus rhythm (panels A & B), supraventricular arrhythmias (panels C, D, E, F, G,
& H), hyperkalemia (panels H & I) or ventricular arrhythmias (panels J, K, & L).
All electrocardiograms were recorded at 25 mm/sec and 10 mm = 1 mV.

physiological hypoxemia during birth
and that their occurrence should be
considered as part of the normal adaptive
process to extrauterine life, as normal
sinus rhythm was recorded by 5 minutes
following birth and the foals subse-
quently developed normally. 5

Cardiac arrhythmias also occur
commonly in association with gastro-
intestinal disorders in the dairy cow 6
and less commonly in the horse 7 and
resolve without specific antiarrhythmic
treatment when the primary gastro-
intestinal disorder is corrected. Atrial
premature complexes, ventricular pre-
mature complexes and atrial fibrillation
have been detected in apparently healthy
dairy cattle by serial monitoring; 8 how-
ever, ventricular premature complexes
should be assumed to indicate the pre-
sence of organic heart disease.

REFERENCES

1. McQuirk SM et al. J Am Vet Med Assoc 1990;
196:894.

2. Austin AR et al. Vet Rec 1997; 141:352.

3. Kiri K et al. Jpn J Vet Sci 1985; 47:45.

4. Dudan F et al. Schweiz Arch Tierheilkd 1985;
127:319.

5. Yamamoto K et al. Equine Vet J 1992; 23:169.

6. Constable PD et al. J Am Vet Med Assoc 1990;
197:1163.

7. Cornick JL, SeahomTL. J Am Vet Med Assoc 1990;
197:1054.

8. Machida N et al. JVet Med A 1993; 40:233.

ARRHYTHMIAS WITH NORMAL
HEART RATES OR BRADYCARDIA

SINUS ARRHYTHMIA

Sinus arrhythmia is a normal physio-
logical arrhythmia that occurs at slow
resting heart rates and is- associated with
variation in the rate of discharge from the
sinoatrial node associated with variation

in the intensity of vagal stimulation.
It is commonly correlated with respira-
tion so that the discharge rate and heart
rate increase during inspiration and
decrease during expiration. In the horse,
sinus arrhythmia unassociated with
respiration also occurs. In the majority ,of
large animals, sinus arrhythmia is much
less overt than in the dog and generally it
is not detected except on very careful
clinical examination or examination of the
electrocardiogram. Sinus arrhythmia is
more clinically obvious in tame sheep and
goats and in the young of all species
and is correlated with respiration. It is
abolished by exercise or by the adminis-
tration of atropine.

In the electrocardiogram sinus
arrhythmia is detected by variations in the
P-P intervals (greater than 10% of the
mean heart rate) with or without
variation in the P-R interval and is
frequently associated with a wandering
pacemaker. This is associated with
differences in the site of discharge from
the sinoatrial node with subsequent
minor variations in the vector of atrial
depolarization with subsequent minor
variations in the configuration of the
P wave. In the horse there may be an abrupt
change in the contour of the P wave so
that the normal biphasic positive P wave
in lead II, for example, changes to one
with an initial negative deflection. There
may or may not be a change in P-R
interval. This is not pathological and is
present in as many as 30% of normal
horses at rest. If sinus arrhythmia is not
abolished by exercise it is considered
pathological. Sinus arrhythmia may be
induced in the early stages of hyper-
calcemia during treatment for milk fever
in cattle.

SINOATRIAL BLOCK

In sinoatrial block the sinus node fails to
discharge or its impulse is not transmitted
over the atrial myocardium. 1 It is associ-
ated with the complete absence of heart
sounds, of jugular atrial wave and of an
arterial pulse for one beat period. The
underlying rhythm is regular unless sinus
arrhythmia is present. In the electro-
cardiogram there is complete absence of
the P, QRS and T complex for one beat.
The distance between the preblock and
postblock P waves is twice the normal P-P
interval or sometimes slightly shorter. This
arrhythmia is not uncommon in fit racing
horses at rest and can be induced in horses
and cattle by procedures that increase vagal
tone. Provided it does not persist during
and following exercise it is considered as a
physiological variant of normal rhythm.

ATRIOVENTRICULAR BLOCK

Atrioventricular block is divided into
three categories depending upon the

6

PARTI GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

degree of interference with conduction at
the atrioventricular node.

First-degree atrioventricular block
This is an electrocardiographic diagnosis

and cannot be detected clinically. It
occurs when conduction is delayed at the
atrioventricular node. The P-R interval is
prolonged beyond normal limits (con-
ventionally > 400 ms in the horse) and the
condition may be transient because of
waxing and waning vagal tone. First-
degree atrioventricular block is generally
considered to have little significance.

Second-degree atrioventricular block
Also called partial heart block, this
occurs when there is periodic interference
with conduction at the atrioventricular
node so that some atrial contractions are
not followed by ventricular contraction
(Figure 8.1). This may occur apparently at
random or occur in a regular pattern, for
example at every third or fourth beat. At
the blocked beat there is complete
absence of the first and second heart
sounds and no palpable pulse. The under-
lying rhythm is still sinus in origin and is
thus regular. In horses the presence of a
fourth heart sound can be a valuable aid
to diagnosis as with careful auscultation it
can be heard during the block period in
the manner of du LLTBB DUPP, du ..., du
LLTBB DUPP. This is diagnostic for this
condition. An atrial jugular impulse can
also be detected during the block period.
The intensity of the first sound in the
immediate postblock beat is usually
intensified.

The electrocardiogram shows the
presence of a P wave but complete
absence of the subsequent QRS and T
waves at the blocked beat. There may be
variations in the P-R intervals preceding
and following the block. With Mobitz
type 1 (Wenkebach) second degree
atrioventricular block there is a gradual
increase in the PQ interval up to the point
of the blocked conduction. With Mobitz
type 2 block the PQ interval remains
unchanged. In most species, Mobitz type
1 is a normal physiological response
reflecting changes in vagal tone, whereas
Mobitz type 2 always indicates the
presence of organic heart disease such as
myocarditis. However, many second-
degree atrioventricular blocks in horses
do not fit these two categories and the PQ
interval increases until the immediate
preblock complex in which it may be
decreased. The clinical significance of
these variations in the horse has not been
established.

Second-degree atrioventricular block
is extremely common in horses and
occurs as a normal physiological varia-
tion due to variations in vagal tone. 1 The
application of a twitch to the upper lip of

a horse will frequently slow the heart rate
and allow the expression of second-
degree heart block. It is more common in
Thoroughbreds and Standardbreds than
in heavy horses and may be detected
in approximately 20% of racehorses. Fre-
quency is highest when they are examined
in quiet surroundings at rest, at night or
early in the morning. 2 Second degree
atrioventricular block can be abolished by
exercise or the administration of atropine.

Second-degree atrioventricular block
can be associated with myocarditis in the
horse and its presence has been asso-
ciated with decreased racing performance
by some clinicians. Second-degree atrio-
ventricular block at fast heart rates has
also been associated with the syndrome
of duodenitis-proximal jejunitis in horses
and was correlated with high serum
bicarbonate concentrations in this
condition. 3 Atrioventricular conduction
disturbances can be associated with
electrolyte imbalance in all species,
overdosing with calcium salts, digoxin
toxicity, cardiomyopathy and myocarditis
associated with nutritional and infectious
disease.

Methods for the clinical differentiation
of physiological (Mobitz type 1) versus
pathological (Mobitz type 2) second-
degree heart block in the horse have
not been established. However, the
persistence of the arrhythmia at heart
rates above resting normal values should
be considered to be abnormal. In all other
species the presence of Mobitz type 2
atrioventricular block should probably be
considered as an indication of myocardial
disease.

There is usually no necessity to treat
this arrhythmia specifically and treatment
is generally directed at the underlying
cause. In cases where the block is fre-
quent and syncopal episodes are likely,
atropine may give some alleviation of the
frequency of the block; however, this is
only short-term therapy. Second-degree
heart block may progress to third degree
(complete) heart block.

Third-degree or complete heart block

This occurs rarely in large animals, or
perhaps is seen only infrequently because
it is almost invariably fatal. In complete
heart block there is no conduction at the
atrioventricular node. The ventricle
establishes a pacemaker in the nodal or
conducting system and the atria and
ventricles beat independently. The ven-
tricular rate is regular but very slow.
Bradycardia is the prominent feature
and it is unresponsive to exercise or
atropine. Atrial contractions are much
faster than the ventricle. Atrial contrac-
tion sounds are rarely heard on auscul-
tation but evidence of the rate may be

detected by examination of the jugular
inlet. Periodically, as the atrium contracts
during the period that the atrioventricular
valves are closed, atrial cannon waves
may occur up the jugular vein. There is
usually variation in the intensity of the
first heart sound due to variation in
ventricular filling. Affected animals show
extremely poor exercise tolerance and
usually have evidence of generalized
heart failure. There is frequently a history
of syncopal attacks.

The electrocardiogram shows a
slow and independent ventricular rate
characterized by QRS complexes that are
completely dissociated from the faster
P waves.

The prognosis in complete heart
block is extremely grave unless it is
associated with a correctable electrolyte
imbalance. The animal should be kept at
rest in quiet surroundings while every
effort is made to correct the underlying
cause. Corticosteroids and dextrose are
usually given intravenously in an attempt
to reduce the severity of the initiating
myocardial lesion. Isoproterenol (isopre-
naline) may stimulate higher nodal tissue
and may increase the heart rate.
Isoproterenol is usually infused intra-
venously at a concentration of 1 mg/L of
infusion fluid and the rate of infusion is
adjusted to effect. This is not a practical
treatment in most situations. The use of
an internal pacemaker has been reported
in the horse but would clearly make the
animal unsuitable for athletic endeavors.

Atrioventricular block and atrioven-
tricular dissociation may develop during
anesthesia and can be associated with
arrhythmogenic anesthetic drugs, hyper-
capnia, hypoxia and electrolyte and
acid-base imbalances. 4,5 In these circum-
stances, the administration of regular
doses of atropine (0.02 mg/kg) may not
alleviate the arrhythmia. Dopamine HC1
infusions (3-5 pg/kg per min) have been
effective/ 1

The Wolff-Parkinson-White syndrome
is recorded as a rare observation in cattle.'

PREMATURE COMPLEXES

Premature complexes or extrasystoles
arise by the discharge of impulses from
irritable foci within the myocardium. They
are classified according to the site of their
origin as atrial, junctional and ventricular
premature complexes. It is often not
possible to distinguish between these by
physical examination, particularly at fast
heart rates. However, auscultation of an
animal with premature beats usually
reveals an occasionally irregular rhythm.

Atrial premature complexes

These arise from the discharge of an
ectopic atrial pacemaker outside the sinus
node. Atrial premature contractions are

Arrhythmias (dysrhythmias)

difficult to detect on physical examination
if they do not affect ventricular rhythm. If
the stimulus from the atrial premature
complex falls outside the refractory period
of the ventricle it will initiate a ventricular
complex that occurs earlier than expected.
Ventricular contractions initiated by atrial
premature complexes have lower intensity
because of lower diastolic filling, and the
associated arterial pulse amplitude is
decreased.

Two main patterns occur. In some
instances the sinus node becomes reset
from the atrial premature complex so that
a regular rhythm is established from this
contraction. In this case atrial premature
complexes are characterized by the
occurrence of periods of regular rhythm
interrupted by beats with exceptionally
short interbeat periods. In other instances
the sinus node is not reset following the
atrial premature complexes and if its
discharge occurs during the refractory
period of the atrium then no atrial or
subsequent ventricular contraction will
occur. This will be detected electro-
cardiographically as an early ventricular
complex followed by a pause follow-
ing which normal rhythm is continued.
This character is identical to that pro-
duced by many ventricular premature
complexes.

At slow heart rates the presence of
atrial premature beats is suggested by
periodic interruption of an underlying
sinus rhythm and by the occurrence of a
'dropped pulse'. The prime differentiation
is from sinoatrial block and second-
degree atrioventricular block, which
have distinguishing electrocardiographic
characteristics.

On the electrocardiogram the P wave
of the premature beat occurs earlier
than expected from the basic rhythm and
is abnormal in configuration. (Figure 8.1)
QRS complexes associated with atrial
premature beats are normal in confi-
guration because this is a supraventricular
arrhythmia and the pathway for ventri-
cular depolarization is not altered.

Junctional premature complexes

These are also called atrioventricular
nodal premature complexes arise from
. the region of the atrioventricular node or
conducting tissue. They produce a pre-
mature ventricular contraction, which is
usually followed by a compensatory
pause due to the fact that the following
normal discharge from the sinus node
usually falls upon the ventricle during its
refractory period.

Junctional premature complexes pro-
duce QRS configurations that are similar
to those of normal beats but they may
produce a P wave that has a vector
opposite to normal.

Ventricular premature complexes

Ventricular premature complexes may
arise from an irritable process anywhere
within the ventricular myocardium. The
normal rhythm is interrupted by a beat
that occurs earlier than expected but the
initial rhythm is established following a
compensatory pause. This can be estab-
lished by tapping through the arrhythmia
as described earlier. The heart sounds
associated with the premature beat are
usually markedly decreased in amplitude
while the first sound following the
compensatory pause is usually accen-
tuated. Occasionally, ventricular premature
complexes may be interpolated in the
normal rhythm and not followed by a
compensatory pause. If the diastolic
filling period preceding the premature
beat is short the pulse associated with it
will be markedly decreased in amplitude
or even absent.

On the electrocardiogram ventricular
premature complexes are characterized
by bizarre QRS morphology (Figure 8.1).
Conduction over nonspecialized path-
ways results in a complex of greater
duration and amplitude to normal and
the complex slurs into a T wave that is
also of increased duration and mag-
nitude.The vector orientation depends on
the site of the ectopic foci initiating the
contraction but it is invariably different
from that of normal contractions. Electro-
cardiographic examination allows a dif-
ferentiation of the site of origin of
premature complexes and further sub-
classification within the categories.

Premature complexes of all site origins
are indicative of myocardial disease, the
one exception being the occurrence of
atrial premature complexes accom-
panying cases of gastrointestinal disease
in cattle. Atrial premature complexes
occur commonly in cattle with gastro-
intestinal disease and their presence
should be suspected whenever there is a
variation in the intensity of the first heart
sound with or without an underlying
detectable cardiac irregularity. 8 Atrial pre-
mature complexes can progress to atrial
fibrillation in these cases where there is
excessive vagal tone. 9,10

Horses in which premature beats
are detected or suspected should be
examined after careful exercise, which will
usually increase the occurrence and
severity of the arrhythmia. Premature beats
are most easily detected during the period
of slowing of heart rate after exercise. 1

REFERENCES

1. Holmes JR. In Pract 1980; 2:15.

2. Scheefer CWJ et al.Vet Rec 1995; 137:371.

3. Cornick JL, Seahorn TL. J Am Vet Med Assoc

1990; 197:1054.

4. Greene SA et al. J Vet Pharmacol Ther 1988;

11:295.

5. Grubb TL et al. J Am Vet Med Assoc 1996;
208:349.

6. Whitton DL, Trim CM. J Am Vet Med Assoc 1985;
187:1357.

7. EndoY et al. Jpn J Vet Sci 1990; 52:1155.

8. Constable PD et al. J Am Vet Med Assoc 1990;
197:1163.

9. Constable PD et al. J Am Vet Med Assoc 1990;
196:329.

10. Machida N et al. J Vet Med A 1993; 40:233.

ARRHYTHMIAS WITH
T ACHYCARDIA

An excitable focus within the myo-
cardium may spontaneously discharge
and cause depolarization of the remain-
ing myocardium. If the discharge rate
approaches or exceeds that of the sinus
node the focus may transiently take over
as the pacemaker of the heart.

PAROXYSMAL TACHYCARDIA

Paroxysmal tachycardia may arise from an
irritant focus within the atria or the
ventricles but in large animals ventricular
paroxysmal tachycardia is more common.
Atrial paroxysmal tachycardia (Figure 8.1)
and atrial flutter are rare and are transients
leading to atrial fibrillation.

In paroxysmal tachycardia the increase
in heart rate is abrupt and the fall to
normal is equally sudden. This charac-
teristic usually serves to distinguish this
arrhythmia from the transient increases in
heart rate that may normally follow such
factors as excitement. Also the heart rate
is elevated to a rate far in excess of that
which would be normally expected from
such stimuli.

More commonly the excitable focus
discharges repetitively over a long period
of time to produce more continual
ventricular tachycardia associated with
ventricular extrasystoles. Sustained tachy-
cardia is not normal and can lead to
myonecrosis; three parturient dairy cows
with sustained tachycardia (heart rate
> 120 beats/min) had multifocal areas of
necrosis throughout the myocardium
characterized by myofibrillar lysis and
disarray.

VENTRICULAR TACHYCARDIA

Ventricular tachycardia may produce
either a regular heart rate or an irregular
heart rate and rhythm.

When the discharge rate of the irritant
focus far exceeds that of the sinoatrial
pacemaker, the ectopic focus will take
over completely as the pacemaker of the
heart and on examination of the cardio-
vascular system a rapid but regular heart
rate and pulse is detected and there is no
irregularity of rhythm or of pulse ampli-
tude or intensity of heart sounds. This is
known as ventricular tachycardia with
atrioventricular dissociation. This abnor-
mality is easily overlooked clinically but

8

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

should be suspected in any adult horse or
cow where the heart rate exceeds 90
beats/min 1 and is frequently the cause of
heart rates in excess of 120 beats/min.
Ventricular tachycardia should also be
suspected where the heart rate is elevated
to a level that is higher than that expected
from the animal's clinical condition.

An electrocardiogram gives the diag-
nosis based on the occurrence of multiple
regular QRS complexes with abnormal
amplitude and duration of the QRS andT
complexes and the T wave oriented in a
direction opposite to the QRS complex
(Figure 8.1). 2 P waves may be detected on
the electrocardiogram but they have no
relationship to the QRS-T complex and
are frequently lost within them.

When the discharge rate of the irritant
focus within the myocardium is similar to
that of the sinoatrial node the ventricular
tachycardia can be manifested by a gross
irregularity in rhythm. This is a common
manifestation in large animals. In this
situation many of the discharges which
originate in the sinus node are trans-
mitted to the ventricle during a refractory
period from a previous ectopic foci, but
some reach the ventricle when it is not in
a refractory state and are conducted
normally. At some periods ventricular
complexes may be initiated by the dis-
charges from both sites.

The varying influence of each pace-
maker on ventricular contraction produces
a marked irregularity in cardiac rhythm
and it is frequently not possible to
establish clinically a regular pattern to the
heart rhythm. Variations between beats in
the degree of atrial filling and in the
diastolic filling period will result in a
marked variation in the intensity of the
heart sounds and in the amplitude of
the pulse. Frequently at fast heart rates
there is a pulse deficit. Cannon atrial
waves can be observed in the jugular vein
when atrial contraction occurs at the
same time as a ventricular extrasystole.

The electrocardiogram shows runs of
extrasystoles interspersed with normally
conducted complexes and usually the
presence of fusion beats.

Ventricular tachycardias are evidence
of severe cardiac disease and are usually
accompanied by signs of acute heart
failure. They may result from primary
myocarditis, nutritional cardiomyopathy,
or myocardial neoplasia 3 or be secondary
to valvular disease and myocardial
ischemia. Ventricular arrhythmias are
common in certain plant poisonings and
other toxicities, and in severe electrolyte
and acid-base disturbance, and commonly
occur in the final stages of heart failure. If
uncorrected, ventricular tachycardia may
lead to ventricular fibrillation and death
and frequently specific antiarrhythmic

therapy is indicated during the period
that the prime cause is being corrected.

Treatment

Lidocaine is the drug of first choice for
treating hemodynamically important
ventricular arrhythmias in large animals.
Lidocaine is an antiarrhythmic agent of
class lb of Vaughan- Williams's classifica-
tion, and slows intracardiac conduction
by blocking the fast sodium channel
while shortening the refractory period of
i myocardial tissue. Typically, lidocaine
is given as an intravenous bolus at
0.5-1. 0 mg/kg BW every 5 minutes for
a total of four treatments (total dose
2-4 mg/kg BW). 4,5 Lidocaine has the
advantages of widespread availability, low
cost and low cardiovascular toxicity, with
the major disadvantage being its very
short duration of action (half-life is
40 minutes in the horse). The most
commonly seen initial sign of lidocaine
toxicity is muscle fasciculations, which
occur at a serum lidocaine concentration
of 1. 9-4.5 mg/L. 5 If infusion is continued,
sedation and altered visual function are
apparent, the latter being manifest as
rapid eye blinking, anxiety and attempts
to inspect closely located objects. Tempor-
ary recumbency, excitement, sweating
and convulsions occur with higher doses. 4

Quinidine sulfate is the drug of
second choice for use in horses. Quinidine
is an antiarrhythmic agent of class la of
Vaughan -Williams's classification, and
slows intracardiac conduction by blocking
the fast sodium channel and prolongs the
action potential duration. An initial dose
of 20 mg/kg is given orally, followed by a
dose of 10 mg/kg given every 8 hours.
The drug is not effective until 1-2 hours
following administration. Intravenous
quinidine gluconate (0.5-2.2 mg/kg BW
bolus every 10 minutes to a total of
12 mg/kg BW) may be of greater value in
: those rare instances when oral quinidine
| is not indicated. Serum quinidine con-
! centrations of 4 mg/L appear effective in
| treatment of cattle with ventricular
; tachycardia but serum concentrations
j following an oral dose of 20 mg/kg vary
j widely between cows and slow intra-
I venous infusion is the preferred method
■ of therapy. 6 There is a very narrow
; therapeutic index in cattle and death can
: occur in some cows at doses that are
j therapeutically effective in others. 6
i Quinidine treatment in cattle should be
approached with caution.

Phenytoin sodium is a good alter-
I native to quinidine sulfate, and has been
j effective in treating ventricular arrhythmias
i in horses. 7 Phenytoin is an antiarrhythmic
| agent of class lb of Vaughan- Williams's
| classification (same as lidocaine), and
I slows intracardiac conduction by blocking

the fast sodium channel while shortening
the refractory period of myocardial tissue.'
The recommended dosage protocol for
the horse requires an initial oral dose of
20 mg/kg BW every 12 hours for four
doses, followed by a maintenance oral
dose of 10-15 mg/kg BW every 12 hours,
with monitoring of phenytoin plasma
concentrations. Plasma concentrations of
5-10 mg/L appear to be effective in
treatment of horses with ventricular
tachycardia. High plasma phenytoin con-
centrations are associated with sedation,
recumbency and excitement, 7 and the
dosage protocol should be altered in
horses that appear sedated. The major
advantage of phenytoin over lidocaine is
its long duration; conversely, its major
disadvantage is the initial time required
(2-6 h) to exert an antiarrhythmic effect.
An intravenous form of phenytoin sodium
has been administered to a pony with
digitalis-induced ventricular arrhythmias,
but the alkaline pH of the infused solu-
tion carries a high risk of thrombophlebitis. 8
Magnesium sulfate (0.004 mg/kg BW
boluses intravenously at 5-minute intervals
to a maximum dose of 0.05 mg/kg BW)
has also been successful in treating
ventricular arrhythmias either alone or in
combination with other antiarrhythmic
agents; however, clinical experience with
magnesium sulfate administration in
horses is minimal.

The severity of ventricular tachycardia
is augmented by factors that increase
sympathetic tone, and affected animals
should be kept in quiet surroundings.

VENTRICULAR FIBRILLATION

Ventricular fibrillation is not usually
observed clinically. It occurs in the ter-
minal stages of most suddenly fatal
diseases, including lightning stroke, plant
poisonings such as acute Phalaris toxicity,
overdose with anesthetics, severe toxemia
and in the terminal phases of most
acquired cardiac diseases. There is
complete absence of the pulse and heart
sounds, the blood pressure falls precipi-
| tously and the animal rapidly becomes
! unconscious and dies within a minute
or two of onset. Treatment is usually
impractical although deaths during
anesthesia maybe prevented by immediate
[ and aggressive external cardiac massage.

' Electrical defibrillation is not feasible in
j large animals due to the bulk of the animal
j and the current required. Intracardiac
j injections of epinephrine are often used
\ in acute cardiac arrest but do not correct
j fibrillation and are of little value.

| ATRIAL FIBRILLATION

j In atrial fibrillation atrial depolarization is
j characterized by numerous independent
| fronts of excitation that course conti-
[ nuously and haphazardly through the

Arrhythmias (dysrhythmias)

atria. There is no synchronous atrial
contraction and atrioventricular nodal
stimulation occurs in an irregular and
random fashion. The effects within the
atria cannot be appreciated on auscultation
and the clinical detection of this arrhy-
thmia occurs through its effects on ven-
tricular function. The random stimulation
of the ventricles produces a heart rate and
pulse that is irregularly irregular. It is
not possible to establish any basic rhythm
by tapping out this arrhythmia and the
rate varies from period to period.

Because there is no atrial contraction,
filling of the ventricles is entirely passive
and very much dependent on diastolic
filling time. Some contractions occur very
quickly following the preceding contraction
with little time for diastolic filling and this
produces a marked variation in the
intensity of the heart sounds and in the
amplitude of the pulse. At fast heart rates
there will be a pulse deficit. There is no
fourth heart sound (S4) or atrial wave at
the jugular inlet because there is no
coordinated atrial contraction, but the
third heart sound is usually grossly accen-
tuated. The degree of cardiac insufficiency
that results from this arrhythmia varies
and depends upon the general rate at
which the ventricles beat at rest. This is
determined primarily by vagal activity.

On the electrocardiogram there are
no P waves discernible but the baseline
shows multiple waveforms (f waves) that
occur with a frequency of between 300
and 600 beats/min (Figure 8.1). QRS-T
complexes are normal in configuration
but there is wide variation and no pattern
in the Q-Q intervals. Atrial fibrillation is
one of the more common arrhythmias in
large animal species.

Atrial fibrillation in the horse

Horses with atrial fibrillation fall into two
categories. In one category, sometimes
called'benign fibrillators', 9 there is no evi-
dence of underlying heart disease whereas
in the other, there is.

Benign fibrillation

In cases that are benign fibrillators the
vagal tone may be high and conduction
through the atrioventricular node is
suppressed to result in heart rates in the
region of approximately 26-48 beats/min.
At this rate there is no cardiac insuffi-
ciency at rest and hemodynamic para-
meters are normal. 10 The horse can
elevate its heart rate with exercise to allow
moderate performance, although it will
never perform satisfactorily as a race-
horse. This is the most common manifes-
tation in this species and it is typified by a
gross irregularity in rate, rhythm and
intensity of the heart sounds and by the
occurrence, at rest, of occasional periods
lasting for 3-6 seconds where there is no

ventricular activity. At very slow rates
periodic syncope may occur.

The benign form of atrial fibrillation
occurs not infrequently in draft horses
and is also seen in racehorses. A survey of
106 cases of atrial fibrillation in horses 11
found the disease most commonly in
Standardbred and Thoroughbred horses
under 7 years of age, with a high pro-
portion under 4 years of age, which may
have been a reflection of the admissions
to the clinic rather than real age incidence.

Exercise intolerance was the most
common clinical history. All horses had
an irregular heart rate and rhythm and
the pulse and intensity of the heart
sounds were variable. A separate study
of 67 horses 12 showed a significantly
higher prevalence in Standardbreds and
Thoroughbreds than other breeds of
horse and a significant difference in
the mean age at diagnosis between
Standardbreds (4 years) and Thorough-
breds (9 years) .

Racehorses commonly have a history
of normality at rest but poor exercise
tolerance following a race in which the
horse ran well for the first 200-300 m but
subsequently faded badly and finished a
long way behind the field. Paroxysmal
atrial fibrillation has also been observed
in the horse under these circumstances.
Horses with paroxysmal atrial fibrillation
show atrial fibrillation when examined
immediately following the race, but
convert to normal sinus rhythm shortly
after and have normal cardiovascular
function if the examination as to cause of
poor racing performance is delayed. A
large scale study of 39 302 racehorses
undergoing 404 090 race starts estimated
a minimum prevalence of atrial fibrilla-
tion of 0.29%. 13 The estimated prevalence
was higher (1.39%) in horses that finished
slowly or did not finish, and the prevalence
increased markedly with age. Atrial
fibrillation was paroxysmal in most horses,
with 93% of horses with atrial fibrillation
spontaneously converting to sinus rhythm
within 24 hours of the race. Attempted
conversion of horses with atrial fibrillation
should therefore be delayed for at least a
couple of days following a race, because
most will convert spontaneously without
treatment.

There is debate as to the cause of the
benign form of atrial fibrillation and
whether myocardial and vascular lesions
are present in the atria of a significant
proportion of animals with this arrhyth-
mia. However, the high rate at which
atrial fibrillation converts spontaneously
or by treatment to be followed by success-
ful racing performance suggests that this
arrhythmia frequently occurs in young
horses in the absence of significant atrial
pathology. Benign atrial fibrillation in

young racing horses therefore has, many
similarities to atrial fibrillation in lactating
dairy cattle with abdominal disease, in
that it is likely that most cases do fiot have
underlying heart disease. The increased
prevalence of atrial fibrillation in race
horses with age 13 suggests, however, that
underlying heart disease does predispose
to developing atrial fibrillation during
a race.

Underlying disease

Horses may develop atrial fibrillation at
fast heart rates in response to underlying
cardiovascular disease. Commonly this
is mitral valve insufficiency, tricuspid
valve insufficiency or a combination of
both but any acquired or congenital lesion
that results in atrial hypertrophy has
this risk.

Where there is underlying heart disease
the ventricular rate at rest is much higher
and the arrhythmia presents as a tachy-
cardia. It has been suggested that a heart
rate greater than 60 beats/min is indi-
cative of underlying cardiac disease in
cases of atrial fibrillation. 12 In horses with
atrial fibrillation ventricular filling is
impaired at heart rates above 70 beats/
min 4 and at resting heart rates above
80-100 beats/min there is severe cardiac
inefficiency and the animal rapidly
develops signs of cardiac failure. At fast
heart rates, atrial fibrillation presents
with a syndrome clinically similar to ven-
tricular tachycardia associated with
multiple ventricular extrasystoles and
electrocardiographic differentiation is
required.

Primary pulmonary hypertension as a
cause of atrial fibrillation is also recorded
in horses, the increased resistance to right
ventricular outflow leading to ventricular
hypertrophy and dilatation, stretching
of the right atrioventricular annulus,
atrial dilatation and subsequent atrial
fibrillation. 14

Paroxysmal atrial fibrillation has been
observed in newborn foals showing signs
of respiratory distress and with birth
anoxia. 13

Atrial fibrillation in the cow

Atrial fibrillation in the cow may occur
secondary to myocardial disease or
endocarditis resulting in atrial enlarge-
ment, but more commonly is functional in
occurrence and traditionally has not been
associated with clinically detectable cardiac
lesions. 16,17 However, a recent histo-
pathological study in nine Holstein-
Friesian cows with atrial fibrillation and
12 healthy controls in sinus rhythm
indicated that multifocal or large areas of
myocardial fibrosis were present more
frequently and with greater severity in
cattle with atrial fibrillation than healthy
controls. 18 Interestingly, the atrial lesions

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

were largely confined to the dorsal
regions of the cranial lateral and medial
regions of the right atrium. Organic heart
disease therefore appears to predispose
cattle to the development of atrial
fibrillation, and an atrial fibrillation
prevalence of 2.5% was recorded in
apparently healthy lactating dairy cows
over an 18 month period. 17 In a large
cross sectional study, atrial fibrillation was
not observed during a 3-5 minute ECG
recording in 952 of dairy cattle aged 1 or

19

more years.

In sick cattle, atrial fibrillation most
commonly occurs in association with
gastrointestinal disease, abnormalities
causing abdominal pain and metabolic
disease. Abnormalities as diverse as acute
enteritis, left displacement of the abo-
masum and torsion of the uterus may
be accompanied by this arrhythmia.
Heightened excitation of the atria, in
association with electrolyte and acid-base
disturbances or due to change in vagal
tone, has been postulated as a cause, and
atrial premature complexes are also seen
in the same types of clinical case. 16 - 20
(Figure 8.1) The administration of neo-
stigmine to cattle with gastrointestinal
disease may precipitate the occurrence
of atrial fibrillation. 21 The arrhythmia
usually converts spontaneously to sinus
rhythm with correction of the abdominal
disorder.

Atrial fibrillation in the sheep and
goat

This may occur as a result of incom-
petence of the tricuspid or mitral valves,
the presence of myocarditis or, in- goats, as
a sequel to interstitial pneumonia along
with cor pulmonale. The presenting signs
are those of respiratory distress and heart
failure. Ascites is prominent and there
is marked jugular distension with an
irregular jugular pulse.

Treatment of atrial fibrillation

Ruminants

Ruminants with atrial fibrillation are not
in general treated with specific anti-
arrhythmic drugs as the heart will usually
revert to sinus rhythm following the
correction of the underlying abdominal
disorder and sufficient time (at least
1 week after return to normal physical
health). However, the intravenous adminis-
tration of quinidine (49 mg of quinidine
sulfate/kg BW, at 0.20 (mg/kg)/min) was
successful in converting seven of nine
cows to normal sinus rhythm at a mean
plasma quinidine concentration of
3.6 |.ig/mL. 22 Oral quinidine administra-
tion is not effective in ruminants because
of the poor oral bioavailability. Side
effects of intravenous quinidine adminis-
tration in cattle include depression, ataxia,
blepharospasm, diarrhea and increased

frequency of defecation. 22 Response to
treatment in sheep and goats is poor,
although one ram was successfully
converted to normal sinus rhythm using
electrical cardioversion using 360 J and
paddles placed over the right heart base
(behind the triceps muscles) and the left
cardiac apex close to the sternum. 23

Horses

Horses with atrial fibrillation at high heart
rates are generally not treated successfully
as serious cardiac pathology is usually
present. Digoxin and quinidine sulfate are
used. The decision to treat a horse with
atrial fibrillation at low heart rates depends
upon the requirement for the horse to
perform work, because horses with this
arrhythmia can be retired and will live for
several years. They may be used success-
fully as brood mares.

Horses with benign atrial fibrillation
can be converted to normal sinus rhythm
with subsequent return to successful
racing or other performance. 24,25 Oral
quinidine sulfate is usually used.
Quinidine is an antiarrhythmic agent of
class la of Vaughan-Williams's classifica-
tion, slows intracardiac conduction by
blocking the fast sodium channel and
prolongs the action potential duration.
Several dose regimens have been used,
but the administration of an oral dose of
22 mg/kg every 2 hours until conversion
is achieved or toxicity is manifest has
proved effective. 11,24 In the majority of
cases, conversion will occur before the
total dose exceeds 40 g. Toxicity is likely
when the total dose exceeds 60 g and the
decision to continue with therapy once
this dose has been reached should be
considered carefully. The plasma quinidine
concentration required for cardioversion
ranges from 2-4 pg/ml. and toxicosis has
been reported at 5 pg/mL.

Toxicity is not uncommon with
quinidine therapy and separate studies
report 48% and 28% of horses with some
form of adverse reaction. 11,24 Depression,
lassitude, anorexia, urticaria, congestion
of the mucous membranes, colic and
death are recorded. Prolongation of the
QRS interval to 25% greater than pre-
treatment values has been considered a
monitor for cardiovascular toxicity. The
toxic effects of quinidine may be corrected
by intravenous administration of sodium
bicarbonate in an attempt to increase the
percentage of quinidine bound to protein.
Such treatment runs the risk of inducing
hypokalemia, which may exacerbate
quinidine toxicity. Some prefer to digitalize
the horse intravenously prior to medica-
tion with quinidine in an attempt to
reduce tachyarrhythmias at the point of
conversion and those associated with
quinidine toxicity. Nephrotoxicity with

uremia and diarrhea can occur at lower
doses. Nephrotoxicity is transient and
repairs rapidly following withdrawal of
the drug but the serum urea nitrogen
concentration and urine should be
monitored during therapy in addition to
cardiovascular function.

There is a much greater success rate
with conversion in young horses and
when it is attempted shortly following the
onset of the arrhythmia. If the arrhythmia
has been present for more than 4 months,
successful conversion is much less
common, and side effects with therapy
are more common. 24 Following cardio-
version the horse should be rested for
3 months. In some horses the conditions
recur after a period of racing and repeated
conversions with quinidine are possible.
Conversion by intravenous quinidine
gluconate is reported in the horse using
an initial dose of 1. 0-1.5 mg/kg, given
over a period of 1 minute and repeated
every 5-10 minutes until sinus rhythm is
restored or the QRS interval increases
25% over baseline, ventricular rate
exceeds 90 beats/min, signs of toxicity
occur or a total dose of 11 mg/kg has
been administered. 25,26 Conversion by
quinidine and atrial pacing is also
recorded in the horse 27

Oral and intravenous flecainide has
been used with mixed success to convert
horses in atrial fibrillation. Flecainide is
an antianhythmic agent of class lc of
Vaughan-Williams's classification, slows
intracardiac conduction by blocking the
fast sodium channel and shortens the
refractory period of the Purkinje fibers.
Intravenous administration of flecainide
acetate (1-2 mg/kg BW) infused at
0.2 (mg/kg BW)/min was effective in
converting experimentally-induced atrial
fibrillation in six horses and naturally
occurring atrial fibrillation in two
horses. 28 The plasma flecainide concen-
tration at the time of conversion was
1.3 mg/L. Oral administration of flecainide
acetate (4-6 mg/kg BW) also produced
plasma flecainide concentrations that
approximated 1.3 mg/L 28 for a number of
hours. However, in a subsequent study in
10 horses with naturally occurring atrial
fibrillation, intravenous flecainide failed
to convert nine horses with long-standing
atrial fibrillation to sinus rhythm, but
did convert one horse who had been in
atrial fibrillation for 12 days. 29 Orally
administered quinidine sulfate subse-
quently converted eight of the nine
horses to normal sinus rhythm. Two
horses administered flecainide developed
potentially dangerous ventricular arrhy-
thmias during treatment.

One horse was converted from atrial
fibrillation using rectilinear biphasic
- electrical cardioversion, which is safer

Diseases of the heart

than conventional monophasic electrical
cardioversion. 30 General anesthesia is
induced using agents that produce
minimal cardiovascular depression (such
as intravenous induction with guaifenesin,
diazepam and ketamine and maintenance
with sevoflurane). The front legs of the
horse were extended and cardioversion-
defibrillation pads were placed over both
sides of the shaved thorax, directly over
the atria, the position of which had been
determined ultrasonographically. The
horse converted to normal sinus rhythm
after delivering 200 J in conjunction with
a small amount of intravenous quinidine.
Three horses were converted from atrial
fibrillation using transvenous electrical
cardioversion via placement of a custom-
length 6.5 French bipolar catheter using
ultrasonographic guidance. 31 Catheter
placement was manipulated so that one
electrode was in the pulmonary artery
and the other electrode in the vicinity
of the right atrium. Cardioversion was
accomplished at 125-300 J using a biphasic
truncated exponential shock delivered
to be not coincident with the T wave.
Concurrent use of antiarrhythmic medi-
cations was not required. The use
of electrical cardioversion should be
considered in cases of atrial fibrillation
refractory to oral or intravenous quinidine
administration.

REVIEW LITERATURE

McQuirk SM, Muir WW. Diagnosis and treatment of
cardiac arrhythmias. Symposium on Cardiology.
Vet Clin North Am Equine Pract 1985; 1:353-370.
Bertone JJ, Wingfield WE. Atrial fibrillation in horses.

Compend Contin Educ PractVet 1987; 9:763.
Fregin GF. Medical evaluation of the cardiovascular
system. Vet Clin North Am Equine Pract 1992;
8:329.

Collatos C. Treating atrial fibrillation in the horse.
Compend Contin Educ Pract Vet 1995;
17:243-245.

Marr CM. Cardiac emergencies and problems of the
critical care patient. Vet Clin North Am Equine
Pract 2004; 20:217-230.

REFERENCES

1. Nielsen I J .Aust Vet J 1990; 67:140.

2. Reimer JM et al. J Am Vet Med Assoc 1992;
201:1237.

3. Delesalle C et al. J Vet Intern Med 2002; 16:612.

4. Muir WW, McQuirk SM. Vet Clin North Am
Equine Pract 1985; 1:335.

5. Meyer GA et al. Equine Vet J 2001; 33:434.

6. Takemura N et al. Jpn JVet Sci 1989; 51:515.

7. Wijnberg ID, Vbrvers FFT. J Vet Intern Med 2004;
18:350.

8. Wijnberg ID et al. Vet Rec 1999; 144:259.

9. Bertone JJ, Wingfield WE. Compend Contin Educ
PractVet 1987; 9:763.

10. Muir WW, McQuirk SM. J Am Vet Med Assoc
1986; 184:965.

11. Deem DA, Fregin GF. J Am Vet Med Assoc 1982;
180:261.

12. ReefVB et al. JVet Intern Med 1988; 2:1.

13. Ohmura H et al. J Am Vet Med Assoc 2003;
223:84.

14. Gelberg HB et al. J Am Vet Med Assoc 1991;
198:679.

15. Machida N et al. Equine Vet J 1989; 21:66.

16. Brightling P, Townsend HGG. Can Vet J 1983;
24:331.

17. Machida N et al. JVet Med A 1993; 40:233.

18. Machida N, Kiryu K. J Vet Med Sci 2001; 63:873.

19. Rezakhani A et al. Rev MedVet 2004; 155:159.

20. Constable PD et al. J Am Vet Med Assoc 1990;
197:1163.

21. Constable PD et al. J Am Vet Med Assoc 1990;
196:329.

22. McGuirk SM et al. J Am Vet Med Assoc 1983;
182:1380.

23. Moresco A et al. J Am Vet Med Assoc 2001;
218:1264.

24. ReefVB et al. JVet Intern Med 1988; 2:1.

25. Collatos C. Compend Contin Educ PractVet 1995;
17:243.

26. Muir WW et al. J Am Vet Med Assoc 1990;
197:1607.

27. Van Loon G et al. Vet Rec 1998; 142:301.

28. Ohmura H et al. JVet Med Sci 2001; 63:511.

29. Van Loon G et al. Equine Vet J 2004; 36:609.

30. Frye MA et al. J Am Vet Med Assoc 2002;
220:1039.

31. Kimberly. M et al. J Vet Intern Med 2003;
17:715.

Diseases of the heart

MYOCARDIAL DISEASE AND
CARDIOMYOPATHY

Etiology Certain bacterial, viral, parasitic
infections, some nutritional deficiencies
and toxic agents

Epidemiology Specific to causative
agent

Clinical findings Reduction of cardiac
reserve and decreased exercise tolerance,
cardiac arrhythmias, congestive heart
failure or acute heart failure
Clinical pathology Electrocardiography,
echocardiography and serum cardiac
troponin I concentrations. Other
examinations directed at determining the
specific cause

Necropsy findings Myocarditis,
myocardial degeneration
Treatment For cardiac insufficiency.
Specific therapy, if available, for specific
cause

ETIOLOGY

A number of diseases are accompanied
by inflammation, necrosis or degener-
ation of the myocardium. These include
several bacterial, viral or parasitic infec-
tions and some nutritional deficiencies
and toxicities. In most cases, the involve-
ment of the myocardium is only part of
the total spectrum of these diseases,
although the cardiac manifestations
may be clinically pre-eminent. The term
cardiomyopathy is generally restricted to
those diseases where myocardial damage
is the prime manifestation. Causes of
myocardial dysfunction include the
following.

Bacterial myocarditis

° Following bacteremia, as in strangles
or from navel -ill

o Tuberculosis - especially horses
« Tick pyemia in lambs
° Clostridium chauvoei
° Histophilus somni

0 Extension from pericarditis, epicarditis
or endocarditis.

Viral myocarditis

° Foot-and-mouth disease - especially
young animals
° African horse sickness
° Equine viral arteritis
° Equine infectious anemia
° Equine herpesvirus-1 in fetus
° Swine vesicular disease
® Parvovirus in piglets
° Encephalomyocarditis virus infection
in pigs

° PRRS virus in piglets
° Bluetongue in sheep.

Parasitic myocarditis

This is primarily associated with Strongylus
spp. (migrating larvae) cysticercosis,
Sarcocystis spp. and Neospora caninum (in
the neonatal calf). In a postmortem study
of over 2000 equine hearts, 15% showed
myocardial fibrosis in association with
occlusive angiopathic change. 1 No age
association was found, but recent infarcts
were more common in yearlings. It was
postulated that these lesions result from
thromboemboli from verminous plaques
in the proximal thoracic aorta.

Nutritional deficiency

° Vitamin E/selenium deficiency in all
large animal species
° Some forms of chronic copper

deficiency in cattle (falling disease) -
experimental copper deficiency in
swine

° Iron deficiency in piglets and veal
calves

0 Copper/cobalt deficiency in lambs.

Toxicity

° Inorganic poisons - selenium, arsenic,
mercury, phosphorus, thallium
° Gossypol from cotton seed cake
0 The mycotoxin fumonisin when
ingested by pigs and horses
° Fluoroacetate (1080) and poisoning
by Acacia georgina, Gastrolobium and
Oxylobium spp., Dichapetalum
cymosum

° Plants and weeds, including
members of Ixiolena, Pachystigma,
Pavette, Asclepias, Geriocarpa,
Cryptostigia, Albizia, Cassia, Digitalis,
Urechites, Punelea, Astragalus, Fadogia,
Cicuta, Colchicum, Kanuinskia, Vida,
Cicuta, Trigonella, Bryophyllum,
Palicourea, Lupinus, Lantana,

Kalanchoe, Homeria, Hynienoxys,
Eupatorium spp.

22

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

° Trees, including gidgee, yew, oleander,
avocado

o Grasses, including Phalaris tuberosa,
corynetoxins in Lolium rigidum
infested with nematodes and
Corynebacterium spp. (also
tunicamycin in rain-damaged infected
wheat, pigs), cantharidin in hay
infested with blister beetles (horses)

° Drugs including succinylcholine,
catecholamines, xylazine (ruminants)
monensin - especially in horses, but
also cattle, sheep, and pigs - lasalocid
and salinomycin in horses, pigs, cattle
and sheep, maduramicin in cattle and
sheep fed poultry litter, and
Adriamycin (used experimentally to
produce cardiomyopathy). Overdosing
with doxycycline in veal calves
° Vitamin D and myocardial and
endocardial calcification following
ingestion of Cestrum diurnum,

Solanum malacoxylon, Trisetum
flavescens (see enzootic calcinosis);
calcification also occurs with
hypomagnesemia in milk-fed calves.

Venoms

0 Rattlesnake ( Crotalus spp.) venom in
horses

° Vipera palaestinae.

Embolic infarction

° Emboli from vegetative endocarditis
or other embolic disease such as
bracken fern poisoning in cattle.

Tumor or infiltration

» Viral leukosis of cattle
° Other cardiac neoplasia
•3 Cardiomyopathy in horses due to
amyloid infiltration of the
myocardium. 2

Inherited

- Malignant hyperthermia of swine
° Hypertrophic cardiomyopathy in swine
° Congenital cardiomyopathy of Polled
Hereford and Horned Hereford calves
with dense curly coats, and Japanese
Black calves

■> Inherited cardiomyopathy in adult
cattle occurring in Red
Holstein-Simmental crossbred cattle
in Switzerland and Austria, Red
Danish dairy cattle in Denmark,
Holstein-Friesian cattle in the UK,
Austria, Denmark, Sweden, Japan,
Canada and Australia (see
cardiomyopathy - inherited as an
autosomal recessive gene)

° Glycogen storage disease - cx-1, 4-
glucosidase deficiency in Shorthorn and
Brahman cattle and Corriedale sheep.

Unknown or uncertain etiology

Myocardial necrosis and hemorrhage
secondary to acute lesions in the
central nervous system 3

° Exertional rhabdomyolysis of horses,
capture myopathy of wild ruminants,
restraint stress in swine
» Sudden death in young calves

associated with acute heart failure and
myocardial necrosis and precipitated
by periods of intense excitement such
as that experienced at feeding time 4,5
° Myocardial lipofuscinosis (brown
atrophy) in aged or cachectic cattle,
especially Ayrshires, but often found
in healthy animals at slaughter 6
o Myocardial disease following mild
upper respiratory disease in horses,
especially when training or exercise is
continued through the respiratory
disease episode.

PATHOGENESIS

The primary effect of any myocardial
lesion is to reduce cardiac reserve and
limit compensation in circulatory emer-
gencies. Minor lesions may only reduce
performance efficiency while more severe
lesions may produce greater clinical
effect.

Most commonly, myocardial disease
results in arrhythmias and conduction
disturbances from primary involvement
of the conduction system or establish-
ment of excitatory foci within the myo-
cardium. While the animal is at rest there
may be minimal evidence of cardiac
disease but catastrophic disturbances in
cardiac conduction may occur under the
adrenergic influences of exercise or excite-
ment. The effects of pharmacological
cardiotoxic agents in poisonous plants are
frequently also initially manifest when the
animals are moved or otherwise excited.

Endogenous or synthetic catechola-
mines, in their own right, can produce
multifocal myocardial necrosis, especially
in the left ventricle. 7 Sympathetic over-
activity and local catecholamine release
in the myocardium has been postulated
as the cause of myocardial disease
accompanying acute brain lesions in
domestic animals and myocardial disease
associated with some forms of stress and
overexertion. 3 ' 8

Myocardial disease may also result in
congestive heart failure through its
primary effect on the myocardium and
the function of the heart as a pump.

CLINICAL FINDINGS

In early cases, or cases with mild or
moderate myocardial damage, a decreased
exercise tolerance is the usual initial
presenting sign. This is usually accom-
panied by an increase in heart rate and
heart size, although the latter may only
be detectable by echocardiography.
There may be clinically recognizable
arrhythmia, particularly tachyarrhyth-
mias associated with multiple ventricular
ectopic foci. The characteristics of the

pulse and heart sounds are also changed
(see arrhythmias).

Animals with suspect myocardial
disease but with no or minimal arrhyth-
mic disturbances at rest can be judiciously
exercised, which will frequently result in
the expression of conduction or arrhyth-
mic abnormality. Exercise or excitement
should be avoided in animals with overt
arrhythmias at rest.

In the late stages, or in cases with more
severe myocardial damage, there may
be sudden death or attacks of cardiac
syncope due to acute heart failure, or
severe dyspnea or general edema due to
congestive heart failure. Details of the
clinical findings associated with conduc-
tion disturbances, arrhythmias and heart
failure have been given earlier.

CLINICAL PATHOLOGY

Electrocardiography and echocardiography
are used in special examination. Hema-
tological examination, blood culture and
serology may be of value in determining
the cause of myocardial disease and a
full biochemical profile is advisable to
determine if multisystemic problems
are present. Myocardial infarction and
necrosis may be associated with the
release of cell enzymes into the blood-
stream during the acute phase and the
determination of the serum activities of
lactate dehydrogenase, creatine kinase
and aspartate aminotransaminase are of
value. 9 ' 10

The cardiospecific isoenzyme troponin
I provides the most sensitive and specific
indication of cardiac necrosis (see chronic
heart failure section) whereas the predic-
tive value of serum creatinine kinase and
lactate dehydrogenase activities is much
lower. 11 ' 12 Toxicological examination and
tests for nutritional trace element defi-
ciencies may be indicated.

NECROPSY FINDINGS

Bacterial infections may cause discrete
abscesses or areas of inflammation in the
myocardium but viral infections and
degeneration due to nutritional deficien-
cies and poisonings usually produce a
visible pallor of the muscle, which may be
uniform or present as streaks between
apparently normal bundles of muscle. In
acute cases, there may be petechial or
linear hemorrhages in the myocardium.
Calcification may occur in areas of
myocardial damage and with enzootic
calcinosis and vitamin D toxicity. The
nature and distribution of myocardial
damage within the heart can vary accord-
ing to the inciting agent and this can
be an aid to diagnosis. The degener-
ated muscle may also be present in
only the inner layers of the wall, leaving
the external layers with a normal
appearance.

Diseases of the heart

In coronary thrombosis infarction of a
large area of the wall may have occurred
but this is not visible unless the animal
survives for at least 24 hours afterwards.
Careful examination of the coronary
arteries is usually necessary to detect the
causative embolus. In horses infarction
occurs most commonly in the right atrium.

The terminal stage of myocardial
degeneration or myocarditis is often
fibrous tissue replacement of the damaged
tissue. The heart is flabby and thin-walled
and shows patches of shrunken, tough
fibrous tissue. Rupture of the atrial walls
may result, with sudden death occurring
as a result of the pressure of blood in the
pericardial sac. The lesions of lympho-
matosis are characteristic of this disease:
large, uneven masses of pale, firm,
undifferentiated tissue with the consistency
of lymphoid tissue.

Focal myocardial fibrosis, possibly
resulting from micro embolism from
strongyle-induced endarteritis, is common
in healthy horses but has also been
ascribed as the predisposing factor to
conduction disturbances such as atrial
fibrillation and heart block. 13

DIFFERENTIAL DIAGNOSIS

• Other cardiac causes of chronic
(congestive) heart failure and acute
heart failure

• Other causes of decreased exercise
tolerance

The diagnosis and differential diagnosis of
the specific etiology of myocardial disease
rests with the epidemiological and other
considerations of the individual causes and
may require specific bacteriological and
virological examinations, toxicological and
nutritional analyses or an examination of
the environment.

TREATMENT

The primary cause must be treated and
details are given under the individual
headings of the specific diseases listed
above. When possible, the primary cause
of the myocardial damage must be
corrected or treated, and details are given
elsewhere for the various etiologies listed
above. The treatment of conduction dis-
turbances, arrhythmias and heart failure
is given elsewhere in this chapter.

REVIEW LITERATURE

Van Vleet JF, Ferrans VJ. Myocardial diseases of
animals. Am J Pathol 1986; 124:98-178.

Van der Lugt JJ, Collett MG. Myocardial conditions of
domestic animals in southern Africa. J S AfrVet
Assoc 1988; 59:99-105.

REFERENCES

1. Baker JR, Ellis CE. Equine Vet J 1981; 123:43 & 47.

2. NoutYS et al. J Vet Intern Med 2003; 17:588.

3. King JM et al. J Am Vet Med Assoc 1982; 180:144.

4. Rogers PAM, Pbole DBR.Vet Rec 1978; 103:366.

5. MeeJF.IrVetJ 1990; 43:61.

6. Bradley R, Duffell SJ. J Comp Pathol 1982; 92:85.

7. Van Vleet JF et al. Am JVet Res 1977; 38:991.

8. Van Vleet JF, FerransVJ.Am J Pathol 1986; 124:98.

9. Fu jiiY et al. Bull Equine Res Inst 1983; 20:87.

10. Zust J et al.Vet Rec 1996; 139:391.

11. Marr CM. EquineVet Educ 1990; 2:18.

12. Preus M et al. J Clin Chem Clin Biochem 1989;
27:787.

13. Cranley JJ, McCullagh KC. Equine Vet J 1981;
13:35.

RUPTURE OF THE HEART AND
ACUTE CARDIOVASCULAR
ACCIDEN TS

Rupture of the heart occurs rarely in
animals. It is recorded in cattle where a
foreign body penetrating from the reticu-
lum perforates the ventricularwall, and in
the left atrium of horses as a consequence
of chronic fibrotic myocarditis. 1 Rupture
of the base of the aorta is not uncommon
in horses and has the same effect as cardiac
rupture. The pericardial sac immediately
fills with blood and the animal dies of
acute heart failure due to pericardial
tamponade. A similar cardiac tamponade
occurs when reticular foreign bodies
lacerate a coronary artery or when foals
suffer severe laceration of the epicardium
during a difficult parturition.

RUPTURE OF THE AORTA

When the aorta ruptures it may do so
through its wall just above the aortic
valves . The wall may have been weakened
previously by verminous arteritis asso-
ciated with migrating strongyles in horses
or onchocerciasis in cattle or by the
development of medionecrosis. Another
form of rupture occurs through the aortic
ring. Death occurs very suddenly; all cases
reported by one author affected stallions
and coincided with the time of breeding.
Cardiac tamponade may occur but the
common finding is a dissecting aneurysm
into the ventricular myocardium.

Rupture of the aortic arch and the
pulmonary artery near the ligamentum
arteriosum occurs occasionally in horses.
The resultant fistula between the aorta
and the pulmonary artery produces a
sudden onset of cardiac failure and respi-
ratory distress. Affected horses usually die
shortly after the onset of clinical signs but
can survive up to 8 days. The rupture is
predisposed by abnormalities in the vasa
vasorum of the vessels and may have a
familial occurrence. 2

Aortocardiac fistulas originating at
the right aortic sinus are recorded in a
series of older horses with sudden onset
acute distress and exercise intolerance. 3
Five of the seven horses had a characteristic
continuous murmur that was loudest at
the right fourth intercostal space. Fistulas
extended into the right ventricle or atrium
in six horses and the left ventricle in one.

Five had dissecting tracts in the septal
myocardium.

Rupture of the aorta is the usual cause
of death in calves with Marfan's syn-
drome. Some have dissecting aneurysms
of the aorta and pulmonary artery. Calves
with Marfan's syndrome are affected from
birth. They have a loud systolic murmur
over the base of the heart on the left side
in association with enlargement of the
aortic root. There are other phenotypic
abnormalities, including long thin limbs,
joint and tendon laxity, and ocular
abnormalities including dorsal displace-
ment of the lens and lens opacity. The
nature of the inheritance in cattle is
uncertain. 4

Cranial mesenteric artery aneurysms

have been reported in cattle less than
4 years of age secondary to inherited
defects in the wall of the celiac and cranial
mesenteric arteries. An autosomal domi-
nant mode of inheritance was suspected. 5
An aneurysm of the cranial mesenteric
artery was diagnosed in a cow with severe
abdominal pain and the presence of a
large pulsatile mass at the root of the
mesentery. 6

RUPTURE OF HEART VALVES

Sudden death, or sudden onset of acute
heart failure can also result from rupture
of components of the heart valves. Rup-
ture of the chordae tendineae of the mitral
valve occurs in horses both without
apparent predisposing lesions and as a
sequel to endocarditis and occurs in adult
horses as well as foals. 7-9 It is manifested
by sudden onset of acute heart failure in
horses apparently previously healthy or,
when a complication of a pre-existing
endocarditis, as a sudden onset compli-
cation of the disease or a cause of death.
The rupture may involve the chordae of
any of the cusps of the valve. 7 Rupture of
the pulmonary valve producing right
heart failure can also occur. 10

REFERENCES

1. Haaland MA, Davidson JP. Vet Clin North Am
1983; 78:1284.

2. Van der Linde-Sipman JS.Vet Pathol 1985; 22:51.

3. Marr CM et al.Vet Radiol Ultrasound 1998; 39:22.

4. Potter KA, BesserTE.Vet Pathol 1994; 31:501.

5. Schuiringa-Sybesma AM. Tijdschr Diergeeskd
1961; 86:1192.

6. Angelos JA et al. J Am Vet Med Assoc 1995;
207:623.

7. Marr CM et al.Vet Rec 1990; 127:376.

8. Ewart S et al. J Am Vet Med Assoc 1992; 200:961.

9. ReefVB. J Am Vet Med Assoc 1987; 191:329.

10. Reimer JM et al. J Am Vet Med Assoc 1991;
198:880.

COR PU LMO NALE

Cor pulmonale is the syndrome of right-
sided heart failure resulting from an
increase in right heart workload secondary
to increased pulmonary vascular resistance

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

and pulmonary hypertension. The most
documented cause of pulmonary hyper-
tension in livestock is alveolar hypoxia.
Acute alveolar hypoxia (lowered alveolar
Po 2 ) is a potent cause of pulmonary
hypertension in several species, but cattle
are especially reactive and this is the
cause of the syndrome of cor pulmonale
in cattle at high altitudes, bovine brisket
disease, which is described in more detail
elsewhere in this text.

An outbreak of cor pulmonale with
pulmonary vascular lesions similar to
those seen with high mountain disease
but occurring in calves not at altitude is
recorded; it was postulated but not
proved to be the result of the ingestion of
feed contaminated with the pyrrolizidine
alkaloid monocrotaline. 1

Pulmonary hypertension can also
result from partial destruction of the
pulmonary vascular bed and a reduction
in its total cross-sectional area. Pulmonary
thromboembolic disease can produce
right heart failure by this mechanism.
Chronic interstitial pneumonia and
emphysema may also induce cor pul-
monale by the same mechanism. 2

Chronic obstructive pneumonia, where
there is airway constriction and accumu-
lation of fluid in distal airways, may induce
pulmonary hypertension by a combina-
tion of chronic hypoxia and reduction of
the pulmonary vascular bed. 3 Mean pul-
monary artery pressures in calves
with respiratory disease was 42 mmHg,
compared to 22 mmHg in healthy age-
matched calves. Although pulmonary
hypertension and right heart hypertrophy
may occur in livestock with primary
pulmonary disease, clinical cardiac
insufficiency is usually minor, and right
heart failure rare. Nevertheless it can
occur and is a cause of congestive heart
failure in cattle. 4,5

In goats, cor pulmonale, with right
ventricular and right atrial hypertrophy
secondary to interstitial pneumonia, may
lead to atrial fibrillation , 6 and cor
pulmonale leading to atrial fibrillation has
also been recorded in horses. 7

In highly conditioned feedlot cattle,
increased intra-abdominal pressure result-
ing from excessive abdominal fat, fore-
stomach engorgement and recumbency
can lead to pulmonary hypoventilation,
with decreased alveolar Po 2 and sub-
sequent right heart failure, a syndrome
analogous to the Pickwickian syndrome
in humans. 8

Chronic severe elevations in pul-
monary venous pressure can lead to
constriction and hypertrophy of the
vascular smooth muscle of precapillary
vessels with resultant pulmonary hyper-
tension. An elevated left ventricular filling
pressure is perhaps the more common

cause and can set the stage for right heart
failure in the left heart failure situations.
The toxic principle in poisoning by Pimelea
spp. appears to act in part by constricting
the pulmonary venules producing pul-
monary hypertension, which contributes
to the clinical syndrome.

Persistent pulmonary hypertension
of the neonate (PPHN) is a common
problem in neonatal foals and calves,
particularly in calves derived from
somatic cell clone technology. Persistent
pulmonary hypertension is characterized
by persistent postnatal hypoxemia
secondary to failure to adapt to extra-
uterine life. An imbalance between
endogenous vasoconstrictors and vaso-
dilators is believed to play a major role in
the development and maintenance of
PPHN. An increase in plasma concen-
tration of endothelin-1 (a potent vaso-
constrictor) has been observed in neonatal
calves with PPHN, and the source of
endothelin-1 is thought to be the
placenta. 9 Many cloned calves have
abnormal placentation, characterized by a
reduction in the number of established
cotyledons that are enlarged and edema-
tous. Treatment is symptomatic, focusing
on intranasal oxygen administration
and maintaining the calf in sternal
recumbency.

REFERENCES

1. Pringle JK et al. J Am Vet Med Assoc 1991;
198:857.

2. Panter KE et al. Vet Hum Toxicol 1988; 30:318.

3. Nuytten J et al. Zentralbl Vet Med A 1985; 32:81.

4. Angel KL, Tyler JW. J Vet Intern Med 1992; 6:214.

5. JubbTF, Malmo J. Aust Vet J 1989; 66:257.

6. Gay CC, Richards WPC. AustVet J 1984; 60:274.

7. Gelberg HB et al. J Am Vet Med Assoc 1991;
198:679.

8. Alexander AF. In: Effects of poisonous plants on
livestock. New York: Academic Press, 1978:285.

9. Wilkins PA et al. J Vet Intern Med 2005; 19:594.

VALVULAR DISEASE AND
MURMURS

Etiology Valvular disease is acquired or
congenital. Endocarditis is the commonest
cause. Some murmurs are functional and
not indicative of disease
Epidemiology Functional murmurs are
common in the horse and vary with breed
and training. Little information is available
on the epidemiology of acquired valvular
disease

Clinical findings Murmur defined by
location, timing, character, intensity and
radiation. Possibly precordial thrill, cardiac
insufficiency and, in severe cases,
congestive heart failure
Clinical pathology Blood culture
echocardiography

ETIOLOGY

Acquired

° Endocarditis. Most common cause -
see following section
° Endocardiosis. Common only in pigs
® Rupture of the chordae tendineae,
either spontaneous or secondary to
endocarditis 1

* Laceration, detachment of aortic valve
leaflets, either spontaneous or
secondary to endocarditis
° Dilatation of the right atrioventricular
valve annulus, such as occurs in
brisket disease and secondary to some
myocardial disease; may result in
functional insufficiency of the valves.

Congenital

e Pulmonic valve stenosis
° Fenestration of the aortic and

pulmonic valves in horses. The cause
of the lesions is unknown, although
their presence in very young animals,
including newborn foals, suggests that
some may be congenital defects. The
importance of these lesions as causes
of valvular insufficiency is doubtful,
although they may cause valvular
murmurs if they are present close to
the attachments of the cusps
0 Blood cysts are common on the
atrioventricular valves of cattle. They
are lined with endothelium, can occur
congenitally 2 and their incidence and
size may increase with age. 3 They
have no clinical significance. Serous
cysts occur occasionally on the mitral
valve of cattle.

EPIDEMIOLOGY

There is limited information on the
epidemiology and the age-specific inci-
dence of valvular disease or murmurs in
large animals, although slaughter surveys
show a high prevalence of endocardial
lesions. Studies at clinical centers indicate
that valvular disease is often under-
diagnosed in both cattle and horses and
that its presence may not be detected in
more than 50% of cases. 4-6

Horses

Auscultatory surveys show a high
prevalence of murmurs with breed and
horse-use differences. Functional (phy-
siological) murmurs are particularly com-
mon in trained, fit racehorses. In a survey
of 545 clinically normal horses in England,
murmurs were heard in 68%, with a
higher prevalence in flat racing and
National Hunt horses than in compe-
tition and pleasure horses. 7 Murmurs
with the characteristics of functional
ejection murmurs were detected on
auscultation over the left hemithorax in
approximately 50% of horses and the
right side in 8%. Murmurs with the
characteristics of early diastolic functional

Diseases of the heart

425

murmurs were detected on the left side in
15% and on the right side in 13%.
Murmurs with the characteristics of
regurgitation at the mitral, tricuspid and
aortic valves were detected in 3.5, 9.2 and
2.2% of horses respectively.

An extensive abattoir survey 8 suggests
that valvular lesions may be more com-
mon in the horse than is clinically
appreciated. Approximately 25 % of horses
had lesions, the majority being nodular or
distorting lesions on the valves or chordae
tendineae of the left side and, in a signifi-
cant proportion, murmurs were detected
prior to slaughter. Chronic trauma of the
valve leaflets was considered an import-
ant initiating factor.

Cattle

A slaughter survey in cattle has reported
endocarditis in 5.2 hearts per 10 000
animals. 4

Pigs

In a slaughter survey of pathology in the
heart of pigs mitral valve endocardiosis
was observed in 63% of pigs and tricuspid
endocardiosis in 18% of pigs. 9 The
prevalence and severity increases with
age. These lesions can be associated with
prolapse of the mitral valve and jet impact
lesions. They have little significance in
growing pigs but the significance of
endocardiosis to clinical cardiac disease in
older sows needs examination.

Bacterial endocarditis in slaughter pigs
has been recorded with a prevalence of
3.1 per 10 000 animals. 10

PATHOGENESIS

The important clinical indications of
valvular disease are audible murmurs and
palpable precordial thrills. Murmurs may
occur at any phase of the cardiac cycle
and are caused by the vibrations of
turbulent flow of blood transmitted to the
surface of the chest. Vibrations of strong
intensity may also result in palpable
vibrations at the surface of the chest.

Generation of murmurs

Blood flow is normally laminar and
without turbulence. Turbulence in flow
may be produced by a sudden change in
the diameter of the vessel through which
the blood is flowing. Its occurrence is
directly related to the velocity of flow
and inversely related to blood viscosity.

Valve lesions

With murmurs associated with valvular
lesions the valve lesion produces a
sufficient change in stream bed diameter
to result in turbulent flow. The turbulence
may occur when the valves do not close
properly (regurgitation or insufficiency)
and blood is forced through atrioven-
tricular orifices during ventricular systole,
or through semilunar orifices during

ventricular diastole. Turbulence may also
occur when the valves do not open
completely (stenosis) and blood is forced
through a stenotic semilunar orifice
during ventricular systole or enters the
ventricle through a narrow atrioventricular
orifice during ventricular diastole.

The severity of the turbulence and
hence the murmur can be increased with
higher flow velocities such as occur with
exercise and by factors that decrease
blood viscosity such as anemia or
hypoproteinemia.

Acquired valvular disease usually results
in insufficiency of the affected valve and
less commonly both insufficiency and
stenosis. Congenital lesions more com-
monly result in stenosis of the valve.

Murmurs without valvular disease
A change in vessel diameter such as
occurs with dilatation of the aorta or
pulmonary artery can produce turbulence
and a murmur. A reduction in blood
viscosity contributes to the frequency of
murmurs occurring in anemic and hypo-
proteinemic states and hemic murmurs
are common in anemic cattle, particularly
over the pulmonic valve.

Functional murmurs

Turbulent flow may occur in the absence
of a change in stream bed diameter if a
certain critical velocity of flow is exceeded.
This is believed to be the cause of
functional or ejection murmurs that occur
commonly in horses and lactating dairy
cows during the rapid ejection phase even
at rest and especially following exercise.

Effects of valvular disease

Stenosis of the outflow valves results in
an increased pressure load on the heart
and compensatory hypertrophy (con-
centric hypertrophy). Insufficiency of the
semilunar valves or of the aortic or
pulmonic valve produces a volume load
on the heart and is followed by com-
pensatory dilatation and hypertrophy
(eccentric hypertrophy). If the valves on
the left side of the heart are affected,
especially the aortic valve, the changes in
ejection of the blood from the ventricle
produce changes in the character of
the peripheral pulse. Involvement of the
tricuspid valve will produce changes in
the jugular pulse.

Cardiac reserve

The presence of valvular lesions and
murmurs may mean little except that
some degree of cardiac reserve is lost.
This may be small in degree, and
moderate stenosis or incompetence can
be compensated and supported for long
periods. The importance of valvular lesions
that do not result in cardiac insufficiency
rests in their possible contribution to
disease in other organs by the liberation

of emboli, and the necessity for close
examination of the heart when’ they are
present.

The purpose for which the animal is
maintained also has some bearing on the
significance of a murmur. Valvular lesions
are of much greater importance in racing
animals than in those kept for breeding
purposes. The challenge to the clinician is
to determine the significance of a murmur
to the health and performance of the
horse and to the safety of the rider.

CLINICAL FINDINGS

Only the clinical findings referable to
valvular disease are discussed here. The
clinical findings in chronic (congestive)
heart failure, which may coexist, are
discussed elsewhere.

Technique of examination

Auscultation is the fundamental basis of
examination and a knowledge of the
optimum areas of auscultation and the
significance of the murmurs encountered
are essential. When a murmur is detected
it should be categorized according to its
timing and duration, intensity, location,
and character. There is room for improve-
ment in the correct identification of heart
murmurs, and specialist clinicians can
more accurately identify the likely site of
heart murmurs than other clinicians. 11

Timing

Timing allows a subdivision into systolic,
diastolic and continuous murmurs and
immediately shortens the list of possible
defects present. There is little problem in
differentiating systolic from diastolic
murmurs at slow heart rates because of
the temporal difference between the
length of the systolic and diastolic period.
However, where there is a murmur
present at fast heart rates this distinction
is less obvious and it is possible to
misclassify the period of the cycle in
which the murmur is occurring.

• Murmurs should be timed with
reference to the arterial pulse, which
occurs in early to mid-systole if a
proximal artery is examined

o A convenient artery is on the

posteriomedial aspect of the carpus
and radius in cattle and horses
® A less satisfactory alternative is timing
with the occurrence of the apex beat

• Timing by relation to the heart
sounds is unreliable as these are
frequently altered in character and at
fast heart rates a diastolic murmur
may be mistaken for a systolic one

« Systolic murmurs are associated
with stenosis of the outflow valves or
insufficiency of the atrioventricular
valves

® Diastolic murmurs are associated
with insufficiency of the outflow

126

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

valves or stenosis of the
atrioventricular valves
° A continuous murmur or one that
occurs during both systole and diastole
may be associated with both stenosis
and insufficiency of the same valve or
with multiple valvular lesions but more
commonly results from the turbulent
flow of blood from a high-pressure to
a low-pressure system with no
intervening valve, such as occurs with
a patent ductus arteriosus.

Duration

Duration during systole or diastole is
determined by a careful examination of
the murmur with relationship to the period
between the heart sounds. Systolic mur-
murs are further classified as early, late,
holo- or pansystolic according to their
occurrence and duration in the period
between the first and the second heart
sounds and diastolic murmurs as early
(occurring between S2 and S3), holo-
diastolic or presystolic (occurring between
the atrial fourth heart sound and SI).
Fhnsystolic and pandiastolic murmurs,
occurring throughout the systole or
diastole, have greater significance than
murmurs that occur, for example, only in
early systole and early diastole.

Intensity

Intensity or loudness of a murmur pro-
vides a guide to its significance. A system
of grading the intensity of murmurs that
has been found to be of clinical value is as
follows:

G Grade I. The faintest audible murmur.
Generally only detected after careful
auscultation by an experienced
clinician

n Grade II. A faint murmur that is
clearly heard after only a few seconds
auscultation

« Grade III. A murmur that is
immediately audible as soon as
auscultation begins and is heard over
a reasonably large area
■ Grade IV. An extremely loud murmur
accompanied by a precordial thrill.

The murmur becomes inaudible if the
stethoscope is held with only light
pressure on the chest
G Grade V. An extremely loud murmur
accompanied by a precordial thrill.

The murmur can still be heard when
the stethoscope is held with only light
pressure against the chest.

Grade I murmurs are not clinically
significant whereas grade IV and V
invariably are. The significance of grade II
and III murmurs varies according to their
cause. A system that grades on a six-grade
basis is also used and differs only in a
further subcategorization of moderately
loud and loud murmurs.

The presence of a precordial thrill is
determined by palpation over the point of
maximal intensity of the murmur and
palpation on the chest over other areas of
the heart. A precordial thrill indicates that
there is considerable energy generated by
the turbulent flow and defines the
intensity of the murmur in the top two
grades in both grading systems.

Location and radiation
Location and radiation of a murmur is
related to its areas of generation and
transmission. The point of maximum
intensity (PMI) is noted with reference to
the areas of maximum audibility of the
heart valves described earlier under
the heading of examination of heart
sounds. Low-intensity murmurs are
generally restricted to the auscultatory
area overlying their area of generation.
The auscultatory areas of the heart and of
the individual heart sounds have been
described earlier in the section on
arrhythmias. The vibrations associated
with very loud murmurs may be
transmitted to other auscultatory areas
but generally they are most intense near
the area of generation, as is any associ-
ated thrill. Murmurs and thrills can be
restricted to local areas and it is essential
to examine several auscultatory areas over
both sides of the heart.

Character

Character is determined by change in
intensity during the duration of a murmur
and is defined as crescendo, crescendo-
decrescendo, decrescendo or plateau.
Murmurs may also be described accord-
ing to their frequency characteristics by
terms such as blowing, honking, musical
and buzzing, but these interpretations are
very subjective and often not repeatable
between examiners. Blowing murmurs do
not have a major frequency peak of
harmonics and therefore do not have an
easily identifiable pitch. In contrast,
musical, honking and buzzing murmurs
have a primary frequency and associated
harmonics. Musical murmurs have a
higher fundamental frequency (pitch)
than honking or buzzing murmurs,
whereas honking murmurs are shorter in
duration than buzzing murmurs. 12

Interpretation

Following this examination the functional
defect producing the murmur and the
valve involved are determined from the
characteristics of timing and duration,
location and radiation, and also any
secondary effects that maybe present in
arterial or venous pulse characteristics.
The severity of the lesion is judged in part
on the intensity of the murmur but also
on the degree of cardiac insufficiency that
is present. As a rule all pansystolic mitral

and tricuspid murmurs, all holodiastolic
murmurs, all right-sided murmurs and all
murmurs with a palpable precordial thrill
should be considered pathological. The
cause of the lesion cannot be determined
from auscultation but may be determined
from the results of general clinical and
special pathological examinations and by
a knowledge and consideration of the
common causes of valvular disease that
involve the particular valve affected in the
animal species being examined.

Functional (innocent) murmurs
Murmurs not associated with cardiac
abnormality occur in all large- animal
species, but particularly the horse and the
lactating dairy cow. Those associated with
turbulence produced during periods
of high-velocity flow are often called
functional murmurs or flow murmurs;
those associated with turbulence resulting
from decreased viscosity and increased flow
are often called physiological murmurs.

Functional systolic ejection murmurs
are very common in young, fit horses and
occur occasionally in cattle, sheep and pigs.
In horses, they are heard best over the base
of the heart, usually on the left side over the
aortic valve region, in some horses on the
right side, but not usually on both sides in
the same horse. They are early to mid
systolic murmurs of low intensity (grade
1-3), and are crescendo decrescendo or
decrescendo in character. In horses they are
usually more audible at heart rates slightly
elevated above the resting rate. Occasion-
ally in horses, an ejection murmur is
audible over the pulmonary valve.

In cattle they are most common at the
base of the heart on the left side. A
systolic ejection murmur is very common
over the left anterior heart base in
lactating dairy cattle and this murmur is
thought to be due to turbulence at the
pulmonic valves. Auscultation of this
murmur requires placement of the
stethoscope directly over the pulmonic
valve; this murmur is usually not auscul-
table when the heart is auscultated at the
fourth to fifth intercostal space. Holo-
systolic murmurs (grade 1-3) are heard in
some calves in the first 2-3 weeks of life.
They are possibly associated with minor
deformation of the atrioventricular valves
by hematocysts at the edge of the valve
leaflets, which are common in young
calves.

An early diastolic murmur occurs in
horses, most commonly in young
Thoroughbreds and Standardbreds, and
is believed to be due to vibrations
associated with the rapid flow of blood
into the heart in early diastole. It is a soft
(grade 1-2), high-pitched, early diastolic
murmur. When heard over the apex area
it is probably a variation of the S3 sound.

Diseases of the heart

A presystolic murmur of grade 1-2
intensity and rumbling sound is occa-
sionally heard in horses and is probably a
component of the atrial fourth heart sound.

Recumbent cattle commonly have a
low intensity (grade 1-3) crescendo-
decrescendo systolic murmur that is
auscultated over the right side. It will dis-
appear when the animal stands. A similar
murmur occurs where there is ruminal
distension and bloat.

In newborn calves and foals a systolic
murmur is frequently audible over the
base of the heart and it is believed to be
due to a partial temporary patency of the
closing ductus arteriosus. In newborn pigs
a continuous murmur may be heard and
this is often replaced by an early systolic
murmur audible for the first week of life.

Insufficiency of the right atrioventricular
valve

Tricuspid valve insufficiency resulting
from endocarditis is the most common
acquired valvular lesion in cattle, pigs and
sheep. Insufficiency may also result from
dilatation of the valve annulus in chronic
anemia and with cor pulmonale in
conditions such as high altitude disease in
cattle. Tricuspid regurgitation can also
occur with general heart failure that
follows left-sided failure. Because of the
association with bacterial endocarditis,
tricuspid insufficiency in cattle, pigs and
sheep is usually indicative of significant
cardiac disease or the presence of marked
pulmonary hypertension. However, in
horses, the murmur of tricuspid insuf-
ficiency may be present with little
evidence of impaired performance. 7

There is a harsh holosystolic or
pansystolic plateau-type murmur most
audible over the tricuspid valve area.
Loud murmurs project dorsally and to the
cranial part of the thoracic cavity on both
right and left sides. The murmur is usually
accompanied by an exaggeration of the
systolic component of the jugular pulse.
Congestive heart failure, if it occurs, will
be manifest in the greater circulation.

Insufficiency of the left atrioventricular
valve

This is the second most common

acquired valvular disease in horses, cattle
and pigs. The insufficiency may result
from endocarditis or rupture of the mitral
valve chordae. 13-15 There is a loud harsh
holosystolic or pansystolic murmur that
is most intense in the mitral area. The
murmur transmits dorsally and in severe
cases may also be heard on the right side.
There is frequently marked accentuation
of the occurrence of the third heart sound,
which may be mistaken for the second
sound. A late systolic crescendo murmur
has also been associated with mitral
insufficiency. 16

The pulse characters are unchanged
until the stage of cardiac failure. Cases of
mitralinsufficiency may compensate at rest
and may be only evidenced by decreased
work tolerance. Failure, if it occurs, will be
initially associated with left ventricular
volume overload; however, in some cases
the retrograde flow of blood through the
mitral valve may lead to pulmonary hyper-
tension and the additional occurrence of
right-sided heart failure.

Acute-onset heart failure is usually
associated with rupture of the valve
chordae. 17 In the horse, mitral in-
sufficiency may predispose to atrial
fibrillation. 18

Insufficiency of the aortic valve
This is the most common acquired
valvular defect in horses. There is a loud
holodiastolic murmur, frequently
accompanied by a thrill caused by the
reflux of blood from the aorta into the left
ventricle during diastole. The murmur is
generally audible over the left cardiac area
and is most intense at the aortic valve
area and radiates to the apex. It may
modify the second heart sound or start
immediately following. The murmur may
be noisy or musical and the relative
intensity varies from horse to horse.
Frequently it is decrescendo in character
but other variations in its intensity occur.
Valvular insufficiency of a sufficient
degree to have functional significance is
accompanied by an arterial pulse of very
large amplitude and high systolic and low
diastolic blood pressures (water-hammer
pulse). The pulse wave may be great
enough to cause a visible pulse in small
vessels and even in capillaries. Rarely this
lesion is accompanied by a diastolic jugular
pulse due to transmission of the impact of
the reflex wave across the ventricular
septum to the right side of the heart.

Stenosis of the aortic valve
There is a harsh systolic murmur, most
audible high up over the base of the heart
on the left side and posteriorly. The
murmur replaces or modifies the first
heart sound and is often crescendo-
decrescendo in character. A systolic thrill
may be palpable over the base of the
heart and the cardiac impulse is increased

j as a result of ventricular hypertrophy. The

j stenosis has most functional significance
when the pulse is abnormal, with a small
amplitude rising slowly to a delayed peak
reflecting the diminished left ventricular
output. There may be signs of left-sided
heart failure and this lesion may also be

| associated with syncope.

I

I Stenosis and insufficiency of the

I pulmonary valve

l Acquired lesions of this valve are rare in
large animals. The auscultatory charac-

teristics are similar to those produced by
aortic valve lesions but there are no
abnormalities of the arterial pulse. Pul-
monary stenosis produces a distinct
murmur at the third intercostal space on
the left side of the chest 19 but some cases
of pulmonary stenosis in the horse have
no murmur. 15 Murmurs may also be
audible anterior to the aortic valve area on
the left side of the chest. Heart failure, if it
occurs, is right-sided.

Stenosis of the right or left
atrioventricular valves
Stenosis of either atrioventricular valve is
uncommon. There is a diastolic murmur
caused by passage of blood through a
stenosed valve during diastolic filling and
audible over the base of the heart on the
relevant side. The severity of the lesion
will govern the duration of the murmur
but there is likely to be a presystolic
accentuation due to atrial contraction.
Right atrioventricular valve stenosis may
be accompanied by accentuation of the
atrial component of the jugular pulse.
Some degree of mitral stenosis may occur
in acquired lesions that manifest primarily
as an insufficiency.

CLINICAL PATHOLOGY

Clinicopathological findings will reflect
the changes caused by the primary
disease and are significant only when
there is endocarditis. Two-dimensional
echocardiography, Doppler echocardio-
graphy and color flow Doppler echo-
cardiography are the most valuable
noninvasive methods for the examination
of valvular disease and allow a detection
of the defect, its nature and its severity. 20-24
Echocardiography may detect regurgitant
flow and flow through stenotic valves that
is not detected by auscultation.

NECROPSY FINDINGS

Care is needed when the heart is opened
to ensure that the valves can be viewed
properly from both upper and lower
aspects. Lesions of endocarditis may be
visible or there may be perforations,
distortion or thickening of the valves or
breakage of the chordae tendineae.
Endocardiosis in pigs is characterized by
accumulation of glycosaminoglycans and
hyaluronan and myofibroblast differen-
tiation of fibroblasts. 23

DIFFERENTIAL DIAGNOSIS

Murmurs must be differentiated from
pericardial and pleural friction sounds and
from murmurs due to congenital defects
with shunts.

TREATMENT

There is no specific treatment for valvular
disease. Methods for the treatment of

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

congestive heart failure and endocarditis
are discussed under those headings.

REVIEW LITERATURE

Fregin GF. Medical evaluation of the cardiovascular
system. Vet Clin North Am Equine Pract 1992;
8:329-346.

Patteson MW, Cripps PJ. A survey of cardiac
auscultatory findings in the horse. Equine Vet J
1993; 25:409-415.

Fhtteson M, Blissitt K. Evaluation of cardiac murmurs
in horses 1. Clinical examination. In Pract 1996;
18:367-373.

Blissitt K, Patterson M. Evaluation of cardiac murmurs
in horses 2. Echocardiography. In Pract 1996;
18:416-426.

ReefVB. Heart murmurs in horses: determining their
significance with echocardiography. Equine Vet J
Suppl 1996; 19:71-80.

REFERENCES

1. Ewart S et al. J Am Vet Med Assoc 1992; 200:961.

2. Kemler AG, Martin JE. Am J Vet Res 1972; 32:249.

3. MarcatoPS etal.Vet Pathol 1996; 33:14.

4. Roussel AJ, Kasari TR. Compend Contin Educ
Pract Vet 1989; 11:769.

5. Power HT, Rebhun WC. J Am Vet Med Assoc
1983; 182:806.

6. Ball MA, Weldon AD. Cornell Vet 1992; 82:301.

7. Fhtterson MW, Cripps PJ. J Equine Vet 1993;
25:409.

8. Else RW, Holmes JR. Equine Vet J 1972; 4:57.

9. Guarda F, Negro M. Dtsch Tierarztl Wochenschr
1989; 96:377.

10. Ichikawa T et al. J JpnVet Med Assoc 1991; 44:153.

11. Naylor JM et al. J Vet Intern 2001; Med 15 507.

12. Naylor JM et al. JVet Intern Med 2003; 17:332.

13. Holmes JR, Miller PJ. Equine Vet J 1984; 16:125.

14. Miller PJ, Holmes JR. Equine Vet J 1985; 17:181.

15. Maxton AD, ReefVB. Equine Vet J 1997; 29:394.

16. Patteson M, Blissitt K. In Pract 1996; 18:367.

17. Brown CM et al. J Am Vet Med Assoc 1983;
182:281.

18. ReefVB et al. Equine Vet J 1998; 30:18.

19. Nilsford L et al. Equine Vet J 1991; 23:479.

20. McGladdery AJ, Marr CM. Equine Vet Educ 1990;
2 : 11 .

21. ReefVB. Compend Contin Educ Pract Vbt 1990;
12:1312.

22. ReefVB. Vet Clin North Am Equine Pract 1991;
7:435.

23. Blissitt K, Fhtterson M. In Pract 1996; 18:416.

24. Blissitt KJ, Bonagura JD. EquineVetJ Suppl 1995;
19:82.

25. Castgnaro M et al. Res Vet 1997; Sci 62:121.

ENDOCARDITIS

Synopsis

tm

Etiology Bacterial, occasionally parasitic
infection

Epidemiology History of ill-thrift,
chronic illness, periodic milk drop, shifting
lameness

Clinical findings Type of murmur
depends on valves of species predilection.
Embolic nephritis, arthritis, tenosynovitis or
myocarditis

Clinical pathology Blood culture
Necropsy findings Valvular lesions,
often vegetative, maybe rupture of
chordae tendineae. Embolic lesions in
other organs

Diagnostic confirmation Murmur or
persistent tachycardia with evidence of
bacteremia, a positive blood culture. Can
be confirmed by echocardiography
Treatment Antimicrobial agents based on
culturing causative agent. Prolonged
therapy required. Case fatality uniformly
high in cases that have heart failure

ETIOLOGY

Most cases of endocarditis in farm
animals are caused by bacterial infection
but whether the infection gains entrance
by direct adhesion to undamaged endo-
thelium, or through minor discontinuities
of the valvular surfaces, or by hemato-
genous spread through the capillaries at
the base of the valve, is uncertain. A
number of different organisms have been
associated with this disease. The common
infectious causes of endocarditis in
animals are listed below.

Cattle 1 " 4

• Alpha-hemolytic streptococci

• Arcanobacterium (. Actinomyces or
Corynebacterium) pyogenes

9 Micrococcus and Staphylococcus spp.

° Pseudomonas spp.

° Clostridium chauvoei (blackleg)

® Mycoplasma mycoides
9 Erysipelothrix rhusiopathiae (insidiosa)
(rare).

Horses 3,5 " 7

0 Actinobacillus equuli
° Streptococcus spp., including

Streptococcus equi and Streptococcus
zooepidemicus

9 Pasteurella/Actinobacillus spp.

° Pseudomonas spp.

0 Migrating Strongylus spp. larvae.

Pigs and sheep 8,9

° Erysipelothrix rhusiopathiae (insidiosa)

° Streptococcus spp. including

Streptococcus equisimilis, Streptococcus
dysgalactia, Streptococcus suis
° Escherichia coli
° A. pyogenes.

EPIDEMIOLOGY

There is limited information on the
epidemiology of the endocarditis. (See
Epidemiology, valvular disease.)

Chronic bacteremia predisposes to
endocarditis. There may be a history of an
ongoing septic process such as mastitis,
metritis, foot abscess or traumatic reticular
peritonitis, or of a procedure, such as the
use of an indwelling intravenous catheter,
that might lead to bacteremia. Commonly
there is a history suggestive of low-grade
infection. In cattle, ill- thrift with periodic,
dramatic but temporary fall in milk
production is a common history. The
animals often have a lower body con-
dition than expected for their stage of

production and there is frequently a
history of intermittent lameness. 4 Horses
may present with similar suggestive
histories, including shifting leg lameness,
intermittent joint distension, coughing,
seizures, jugular vein thrombosis, colic,
diarrhea, poor growth and umbilical
infection. 6 In sows it is common for
agalactia to develop in the first 2-3 weeks
after farrowing, followed by a loss of weight,
intolerance to exercise and dyspnea at rest.

PATHOGENESIS

Endocarditis may arise from implantation
of bacteria onto the endocardium from
the bloodstream or by bacterial embolism
of the valve capillaries. Endocarditis is
predisposed by trauma to the endo-
thelial surface exposing collagen and
leading to binding of platelets, activation
of the extrinsic coagulation cascade with
deposition of fibrin and the formation of
sterile platelet-fibrin deposits.

Endothelial damage may occur along
the lines of closure of valves in association
with turbulent flow and also can occur for
the same reason on areas of the mural
endocardium. These areas are subse-
quently colonized by circulating bacteria
and the organisms grow in these areas
enmeshed in a tight, avascular network of
fibrin and platelets with further serial
deposition of platelets and fibrin. 10 This is
the mechanism of endocarditis that
occurs secondary to turbulent flow in
congenital heart disease and of that
produced by trauma such as cardiac
catheterization. Myocardial disease may
lead to edema of the valves, which may
also predispose to endothelial damage.

Endocarditis in large animals occurs
most commonly secondary to a chronic
infection at some distant site and a
persistent bacteremia without predis-
posing lesions in the heart. Certain
organisms have the ability to directly
adhere to endothelium and it is probable
that this is the major pathogenic factor.

The major clinical abnormalities
associated with endocarditis result from
the effect of endocarditis on heart
function and from the effects of embolic
showering of microorganisms, which can
lead to infarction or infection at other
sites in the body. The valvular lesions may
be vegetative in the early stages of the
disease or, more often, there may be
fibrosis and shrinking, distortion and
thickening of the valve cusps. Both
interfere with valve function, leading to
cardiac insufficiency and possibly cardiac
failure. The functional defect produced by
valvular endocarditis is usually, but not
invariably, valvular insufficiency. Infected
emboli most commonly produce pulmon-
ary embolism with miliary pulmonary
abscessation, or infection or abscesses in

Diseases of the pericardium

429

other organs, including myocardium,
kidneys and joints.

Valve predilection

In cattle, endocarditis occurs most com-
monly on the right atrioventricular
(tricuspid) valve. The left atrioventricular
(mitral) valve is the second valve of
predilection, and bilateral involvement
of the atrioventricular valves is not
uncommon. 1,4 In the horse the most
common site of infection is the aortic
valve, with the left and the right
atrioventricular valves being the second
and the third valve sites of predilection. 11
Endocarditis of the pulmonary valve is
uncommon, but is recorded. 6,12 The
atrioventricular valves are the predilection
sites in sheep and swine.

CLINICAL FINDINGS
Cardiac signs

The important finding is a murmur on
auscultation or a thrill on palpation of the
cardiac area. Details of the specific find-
ings for individual valve abnormalities
can be found in the preceding section on
valvular disease. A major problem with
diagnosis based on the presence of
murmurs is that they are not always
present or detected in cases of endo-
carditis, particularly with right sided
lesions. 1,4,13 Persistent tachycardia should
be regarded as the most consistent
clinical sign in endocarditis.

Embolism

Chronic bacteremia and embolic shower-
ing of microorganisms results in signs
referable to infection and infarction at
other sites in the body. There is a constant
moderate, fluctuating fever and secondary
involvement of other organs may cause
the appearance of signs of peripheral
lymphadenitis, embolic pneumonia,
nephritis, arthritis, tenosynovitis or
myocarditis. There is usually much loss of
condition, pallor of mucosae and an
increase in heart rate.

Clinical course

The clinical course in endocarditis may be
as long as several weeks or months, or
animals may drop dead without pre-
monitory signs. Endocarditis is also a
cause of acute heart failure and sudden
death in sows . 14 Because sows are con-
fined with minimal exercise during much
of the production cycle, the presence of
cardiac insufficiency from chronic
endocarditis can be masked and sows
with chronic endocarditis may have acute
heart failure and die at times of intense
exercise, such as mating or during
movement to other housing.

Rupture of the chordae tendineae

Rupture of the chordae tendineae of
the mitral valve in horses may be pre-

disposed by endocarditis 15 or may occur
spontaneously, 16,17 and occurs in both
adults 16,17 and foals. 18 It is manifested by
sudden onset of acute heart failure in
horses apparently previously healthy or,
when a complication of a pre-existing
endocarditis, as a sudden onset compli-
cation of the disease or a cause of death.
There are signs of acute left failure and
there is usually a prominent third heart
sound. 19 The rupture may involve the
chordae of any of the cusps of the valve. 17
Rupture of the medial cusp of the aortic
valve to produce acute left heart failure
and rupture of the pulmonary valve

producing right heart failure can also
20

occur.

Cardiography

Electrocardiographic findings sugges-
tive of endocarditis are sinus tachycardia
and decreased QRS amplitudes in a base-
apex lead; 21 ectopic foci may also be
present.

Echocardiographic findings suggestive
of endocarditis are hypoechoic and
echogenic masses, irregular thickening
of valves and rupture of the chordae
tendinae 6

CLINICAL PATHOLOGY

A nonregenerative anemia, leukocytosis,
neutrophilia, hyperfibrinogenemia and
hyperglobulinemia are common but not
specific for endocarditis. In chronic cases,
where the lesions are due largely to
scarring of the valves, hematological
findings may be normal. Hypergam-
maglobulinemia is the most common and
consistent finding and an indication of
chronic bacterial infection. V\Tiere there is
passive hepatic congestion there may be
an increase in serum alkaline phos-
phatase and gamma-glutamyltransferase
activity. Repeated examination of the
urine may reveal transient episodes of
proteinuria and the shedding of bacteria
associated with renal embolization and
infarction.

Blood cultures should be attempted.
The avoidance of skin contamination is
important and the site should be
adequately prepared by initial skin
cleansing with 70% alcohol followed by
1% povidone-iodine applied in a circular
pattern around the intended vene-
puncture site. A contact time of at least
2 minutes should be allowed before
obtaining blood for culturing. 10 The ratio
of blood to broth culture medium should
be 1:10-1:20, and the broth should be
incubated at 37°C for 24 hours before
being examined for the presence of
turbidity and plated on to traditional
blood agar plates. Blood culture is fre-
quently negative and it is recommended
that three samples be obtained from
separate venepuncture sites during a

1-hour period. 10 Sampling at the start
of a fever is preferred but clearly imposs-
ible; however in animals with a more
constant bacteremia, repeat culturing
without regard to fever is successful. 2,11
Determination of the susceptibility of the
organism to antimicrobial agents may aid
in treatment.

NECROPSY FINDINGS

The lesions are termed vegetative when
they are large and cauliflower-like and
verrucose when they are small and wart-
like. The former are present on the valves
in most fatal cases. In the later stages the
valves are shrunken, distorted and often
thickened along the edges. This stage of
recovery is rare in farm animals but may
be observed in the semilunar valves in
horses. Spontaneous healing is rare and
in most cases treatment is commenced at
too late a stage.

Embolic lesions may be present in any
other organ. Culture of the valvular
lesions should be undertaken but in
many cases no growth is obtained. The
examination of direct smears should
always be undertaken.

DIFFERENTIAL DIAGNOSIS

• Pericarditis

• Brisket disease (cattle)

• Cardiac lymphosarcoma

TREATMENT

Treatment is not highly successful
because of the difficulty in controlling the
infection. The thickness of the lesions
prevents adequate penetration of anti-
microbial agents and unless the suscep-
tibility of the causative organism is
known a range of antibacterial drugs may
have to be tried. For this reason there
should be repeated attempts at blood
culture until the causative organism is
cultured in order to allow drug selection
on the basis of susceptibility testing. The
choice of antimicrobial agent should be
one that allows high concentrations in
serum relative to the minimal bactericidal
concentration, that has minimal side
effects over a prolonged period of admin-
istration and has a prolonged half-life. 12

In the absence of a positive culture the
types of organism commonly isolated in
cattle suggest the use of penicillin,
possibly combined with gentamicin or the
use of a potentiated sulfonamide. 3,13 The
variety of causative organisms in horses
recommends the use of broad-spectrum
antibacterial treatment.

Duration of treatment needs to be
prolonged. It is difficult to judge the
duration of therapy required. A fall in
temperature can be taken as an indication
that infection is being brought under

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

control, but treatment needs to be
continued if there is to be success in
therapy. 3,10 ' 14,15 A period of continual
treatment for 4 months with periodic
treatment continuing for 14 months in a
cow has been recorded. 2

Relapse is common. Treatment is
expensive and in food animals must be
extra-label and is probably uneconomic
except for particularly valuable animals.
Consequently the treatment of endo-
carditis should be approached with
reservation. Case fatality is high if signs
of congestive heart failure are present.

The sequel of embolic lesions in other
organs and permanent distortion of
valves resulting in valvular insufficiency
also militate against a satisfactory out-
come. The use of parenteral anti-
coagulants, as used in humans to prevent
further deposition of material on vegeta-
tive lesions and to limit embolic disease,
has questionable value 21 and requires
monitoring that is not usually available in
veterinary practice.

REVIEW LITERATURE

Evans ET. Bacterial endocarditis of cattle. Vet Rec 1957;
69:1190.

Kasari TR, Rousell AJ. Bacterial endocarditis. Part I.
Pathophysiologic, diagnostic and therapeutic
considerations. Compend Contin Educ Pract Vet
1989; 11:655-671.

Kasari TR, Rousell AJ. Bacterial endocarditis in large
animals. Phrt II. Incidence, causes, clinical signs,
and pathologic findings. Compend Contin Educ
PractVet 1989; 11:769-774.

Fregin GF. Medical evaluation of the cardiovascular
system. Vet Clin North Am Equine Pract 1992;
8:329-346.

Dowling PM, Tyler JW. Diagnosis and treatment of
bacterial endocarditis in cattle. J Am Vet Med
Assoc 1994; 204:1013-1016.

REFERENCES

1. Roussel AJ, Kasari TR. Compend Contin Educ
PractVet 1989; 11:769.

2. Tyler JW etal. JAmVetMed Assoc 1991; 198:1410.

3. Brown CM. Vet Clin NorthAm Equine Pract 1985;
2:371 .

4. Evans ET.Vet Rec 1957; 69:1190.

5. Bucrgellt CD et al. Vet Pathol 1985; 22:333.

6. Maxson AD, RecfVB. Equine Vet J 1997; 29:394.

7. Travers CW et al. J S AfrVet Assoc 1995; 66:172.

8. Ichikawa Tetal.JJpn Vet Med Assoc 1991; 44:153.

9. Katsumi M et al. J Jpn Vet Med Assoc 1998;
60:129.

10. Kasari TR, Roussel AJ. Compend Contin Educ
Pract Vfet 1989; 11:655.

11. Hillyer MH et al. Equine Vet Educ 1990; 2:5.

12. Nillsford L et al. Equine Vet J 1991; 23:479.

13. Power HT, Rebhun WC. J Am Vet Med Assoc
1983; 182:806.

14. Drolet R et al. CanVetJ 1992; 33:325.

15. Ewart S et al. J Am Vet Med Assoc 1992; 200:961.

16. Brown CM et al. J Am Vbt Med Assoc 1983;
182:281.

17. Marr CM et al.Vet Rec 1990; 127:376.

18. ReefVB. J Am Vet Med Assoc 1987; 191:329.

19. Holmes JR, Miller PJ. Equine Vet J 1984; 16:125.

20. Reimer JM et al. J Am Vet Med Assoc 1991;
198:880.

21 . Constable P. J Am Vet Med Assoc 1991; 199:299.

Diseases of the pericardium

PERICARDITIS

Etiology Traumatic, extension from other
infection, as component of infections
causing polyserositis, or idiopathic
Epidemiology Poorly defined other than
for traumatic pericarditis in cattle
Clinical findings Friction sound initially,
followed by muffling of the heart sounds,
venous congestion, decreased pulse
pressure and congestive heart failure
Clinical pathology Pericardiocentesis,
echocardiography, radiography
Necropsy findings Inflammation, fibrin
and fluid, in pericardial sac. Fibrous
pericarditis

Diagnostic confirmation Triad of
muffling of the heart sounds, venous
congestion, decreased pulse pressure.
Pericardiocentesis, echocardiography
Treatment Antimicrobials and drainage.
Poor prognosis and supportive treatment

ETIOLOGY

Pericarditis is not common but presents in
three general forms; effusive, fibrinous
and constrictive, although combinations
of one or more of the three forms can
occur. Effusive pericarditis is charac-
terized by the accumulation of a protein-
rich fluid within the pericardial sac.
Subsequent fibrin deposition can lead to
fibrinous pericarditis, and if fibrin
within the pericardial sac matures to
fibrous tissue and fibrosis of the peri-
cardium or epicardium then constrictive
pericarditis will result. 1 Traumatic
pericarditis, perforation of the pericar-
dial sac by an infected foreign body,
occurs commonly only in cattle. Traumatic
pericarditis is also recorded in the horse 2
and in a lamb. 3 Localization of a blood-
borne infection occurs sporadically in
many diseases. Direct extension of infec-
tion from pleurisy or myocarditis may also
occur in all animals but the clinical signs
of pericarditis in such cases are usually
dominated by those of the primary
disease.

In most cases of pericarditis in horses
no causative agent is isolated. 1 There is
commonly a history of upper or lower
respiratory tract disease. Most cases are
fibrinous or septic 4,5 but an effusive non-
septic form is also described and has been
j called idiopathic effusive pericarditis . 6
| Pericarditis in horses occurs predominantly
j in adults. Idiopathic effusive pericarditis
| has been diagnosed in two dairy cows. 7

Cattle

° Mannheimia hemolytica
c Black disease - if patients survive
more than 24 hours

° Sporadic bovine encephalomyelitis
° Haemophilus spp., including
Histophilus somni
° Tuberculosis
° Pseudomonas aeruginosa
• Mycoplasma spp.

° Klebsiella pneumoniae
° Actinobacillus suis
° Idiopathic effusive (nonseptic)
pericarditis.

Horses

° Streptococcus spp., including S. equi,

S. zooepidemicus and S. faecalis
° Tuberculosis

° Corynebacterium pseudotuberculosis
° Actinobacillus equuli
° In association with EHV-1 infection
° Idiopathic effusive (nonseptic)
pericarditis.

Sheep and goats

° Pasteurellosis
° Staphylococcus aureus
° Mycoplasma spp.

Pigs

° Pasteurellosis
° Mycoplasma spp. especially
Mycoplasma hyorhinis
° Haemophilus spp. - Glasser's disease
and pleuropneumonia
0 Streptococcus spp.

° Salmonellosis.

PATHOGENESIS

In the early stages, inflammation of the
pericardium is accompanied by hyperemia
and the deposition of fibrinous exudate,
which produces a friction sound when the
pericardium and epicardium rub together
during cardiac movement. As effusion
develops the inflamed surfaces are
separated, the friction sound is replaced
by muffling of the heart sounds, and the
accumulated fluid compresses the atria
and right ventricle, preventing their
complete filling. Congestive heart failure
follows. A severe toxemia is usually present
in suppurative pericarditis because of the
toxins produced by the bacteria in the
pericardial sac. Gas will occur along with
fluid in the sac if gas-producing bacteria
are present. If sufficient gas is present, the
classical washing machine sound of fluid
splashing with each heart beat will be
auscultated. This is not as commonly
heard in clinical cases as muffling of the
heart sounds.

In the recovery stage of nonsuppu-
rative pericarditis the fluid is reabsorbed
and adhesions form between the
pericardium and epicardium to cause an
adhesive pericarditis, but the adhesions
are usually not sufficiently strong to
impair cardiac movement.

In suppurative pericarditis the ad-
hesions that form become organized,
starting on day 4-6, 8 and may cause

Diseases of the pericardium

complete attachment of the pericardium
to the epicardium, or this may occur only
in patches to leave some loculi which are
filled with serous fluid. 6 In either case
restriction of cardiac movement will
probably be followed by the appearance
of congestive heart failure.

CLINICAL FINDINGS

In the early stages there is pain, avoid-
ance of movement, abduction of the
elbows, arching of the back and shallow,
abdominal respiration. Pain is evidenced
on percussion or firm palpation over the
cardiac area of the chest wall, and the
animal lies down carefully. A pericardial
friction sound is detectable on auscul-
tation of the cardiac area. The tempera-
ture is elevated to 39.5-41°C (103-106°F)
and the pulse rate is increased. Associated
signs of pleuritis, pneumonia and peritonitis
may be present.

In most cases of pericarditis caused by
traumatic reticuloperitonitis, hemato-
genous infection or spread from pleuritis,
the second stage of effusion is manifested
by muffling of the heart sounds, decreased
palpability of the apex beat and an
increase in the area of cardiac dullness
with decreased amplitude of the periph-
eral pulse. If gas is present in the
pericardial sac each cardiac cycle may be
accompanied by splashing sounds. Signs
of congestive heart failure become
evident. Fever is present, the heart rate is
markedly increased and toxemia is severe,
although this varies with the types of
bacteria present. This is the most
dangerous period and affected animals
usually die of congestive heart failure, or
of toxemia, in 1-3 weeks 9 ^ n Those that
survive pass through a long period of
chronic ill health during which the
toxemia subsides relatively quickly but
congestive heart failure diminishes
slowly. In this stage of chronic pericarditis
additional signs of myocarditis, particu-
larly irregularity, may appear. The heart
sounds become less muffled and fluid
sounds disappear altogether or persist in
restricted areas. Complete recovery is not
common.

In the horse, both the idiopathic
effusive and the septic forms of peri-
carditis present with marked muffling of
the heart sounds, tachycardia, distension
of the jugular veins and subcutaneous
edema of the ventral body wall. 4,12 A
nonseptic pleural effusion is also com-
monly present in cases of septic pericarditis
in the horse 9,13 but not in idiopathic
effusive pericarditis. 14

CLINICAL PATHOLOGY

A marked leukocytosis and neutrophilia,
as well as hyperglobulinemia, are usually
present in traumatic pericarditis because
this has many of the characteristics of a

large internal abscess. In the other forms
of pericarditis changes in the blood
depend upon the other lesions present
and on the causative agent. In the stage in
which effusion occurs a sample of fluid
may be aspirated from the pericardial
sac and submitted for bacteriological
examination. The technique is not with-
out danger, as infection may be spread to
the pleural cavity.

Pericardial fluid can also be examined
cytologically but usually the smell
(reminiscent of retained placenta and
toxic metritis in cattle) is sufficiently
diagnostic in cattle with traumatic peri-
carditis. In septic pericarditis the fluid
represents an inflammatory response,
whereas in idiopathic effusive pleuritis in
horses there are very few cells in the
sediment. 12,15 Mean right ventricular dias-
tolic and intrapericardial fluid pressures are
increased in a corresponding manner in
cows with clinical signs of right-sided
heart failure. 10 Cattle with muffled heart
sounds and a large pericardial fluid
volume also have a decrease in cardiac
output to approximately two-thirds of
normal values. 10

Electrocardiography can aid in diag-
nosis. Electrocardiographic changes
include sinus tachycardia and, in animals
with right-sided heart failure and
hydrothorax, diminished amplitude of the
QRS complex. 10 Contrary to popular
belief, hydropericardium in the absence of
hydrothorax leads to an increase, and not
a decrease, in QRS amplitude. Moreover,
removal of large volumes of pericardial
fluid does not usually result in an
immediate change in QRS amplitude. Also
contrary to popular belief, electrical
altemans is not commonly present in dogs
and humans with pericardial effusion and if
present, occurs only within a narrow range
of heart rates. The prevalence of electrical
altemans is unknown in large animals with
pericardial effusion but is suspected to be
extremely low because the pericardium and
heart are much more fixed in position
within the thorax.

Radiography may be of diagnostic
value, with six of seven cows having a
gas-fluid interface present on standing
lateral thoracic radiographs. 16 Radio-
graphy has the additional benefit of
potentially identifying the location of the
penetrating wire; this information would
assist surgical removal of the wire via a
rumenotomy. Radiography may also aid
in the clinical differentiation of pericardial
effusion from pleural effusion.

Echocardiography is the most valuable
diagnostic procedure and will show the
presence of fluid in the pericardial
sac. Echocardiography usually permits
differentiation of effusive and fibrinous
pericarditis. 5,7,9,14

NECROPSY FINDINGS

In the early stages there is hyperemia of
the pericardial lining and a deposit of
fibrin. When effusion occurs there is an
accumulation of turbid fluid and tags of
fibrin are present on the greatly thickened
epicardium and pericardium. Gas may
also be present and the fluid may have a
putrid odor. When the pericarditis has
reached a chronic stage the pericardium is
adherent to the epicardium over a greater
or lesser part of the cardiac surface. 6
Loculi containing serous fluid often
remain. Embolic abscesses may be pre-
sent in other organs. Lesions typical of
the specific causative diseases listed
above are described under their specific
headings.

DIFFERENTIAL DIAGNOSIS

• Pleuritis

• Cardiac valvular disease

• Mediastinal abscess 15

• Hydropericardium occurs in congestive
heart failure, mulberry heart disease of
pigs, herztod of pigs, gossypol
poisoning, clostridial intoxications of
sheep and lymphomatosis

TREATMENT

Antibacterial treatment of the specific
infection should be undertaken if possible
on the basis of susceptibility on organisms
cultured from the pericardial fluid. Where
the inciting agent cannot be grown a
broad-spectrum antibiotic or a combi-
nation to give a broad spectrum is used. A
combination of penicillin and gentamicin
is common and provides cover of the
likely organisms associated with this
infection. Pericardiocentesis, copious
lavage with warmed 0.9% NaCl solution,
and drainage should be conducted as
required to relieve the fluid pressure in
the pericardial sac, decrease the trans-
mural pressure gradient across the atrial
and ventricular walls and caudal and
cranial vena cava, and thereby facilitate
diastolic filling. Pericardiocentesis should
be performed under ultrasonographic
guidance and with electrocardiographic
monitoring.

The prognosis varies with the
etiological agent but it is generally grave
in cases of septic pericarditis in horses 4,5
mainly because the stage of effusion is
followed by one of fibrosis and constric-
tive pericarditis. 17 Success in treatment of
a series of six cases of septic pericarditis in
the horse is recorded with the use of
indwelling pericardial drains to allow
twice-daily lavage and drainage and the
instillation of antibiotics directly into the
pericardial sac. This allows high concen-
trations of antimicrobial agents and the
twice-daily infusion of 1-2 L of fluid may

132

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

help prevent the development of constric-
tive pericarditis. In cattle thoracotomy
and pericardiotomy are used to establish
drainage or to allow marsupialization of
the pericardium to the body wall. 18 Low
treatment success rates are generally
reported for the disease in cattle with or
without surgical drainage, 16 - 19 and it is
likely that cases that responded to fifth rib
resection and pericardial marsupialization
would have responded to pericardial
drainage and intrapericardial lavage and
antimicrobial administration.

There is a more favorable prognosis for
the treatment of idiopathic effusive
pericarditis in horses and cattle with
aggressive therapy and the use of
pericardiocentesis, pericardial lavage and
corticosteroid or NSAIDs is an effective
therapy. 7,12 ' 14

REFERENCES

1. Perkins SL et a!. J Am Vet Med Assoc 2004;
224:1133.

2. Bertone JJ et al. J Am Vet Med Assoc 1985;
187:742.

3. Abo-Shekada MN et al. Br Vet J 1991; 147:78.

4. Dill SG et al. J Am Vet Med Assoc 1982; 180:266.

5. Buergelt CD et al. Compend Contin Educ Pract
Vet 1990; 12:872.

6. Roth L, King JM. J Vet Diagn Invest 1991; 3:52.

7. Jesty SA et al. J Am Vet Med Assoc 2005; 226:1555.

8. Leak LV et al. Am J Anat 1987; 180:373.

9. Bernard W et al. J Am Vet Med Assoc 1990;
196:468.

10. Fisher EW, Pirie HM. Br Vet J 1965; 121:552.

11. Holmes JR. Vet Rec 1960; 72:355.

12. FreestanceJF. Equine Vet J 1987; 19:38.

13. Bennett DG. J Am Vet Med Assoc 1986; 188:814.

14. Worth LT, Reef VB. J Am Vet Med Assoc 1998;
212:248.

15. Smith BP. J Am Vet Med Assoc 1977; 170:208.

16. Ducharme NG et al. J Am Vet Med Assoc 1992;
200 : 86 .

17. HardyJ et al. EquineVet J 1992; 24:151.

18. Rings DM. Vet Clin North Am Food Anim Pract
1995; 11:177.

19. Bemand W et al. J Am Vet Med Assoc 1990;
196:468.

CONGENITAL CARDIAC DEFECTS

Etiology Abnormality in heart or vascular
structure results in anomalous blood
circulation. Cause of congenital defects
unknown, some may be heritable
Epidemiology Sporadic occurrence.
Usually present with cardiac failure shortly
after birth but some defects compatible
with life and detected incidentally
Clinical and necropsy findings
Specific for individual defects
Clinical pathology Echocardiography
most useful diagnostic aid
Diagnostic confirmation
Echocardiography and postmortem
examination

Treatment Surgery for some

ETIOLOGY

An increasing number of clinical reports
on congential cardiovascular defects are
appearing in the veterinary literature.
However, their general importance is low.

The cause of congenital cardiac defects
is unknown, but it is assumed they result
from injury during development or from
single recessive genes or polygenic sets
that have lesion-specific effects on cardiac
development. 1 Ventricular septal defects
have been observed in twin cattle. 2
Heritable ventricular septal defect is
recorded in miniature pigs 3 and suspected
in cattle. 4

EPIDEMIOLOGY

Congenital cardiac anomalies occur in all
species but are not common in any one of
them. The prevalence is probably highest
in cattle and lowest in horses. 3

Cattle

The relative frequency of individual
cardiac defects in 36 calves at postmortem
examination in one study 5 was:

Ventricular septal defect - 14%

Ectopic heart - 13%

Right ventricular hypoplasia - 13%

Left ventricular hypoplasia - 13%
Dextroposed aorta - 10%

Valvular hematomas - 9%

Patent ductus arteriosus - 6%

Patent foramen ovale - 6%

Endocardial fibroelastosis - 4%

Common aortic trunk - 4%

Other cardiac defects - 10%.

The animals were neonatal calves and the
relative frequencies are biased towards
defects that are incompatible with longer
life. In general, ventricular septal defect is
the most common cardiac defect in cattle.

Sheep

In a large series of necropsy examinations
on lambs, 6 1.3% had cardiac anomalies,
of which approximately 90% were ven-
tricular septal defects.

Pigs

The relative frequency of congenital
cardiac malformations in pigs 7 has been
reported as:

Dysplasia of the tricuspid valve - 34%
Atrial septal defect - 25%

Subaortic stenosis - 18%

Ventricular septal defect - 9%

Persistent common atrioventricular
canal - 9%

Other defects - 10%.

Horses

A review of 82 publications on congenital
cardiac defects in horses showed the
following prevalence in the total cases: 8

Ventricular septal defect - 28%

Tetralogy of Fallot - 16%

Truncus arteriosus - 8.5%

Aortic, pulmonary or mitral valve
abnormalities - 13.2%

Tricuspid atresia - 14.6%

Abnormality of the aorta - 4.8%

Patent ductus arteriosis - 3.7%

Atrial septal defects - 1.2%.

Other lesions account for the remainder.

PATHOGENESIS

Congenital cardiac defects may result in a
pressure load or a volume (flow) load in
one or more chambers of the heart. In
general the left ventricle can tolerate a
pressure load better than the right
ventricle and the right ventricle can
tolerate a volume load better than the left
ventricle. The heart may compensate for
the increase in load with minor loss in
cardiac reserve or the defects may lead to
cardiac failure.

Shunts

The mixing of oxygenated and venous
blood due to the presence of an anatomic
abnormality that allows a shunt of blood
from the pulmonary circulation to the
systemic circulation in the face of high
pulmonary vascular resistance is an
important factor in the pathogenesis of
the clinical signs of some congenital
cardiac defects. The resulting anoxic
anoxia causes severe dyspnea, and
cyanosis may be marked if the right-to-
left shunt is large. There is a notable
absence of fever and toxemia if inter-
current disease does not develop. Cardiac
enlargement is usually detectable if the
animal survives past the first week of life.

Age at manifestation

Animals with some congenital cardiac
defects can survive to maturity and be
productive and perform adequately. Acute
heart failure or chronic (congestive) heart
failure may occur when the animals are
subjected to a physical stress such as the
first pregnancy or activity on the range.
The primary appearance of signs of
cardiac disease when an animal is
2-3 years of age should not eliminate
congenital defects from consideration.

CLINICAL FINDINGS

A general description of the more common
defects is given below. Some of the defects
described in this section are actually defects
of the vascular system but are described
here for convenience. Diagnosis can be
confirmed by the detection of a pressure
differential across valves, the detection of
shunts by dye dilution and serial blood
gas analysis, and by angiocardiography.
Echocardiography has developed as an
important aid to diagnosis. 9

Ectopic heart

An abnormal position of the heart outside
the thoracic cavity is most common in

Diseases of the blood vessels

433

cattle, the displacement usually being to
the lower cervical region. The heart is
easily seen and palpated and there is an
accompanying divergence of the first ribs
and a ventrodorsal compression of the
sternum, giving the appearance of
absence of the brisket. Affected animals
may survive for periods of years, as they
also may with an abdominal displace-
ment, but those with a displacement
through a defective sternum or ribs rarely
survive for more than a few days.

Patent foramen ovale

This defect of the atrial septum is
reasonably common in cattle, usually
causes no clinical signs if present as an
isolated defect and is detected inciden-
tally at necropsy. Ostium secundum
defects are also common in cattle. 10 Large
defects may allow a shunt in both
directions. Relative resistance to outflow
from the atria is greater in the left than
the right and the shunt, if it occurs, is
from left to right. This induces a moderate
flow load on the right side of the heart,
which is well tolerated. Large flows will
generally increase pulmonary vascular
resistance and result in moderate right
ventricular and right atrial hypertrophy.
The increase in outflow resistance from
the right atrium results in a decreased
flow across the shunt and control of the
effects of the defect. Atrial septal defects
are of much greater significance when
they are present with other cardiac
defects and it is extremely rare for an
atrial septal defect alone to cause clinical
signs of circulatory failure. If these result
in a severe right ventricular hypertrophy
the shunt may reverse from right to left
and cyanosis will occur.

Ventricular septal defects

These are one of the most common con-
genital cardiac defects in sheep, cattle and
horses. They are almost invariably subaortic
defects occurring high in the septum at
the pars membranaceae. In the absence of
other defects their presence results in the
shunting of blood from the left to the
right ventricle, producing a volume load
on the left ventricle and left atrium. 11

On auscultation there is a loud blowing
pansystolic murmur audible over both sides
of the chest. It is usually audible over a large
area on both sides but most intense at the
left fourth intercostal and the right third
intercostal space and more intense on the
right than the left side. The murmur in this
defect is one of the loudest and most
obvious murmurs encountered. It does
not modify the heart sounds, which are
usually increased in intensity. A precordial
thrill is frequently palpable on both the
left and the right side.

The outcome is determined by the
magnitude of the shunt and the degree of

resistance to flow from the right ventricle as
determined by pulmonary vascular resist-
ance. With large defects the shunt of blood
can be considerable and the animal may die
at birth or show clinical signs at a few
weeks to a few months of age. The major
presenting signs during this period are of
left-sided heart failure with lassitude, failure
to grow well and dyspnea with moderate
exercise. The shunt may be less severe and
allow an apparently normal existence until
maturity, when left-sided or right-sided
failure can occur, or cause no apparent
problem during life and be detected
incidentally on necropsy or abattoir
examination. Horses with this defect have
raced successfully^and dairy cows have
had many productive lactations.

Complications

An increase in pulmonary vascular
resistance occurs as the result of increased
pulmonary blood flow. In cattle, this
increase maybe sufficient to cause reversal
of the shunt, and cyanosis develops. This
syndrome, sometimes referred to as an
Eisenmenger complex , 1213 develops in
young calves but also in mature animals
between 1 and 3 years of age and should
always be suspected where there is a
sudden onset of cyanosis and exercise
intolerance in an animal of this age.

The turbulence associated with flow
across the defect may produce secondary
changes in the valves located close to the
defect, which may complicate the clinical
picture. Cattle are prone to develop
endocarditis in the region of the septal
cusp of the right atrioventricular valve. In
horses, endocarditis more commonly
involves the medial cusp of the aortic
valve.

Other complications are prolapse of
the cusps into the septal defect due to
lack of aortic root support with the
development of aortic regurgitation . 11,14
Rupture of the valve may occur to pro-
duce a severe additional flow load on the
left ventricle, with rapid onset of acute left
heart failure and death.

Ventricular septal defects may occur in
association with other congenital cardiac
or vascular defects, and the clinical find-
ings are varied. 11,15,16

Prognosis

There is no practical correction for ven-
tricular septal defects in large animals. It
should be emphasized that small defects
can produce dramatic auscultatory
findings and, unless signs of cardiac
insufficiency are present, care should be
taken in giving an unfavorable prognosis
in pleasure or breeding animals. Pleasure
animals with this defect should never be
ridden but it is possible for them to live a
reasonable lifespan and to breed. Pood
animals can be sent for early slaughter.

There is insufficient information on the
advisability of breeding animals that have
this defect. An inheritable predisposition
has been suspected in Hereford cattle, 4
and chromosomal abnormalities have
been demonstrated in association with
this defect in cattle. 1 Ventricular septal
defects have high prevalence in calves
and lambs with microphthalmia.

Tetralogy of Fallot

This is almost always a lethal defect in
farm animals. The tetralogy consists of
three primary abnormalities (ventri-
cular septal defect, pulmonary stenosis,
and dextral position of the aorta so that it
overrides both ventricles) and secondary
right ventricular hypertrophy. The
marked increase in resistance to outflow
into the pulmonary artery results in a
shunt of blood from the right to left with
the major outflow of blood through the
aorta. The condition presents with clinical
signs very early in life, frequently results
in death at or shortly following birth and
has been reported predominantly in foals
and calves. Occasionally, affected animals
may live for longer periods and cases are
recorded in mature animals. 17,18

Affected animals show lassitude and
dyspnea after minor exertion such as
suckling, with the clinical signs resulting
primarily from systemic hypoxemia.
Cyanosis may or may not be present,
depending upon the degree of pulmonary
stenosis, but is usually prominent,
especially following exercise. On auscul-
tation a murmur and sometimes a thrill is
present and most intense in the left third
or fourth intercostal space.

Other cardiac defects that result in
cyanosis as a prominent sign occur when
there is right-to-left shunting of blood
through a patent foramen ovale, a patent
ductus arteriosis or ventricular or atrial
septal defects as a result of tricuspid
atresia or pulmonary atresia. 15-21 Right-
to-left shunting through these defects is
rare and, if present, is usually a terminal
event.

Tetralogy of Fallot should be differen-
tiated from an even rarer condition,
double outlet right ventricle; the latter
is characterized by having both the aorta
and pulmonary artery arise from a distinct
conus originating from the morphologic
right ventricle and from which no fibrous
continuity with the atrioventricular valves
can be demonstrated. Double outlet right
ventricle has been diagnosed in three
calves and a foal, 22 with clinical signs
similar to tetralogy of Fallot.

Patent ductus arteriosus

This defect results from a failure of closure
of the ductus arteriosus following birth
and is probably the second most common

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

defect in horses after ventricular septal
defect. There is some controversy over the
period of time involved in normal closure
in large animals. Clinically, murmurs
associated with a patent ductus arteriosus
are frequently heard during the first day
after birth in normal foals and may persist
for periods of up to 5 days. Physiological
studies in foals 23 suggest that closure
occurs before 24 hours after birth. Patent
ductus arteriosus is not a common clinical
cardiac defect in older animals, but can
occur. 24 The ductus arteriosus closes
within minutes of birth in calves.

Patent ductus arteriosus produces a
loud continuous murmur associated
with the left-to-right shunting of blood
from the aorta to the pulmonary artery.
The intensity of the murmur waxes and
wanes with each cycle because of the
effects of normal pressure changes on
blood flow, giving rise to the name of
'machinery murmur'. The systolic
component of the murmur is very loud
and usually audible over most of the
cardiac auscultatory area, but the diastolic
component is much softer and con-
fined to the base of the heart. The pulse
is large in amplitude but has a low
diastolic pressure. Surgical correction is
possible.

Coarctation of the aorta

Constriction of the aorta at the site of
entrance of the ductus arteriosus causes a
syndrome similar to that of stenosis of the
aortic semilunar valves; there is a systolic
murmur and a slow-rising pulse of small
amplitude.

Persistence of the right aortic arch

Persistence of the right fourth aortic arch
causes constriction of the esophagus with
dysphagia and regurgitation. The aorta is
situated to the right of the esophagus and
trachea and the ligamentum arteriosum
in its connection to the pulmonary artery
encloses the esophagus in a vascular ring
and compresses it against the trachea.
Clinical signs are usually evident soon
after birth and consist primarily of
regurgitation of milk from the mouth
and nostrils after suckling, but survival
until 5 years of age has been recorded in a
bull that showed chronic bloat and
visible esophageal dilatation. Resistance
to the passage of a stomach tube is
encountered just behind the first rib and
the diagnosis can be confirmed by radio-
logical examination following a barium
swallow. Medical treatment is concerned
with the control of aspiration pneumonia,
but the correction of the defect is surgical.

Persistent truncus arteriosus

This defect 25,26 and other defects of the
outflow vessels, including pulmonary and
aortic hvDODlasia and congenital absence

of the aortic arch, have been recorded in
animals but their prevalence is low.

Fibroelastosis

Congenital fibroelastosis has been
observed in calves and pigs. The endo-
cardium is converted into a thick fibro-
elastic coat and, although the wall of the
left ventricle is hypertrophied, the capacity
of the ventricle is reduced. The aortic
valves may be thickened and irregular
and obviously stenosed. The syndrome is
one of congestive heart failure. The defect
may cause no clinical abnormality until
the animal is mature.

Subvalvular aortic stenosis

Stenosis of the aorta at or just below the
point of attachment of the aortic semi-
lunar valves has been recorded as a
common, possibly heritable, defect in
pigs 27 but its differentiation from other
causes of heart failure is difficult. Clinically
affected animals may die suddenly with
asphyxia, dyspnea and foaming at the
mouth and nostrils, or after a long period of
ill-health with recurrent attacks of dyspnea.
In the acute form death may occur after
exercise or be unassociated with exertion.

Parachute left atrioventricular valve

This is an extremely rare congenital
anomaly defined by the presence of a
single papillary muscle that receives all
chordae tendineae from the left atrio-
ventricular valve. An 8-month old colt
with a loud left-sided holosystolic murmur
was diagnosed with this condition using
echocardiography. 28

Anomalous origin of coronary
arteries

Either or both coronary arteries may
originate from the pulmonary artery
instead of the aorta. The resulting anoxia
causes myocardial weakness in the
ventricle of the affected side. Congestive
heart failure usually follows. Congenital
deformities of the coronary arteries have
been recorded in cattle and pigs. 29

REFERENCES

1. Tschudi P. SchweizArchTierheilkd 1975; 117:335.

2. Besser TE, Knowlen GG. J Am Vet Med Assoc
1992; 200:1355.

3. Swindle MM et al. Lab Anim Sci 1990; 40:155.

4. Penrith ML et al. J S AfrVet Assoc 1994; 65:31.

5. GopalT et al. Am JVet Res 1986; 47:1120.

6. Dennis SM, Leipold HW. Am J Vet Res 1968;
29:2337.

7. Hsu FS, Du SJ. Vet Fhthol 1982; 19:676.

8. Cotterill CM, Rossdale PD. Equine Vet J 1992;
24:338.

9. Reef VB. Compend Contin Educ Pract Vet 1991;
13:109.

10. Marakami T et al. J Jpn Vet Med Assoc 1991;
44:696.

11. ReefVB. Equine Vet J Suppl 1996; 19:86.

12. Machida N. Jpn JVet Sci 1986; 48:1031.

13. McLennan MW et al. AustVet J 1996; 74:22.

14. ReefVB, Spencer P. Am JVet Res 1987; 48:904. -

15. Wilson RB, Hoffner JC. ComellVet 1987; 77:187.

16. EckePetal.NZVetJ 1991; 39:97.

17. Cargile J et al. ComellVet 1991; 81:411.

18. Rahal C et al. J Equine Vet Sci 1997; 17:604.

19. Young LE et al. EquineVet Educ 1997; 9:123.

20. Anderson RH. EquineVet Educ 1997; 9:128.

21. Meurs KM et al. Equine Vet J 1997; 29:160.

22. Prosek R et al. J Vet Intern Med 2005; 19:262.

23. Scott EA et al. Am J Vet Res 1975; 36:1021.

24. Prescott JRR et al.Vet Rec 1997; 74:471.

25. Sandusky GE, Smith CW.Vet Rec 1981; 108:163.

26. Reppas GP et al. AustVet J 1996; 73:115.

27. Van Nie CJ,Vincent J.Vet Q 1980; 2:160.

28. Kimberly M et al. J Vet Intern Med 2003; 17:579.

29. Bildfell RJ et al. JVet Diagn Invest 1996; 8:500.

Cardiac neoplasia

Primary neoplasia of the heart is exceed-
ingly rare and cardiac disease secondary
to metastatic neoplasms occurs in-
frequently. Aortic body adenoma, cardiac
fibrosarcoma and pericardial mesothelioma
are reported. 1 ' 3

Lymphosarcoma is probably the most
common metastatic tumor in both cattle
and horses but cardiac involvement by
melanoma, hemangiosarcoma, testicular
embryonal carcinoma, squamous cell
carcinoma, lipoma and other tumors is also
recorded. 4 Angiomas, benign vasoformative
tumors, can occur in the heart and are
recorded as obstructing blood flow and
producing heart failure in a young calf. 5

REFERENCES

1. Camine BL et al.Vet Pathol 1977; 14:513.

2. Barros CSL, Santos MND. AustVet J 1983; 60:61.

3. Braun U et al. Schweiz Arch Tierheilkd 1995;
137:187.

4. Dill SG et al. EquineVet J 1986; 18:414.

5. Watson TDG, Thompson H.Vet Rec 1990; 127:279.

Diseases of the blood
vessels

ARTERIAL THROMBOSIS AND
EMBOLISM

Synopsis ^ ■

A. 7 , . . , A „ - . , ' ■ - *V. ... ,/ ••:- ' A _ .

Etiology Arteritis leading to thrombus
formation causes ischemia of the tissues
supplied by the affected artery
Clinical findings Reduced function or
ischemic necrosis vary with the site of the
obstruction. Aortic-iliac thrombosis manifest
with lameness, muscular weakness,
decreased pulse amplitude in affected leg
Clinical pathology Leukocytosis,
hyperfibrinogenemia, elevated serum
concentrations of muscle enzymes in some
cases. Ultrasound more sensitive for
diagnosis than rectal palpation
Necropsy findings Thrombosis and
embolic lesions, muscle ischemia and
necrosis

Diagnostic confirmation

Ultrasonography for aortic-iliac thrombosis
Treatment Fibrinolytic enzymes. Surgical
removal of thrombus

ETIOLOGY

Injury to vascular endothelium, alteration
to normal blood flow (turbulence or
stasis) and alterations to the coagulability
of blood can predispose thrombosis and
thromboembolism.

Coagulopathies

Coagulopathies and disseminated intra-
vascular coagulation are important in the
pathogenesis thromboembolism, which
occurs in many infectious diseases. 1

Parasitic arteritis

G Strongylus vulgaris - horses. Migrating
larvae cause arteritis of the anterior
mesenteric artery, iliac arteries, base of
aorta and occasionally cerebral, renal
or coronary arteries. This is a major
cause of arteritis and associated
clinical disease in horses 2
° Aortic-iliac thrombosis in horses.
There is some controversy over the
etiology of this disease. It may result
from strongyle-related
thromboembolism with organization
of thrombi and their incorporation
into the arterial wall with centripetal
development of progressive
thrombosis. Alternatively spontaneous
degenerative vascular disease of
unknown etiology, but particularly at
the aortic quadrifurcation may result
in thrombosis in the area and
subsequently thromboembolism of
more distal vessels

° Onchocerciasis and elaeophoriasis in
cattle, sheep, goats, and horses.

Viral arteritis

0 Important in pathogenesis of several
viral diseases, including malignant
catarrhal fever, equine viral arteritis,
African swine fever, hog cholera,
bluetongue, African horse sickness.

Bacterial arteritis

0 Including septicemic salmonellosis,
erysipelas, Histophilus somni,
Haemophilus pleuropneumoniae,
pasteurellosis.

Embolic arteritis and
thromboembolism

- From vegetative endocarditis or
emboli from arterial thrombus in
various sites

° Hyperlipemia and hyperlipidemia in
horses

0 Fat emboli following surgery
0 Associated with subclinical Salmonella
dublin infection in calves
0 Rupture of abscesses into blood
vessels - pulmonary embolism
resulting from caudal vena caval
thrombosis or jugular thrombosis
0 From indwelling catheters.

Microangiopathy

0 Vitamin E/selenium deficiency

Diseases of the blood vessels

435

® Cerebrospinal angiopathy
° Terminal in most septicemic disease. 1

Calcification

° Enzootic calcinosis
• Vitamin D toxicity
0 Chronic hypomagnesemia in calves
0 Lymphosarcoma in some horses.

Vasoconstrictive agents

° Ergot poisoning
° Fescue poisoning.

EPIDEMIOLOGY

Clinical atherosclerosis occurs rarely in
farm animals. It has been recorded in a
horse in which sufficient vascular obstruc-
tion occurred to cause severe central
nervous signs and a fatal outcome.
Spontaneous atherosclerosis is a common
necropsy finding in swine, cattle, goats,
horses and wild animals but is not
associated with clinical disease. Arterio-
sclerosis and calcification are major
findings in enzootic calcinosis and occur
following overdosing with vitamin D or
its analogs in the prevention of milk fever
in cattle and in hypomagnesemia in
calves.

PATHOGENESIS

In parasitic arteritis, inflammation and
thickening of the arterial wall result in the
formation of thrombi, which may partially
or completely occlude the artery. The
common site is in the anterior mesenteric
artery, obstruction of the vessel causing
recurrent colic or fatal ischemic necrosis
of a segment of the intestine. Less com-
mon sites include the origin of the iliac
artery at the abdominal aorta causing iliac
thrombosis, the base of the aorta leading
to rupture and hemopericardium, and the
coronary arteries causing myocardial
infarction.

With other causes of arteritis, the
clinical syndrome is dependent upon the
site of arteritis or embolism. Arteritis
associated with bacterial and viral infec-
tions is usually widespread and several
organ systems are involved. Bacterial
emboli have a predilection to lodge in:

° Vascular plexuses in the kidney to
produce renal disease
° The synovial membranes to produce
arthritis and tenosynovitis
° The endocardium to produce
endocarditis.

Less commonly, they may lodge in other
vascular plexuses such as the rete cerebri.
Large emboli that lodge in the pulmonary
arteries cause anoxic anoxia. Embolism in
the renal artery causes acute cortical
necrosis and gross hematuria.

Vasoconstrictive alkaloids produced
by Claviceps purpurea infestation of grass
seed heads and Acremonium coenophalium,
which infests Festuca arundinaceae and

Lolium perenne, cause arteriolar constric-
tion and result in ischemic necrosis and
gangrene of distal extremities in cattle.

CLINICAL FINDINGS

The clinical findings in mesenteric
verminous arteritis of horses and renal,
and myocardial infarction, gangrene
associated with C. purpurea or endophyte
infestation of grasses and other diseases
listed above are described elsewhere
under those headings. The clinical signs
of aortic-iliac thrombosis and pulmonary
embolism are described here.

Aortic-iliac thrombosis in the horse

Aortic-iliac thrombosis 3-4 is reported most
commonly in racehorses but occurs in
other breeds. It is primarily a disease of
horses of over 3 years of age. Either one or
both hindlegs may be involved. The
clinical manifestations vary according to
the stage of progression of the disease
and are associated with ischemia of the
hindlimbs.

Early mild cases are usually detected
in racehorses or horses subjected to
maximal exertion where the disease may
be a cause of poor performance. In early
cases there is lameness only on exercise,
the animal returning to normal after a
short rest. If the horse is forced to work
when lameness develops, the signs may
increase to resemble those of the acute
form. The lameness takes the form of
weakness, usually of one hindlimb, which
tends to give way, especially when the
animal turns on it. Frequent lifting of the
foot or cow-kicking may also be shown.

In more severe cases, lameness or
refusal to work may be evident after
minimal exercise:

The disease is chronic and progressive,
but occasionally the onset may be acute.

In the acute form there is great pain
and anxiety and the pulse and respiration
rates are markedly increased Profuse
sweating may be evident, but the affected
limb is usually dry and may be cooler than
the rest of the body The pain is often
sufficiently severe to cause the animal to
go down and refuse to get up.

Suspect animals should be examined
following exercise.

° The affected limb is cool from the
mid-gaskin distally and there is
usually diminished or variable
sweating over this area
0 The amplitude of the pulse in the
common digital artery is less in the
affected limb than in the normal limb
or the front limbs

° Slow filling of the saphenous vein

of the affected limb can usually be
detected

° Palpable abnormalities on rectal
examination include enlargement

436

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

and firmness of the aortic
quadrifurcation, irregularity and
asymmetry of the internal and
external iliac arteries and decreased
amplitude or absence of an arterial
pulse.

Recovery by the development of collateral
circulation or shrinkage of the thrombus
is unlikely to occur and the disease is
usually chronically progressive with a
poor prognosis.

Until recently the detection and diag-
nosis of the occurrence of this abnor-
mality was limited to horses showing
clinical signs and horses where abnor-
mality could be palpated on rectal
examination. Ultrasonography is a more
sensitive method of detection than rectal
palpation. 5 Its use as a diagnostic tech-
nique may lead to a better definition of
the occurrence of this disease and
ultimately its pathogenesis. Ultra-
sonographic measurements are avail-
able for the common carotid artery of
cattle. 6

Iliac thrombosis may also be associ-
ated with impotence in stallions due to
failure to mount or accompanied by
testicular atrophy. 7 It has also been
associated with a syndrome of ejaculatory
failure in which the stallion has excellent
libido, good coupling and vigorous
thrusting but a failure to ejaculate. 8 The
reason for this manifestation is not known
but it is postulated that the enlarged
arteries might impinge on the caudal
mesenteric plexus and the hypogastric
nerve. 8

Aortic-iliac thrombosis in calves

Aortic and iliac artery thrombosis is
reported as an occasional disease of
unknown etiology in calves less than
6 months of age. 9 Affected calves have a
rapid onset of ataxia, paresis or paralysis
of one or both hind limbs. Within
24 hours of onset the calves do not bear
weight on the affected leg and, in calves
affected in both hindlimbs, signs initially
occur in a single limb. Affected legs are
cold to touch, especially distal to the stifle,
have poor muscle tone and the with-
drawal reflex and deep pain sensation is
absent in the distal portions. Subcutaneous
swelling and crepitation is present in
some. Thrombosis at the terminal part of
the aorta and the iliac quadrifurcation is
found at postmortem examination. The
umbilical arteries arise from the iliac
arteries near the iliac quadrifurcation and
it is thought that thrombus formation in
the iliac arteries may predispose to this
disease.

Pulmonary embolism

Severe dyspnea develops suddenly and is
accompanied by profuse sweating and

anxiety. The temperature and pulse rate
are elevated but the lungs are normal on
auscultation. In horses the signs usually
pass off gradually in 12-24 hours but in
cattle the hypoxemia may be more severe
and cause persistent blindness and
imbecility. Infected emboli may lead to
more severe pulmonary embolic disease
with arteritis and pulmonary abscessation.
There is pulmonary hypertension, and cor
pulmonale is a possible sequel. Pulmon-
ary arteritis and aneurysm may be
followed by rupture and pulmonary
hemorrhage and hemoptysis.

CLINICAL PATHOLOGY

Extensive thrombus formation is usually
associated with a leukocytosis and a shift
to the left and there is an increase in
serum fibrinogen concentration. In the
majority of cases of iliac thrombosis
serum aspartate aminotransferase and
creatine kinase activities are within the
normal range both before and after
exercise 7 but in severe cases there may be
enzymic evidence of myonecrosis with
secondary hyperkalemia and uremia. 10
Elevated serum creatine kinase and
aspartate transaminase activities are pre-
sent in aortic and iliac thrombosis in
calves. Angiography or ultrasonography
are used for diagnostic confirmation.

NECROPSY FINDINGS

Obstruction of the affected artery is easily
seen when it is opened. The thrombus or
embolus is adherent to the intima and is
usually laminated. Local or diffuse
ischemia or infarction may be evident if
the embolus has been present for some
time and may have progressed to the
point of abscess formation.

DIFFERENTIAL DIAGNOSIS

Aortic-iliac thrombosis in the horse

• Paralytic myoglobinuria

• Hyperkalemic periodic paralysis
Aortic-iliac thrombosis in calves

• Vertebral osteomyelitis (spinal abscess)

• White muscle disease

• Vertebral fracture

• Clostridial myositis

• Pulmonary embolism

• Pneumonia.

TREATMENT

Treatment with parenteral anticoagulants
or enzymes is carried out only rarely.
There are several records of good results
in iliac thrombosis in horses after the
intravenous injection of sodium gluconate
or fibrinolytic enzymes, 10 and retrograde
catheterization of the ventral coccygeal
artery can allow the deposition of these
materials at high local concentration.
Stallions with ejaculatory failure have had

some success at service following treat-
ment with phenylbutazone to reduce pain
and gonadotropin-releasing hormone
to maximize sexual arousal and lower
the ejaculatory threshold. 8 Ivermectin in
combination with phenylbutazone may
aid recovery. A gradually increasing
exercise program may improve collateral
circulation. Surgical treatment is recorded
by partial or complete removal of the
thrombus with a thrombectomy catheter. 4

REFERENCES

1. Morris DD. Compend Contin Educ Pract Vet
1989; 11:1386.

2. Baker JR, Ellis CE. Equine Vet J 1981; 13:43, 47.

3. Ma*ie MG, Physick-Sheard PW.Vet Pathol 1985;
2:238.

4. Brama PAJ et al. Vet Q 1996; 18(SuppI 2):S85.

5. Reef VB et al. J Am Vet Med Assoc 1987; 190:286.

6. Braun U, Hohn J. Am J Vet Res 2005; 66:962.

7. Azzie MAJ. In: Proceedings of the 18th Annual
Convention of the American Association of
Equine Practitioners 1972:43.

8. McDonnell SM. J Am Vet Med Assoc 1992;
200:954.

9. Morley P et al. J Am Vet Med Assoc 1996; 209:130.

10. Pause B et al. Tierarztl Praxis 1988; 16:377.

VENOUS THROMBOSIS

The development of thrombi in veins may
result in local obstruction to venous
drainage, in liberation of emboli that
lodge in the lungs, liver or other organs,
and in the development of septicemia or
of endocarditis.

PHLEBITIS

Phlebitis is the common origin of thrombi
and may be caused by localization of a
blood-borne infection, by extension of
infection from surrounding diseased
tissues, by infection of the umbilical veins
in the newborn and by irritant injections
into the major veins.

Thrombophlebitis of the jugular
vein is a complication of injections or
catheterization in some animals and
occurs in all species. It can result from
damage to the vascular endothelium by
cannula or indwelling intravenous cath-
eters, inflammation caused by chemical
irritation or bacterial invasion from
contamination during insertion of the
needle or catheter or migration along the
catheter from the skin. 1,2 Phlebitis
develops and can be detected clinically
24-72 hours after catheter insertion. A
retrospective study of 46 cases in horses
indicated that ongoing infectious disease
was a risk factor for the development of
catheter-associated thrombophlebitis 3
and thrombophlebitis is especially com-
mon in horses with severe gastro-
intestinal diseases that are accompanied
by endotoxemia. Horses are also at higher
risk following surgery. 4 Severely ill cows are
also more likely to develop jugular vein
thrombophlebitis than healthy cows. 2

Diseases of the blood vessels

437

Intravenous injections of irritating
materials, such as tetracycline, phenylbu-
tazone, 50% dextrose, hypertonic solutions
of calcium gluconate, borogluconate and
chloride, or hypertonic saline (7.2%
NaCl), may cause endothelial damage
followed by cicatricial contraction, with or
without thrombus formation. Jugular
phlebitis with thrombosis is not uncom-
mon in feedlot cattle that have received
repeated intravenous antibiotic medication,
and may lead to thromboembolic respir-
atory disease.

Accidental injection of irritating
materials around the vein usually cause a
marked local swelling, sometimes with
necrosis and local sloughing of tissue,
which may be followed by cicatricial
contraction of local tissues.

Phenylbutazone

Commonly used as an NSAID, its use in
horses may be associated with toxicity,
which is manifest with oral and gastro-
intestinal ulceration and renal medullary
crest necrosis. 5-7 Affected horses show
depression, anorexia and neutropenia
with ulcers in the mouth, especially on
the ventral aspect of the tongue. Ulcers in
the fundic and pyloric portion of the
stomach also develop but are usually
subclinical, although they may be evident
on gastroscopic examination or at
necropsy. More severe cases show signs of
colic and diarrhea in association with
intestinal ulceration and duodenitis, and
show evidence of renal disease. Toxicity
may develop following either intravenous
or oral administration of the drug. Intra-
venous administration is frequently associ-
ated with the development of phlebitis and
jugular thrombosis at the site of injection.

Phlebitis may also develop in these
animals at sites of venepuncture performed
for purposes other than phenylbutazone
administration. Experimental studies 6
suggest that a phlebopathy induced by
phenylbutazone is central to the develop-
ment of all these lesions, including the
oral and gastrointestinal ulceration and
the renal crest necrosis. The exact
pathogenesis of the vein damage in
phenylbutazone toxicity has not been
elucidated but, experimentally, toxicity
can be prevented by the concurrent
administration of prostaglandin E 2 . 7
Clinical pathological examination for
leukopenia and a fall in serum aspartate
aminotransferase may be of value as a
monitoring technique for the develop-
ment of toxicity during phenylbutazone
therapy of disease.

Venous thrombi are relatively common
in strangles in the horse, and may affect
the jugular veins or the caudal vena cava.
Thrombosis of the caudal vena cava due
to hepatic abscessation and resulting in

embolic pneumonia and pulmonary
arterial lesions occurs in cows and is
described together with cranial vena
caval thrombosis in Chapter 10.

Less common examples of venous
thrombosis are those occurring in the
cerebral sinuses, either by drainage of an
infection from the face or those caused by
the migration of parasite larvae. Purpling
and later sloughing of the ears which
occur in many septicemias in pigs are
also caused by phlebitis and venous
thrombosis. Thrombosis of the tarsal vein
is a complication of infections in the claw
of cattle 8 and intravenous administration
of antimicrobial agents as part of the
treatment of septic arthritis or the distal
interphalangeal joints.

CLINICAL SIGNS

Clinical signs of venous thrombosis are
engorgement of the vein, pain on palpa-
tion and local edema. In unsupported
tissues rupture may occur and lead to fatal
internal or external hemorrhage. Ultra-
sonographic examination assists the
diagnosis and the detection of a cavitating
area within the thrombus supports a
diagnosis of septic thrombophlebitis. 2,3 ' 8
Angiography can also assist in diagnosis.
Bacteriological culture should be attempted,
preferably from the tip of the removed
catheter. A variety of different organisms
have been isolated from different cases. 3
There are no typical findings on clinico-
pathological examination but there is
often an abnormal leukogram and hyper-
fibrinogenemia. At necropsy the obstructed
vessel and thrombus are usually easily
located by the situation of the edema and
local hemorrhage.

Diagnosis depends on the presence of
signs of asymmetric local venous
obstruction in the absence of obvious
external pressure by tumor, enlarged
lymph nodes, hematomas or fibrous tissue
constriction. Pressure of a fetus may cause
symmetric edema of the perineum, udder
and ventral abdominal wall during late
pregnancy, and can be easily differen-
tiated from thrombophlebitis by its
symmetry and lack of pain. Local edema
due to infective processes such as
blackleg, malignant edema and peracute
staphylococcal mastitis are accompanied
by fever, severe toxemia, acute local
inflammation and necrosis.

TREATMENT

Parenteral treatment with antimicrobial
agents and hot fomentations to external
veins, or treatment with a topical anti-
inflammatory agent such as 50% dimethyl
sulfoxide, is usually instituted to remove
the obstruction or allay the swelling. If a
catheter is being used it should be imme-
diately removed. Heparin and warfarin

treatment in horses is not recommended. 9
Ultrasonography is useful to monitor
recanalization of the thrombosed vein 2 and
measurements of the external jugular vein
are available for cattle. 10

REVIEW LITERATURE

Deem DD. Thrombophlebitis in horses: the contri-
bution of hemostatic dysfunction to pathogenesis.
Compend Contin Educ PractVet 1989; 11:1386.

REFERENCES

1. Bayly WM, Vale BH. Compend Contin Educ Pract
Vet 1982; 4:5227.

2. Pusterla N, Braun U.Vet Rec 1995; 137:431.

3. Gardner SY et al. J Am Vet Med Assoc 1991;
199:370.

4. Gerhards H. Dtsch Tierarztl Wochenschr 1987;
94:173.

5. Tobin T et al. JVet PharmacolTherl986; 9:1.

6. Meschter CL et al. Cornell Vet 1984; 74:282.

7. Collins LG, Tyler DE. Am J Vet Res 1985; 46:1605.

8. KoflerJ etal. Vet Rec 1996; 138:34.

9. Deem DD. Compend Contin Educ PractVet 1989;
11:1386.

10. Braun U, Hohn J. Am JVet Res 2005; 66:962.

HEMANGIOMA AND
HEM ANGIOSARCOMA

Hemangioma and hemangiosarcoma are
rare in large animals but are described
and may be associated with hemorrhage
related to the site of the tumor.

HEMANGIOMA

Hemangiomas in the skin occur most
commonly in young animals and may be
congenital. 1,2 The tumors grow with age;
those on the skin may ulcerate and bleed
and may necessitate euthanasia because
of their eventual size. Similar tumors may
occur in the mouth as pedunculated pink
granular masses that ulcerate and bleed.
Local hemangiomas on the skin and in
the mouth may respond to surgical excision,
thermocautery or radiation therapy.
Widespread disseminated hemangioma is
also recorded in young cattle presenting
with multiple skin lesions and multiorgan
involvement. 3,4 Hemangioma has also
been reported with moderate prevalence
affecting the ovaries of sows. 5

HEMANGIOSARCOMA

Hemangiosarcoma occurs in horses but is
not a common tumor. It is more prevalent in
middle-aged and older animals. Affected
horses may present with a bleeding sub-
cutaneous mass or with signs of dis-
seminated hemangiosarcoma. Dissemi-
nated hemangiosarcomas in horses cause
anemia due to hemorrhage into the tumor
or into body cavities. In addition there is
weight loss, but good appetite, and weak-
ness. Metastasis is extensive to lung, myo-
cardium, brain, retroperitoneum and
skeletal muscle, 5-8 and myocardial lesions
can lead to cardiac arrhythmias. Lesions in
skeletal muscle cause difficulties in move-
ment and tumors in the nervous system

PART 1 GENERAL MEDICINE ■ Chapter 8: Diseases of the cardiovascular system

present with signs of ataxia . 9 The thoracic
cavity is a common site for metastasis 6 and
can also be a primary site of the neoplasm . 10

A common clinical manifestation is
pleural effusion and hemorrhage 1112
and a clinical picture which requires
differentiation from other causes of
thoracic mass with effusion, which in the
horse is more commonly mediastinal
abscess, lymphosarcoma, squamous cell
carcinoma or pleurisy. Hemoperitoneum,
detectable by paracentesis, is present with
peritoneal tumors. All the tumors are

cavitatious and bleed profusely if incised.
Early histopathologic diagnosis may
permit a cure in animals with localized
masses that can be surgically resected. If
masses are not interfering with quality
of life and the horse is medically
stable, observation may be warranted
because spontaneous resolution has been
reported . 8

RHABDOMYOSARCOMA

Primary cardiac rhabdomyosarcoma
occurs rarely in cattle and sheep.

REFERENCES

1. Sartin EA, Hodge TG. Vet Pathol 1982; 19:569.

2. Lopez MJ et al. Agri Pract 1994; 15:24.

3. Baker JC et al. J AniVetMed Assoc 1982; 181:172.

4. Munroe R et al.Vet Rec 1994; 135:333.

5. Hargis AM, McElwain TF. J Am Vet Med Assoc
1984; 184:1121.

6. Johnson JE et al. J Am Vet Med Assoc 1988;
193:1429.

7. Delesalle C et al. J Vet Intern Med 2002; 16:612.

8. Johns I et al. J Vst Intern Med 2005; 19:564.

9. Newton-Clarke MJ et al.Vet Recl994; 135:182.

10. Freestone JF et al. AustVet J 1990; 67:269.

11. Brink P et al. Equine Vet J 1996; 28:241.

12. Collins MB et al. AustVet J 1994; 71:296.

PART 1 GENERAL MEDICINE

Diseases of the hemolymphatic and
immune systems

ABNORMALITIES OF PLASMA
PROTEIN CONCENTRATION 439

Hypoproteinemia 439
Hyperproteinemia 441

HEMORRHAGIC DISEASE 441

Diseases causing hemorrhage 443

PURPURA HEMORRHAGICA 443

Disseminated intravascular coagulopathy
and hypercoagulable states 447
Thrombosis 450

DISORDERS OF RED CELL NUMBER
OR FUNCTION 450

Anemia 450

Erythrocytosis 459
Abnormal red cell function 460

DISORDERS OF WHITE CELLS 460

Leukopenia 460
Leukocytosis 461
Abnormal white cell function 461
Leukoproliferative disease (leukemia,
lymphoma) 461

LYMPH ADENOPATHY
(LYMPHADENITIS) 464

DISEASES OF THE SPLEEN AND
THYMUS 464

Splenomegaly 465

Splenic abscess 465
Splenic hematoma, rupture or
infarction 465
Congenital anomalies 466
Thymus 466

IMMUNE DEFICIENCY DISORDERS
(LOWERED RESISTANCE TO
INFECTION) 466

Primary immune deficiencies 466
Secondary immune deficiencies 467

AMYLOIDOSES 467

PORPHYRIAS 469

Abnormalities of plasma
protein concentration

Plasma contains hundreds of proteins,
including albumin, immunoglobulins,
clotting factors, acute phase proteins,
hormones and cytokines. The proteins in
plasma are produced by the liver
(albumin, acute phase proteins (fib-
rinogen, serum amyloid A), clotting
factors) and lymphoid organs (the
gamma-globulins and many cytokines).
The plasma proteins serve as sources of
amino acids for tissues, as carrier mol-
ecules, maintain plasma oncotic pressure,
regulate immune function, and effect
hemostasis and fibrinolysis. Defects or
deficits of individual proteins can result in
specific diseases, including immune
deficiency, defective hemostasis and
endocrinopathy. The individual diseases
resulting from loss of activity of specific
proteins are dealt with under the head-
ings of those diseases. Provided here is an
overview of hypoproteinemic and hyper-
proteinemic states.

HYPOP R OTE I NEM 1A

ETIOLOGY

Hypoproteinemia is a plasma or serum
total protein concentration that is below
that expected in animals of the same age,
sex, physiological state and species.
Hypoproteinemia can be a result of a
reduction in concentration of albumin
and globulin, or a reduction in either
albumin or globulin concentrations.
Abnormalities in plasma protein concen-
tration include:

° Panhypoproteinemia with
hypoalbuminemia and
hypoglobulinemia

° Hypoproteinemia with

hypoalbuminemia and normal
globulin concentration
o Hypoproteinemia with

hypoglobulinemia and normal albumin
° Normal total protein concentration
with hypoalbuminemia and
hyperglobulinemia, and less
commonly, hyperalbuminemia and
hypoglobulinemia.

The specific deficiency has important
diagnostic significance.

Panhyproteinemia

Hypoproteinemia with hypoalbuminemia
and hypoglobulinemia can be either
relative or absolute.

Relative hypoproteinemia occurs
when plasma protein concentrations are
lower than normal but the absolute content
of protein in the vascular space is normal.
This is a dilutional hypoproteinemia and is
attributable to either excessive fluid therapy
or excessive water intake. These causes are
readily determined from a review of the
history and treatment of the animal and
resolve within hours of discontinuation of
fluid therapy or restriction of fluid intake.

Absolute hypoproteinemia occurs
when there is a reduction in the amount
of plasma proteins in the vascular space
in the presence of normal or almost
normal plasma volume. The reduced
protein concentration can be the result of
impaired production or accelerated loss.
Reduced production of all plasma proteins
occurs only as part of malnutrition and
starvation. Liver disease can cause a
reduction in the concentration in plasma
of those proteins produced by the liver
(see below) but in large animals is an
unusual cause of hypoproteinemia. Loss
of protein is a more common cause of
hypoproteinemia.

The loss of proteins can be either from
the vascular space into the extravascular
compartment (e.g. endotoxemia,
vasculitis) or from the body (compensated
hemorrhage, glomerulonephritis, protein-
losing enteropathy). This situation is
evident as a reduction in concentrations
of both albumin and globulins, and
in hemorrhagic disease by a reduction in
hematocrit. Loss because of vascular leak-
age is usually evident as hypoproteinemia
with normal or elevated hematocrit.
Diseases causing panhypoproteinemia
include:

° Hemorrhage - hypoproteinemia
occurs when plasma volume is
restored after severe hemorrhage, or
in normovolemic anemia when there
is persisting loss of blood (see
page 451 for a list of diseases causing
chronic hemorrhagic anemia). All
causes of chronic blood loss can cause
hypoproteinemia
e Endotoxemia - protein loss is

secondary to leakage of protein from
the vascular space into interstitial
spaces because of increased capillary
permeability

° Vasculitis - causing increased capillary
permeability and leakage of protein.
Evident in many systemic diseases,
including African horse sickness,
purpura hemorrhagica, swine fever,
and malignant catarrhal fever
° Protein-losing enteropathy - the
initial change is in plasma albumin
concentration, but
panhypoproteinemia ensues as the
disease progresses. Diseases
causing protein-losing enteropathy
include:

o Intestinal parasitism
• Abomasal ulceration in cattle

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

® Lymphosarcoma in cattle and horses
° Granulomatous/inflammatory
intestinal disease in horses
(granulomatous enteritis,
eosinophilic enteritis) and cattle
(Johne's disease)

° Enteritis/colitis (salmonellosis,
equine neorickettisosis
( Neorickettsia risticii))

® Nonsteroidal anti-inflammatory
drug (NSAID) toxicosis
o Lawsonia intracellularis proliferative
enteropathy in young horses and
pigs

0 Urinary tract disease including cystic
calculi, pylonephritis,
glomerulonephritis
" Acute, severe inflammation of the
peritoneal or pleural membranes
(peritonitis, pleuritis). The
hypoproteinemia occurs early in the
disease but if the disease becomes
chronic hyp ergammaglobulinemia
ensues

o Chronic heart failure.

Hypoalbuminemia

Hypoalbuminemia with normal or elevated
plasma globulin concentration occurs in
diseases in which there is insufficient
production of albumin by the liver or
excessive or selective loss of albumin
compared to loss of globulin. Insufficient
production of albumin occurs in diseases
of the liver, although these animals might
not necessarily be hypoproteinemic, 1 and
malnutrition or starvation. Diseases of the
liver that cause hypoalbuminemia are
usually diffuse, severe and chronic. The
prolonged half-life of albumin in cattle
and horses (approximately 18 d) renders
them less liable to hypoalbuminemia than
smaller animals.

Albumin has a lower molecular weight
than most globulins, especially the
immunoglobulins, and can be lost selec-
tively in renal or gastrointestinal disease.
Diseases associated with hypoalbu-
minemia and normal to elevated globulin
concentrations include:

“ Amyloidosis - loss of albumin into
urine or the gastrointestinal tract is
sometimes offset, in terms of plasma
protein concentration, by increases in
plasma globulin concentration
" Chronic peritonitis or pleuritis - loss of
albumin into the inflammatory exudate
is offset, in terms of plasma total
protein concentration, by increases in
plasma globulin concentration
° Intestinal parasitism
° Renal disease

° Glomerulonephritis - because of
changes in the size and charge on
proteins of the glomerular
membrane, albumin is not
prevented from entering the

ultrafiltrate and is lost in urine. Any
diseases affecting the glomeruli
can cause albumin loss
0 Pyelonephritis.

Hypogammaglobulinemia

Hypoglobulinemia with normal plasma
albumin concentration occurs in few
diseases. Notably, it is a feature of failure
of transfer of passive immunity in neonates
(Ch. 3). Hypoglobulinemia is an unusual
isolated defect in other diseases. It can be
detectable in immunodeficiencies causing
decreased production of gammaglobulins,
such as combined variable immuno-
deficiency in horses. 2

Hypofibrinogenemia

This only occurs as part of disseminated
intravascular coagulation.

PATHOPHYSIOLOGY

Panhypoproteinemia and hypoalbu-
minemia cause a reduction in concentra-
tion in plasma of proteins essential for a
variety of functions. Overall, the reduction
in plasma albumin concentration results
in a low plasma oncotic pressure. Low
plasma oncotic pressure allows move-
ment of fluid from the vascular space,
causing a reduction in plasma volume
and increases in extravascular volume.
The reduction in plasma volume lowers
blood flow to tissues and can result in
organ dysfunction. The increased extra-
vascular volume is evident as edema.

Low plasma albumin concentration, in
addition to the reduction in plasma oncotic
pressure, reduces opportunities for trans-
port of substances in the plasma, includ-
ing hormones and electrolytes (calcium).

Hypogammaglobulinemia increases
the risk of infectious disease (see Ch. 3).

CLINICAL SIGNS

The clinical signs of hypoproteinemia are
lethargy, ill-thrift and edema. The edema
is usually distributed symmetrically,
with some species predilection for site of
accumulation - ventral edema in horses,
submandibular edema in cattle and sheep.
Affected animals are often tachycardic
because of the reduced plasma volume.

Signs of the inciting disease will also
be present (weight loss, diarrhea, melena,
polyuria).

CLINICAL PATHOLOGY

Detection of hypoproteinemia is readily
achieved by routine hematologic or serum
biochemical testing. The albumin to
globulin (A:G) ratio can be useful in
assessment of the hypoproteinemia.
Hypoalbuminemia with normal globulin
concentration results in a low A:G ratio,
whereas panhypoproteinemia results in a
normal A:G ratio. Selective deficiencies
can be detected by protein electro-
phoresis or measurement of concen-

trations of specific proteins, such as the
immunoglobulins by enzyme-linked
immunosorbent assay (ELISA), radial
immunodiffusion (RID), or immunotur-
bidimetric analysis (see Failure of transfer
of passive immunity in Ch. 3).

Measurement of plasma oncotic
pressure is useful in detecting low plasma
oncotic pressure, which contributes to a
reduction in plasma volume and increases
in extravascular fluid which can lead to
formation of edema. Plasma oncotic
pressure is proportional to the plasma
protein concentration, with the greatest
correlation being with plasma albumin
concentration in animals that have not
received dextran solutions. Intravenous
administration of dextran or hydroxyethyl
starch increases plasma oncotic pressure. 3

NECROPSY

The changes are those of the inciting
disease, or secondary infection in animals
with hypogammaglobulinemia. Edema
can be present in subcutaneous and
internal connective tissues.

TREATMENT

The principles of therapy are treatment
of the inciting disease, and correction of
hypoproteinemia or low plasma oncotic
pressure. Correction of hypoproteinemia
(hypoalbuminemia, hypogammaglobu-
linemia) is achieved by administration of
plasma by transfusion. Unless anemia is
also present, plasma transfusion is preferred
over blood transfusion. The amount of
plasma transfused to neonates is dis-
cussed in Chapter 3. Plasma transfusion
to adult horses and cattle is often limited
by the cost of the plasma. Ideally, plasma
should be transfused to increase plasma
albumin concentrations to more than
2.0 g/dL (20 g/L).This can be calculated as
(where 0.05 is the proportion of body
weight that is plasma):

Current plasma albumin content =
body weight (kg) x 0.05 x (plasma
albumin concentration in g/L)

Desired plasma albumin content =
body weight (kg) x 0.05 x (desired
albumin concentration in g/L)

Amount of albumin required (g) =
Desired plasma albumin content -
current albumin content

Volume of plasma required (L) =

Amount of albumin required
(gValbumin concentration in
transfused plasma (g/L).

A numerical example is of a 500 kg horse
with a plasma albumin concentration
of 1.5 g/dL (15 g/L) and a target plasma
albumin concentration of 2.5 g/dL (25 g/L):

Current plasma albumin content =

500 (kg) x 0.05 x 15 (g/L) = 37 5 g

Hemorrhagic disease

441

Desired plasma albumin content =

500 (kg) x 0.05 x 25 (g/L) = 525 g

Amount of albumin required (g)

= 525 - 375 = 150 g

Volume of plasma required (L)

= 150 (g)/30 (g/L) = 5 L.

It is a frequent observation that trans-
fusion of the calculated volume of plasma,
while improving clinical signs, does not
result in the expected increase in plasma
albumin concentration. This is probably
because transfusion of albumin results in
an increase in plasma oncotic pressure
and a net movement of fluid from the
extravascular space into the vascular
space with subsequent expansion of the
plasma volume. The expansion of plasma
volume dilutes the administered albumin
and attenuates the increase in plasma
protein concentration.

Plasma oncotic pressure can be
increased by intravenous administration
of hydroxyethyl starch or high-molecular-
weight dextrans. The dose is 8-10 mL/kg
of 6% solution delivered intravenously
over 6-12 hours. 3 ' 4

HYPERPROTEINEMIA

ETIOLOGY

Panhyperproteinemia

An increase in concentration of all plasma
proteins occurs only in situations in
which there is a reduction in plasma
water content. This occurs in animals that
are severely dehydrated through lack of
access to water, inability to drink, loss of
protein-poor body fluids (diarrhea,
vomitus) or excessive polyuria with
inadequate water intake.

Hyperglobulinemia

Hyperglobulinemia occurs as a conse-
quence of chronic inflammation or
abnormal production of globulins. Chronic
inflammation causes a polyclonal gam-
mopathy whereas plasma cell neoplasia
(plasmacytoma, myeloid leukemia, see
'Leukoproliferative disease') causes a
monoclonal gammopathy. Any chronic
inflammatory disease, including those of
infectious, toxic or neoplastic origin, can
cause hyperglobulinemia.

Hyperfibrinogenemia

Fibrinogen is an acute phase protein
(along with serum amyloid A, hapto-
globin, C-reactive protein and others) the
concentration of which increases in
plasma in response to inflammation. Any
disease that causes inflammation can
increase plasma fibrinogen concentration.

PATHOPHYSIOLOGY

Chronic inflammation results in chronic
stimulation of the immune system with
subsequent increased production of

immune globulins and acute-phase
proteins. Monoclonal gammaglobulinemia
occurs as a result of unrestrained pro-
duction of gammaglobulins by neoplastic
plasma cells.

CLINICAL SIGNS

The clinical signs are of the underlying
inflammatory disease.

CLINICAL PATHOLOGY

Measurement of plasma protein concen-
tration reveals hyperglobulinemia and/
or hyperfibrinogenemia. Serum protein
electrophoresis demonstrates whether
the abnormality is a polyclonal or mono-
clonal gammaglobulinopathy. Measure-
ment of specific immunoglobulins (IgG,
IgA, etc.) can be useful. Fibrinogen con-
centration must be measured in plasma as
it is consumed during the clotting process
when blood is allowed to clot.

NECROPSY

The findings are those of the underlying
disease.

TREATMENT

Treatment is directed towards the under-
lying disease.

REFERENCES

1. Parrage ME et al. J Vet Intern Med 1995; 9:154.

2. Flaminio MJ et al. J Am Vet Med Assoc 2002;
221:1296.

3. Jones PA etal.J Am Vet Med Assoc 2001; 218:1130.

4. Jones PA et al. Am J Vet Res 1997; 58:541.

Hemorrhagic disease

Hemorrhagic disease is manifest as the
presence of hemorrhage of unusual dur-
ation or severity, either externally from
apparently minor wounds,' or into body
cavities, or as the presence of petechial
and ecchymotic hemorrhages in mucous
and conjunctival membranes and the
skin. Petechial and ecchymotic hemor-
rhage, spontaneous hemorrhage or
excessive bleeding after minor injury may
result from increased capillary fragility,
disorders in platelet function or defects in
the coagulation mechanism of the blood.

Diagnosis

Diagnosis of hemorrhagic disease is based
on the demonstration of abnormalities in
the activity, concentration or function of
components of blood coagulation and
fibrinolysis. The exception is diagnosis of
vasculitis, which is achieved by biopsy,
usually of skin, and histologic examination
and demonstration of inflammatory lesions
in the walls of blood vessels.

Demonstration of prolonged bleeding
time is achieved using devices that inflict
a controlled wound on either the skin or a
mucous membrane (template bleeding
time). A wound is inflicted in the skin and

blood is periodically collected- on to
absorbent filter paper until bleeding ceases.
The time from discharge of the device until
bleeding stops is the 'bleeding time'. The
mean template bleeding time is less than
5 minutes in most healthy animals. 1

Care must be taken when collecting
specimens of blood for measurement of
factors involved in coagulation or fibri-
nolysis. Blood samples collected into
containers that do not contain an anti-
coagulant will rapidly clot and the resulting
serum sample will be minimally useful for
any tests of clotting or fibrinolysis. The ideal
anticoagulant for assays of clotting and
fibrinolysis is trisodium citrate (1 part of
3.8% trisodium citrate to 9 parts of blood).
Sodium citrate decreases the concentration
of ionized calcium in blood and thereby
inhibits platelet activity. 2 Heparin, both
unfractionated (conventional) and low-
molecular-weight inhibits thrombin
activity and activates platelets and is not a
suitable anticoagulant for measurement
of clotting times or platelet activity. 2
Potassium ethylenediamine tetraacetic acid
(EDTA) interferes with platelet function.

An integrated measure of the capacity
of blood to clot is the activated clotting
time. In this test, blood is collected into
plastic syringes that do not contain an
anticoagulant and then immediately
injected into glass tubes containing
diatomaceous earth. The tubes are gently
agitated and then incubated for 1 minute
in a water bath at 37°C. The tubes are
then removed from the water bath and
examined for clotting of blood by gently
rolling the tube. The tube is then returned
to the water bath and reexamined every
30-60 minutes.

The rate of clot retraction of blood
collected into a glass tube that does not
contain anticoagulants is a measure of
platelet activity. The time until maximum
clot retraction is 1-2 hours in most
species when the blood is held at 37°C.

Measurement of prothrombin time
(an indicator of activity of the extrinsic
clotting system), activated partial
thromboplastin time (an indicator of
functionality of the intrinsic clotting
system) and thrombin time (common
pathway) are routinely performed for
animals. The tests are reliable when
performed properly; however, values for
normal animals can vary and the recom-
mendation is that, when submitting a
sample from an animal with suspected
coagulopathy, a sample from a similar
healthy animal should also be examined.
If prothrombin or activated partial throm-
boplastin time are prolonged, other tests
to detenmine the specific factor(s) involved
might be warranted.

Measurement of the activity or con-
centration of blood clotting factors is

12

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

routine in human medicine and many of
these tests have been adapted for use in
animals. Chromogenic assays of factors
VII, VIILC, IX and X developed for testing
of human plasma are reliable when used
for testing of horse plasma. 3 An ELISA for
von Willebrand factor is available that is
suitable for use in a number of species,
including horses, pigs, and cattle. 4 While
most functional assays, including chromo-
genic assays, are suitable for use among
species, most immunologically based
assays developed for use in humans are
not suitable for use in animals. 5 It is
important that assays should be validated
in the species of interest before clinical use
in animals.

Fibrinogen is an essential substrate
for clot formation, and low plasma
concentrations of fibrinogen, such as can
be encountered in animals with dissemi-
nated intravascular coagulation, can
impair blood clotting. Measurement of
fibrin (fibrinogen) degradation products
(FDP) has been used to detect dis-
seminated intravascular coagulation in
horses but the test has poor sensitivity
and specificity. Measurement of D-dimer
concentration has the potential to be
much more useful than FDP in assess-
ment of fibrinolysis and detection
of thromboembolic disease, including
disseminated intravascular coagulation
and coagulopathies. 6 ' 9 Performance
characteristics vary among assays and kit
suppliers. The FDP assays had low
sensitivity (< 40%), whereas the most
accurate D-dimer kit had 50% sensitivity
and 97% specificity for diagnosis of
disseminated intravascular coagulation
in horses with colic. 9 The activity of
antithrombin (previously antithrombin
III), a cofactor of heparin, is measured in
horses as a means of assessing the
anticoagulant activity of plasma. Activity
of antithrombin is reduced in animals
with coagulopathies secondary to gastro-
intestinal disease. This factor is best
measured in concert with thrombin-
antithrombin complex concentration, and
protein C and plasminogen activity to
detect hypercoagulable states. 10

Platelet count in blood should be
evaluated in any animal with a hemor-
rhagic diathesis. Caution should be
exercised in interpreting low platelet
counts determined by automated analyzers,
as clumping of platelets can cause arti-
ficially low values. This pseudothrombo-
cytopenia can be a result of anticoagulant
induced ex- vivo aggregation of platelets, 11
which can be readily detected by micro-
scopic examination of the blood smear.
Platelets counts of less than 100 OOOcells/pL
are considered abnormal, although
excessive hemorrhage is usually not
apparent until platelet counts are below

40 000 cells/pL. Determination of the
proportion of platelets that stain with
thiazole orange dye (reticulated platelets)
can be useful in determining the bone
marrow regenerative response in horses,
and probably other species, with thrombo-
cytopenia. 12,13 Reticulated platelets are
those platelets that have been recently
released from bone marrow. Healthy
ponies have 1.3-2. 8%, and horses have
1-3.4 % of platelets in circulation that stain
with thiazole orange. Thrombocytopenic,
equine-infectious-anemia-positive ponies
have 11-48% and thrombocytopenic,
equine-infectious-anemia-negative horses
have 2-9% thiazole-orange-staining
platelets in the circulation. 13 Platelet
function of horses can be evaluated using
platelet function analyzers designed for use
with human blood, ultrastructure and flow
cytometry. Impaired platelet aggregation
can be detected as a prolongation in
closure time using cartridges with
collagen- adenosine diphosphate (CT-
ADP) and collagen- epinephrine (CT-
Epi) as platelet agonists. In normal horses
calculated reference ranges are 60.5-115.9
seconds and 158.5->300 seconds for CT-
ADP and CT-Epi, respectively. 14

Values of the above variables in normal
animals have been reported inconsistently
and are available in textbooks dealing with
hematology Values in foals and calves of
increasing age are reported. 15,16

Treatment of coagulopathies
Plasma is often administered to animals
with hemorrhagic diatheses to replace
clotting factors that are deficient because
of failure of production (e.g. warfarin
intoxication), increased consumption (e.g.
in disseminated intravascular coagula-
tion) or dilution (e.g. in animals with
severe hemorrhage treated by administra-
tion of large quantities of fluids). The
actual concentration or activity of factors
involved in clotting or fibrinolysis
depends upon the methods used to
collect and store the plasma. Fresh frozen
plasma kept at -80°C retains much of the
activity of clotting factors (VII, VIII, etc.)
and inhibitors of coagulation, including
antithrombin, protein C, protein S and
antitrypsin, for up to 1 year, whereas
plasma stored at higher temperatures
might not retain as much activity. The
dosage varies from 2-10 mL/kg body
weight (BW) intravenously, but this has
not been critically evaluated. Platelet-rich
plasma, which requires more sophisti-
cated collection techniques, is useful for
treatment of severe thrombocytopenic
purpura. Platelet rich plasma can be
prepared by centrifugation of blood at
150 x g for 20-30 minutes. Plasma is
preferred over whole blood for treatment
of nonanemic hemorrhagic diatheses.

Aminocaproic acid (30-100 mg/kg
intravenously) reduces plasma fibrinogen
concentration and decreases partial
thromboplastin time of horses for up to
5 hours after administration. At the
higher dose, alpha-2-antiplasmin activity
is increased and fibrinogen concentration
is decreased, consistent with an action of
the drug to inhibit fibrinolysis. 17 The
utility of aminocaproic acid to inhibit
bleeding in clinical situations has not
been determined.

Tranexamic acid inhibits fibrin degra-
dation and is used as adjunctive treatment
in animals with hemorrhagic diathesis. Its
efficacy in farm animals has not been
reported. Carbazochrome is a compound
that stabilizes capillary membranes and is
used for treatment of exercise-induced
pulmonary hemorrhage in horses,
although with undetermined efficacy.

Formalin has been suggested as an
effective treatment of excessive hemor-
rhage in horses, although it does not
appreciably alter bleeding time or indices of
coagulation. 17 A common dose for an adult
horse is 1 L isotonic electrolyte solution
(saline or lactated Ringer's solution) with
a final concentration of formalin of
0.37-0.74%. Adult goats administered a
5.5% solution of formalin in lactated
Ringer's solution intravenously had a
marked decrease in clotting time. However,
this dose in horses is expected to be toxic. 1

Administration of aspirin to horses
inhibits platelet function in a dose-
dependent fashion for 48 hours after a
single dose of 12 mg/kg. 18 This is not the
case in cattle, in which aspirin does not
inhibit platelet aggregation even at doses
of 100 mg/kg orally. 19 Aspirin irreversibly
inhibits activity of thromboxane syn-
thetase in both cattle and horses for a
prolonged period (days) despite having
a short plasma elimination half-life (hours).
The bleeding time in horses is not
restored until the affected platelets have
been replaced by unaffected platelets. 18
Dosages of aspirin in horses range from
15-100 mg/kg orally every 8-12 hours to
10 mg/kg orally every 48 hours.

Warfarin reduces the concentration of
vitamin-K-dependent clotting factors by
inhibiting hepatic production of these
compounds. Therapeutic use of warfarin
was limited to treatment of navicular
disease in horses, although its use for this
purpose is now archaic.

Heparin, and the newer heparin-
related compounds (low-molecular-weight
heparins) dalteparin and enoxaparin,
have been used in horses with, or at risk
of developing, coagulopathies. 20,21 The
low-molecular-weight heparins appear to
be effective in reducing the frequency of
coagulopathy in horses with colic 20 with-
out the adverse effect of heparin on

Hemorrhagic disease

hematocrit and dotting time. 22 Calcium
heparin causes in-vivo red cell aggrega-
tion in horses, with a resultant reduction
in hematocrit and hemoglobin concentra-
tion and a reduction in platelet count 21-23
The low-molecular-weight heparins are
dosed on the basis of anti-factor-Xa
activity. At doses of these compounds that
prolong factor Xa activity and thrombin
time, they have a minimal effect on
bleeding time or activated partial throm-
boplastin time in horses. 20,22,24 A range of
doses of heparin calcium have been
employed, ranging from 40IU/kg BW
intravenously or subcutaneously every
12-24 hours to 150IU/kg BW initially
followed by 125 IU/kg BW every 12 hours
for 3 days and then 100 IU/kg BW every
12 hours. 20,21 Dalteparin (50 and 100
anti-Xa U/kg) and enoxaparin (40 and
80 anti-Xa U/kg) can be administered
once daily to horses. 24

Sodium pentosan polysulfate, a
compound with heparin-like activity used
for treatment of arthritis in horses, at doses
of 3, 6 or 10 mg/kg, causes dose- dependent
increases in partial prothrombin time that
persist for 24-48 hours. 25 This drug is not
used for treatment of coagulopathies.

Hirudin, an anticoagulant originally
derived from leaches but now available as
a recombinant compound, is a specific
inhibitor of thrombin that is independent
of antithrombin activity. The compound
could be useful in treatment of hyper-
coagulable states in which there is
diminished thrombin activity. Recombi-
nant hirudin has been investigated in
horses in which the maximum plasma
concentration occurred at approximately
130 minutes and declined with a terminal
half-life of approximately 600 minutes.
A doubling of activated partial throm-
boplastin time occurred 1.5 hours after sub-
cutaneous administration of 0.4 mg/kg. 26
The clinical efficacy of recombinant hirudin
has not been determined.

Tissue plasminogen activator
increases the activity of plasmin, thereby
facilitating dissolution of clots. Its use in
farm animals has not been reported, with
the exception of its injection into the
anterior segment of the eye to dissolve
fibrin associated with uveitis in horses.

Streptokinase and urokinase have
been used to facilitate dissolution of fibrin
clots in farm animals, but there has been
no critical analysis of their effectiveness.

DISEASES CAUSING
HEMORRHAGE

Vasculitis

Septicemic and viremic diseases
The vasculitis is associated with endo-
thelial damage occurring as a direct result
of infection of the endothelium (e.g.

equine herpesvirus-1 myeloencephalo-
pathy, African horse sickness) or from
immune-mediated events centered on the
endothelium (e.g. purpura hemorrhagica).
It may be complicated by defects in blood
coagulation and platelet disorders
depending upon the infection. In many
instances coagulation defects are a mani-
festation of early disseminated intra-
vascular coagulation. Clinically, petechial
and ecchymotic hemorrhages associated
with septicemia are most obvious in the
mucous membrane of the mouth, vulva
and conjunctiva or in the sclera but they
are widely distributed throughout the body
on postmortem examination. Diseases
causing vasculitis include:

• Systemic viral diseases: equine
viral arteritis, equine infectious
anemia, African horse sickness,
malignant catarrhal fever, bovine
ephemeral fever, bovine virus
diarrhea, bluetongue, hog cholera,
swine fever, equine herpesvirus- 1
myeloencephalopathy

• Chlamydial and rickettsial diseases:
Anaplasma phagocytophila

• Bacterial diseases: salmonellosis,
Histophilus somni infection,
Actinobacillus sp. pleuropneumonia
infection, pasteurellosis, erysipelas
in pigs

• Miscellaneous: aspergillosis,
Strongylus vulgaris infection.

Purpura hemorrhagica
This is a hemorrhagic disease of horses
associated with a leukocytoclastic vascu-
litis. The majority of cases occur as a
sequel to strangles. Cases also occur
following immunization against Strepto-
coccus equi and as a sequel to infection
with other streptococci. The disease
appears to be an immune complex-
mediated disease with deposition of IgA-
containing immune complexes on vessel
walls 27,28 Hemorrhagic tendencies in the
disease include petechial and ecchymotic
hemorrhages but also may result in large
extravasations of blood and serum into
tissues. The hemorrhage and exudation of
serum may result in anemia and a
depression in the circulating blood
volume. Hemorrhage associated with
purpura is usually treated with blood
transfusions and corticosteroids. A fuller
description of the syndrome is given
elsewhere.

Necrotizing vasculitis

Of unknown etiology but possibly immune
mediated, this syndrome occurs in all
species. 29 It is similar to purpura and may
be local or generalized with petechial
hemorrhage and serosanguineous exuda-
tion subcutaneously and into tissue spaces.
Hemorrhagic tendencies associated with

vasculitis may be confused with those
associated with a defect in the clotting
mechanisms as the primary cause. Differ-
entiation depends on accurate laboratory
examination.

Treatment

Treatment of vasculitis centers on removal
of the inciting cause and minimizing or
eliminating inflammation in the vessel.
Disease-specific treatments are discussed
under each of those topics. Inflammation
can be reduced by administration of
glucocorticoids, the selection and dose of
which vary with species (see Formulary in
the Appendix). General supportive treat-
ment can include the administration of
blood or plasma if severe anemia or hypo-
proteinemia occur.

Coagulation defects

Coagulation defects can be either acquired
or inherited. Acquired defects are usually
related to exposure to compounds that
interfere with production of clotting
factors, or that cause depletion of these
factors. Inherited defects usually present
in young animals, but defects that only
marginally increase clotting time might
not be detected until the animal under-
goes surgery or suffers trauma. Demon-
stration of defects in blood clotting is
based on observation of signs of excessive
hemorrhage, with confirmation achieved
by measurement of bleeding time and
laboratory examination of the activity or
concentration of soluble blood clotting
factors.

Acquired hemostatic defects
Acquired clotting defects include those
associated with intoxications that impair
production or function of clotting factors,
and those related to depletion of clotting
factors. Disseminated intravascular co-
agulation is a common cause of hemor-
rhagic diathesis in animals that is discussed
in detail under that heading. Protein
losing nephropathy is associated with loss
of antithrombin in urine and increased risk
of thrombosis in cattle. Similarly, horses
with protein-losing enteropathy have low
plasma concentrations of antithrombin,
which could contribute to the thrombotic
tendency noted in these animals. 30

Reduction of vitamin Kj-dependent
clotting factors II, VII, IX and X may
result from coumarol poisoning following
ingestion of coumarol containing plants
such as Melilotus alba, Anthoxanthum
odoratum, Apium nodiflorum, Ferula
communis (giant fennel) or warfarin,
brodifacoum and related compounds. 31-33
This syndrome is discussed in detail
under each of those headings. Vitamin K
deficiency, other that induced by
intoxication with the compounds listed
above and the disorder in postweaned

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

pigs discussed below, has not been reported
in farm animals, probably because forage
contains high concentrations of this
compound.

A hemorrhagic syndrome in post-
weaned pigs is recorded from the USA,
New Zealand, France, Japan, Germany,
Brazil and South Africa. 34 " 36 The syndrome
occurs as an outbreak with anemia,
hemarthrosis, spontaneous hemorrhage
under the skin of the legs and body and
hemorrhage following management
procedures such as castration. There is a
high case fatality and the syndrome is
particularly common in pigs a few weeks
after weaning. There is prolongation of
the prothrombin time and activated
partial thromboplastin time. The out-
breaks resolve promptly following the
injection of vitamin K or its inclusion in
the diet. An association has been made
with housing on mesh floors. 36 The
disease is believed to be due to a
deficiency of vitamin K in the diet coupled
with housing that precludes intake of
vitamin K 2 from the feces or bedding and
decreased synthesis in the gut as a result
of antibiotics in the feed, especially
sulfonamides.

Snake venom may have procoagulant
or anticoagulant action. 37 In both cases
coagulation defects may occur as proco-
agulant toxins result in the activation,
consumption and depletion of pro-
thrombin and fibrinogen, leading to a
coagulopathy, prolonged clotting times
and epistaxis. 38,39

Carcass hemorrhage or blood splash
in slaughter lambs has been associated
with extended prothrombin times
because of prior grazing of coumarin-
producing plants. The method of electrical
stunning at slaughter can also result in
carcass hemorrhage. 40

Pamfilaria bovicola produces large
extravasations of blood under the skin of
cattle and to some extent in tissue
spaces. 41 Bleeding from the skin may be
the presenting sign of infestation.

A number of fungal toxins can cause
hemorrhagic disease when ingested:

• Aflatoxins produced by Aspergillus
spp. do so in association with
increased prothrombin time in cattle,
swine and horses

° Trichothecene toxins produced by
fungal infestations of feed by
Fusarium spp., Myrothecium spp.,
Cephalosporium spp.

° Trichothecium spp. also produce
hemorrhagic disease
0 Toxins associated with Penicillium
rubrum

° Grass nematodes that infest Lolium
rigidum.

Hydroxyethyl starch solution (Heta-
starch), used to increase plasma oncotic
pressure in animals with hypopro-
teinemia, prolongs cutaneous bleeding,
prothrombin and activated partial throm-
boplastin times and decreases fibrinogen
concentration and von Willebrand antigen
and factor VIII:C activities in ponies,
apparently by dilution of clotting factors 42

Navel (umbilical) bleeding in new-
born piglets is a syndrome of unknown
etiology. Following birth and for periods
up to 2 days afterwards, blood drips or
oozes from the umbilicus of affected pigs
to produce severe anemia, with death
frequently occurring from crushing. The
navel cords are abnormally large and
fleshy and fail to shrink after birth. The
defect appears to be one of immaturity of
collagen so that a proper platelet clot does
not form. Ear-notching for identification
is also followed by excessive bleeding. A
variable number of piglets within the
litter may be affected and the syndrome
may have a high incidence on certain
problem farms. The addition of vitamin K
and folic acid to the sows' ration may
be followed by a drop in incidence but
controlled trials with menadione have
shown no effect. Vitamin C given to preg-
nant sows for at least 6 days before
farrowing appears to prevent the syndrome.

Jejunal hemorrhage syndrome in
cattle is discussed in Chapter 5. 43

Infestation of sheep by Fasciola hepatica
shortens activated partial thromboplastin
time and prolongs prothrombin and
thrombin times. 44

Inherited or congenital defects in

hemostasis

Hemophilia A

Factor VIIF.coagulant (VIII.C) deficiency,
hemophilia A, is recorded in Thorough-
breds, 45 Standardbreds, Arabian and
Quarter horse colt foals 46 and sheep 47 and
is associated with a deficiency in factor VIII.
The disease in the Quarter horse colt also
involved deficiency of factors IX and XI. It is
inherited as a sex-linked recessive trait
with the defective gene located on the
X chromosome. Clinically affected foals
show signs of a hemorrhagic tendency
within a few weeks of birth, with the
development of hematomas, persistent
nasal bleeding, bleeding from injection sites
and sudden death from massive internal
hemorrhage. Affected foals are anemic. The
diagnosis is made by the finding of very low
plasma factor VHI:C activity (usually < 10%
of values in unaffected animals). Treatment
requires fresh frozen plasma or plasma
concentrates but is not recommended
because of the unavailability of sufficient
plasma concentrates, the recurrent nature
of the problem and the poor prognosis for
long-term soundness 46

Von Willebrand disease (factor VIII:vWF
deficiency)

Von Willebrand factor is a large adhesive
glycoprotein that mediates adhesion of
platelets to exposed subendothelium and
that also is a carrier for coagulation factor
VIII, protecting it from degradation in the
circulation. There are three variations of
von Willebrand's disease - types I, II and
III. Two variations of von Willebrand's
disease are recorded in pigs 47,48 - both
inherited as simple autosomal recessive
traits. The disease in pigs is used as an
experimental model for the disease in
humans and the pig gene for von
Willebrand factor is similar in size and
complexity to its human counterpart, with
affected pigs having a point mutation
within the vWF gene. Type 1 von
Willebrand's disease occurred in an
8-day-old Quarter horse colt that was
examined because of extensive purpura 49
The colt had a concentration of von
Willebrand factor that was 9% of that of
normal horses. The dam of the colt also
had prolonged bleeding time and a
concentration of von Willebrand factor
30% of that of normal animals, 49 suggest-
ing a familial and possibly heritable trait.
Type II von Willebrand disease is recorded
in a Quarter horse with hemorrhage
associated with trauma, prolonged bleed-
ing, lasting several hours, at an injection
site, and spontaneous conjunctival hemor-
rhage, 50 and in a Thoroughbred mare and
her colt. 51 The hemorrhage in the
Thoroughbred mare and foal was not life-
threatening. Type III von Willebrand's
disease is usually associated with low
concentrations of factor VIII. Suspect
factor VIII deficiency has been reported in
Hereford calves. 52 The prime mani-
festation was death shortly following
castration with bleeding from the surgical
site, intra-abdominal hemorrhage
and severe anemia. The disease also
occurs in sheep, and is linked to the
X chromosome. 53

Diagnosis is based on the observation
of prolonged bleeding after minor trauma
or surgery, prolonged activated partial
thromboplastin time, although this can be
minimal, normal prothrombin time, and
decreased factor VIII:C activity and von
Willebrand antigen concentration. 49,51
The ristocetin cofactor activity of von
Willebrand factor is reduced in animals
with type II von Willebrand's disease 49,51
An ELISA is available that is suitable for
use in a number of species, including
horses, pigs and cattle. 4 Chromogenic
assays of factors VII, VIII:C, IX and X
developed for testing of human plasma
are reliable when used for testing of horse
plasma. 3 Desmopressin increases the
release of von Willebrand factor from
vascular endothelium and is used for

Hemorrhagic disease

445

treatment of the disease in humans. There
are no reports to date of its use in
farm animals or horses. The disease can
be managed by housing to minimize
trauma and administration of plasma
before elective surgery, although this
did not completely prevent excessive
bleeding.

Factor XI deficiency

Factor XI deficiency is recorded in
Holstein-Friesian cattle in Canada 54 and
in Great Britain. 55 It is transmitted as an
autosomal recessive gene and occurrence
in Britain has been traced to the import-
ation of Canadian semen, with genetic
links between carriers in the two
countries. 56 Heterozygous cattle have
decreased levels of factor XI but are
usually asymptomatic. The severity of
clinical disease varies in homozygous
cattle but they usually show prolonged or
repeated bleeding episodes after trauma
such as dehorning and hemorrhage
following venepuncture. There are oc-
casional deaths associated with multiple
hemorrhages. Heterozygote carriers have
decreased factor XI coagulant activity but
measurement of factor XI activity is not a
sensitive test for the carrier status, and a
DNA-based tested is available that
accurately identifies heterozygotes. 54 ' 56-58

Other clotting factor disorders
Prekallikrein deficiency is recorded in a
family of miniature horses . 59 The con-
dition was not associated with clinical
disease in these horses but blood samples
failed to clot. It has also been recorded in
three Belgian horses and was detected in
this group because one hemorrhaged
following castration. 60 The mode of trans-
mission is not known, but the familial
nature of the disease suggests that it is
heritable.

Heritable fibrinogen deficiency was

found in a Border Leicester lamb manifest
with inflammation and bleeding at the
umbilicus and ear tag wound at 7 weeks
of age 61 and in Saanen goats.

Platelet disorders

Disorders of platelets include alterations
in the number of platelets in blood
(thrombocytopenia or thrombocytosis)
and their function (with reduced function
referred to as thrombasthenia). The
physiology of platelets varies in important
ways among the farm animal species. For
instance, aggregation of platelets from
horses, but not cattle, is inhibited by
aspirin (acetylsalicylic acid), and horse
platelets adhere to immobilized auto-
logous fibrinogen while those of sheep
do not. 62 Platelets of different species
respond differently to some agonists of
platelet aggregation, such as ristocetin. 63

Thrombocytopenia

Clinical signs associated with thrombocy-
topenia or thrombasthenia are petechial
and ecchymotic hemorrhages, prolonged
bleeding after venipuncture or from injec-
tion sites, epistaxis, hyphema and melena.
A combination of some or all of these
clinical signs is referred to as purpura.
Thrombocytopenia can result from
decreased production of platelets in the
bone marrow or by increased con-
sumption, increased peripheral destruc-
tion or a combination of these factors 64

Decreased platelet production is
commonly associated with disorders that
impair bone marrow function and there is
usually simultaneous suppression of
granulocyte and erythrocyte production.
Thrombocytopenia and neutropenia
develop before anemia because of the
short life span of these cells relative to
erythrocytes. Increased destruction, that
is, the abnormal consumption of platelets,
is most commonly immune-mediated.
Increased consumption also occurs with
severe trauma and disseminated intra-
vascular coagulation, both of which
increase the rate at which platelets are
incorporated into clots.

Pseudothrombocytopenia occurs as
a result of aggregation of platelets after
collection into a glass tube containing
EDTA. 11 Ex-vivo aggregation can occur
with other anticoagulants, including
heparin. This situation can be recognized
by the presence of abnormally low
platelet counts in animals without
evidence of excessive hemorrhage, or by
the presence of clumps of platelets on
microscopic examination of blood smears.
Collection of blood into an anticoagulant
other than EDTA or heparin, such as
citrate, and measurement ' of a normal
platelet count confirms the diagnosis of
pseudothrombocytopenia.

Differentiation of the causes of
thrombocytopenia is by clinical exami-
nation to detect underlying disease,
hematology, examination for anti platelet
antibody and examination of bone
marrow aspirates.

Decreased production
Thrombocytopenia due to decreased pro-
duction, as opposed to increased destruc-
tion within the marrow, usually occurs
with granulocytopenia because of the short
intravascular half-life of both granulocytes
and platelets.

This occurs with poisonings by
Pteridium spp. (bracken fem) or Cheilanthes
seiberi in cattle; the fungus Stachybotnjs
spp. (which produces a trichothecene) in
cattle, pigs, sheep and horses; chronic
furazolidone poisoning in calves; poison-
ing caused by trichloroethylene- extracted
soybean meal; drugs that cause bone-

marrow suppression, and radiation
injury 65,66 Severe myelophthisis, such as is
associated with myeloid dysplasia or
myelofibrosis, causes thrombocytopenia
in association with anemia and leukopenia.
A familial myelofibrosis is reported in
pygmy goats with anemia, granulo-
cytopenia and thrombocytopenia. 67

The syndrome is predominantly one of
spontaneous hemorrhage but is compli-
cated by bacteremia and fulminant infec-
tions facilitated by severe leukopenia. A
granulocytopenic syndrome of unknown
origin, occurring in all ages of cattle and
manifest with a severe hemorrhagic
diathesis, high morbidity and high case
fatality, has been reported on various
occasions in Australia. 68

Familial diseases resulting in throm-
bocytopenia secondary to decreased pro-
duction are recorded in Standardbred
horses in which there is generalized
bone marrow hypoplasia. 69 Pancytopenia
secondary to bone marrow aplasia is
reported in a Holstein heifer. 70

Increased destruction
Inflammation and infection The most
common causes of thrombocytopenia are
severe gastrointestinal disease (strangu-
lating intestinal obstruction, anterior
enteritis, colitis) and infectious and inflam-
matory disease, where a combination of
increased destruction and increased con-
sumption is the cause. 64,71

Infection by a variety of viral, bacterial
or rickettsial agents causes mild to severe
thrombocytopenia. African horse sickness,
equine infectious anemia, Anaplasma
phagocytophila (equine granulocytic
ehrlichiosis) and infection by Neorickettsia
risticii (Potomac horse fever) cause mild
to moderate thrombocytopenia.

Infection such as occurs in hog cholera
and African swine fever can result in
thrombocytopenia and contributes to the
hemorrhagic tendency seen in these
diseases. 72 Outbreaks of hemorrhagic
disease due to thrombocytopenia in veal
calves have been attributed to infection
with bovine virus diarrhea (BVD) virus
type 2 and the disease has been repro-
duced experimentally with noncytopathic
BVD virus. 73 The appearance of hemor-
rhage was directly related to the number
of circulating platelets and bleeding was
seen when platelet numbers fell below
500/mL. Calves that developed throm-
bocytopenia had low (+ 1:32) BVD
neutralizing titers. The virus infects
megakaryocytes. 74 Thrombocytopenia with
a bleeding tendency (bloody diarrhea,
petechial and ecchymotic hemorrhage) is
also recorded in approximately 10% of
adult cattle with acute BVD infection. 75
Infection by Theileria annulata causes
thrombocytopenia and prolonged

16

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

prothrombin time in cattle. 76 Other
infectious causes in cattle include bovine
leukemia virus, sarcocytosis and
salmonellosis.

Immune-mediated (idiopathic) throm-
bocytopenia Most instances of throm-
bocytopenic purpura in the past have
been described as idiopathic. However,
the development of newer diagnostic
tests, including flow cytometry, that can
reveal the presence of antibodies on
the surface of platelets has permitted
the classification of many of these cases
as immune-mediated. 12,77 Among the
immune-mediated thrombocytopenias
there are autoimmune and isoimmune
diseases.

Isoimmune thrombocytopenia can

be a complication in neonatal isoerythro-
lysis in foals and mules as a result of
absorption of colostrum containing anti-
platelet antibodies. 78,79 The disease also
occurs as only thrombocytopenia in mule
foals and is attributable to antiplatelet
IgG antibodies in the mule foal's serum. 80
In addition to thrombocytopenia, there is
also depression of platelet aggregation in
these foals, probably because of binding
of IgG to collagen-binding sites on the
platelet surface. Thrombocytopenia and
neutropenia, assumed to be isoimmune-
mediated, were found in foals with ulcer-
ative dermatitis and mucosal ulceration. 81
The foals had purpura and responded to
supportive treatment and administration
of corticosteroids.

The disease is observed in newborn
pigs as a result of maternal isoimmuniza-
tion, and has been reproduced experi-
mentally. Piglets are normal at birth but
become thrombocytopenic after suckling
colostrum containing antiplatelet anti-
body. Clinical signs do not develop until
after the fourth day of life. There is a heavy
mortality rate, death being preceded by a
generalized development of submucosal
and subcutaneous hemorrhages, drowsi-
ness, weakness and pallor. There is no
practicable treatment. The sow should be
culled. Thrombocytopenic purpura has
occurred in a group of lambs given a
single cow's colostrum and was manifest
with multiple hemorrhages and death by
two days of age. 82

Thrombocytopenia in adult animals with
normal prothrombin times and partial
thromboplastin times and with no evidence
of disseminated intravascular coagulation is
considered most likely to develop by
autoimmune- mediated mechanisms. 83-85
Immune-mediated thrombocytopenia can
be induced by drugs or can be secondary to
infectious or neoplastic disease 64 but most
cases are idiopathic. 83,84 The disease is
reported most commonly in horses but
does occur in cattle. 55

Horses of any age can be affected. The
cause is usually not identified but the
disease can be associated with admin-
istration of drugs, especially penicillin.
The disease is caused by binding of IgG
to platelets or to megakaryocytes,
with subsequent impaired maturation,
enhanced clearance or both, resulting
in low platelet counts in blood. 86
Petechiation and hemorrhage may be
confined to single systems, such as the
respiratory system with epistaxis and
hematomas in the nasal sinuses, or the
genital tract producing a bloody vulval
discharge, with no detectable abnormality
at other mucous membranes. More
generalized involvement with widespread
petechiation of mucous membranes,
epistaxis and melena can also occur.
Diagnosis is by measurement of blood
platelet concentration and elimination of
disseminated intravascular coagulation or
primary diseases. Demonstration of
platelet-surface-bound IgG on a signi-
ficant proportion of platelets is diagnostic.
Fewer than 0.15% of platelets from
normal horses have IgG bound to the
surface, whereas more than 4% of
platelets of thrombocytopenic horses
have IgG on the surface. 77 Treatment
includes the immediate removal from any
medication and the administration of
dexamethasone (0.040 mg/kg intramus-
cularly, intravenously or orally, once daily)
or prednisolone (1 mg/kg orally), but
not prednisone. This is usually effective in
restoring platelet count and controlling
hemorrhage. Resolution of hemorrhage
can occur even before there are marked
changes in platelet count. Treatment
might need to be continued for days to
weeks. Most horses do not require long-
term treatment. For horses with life-
threatening hemorrhage, administration
of platelet-rich plasma or blood is
needed. A transfusion volume of 10 mL
blood per kg BW can be effective.
Successful treatment with azathioprine in
horses that do not respond to gluco-
corticoids is reported (0. 5-1.5 mg/kg
orally every 24 h). 77,83 Splenectomy has
been used to treat horses with chronic,
idiopathic thrombocytopenia that is
refractory to medical therapy. However,
surgical treatment should be undertaken
only in extreme cases, and with attention
to the effect of thrombocytopenia on
hemostasis during surgery.

Idiopathic thrombocytopenia purpura
is also recorded in a 10 -month-old bull , 87
and immune-mediated thrombocytopenia
and anemia occurred in a cow after
vaccination with a polyvalent botulism
vaccine 88 Corticosteroid-responsive throm-
bocytopenia occurred in two beef-breed
cows with subcutaneous hematomas and
epistaxis. 89

Increased consumption
Increased consumption of platelets occurs
in animals with severe trauma or disse-
minated intravascular coagulation.

Other causes

Thrombocytopenia occurs in horses with
lymphosarcoma or myeloproliferative
disease. 64 Thrombocytopenia is usually
associated with myelophthisic disease
and is therefore a result of reduced platelet
production. Heparin causes thrombo-
cytopenia in horses, but the mechanism
has not been determined. 21,22

Thrombasthenia

Disorders of platelet function can result in
purpura even in the presence of normal
platelet counts. Disorders of platelet func-
tion can be congenital or acquired.

Acquired defects of platelet function
are usually secondary to severe metabolic
abnormalities such as uremia, liver failure
or septicemia, or to administration of
drugs. Among the compounds commonly
administered to animals, aspirin is most
notable in that it inhibits platelet
aggregation in horses but not in cattle,
despite inhibition of platelet generation of
thromboxane-2 in both species. 19 Other
NSAIDs have minimal, if any, effect on
platelet function. Dextran inhibits platelet
function when administered to horses 90

A bleeding tendency is present in the
Chediak-Higashi syndrome in cattle. A
prolonged bleeding time is demonstrable
despite the presence of normal soluble
coagulation factors and platelet numbers,
and is due to a defect in platelet aggre-
gation. 91 Thrombasthenia, 92,93 possibly
also associated with variant von Willebrand
factor, 94 is also recorded in bleeding
disorders in Simmental and Simmental
crossbred cattle in Canada and the USA,
and manifests with epistaxis in cold
weather, subcutaneous hematomas and
prolonged bleeding following minor
procedures such as vaccination and ear-
tagging. 92,93 Platelet dysfunction and
purpura were diagnosed in a 5 -day-old
Simmental heifer. 95 Umbilical bleeding
in calves has also been reported as an
inherited condition in Japanese black
cattle 96,97 with low ADP-induced platelet
aggregation. Affected cattle die by 1 year
of age from repeated umbilical cord
hemorrhage.

Thrombasthenias are also reported in
horses. Glanzmann's disease is reported
in horses with a prolonged history of
epistaxis not associated with exercise. 98
The horses had prolonged bleeding time,
markedly delayed clot retraction and a
decrease in concentration of fibrinogen
receptors on the platelet surface. Treat-
ment with glucocorticoids was not effec-
tive in preventing epistaxis. Another form
of platelet defect was diagnosed in a

Hemorrhagic disease

447

Thoroughbred filly with excessive hemor-
rhage after pin firing. The filly had
prolonged bleeding time and normal clot
retraction.The filly's platelets did not bind
to collagen and the defect was deduced
to be in calcium signaling within the
platelets."

Thrombocytosis

Thrombocytosis is not usually asso-
ciated with purpura or a tendency to
hemorrhage unless the platelets have
abnormal function. Thrombocytosis is
considered to be either primary or
secondary. 100,101 Primary thrombocytosis
is a result of excessive production of
megakaryocytes in the absence of any
inciting disease or increased release into
the circulation. While exercise, epine-
phrine and vincristine can increase
platelet counts, the most important cause
of primary thrombocytosis is myelopro-
liferative disorder resulting in abnormal
rate of platelet production. Primary
thrombocytosis is rare in farm animal
species.

Secondary thrombocytosis occurs in
animals with severe systemic inflam-
matory or infectious diseases of more
than several days duration, and usually of
several weeks duration. Young animals
appear to be more susceptible but the
condition can occur in animals of any age.
Detection of thrombocytosis should
prompt a thorough clinical examination
for a cause of chronic inflammation in the
animal. Common causes in horses include
pneumonia, Rhodococcus equi infection,
septic arthritis and colitis. 97 Thrombocytosis
with Heinz body anemia is reported in
cattle fed cabbage.

DISSEMINATED INTRAVASCULAR
COAGULOPATHY AND
HYPERCOAGULABLE STAT ES

There is increasing recognition that
abnormalities in blood clotting and
fibrinolysis exist in both subclinical and
clinical forms in many diseases of farm
animals, and that the presence and
severity of these disorders is related to
prognosis for survival. There is a spectrum
of abnormalities ranging from mild
changes in concentration or activity of
clotting factors and indicators of fibrino-
lysis, through evidence of excessive
coagulation or impaired fibrinolysis, to a
hemorrhagic diathesis. Previously, the
most extreme form of this disorder was
recognized as a hemorrhagic diathesis
and termed disseminated intravascular
coagulation (DIC). Increasing sophistica-
tion and availability of measures of
coagulation and fibrinolysis have revealed
that abnormalities of hemostasis exist
even in animals without clinical evidence
of excessive hemorrhage. These milder

changes in hemostasis and fibrinolysis
are, not surprisingly, much more common
than is DIC, but are still associated with
am increased case fatality rate.

ETIOLOGY AND EPIDEMIOLOGY

DIC and hypercoagulable states are
acquired disorders of hemostasis in
animals that occur as a consequence of
severe disease that induces systemic
inflammation (systemic inflammatory
syndrome). DIC is now regarded as a
component and consequence of systemic
inflammation, rather than being an isolated
disorder of hemostasis. 100 DIC and hyper-
coagulable states are therefore associated
with any severe disease that initiates a
systemic inflammatory response. A partial
listing is-, colitis, enteritis, infarctive
lesions of the intestines, septicemia,
abomasal torsion, metritis, severe trauma,
immune-mediated inflammation (e.g.
purpura hemorrhagica), hyperthermia and
neoplasia. A common, but not universal
feature, of diseases that induce DIC or a
hypercoagulable state is the presence of
presumed or documented endotoxemia,
although DIC can be induced by most
infectious organisms. It is important to
recognize that any severe disease that
causes a systemic inflammatory response
can incite changes in hemostatic function.

The presence of a hypercoagulable
state or DIC is most well recognized in
horses with gastrointestinal disease. 10,102-104
It also occurs in cattle with abomasal dis-
placement and in endotoxemic calves. 105,106
Low plasma antithrombin concentrations
occur in cows with hepatopathy, peritonitis
or acute enteritis. 107 The disease has been
reproduced experimentally in pigs, and
probably occurs naturally in that species
in many diseases, including African swine
fever. 108,109 The prevalence of DIC (clinically
evident hemorrhage) is uncommon, while
the prevalence of a hypercoagulable state
detectable only by clinicopathologic
testing is much more common. 30,104

The prevalence of the syndrome is not
well defined, partly because of problems
in achieving a confirmatory diagnosis by
laboratory assessment of factors involved
in coagulation or fibrinolysis because of
the lack of laboratories providing the
necessary assays, and partly because of
lack of recognition of the disease. Five of
20 cattle with either left or right displace-
ment of the abomasum had a hypercoa-
gulable state. 106 Of horses examined at a
referral institution for colic, 3.5% had
clinical signs consistent with DIC and
supportive laboratory evidence. 110 All
these horses had severe inciting disease,
with most requiring surgical intervention
for infarctive intestinal disease. This study
probably under-represents the proportion
of horses with severe gastrointestinal

disease that have hemostatic -abnor-
malities, given that many horses with
severe gastrointestinal disease have
subclinical abnormalities in hemostasis
and fibrinolysis. 30 The survival rate among
horses with colic and DIC or a hyper-
coagulable state was 19%, whereas that in
horses with colic but no clinicopathologic
evidence of a hemostatic disorder was
80%. 102 Twelve of 37 horses with colitis
had clinicopathological evidence of a
hypercoagulable state, although none
had clinical signs of DIC at the time of
sample collection. 30 Of the 12 horses
with a hypercoagulable state, five died,
compared to two of 25 horses with colitis
that did not have evidence of a
coagulopathy.

Clinically relevant alternations in
hemostatic and fibrinolytic indices occur
in neonatal foals with septicemia. 111
Derangements in hemostatic or fibrino-
lytic indices were helpful in identification
of septic foals with increased risk of
coagulopathy, but were not helpful in
predicting hemorrhage as compared to
thrombus formation. Twenty-three of
the 34 septic foals did not survive.
Survival of septicemic foals was correlated
with Gram-negative bacteremia but not
with the presence of endotoxin or
coagulopathy. 111

PROGNOSIS

The prognosis for animals with clinical
signs of disseminated coagulation is very
poor. Horses without physical signs of
hemorrhage or defective fibrinolysis but
with clinicopathological evidence of a
hypercoagulable state have a worse prog-
nosis than horses without evidence of a
hypercoagulable state. 10,30,102-104 When
evaluating the prognosis of an animal with
evidence of a coagulopathy as part of the
systemic inflammatory syndrome it must be
borne in mind that the coagulopathy is
secondary to the initiating disease; the more
severe the initiating disease the greater the
likelihood that the animal will have a
coagulopathy, and the more severe the
initiating disease the poorer the prognosis.
DIC and lesser abnonnalities of hemostasis
can therefore be regarded as markers of
disease severity and considered accordingly
when determining a prognosis. This is not
to minimize the importance of DIC and
hemostatic defects of lesser severity in the
pathogenesis of severe disease, and the
need to institute effective preventive
measures and treatment.

PATHOPHYSIOLOGY

DIC, or consumption coagulopathy, can
develop in a number of diseases which, in
themselves, are not diseases that pri-
marily affect hemostatic mechanisms. The
pathogenesis involves systemic activation
of coagulation with intravascular deposition

18

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

of fibrin leading to thrombosis of small
and medium-sized blood vessels with
subsequent organ failure. Depletion of
platelets as a result of platelet activation
and binding to fibrin to form clots, and of
coagulation factors, results in excessive
bleeding. The systemic formation of fibrin
results from increased generation of
thrombin and the simultaneous sup-
pression of anticoagulation mechanisms
(which are detectable in animals as
reduced concentration of antithrombin)
and impaired fibrinolysis. 112 Products of
fibrinogen activation, including fibrino-
peptides A and B, contribute to systemic
vasoconstriction and the hypoperfusion
of some organs. The disorder, in its most
extreme form, involves both excessive
coagulation and, seemingly paradoxically,
bleeding.

Systemic activation of coagulation is
part of the systemic inflammatory response
syndrome, which is dominated by
interleukins 1 and 6 and tumor necrosis
factor-alpha. 100,112 There might be a
contribution of complement activation to
the hypercoagulability. Activation of
clotting occurs through either damage to
endothelium or activation and release of
tissue factor. Tissue factor expression is
increased by one or more of the pro-
inflammatory cytokines (interleukin-1, -6,
-8 and tumor necrosis factor), which are
almost universally increased in diseases
that feature systemic inflammation.
Generation of tissue factor results in
activation of the extrinsic clotting cascade
with resultant increases in thrombin. The
increased activity of the coagulation
cascade is temporally associated with
impaired activity of anticoagulant mech-
anisms, demonstrable as decreases in
plasma concentration of antithrombin
and protein C. Further exacerbating the
effect of increased rate of fibrin synthesis
is impaired fibrinolysis, indicated by
diminished activity of plasminogen and
increased activity of plasminogen-
activator inhibitor. 112

In summary DIC is a hemorrhagic
diathesis, characterized by an augmen-
tation of normal clotting mechanisms that
results in depletion of coagulation factors,
deposition of fibrin clots in the microvas-
culature and the secondary activation of
fibrinolytic mechanisms. The augmenta-
tion of clotting mechanisms can result in
a depletion of platelets and factors V, VIII,
IX, XI and Xlla, and the depletion of fibri-
nogen in association with the formation
of fibrin clots in the microvasculature.
These fibrin clots decrease tissue per-
fusion, which can then lead to further
activation and depletion of clotting fac-
tors by the release of tissue thrombo-
plastin as a result of tissue hypoxia. The
bleeding tendency occasioned by the

depletion of these clotting factors is
further accentuated by the secondary
activation of the thrombolytic system
with the production of fibrin degradation
products that have anticoagulant
properties.

Impaired capacity of the monocyte
phagocytic system contributes to the
disease. Macrophages in the reticulo-
endothelial system remove fibrin degra-
dation products and activated clotting
factors from the circulation. Loss or
diminution of the capacity to remove
hemostatic and fibrinolytic compounds
causes increases in plasma concentration
of these products and exacerbation of the
disease. Damage to the reticuloendo-
thelial system, notably in the liver and
spleen, resulting from damage as a con-
sequence of the underlying disease
(endotoxemia) or lack of perfusion of liver
and spleen as part of DIC, decreases
removal of these compounds and induces
a viscous cycle of disease.

DIC can be initiated by a variety of
different mechanisms.

° Extensive tissue necrosis, such as
occurs in trauma, rapidly growing
neoplasm, acute intravascular
hemolysis and infective diseases such
as blackleg, can cause extensive
release of tissue thromboplastin
and initiate exuberant coagulation via
the extrinsic coagulation pathway
° Exuberant activation of the intrinsic
pathway can occur when there is
activation of the Hageman factor by
extensive contact with vascular
collagen, as occurs in disease with
vasculitis, or those associated with
poor tissue perfusion and tissue
hypoxia with resultant endothelial
damage

° Factors that initiate platelet

aggregation, such as endotoxin, that
cause reticuloendothelial blockage,
such as excessive iron administration
to piglets, or that cause hepatic
damage to interfere with clearance of
activated clotting factors, can
contribute to the occurrence of
disseminated intravascular
coagulation.

CLINICAL SIGNS

As discussed above, defects in hemostasis
and fibrinolysis range from those that are
detectable by clinicopathologic examina-
tion but are not associated with clinical
signs of excessive bleeding or coagulation,
through fulminant hemorrhagic diathesis.

The presence of a hypercoagulable
state that is not associated with signs of
excessive bleeding or thrombosis none-
theless worsens the prognosis of severe
diseases. This is probably due to DIC-
induced injury to organs that is not

detectable against the background of
damage caused by the primary disease-
but that has an important or pivotal effect
on the animal's well being. The next
progression of the disease is evidence of
enhanced thrombosis, most evident as
thrombosis of large vessels after minor
damage such as that associated with
intravascular catheterization or simple
venipuncture. In some cases vessels can
thrombose without obvious inciting
cause. An example of a common mani-
festation of this stage of the disease is
jugular vein thrombosis in horses or cattle
with severe disease and low plasma
concentration of antithrombin. 30 ' 107

An unusual, but severe, manifestation
of DIC in horses is thrombosis of the
distal limbs, resulting in ischemic necrosis
of the limb and death of the animal. This
clinical manifestation of DIC occurs in
foals and, to a lesser extent, in adults with
evidence of septicemia or severe gastro-
intestinal disease. 113

The most severe acquired hemostatic
defect in animals with systemic disease is
DIC. This extreme of the clotting disorder
is manifested by local or generalized
bleeding tendencies that vary in severity
from occurrence of petechial hemorrhages
in mucous membranes to life-threatening
hemorrhage or infarction of organs.
Ischemic damage to a wide variety of
organs is possible, with the gastro-
intestinal tract and kidneys being com-
monly affected. 49

CLINICAL PATHOLOGY

There are a large number of hemostatic
and fibrinolytic factors that can be
measured in research laboratories, only a
few of which are routinely available
in clinical laboratories. The following
measures are commonly used to detect
hypercoagulable states or DIC in clinical
situations:

° Platelet count. The abnormality
consistent with DIC is
thrombocytopenia
° Prothrombin time. This is usually
prolonged in animals with DIC but
can occasionally be shortened in
animals with a hypercoagulable
state

0 Activated partial thromboplastin time.
This measure of hemostasis is usually
prolonged in animals with
coagulopathies

° Serum markers of fibrinogen
activation/fibrin degradation. FDPs
have poor sensitivity and specificity
for detection of DIC. Plasma D-dimer
concentration is more sensitive for
detection of abnormalities in
hemostatis/fibrinolysis 9
0 Fibrinogen concentration. Classical
descriptions of DIC include

hypofibrinogenemia as a common
finding. However, this is uncommonly
the case in horses and cattle, 103,106
probably because fibrinogen is an
acute-phase protein the concentration
of which increases in inflammatory
diseases in these species. Declines in
plasma fibrinogen concentration, with
values remaining above the lower
bound of the reference range, are
often noted in horses with
coagulopathy and impending
death 30

• Antithrombin activity is often reduced
in animals with a hypercoagulable
state or DIC.

A number of studies provide detailed
description of the occurrence, and time
course, of abnormalities in hemostatic
and fibrinolytic function in horses with
gastrointestinal disease . 26,102 " 104,114 The
general pattern is that of prolonged
clotting times (prothrombin (PT),
activated partial thromboplastin (APT!))
with diminished activity of antithrombin
and protein C, and increased plasma
concentrations of fibrinogen and fibrin
degradation products. D-dimer concen-
tration has been reported to increase in
horses undergoing surgery for colic 115 or
to be lower in horses with colic than in
healthy horses. 102 Platelet concentration
is reduced in horses with colic and
evidence of coagulopathy. Abnormalities
in hemostatic factors are more common
in peritoneal fluid than in blood of horses
with colic. 114 Tissue plasminogen activator,
plasminogen, protein C, antithrombin III,
and alpha-2-antiplasmin activities and
concentrations of fibrinogen and fibrin
degradation products are greater in
peritoneal fluid from horses with colic
than in peritoneal fluid of healthy horses.

Compared to healthy foals, the PT,
APTr and whole blood recalcification
times are significantly longer in septic
foals. The fibrinogen and fibrin degrada-
tion products concentrations, percentage
plasminogen, alpha-2-antiplasmin and
plasminogen activator inhibitor activities,
and tumor necrosis factor and interleukin-6
activities are greater, and protein C
antigen and antithrombin III activity are
lower in septic foals. 111

Cattle with displaced abomasum often
have abnormalities in one or more of PT,
APTr, thrombin time, platelet count and
plasma concentration of fibrin degrada-
tion products. 106 Pigs with induced
endotoxemia have increases in activity of
tissue factor, plasminogen activator and
plasminogen activator-inhibitor, and
concentrations of thrombin-antithrombin
complexes and fibrin monomer, and a
decline in fibrinogen and factor VII
concentrations. 108

NECROPSY EXAMINATION

It is important to differentiate the
abnormalities at necropsy caused by DIC
from those of the underlying disease. This
can be challenging. The presence of DIC
is suspected by the presence of hemor-
rhage in the carcass. Hemorrhage can
vary from occasional petechiation to frank
hemorrhage into body cavities. Horses
dying of DIC usually have widespread
lesions, including petechiation of mucosal
and serosal surfaces, including the
mesentery and pleura. There is often
hemorrhage into parenchymatous organs
(kidneys, adrenals), lungs and the myo-
cardium, and infarcts in the adrenals and
kidney. Microthrombi are detectable in
the intestine and kidney of some horses
with DIC.

DIAGNOSTIC CONFIRMATION

The presence of a hypercoagulable state
is determined by clinicopathological
testing. DIC is diagnosed by the presence
of clinical signs of a hemorrhagic diathesis
and laboratory confirmation of abnor-
malities in hemostasis and fibrinolysis. A
conventional definition of DIC requires
the presence of clinical evidence of
coagulopathy and the presence of at least
three abnormal measures of coagulation
or fibrinolysis. It is likely that this
definition will change as our under-
standing of the spectrum of abnormalities
and manifestations of the disorder
matures.

Differential diagnoses include all of
the acquired or inherited coagulopathies.
However, the cardinal differentiating
attribute of DIC or the lesser hyper-
coagulable states is the presence of severe
inciting disease.

TREATMENT

Most recommended therapies for DIC
have been extrapolated from the human
literature and may not be applicable to
farm animals. However, generally stated,
the principles of therapy are:

0 Treatment of the underlying disease
and correction of acid-base,
inflammatory, electrolyte and
perfusion abnormalities
0 Restoration of normal activity or
concentration of clotting factors in
blood

° Halting or attenuating the increased
coagulopathy

0 Minimizing effect of microthrombi
and thrombi on organ function.

Disseminated intravascular coagulation
is invariably secondary to an initiating
primary disease. Vigorous therapy should
consequently be directed toward correc-
tion of the primary initiating disease.
Aggressive intravenous fluid administra-
tion to maintain tissue perfusion and to

Hemorrhagic disease

correct any acid-base and electrolyte
imbalance is also very important. There
should be aggressive treatment of endo-
toxemia and of diseases likely to induce
endotoxemia. Treatment of endotoxemia
is discussed elsewhere in this text, and
current reviews are available. 116

The plasma concentration of clotting
factors should be restored, or supple-
mented, in horses with clinical or clinico-
pathological evidence of a coagulopathy.
The practice of blood component therapy
is well accepted in human medicine but
because of technological limitations is not
generally available in farm animals.
However, stored plasma, preferably fresh
frozen, can be administered to increase
the concentration of clotting factors that
are depleted during hypercoagulable
states or DIC. Antithrombin is often
readily measured and horses with low
plasma antithrombin activity should be
administered plasma. The dose of plasma
necessary to increase blood antithrombin
activity to appropriate levels has not
been determined. However, many
clinicians use a plasma antithrombin
activity 60% of that of healthy horses as
a minimal acceptable activity. This choice
has not been verified empirically. Dosages
of plasma vary from 2-10 mL/kg,
intravenously. Platelet-rich plasma, or
whole blood, can be used to treat
thrombocytopenia.

Heparin and low-molecular-weight
heparin is used to treat horses with
hypercoagulable states 2,24 and its use is
discussed above. The aim is to prevent
formation of thrombi and micro thrombi.
Heparin requires antithrombin as a
cofactor, and it might not exert its full
therapeutic activity in horses with
abnormally low blood antithrombin
concentrations.

Aspirin is used to inhibit platelet
activity in horses with prothrombotic
states. Its efficacy in reducing morbidity
or mortality has not been determined.

REVIEW LITERATURE

Darien BJ. Hemostasis - a clinical review. Equine Vet
Educ 1993; 5:33-36.

Sellon DC, Grindem CB. Quantitative platelet
abnormalities in horses. Compend Contin Educ
PractVet 1994; 16:1335-1346.

Davis EG et al. Flow cytometry: clinical applications in
equine medicine. JVet Intern Med 2002; 16:404-410.
Dallap BL. Coagulopathy in the equine critical care
patient. Vet Clin North Am 2004; 20:231-251.

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THROMBOSIS

(HYPERC OAGULAB I LITY)

Abnormal formation of thrombi is often a
consequence of diminished concentra-
tions or activity of anticoagulant factors,
such as antithrombin, protein C and
antiplasmin, increased concentrations
of plasminogen activator-inhibitor or
abnormalities of vessel walls. Thrombotic
disease is usually a consequence of a
primary disease that depletes anti-
coagulant factors and involves mech-

anisms discussed above under Dis-
seminated intravascular coagulopathy.'
Thrombosis of the jugular vein is
discussed elsewhere. Primary diseases
involving thrombosis are thrombo-
embolic colic in horses and aortoiliac
thrombosis in horses.

An apparently primary defect in
protein C activity in a Thoroughbred colt
with a hypercoagulable state has been
described. 1 The colt had repeated epi-
sodes of venous thrombosis and devel-
oped renal failure. Plasma concentrations
of protein C were within the reference
range for healthy horses, but the activity
of protein C in plasma was 32% of that of
healthy horses, suggesting a defect in the
protein.

REFERENCE

1. Edens LM et al. J Vet Intern Med 1993; 7:190.

Disorders of red cell
number or function

ANEMIA

Etiology Deficiency of circulating
erythrocytes associated with hemorrhage,
increased destruction or the inefficient
production of erythrocytes. There are a
large number of specific etiologies
Epidemiology Specific to the underlying
cause of the anemia
Clinical findings Pallor of mucosae,
tachycardia, lethargy, exercise intolerance,
arrhythmia, ileus, decreased ruminations
and colic. Petechial and ecchymotic
hemorrhages, icterus, hemoglobinuria,
bleeding tendencies can be seen if the
underlying cause is excessive hemorrhage
Clinical pathology Examination of
erythron, bone marrow and serum total
protein for nature and severity of anemia;
clinical chemistry for associated organ
damage. Specific tests for etiology
Necropsy findings Pallor of tissues.
Findings specific to specific etiology
Diagnostic confirmation Decreased
erythrocyte count or packed cell volume
Treatment Treatment of specific etiology
Transfusion of whole blood, packed red
cells, or stromal free hemoglobin if the
anemia is severe. Corticosteroids for
immune-mediated anemias and supportive
treatment.

ETIOLOGY

Anemia can be classified as hemorrhagic
anemia, hemolytic anemia, or anemia due
to decreased production of erythrocytes.
Another classification system is based on
evidence of regeneration of anemia, with
anemia classified as either regenerative
or nonregenerative. Both classifications
are useful in determining the cause,
treatment and prognosis. Diseases causing

Disorders of red cell number or function

anemia in horses are listed in Table 25.2
and those causing hemolytic anemia in
cattle in Table 20.4.

Hemorrhagic anemia

Acute hemorrhage and hemorrhagic
shock are discussed in Chapter 2. The
diseases discussed here are those that
cause normovolemic anemia. While
anemia occurs after restitution of plasma
volume in animals with severe hemor-
rhage, most diseases that cause normo-
volemic anemia do so because of the
chronic loss of blood either from the body
or into a body cavity. The most common
route of loss is through the gastro-
intestinal tract. Diseases include:

° Parasitism - intestinal nematodiasis:
Teladorsagia circumcincta or
Haemonchus contortus in lambs and
sheep, Ostertagia ostertagi in cattle,
Strongylus sp. and cyathostomes in
horses; trematodiasis including
Fasciola hepatic in sheep and cattle;
hematophagous lice and ticks,
including Linognathus vituli in calves
Gastrointestinal disease, including:

« Abomasal ulceration in cattle (both
spontaneous and associated with
abomasal lymphoma)

° Gastric ulceration in horses
(anemia is an unusual
manifestation of this disease)

° Gastric squamous cell carcinoma in
horses

o Esophagogastric ulceration in pigs
® Proliferative enteropathy in pigs
(usually a peracute disease)

° Bleeding from lesions in the small
intestine (neoplasia, fungal
infection, mural hematoma)

® Respiratory tract:

® Guttural pouch mycosis in horses
® Ethmoidal hematoma in horses
® Caudal vena cava thrombosis and
pulmonary embolism in cattle
° Genitourinary tract disease, including:
■3 Enzootic hematuria in cattle
(bladder cancer) and bladder
transitional cell tumor (horse)

° Pyelonephritis

0 "Vhginal varicose vein hemorrhage
in mares

® Ureteral lesion and hematuria in
geldings and stallions
•a Middle uterine artery rupture of
mares (usually a peracute disease)

° Idiopathic renal hematuria in
horses

0 Hemorrhage into body cavities:

0 Hemangiosarcoma
• Juvenile bovine angiomatosis
• Defects in clotting (see 'Diseases
causing hemorrhage')

° Thrombocytopenia
° Deficiency of clotting factors
° Umbilical bleeding in piglets.

Hemolytic anemia

Cattle and sheep

• Babesiosis, anaplasmosis, Mycoplasma
ovis comb. nov. (formerly Eperythrozoon
ovis) eperythrozoonosis,
trypanosomiasis, nagana, theileriosis,
alone or in various combinations 1
® Bacillary hemoglobinuria
® Leptospirosis (L. interrogans serovar
pomona)

® Bovine virus diarrhea and mucosal
disease 2

® Fbstparturient hemoglobinuria
o Associated with grazing Brassica spp.
rape, kale, chou moellier, turnips,
cabbages

° Associated with the excessive feeding
of culled onions 3 or cannery offal,
especially tomatoes and onions
<3 Fbisoning by Mercurialis, Ditaxis,
Pimelia and Allium spp.
o Poisoning by miscellaneous agents,
including phenothiazine, guaifenesin
<3 Poisoning - chronic copper poisoning.
In sheep secondary to pyrrolizidine
alkaloids as in toxemic jaundice or
primary from the feeding of diets too
high in copper. Cattle are much less
susceptible than sheep, although
preruminant calves are very
susceptible

® Treatment with long-acting
oxytetracycline

° Water intoxication and drinking cold
water in calves, 4 and in goat kids fed
water from a nipple bottle 5
® Inadvertent administration of
hypotonic fluids intravenously
« Part of a transfusion reaction
° Rare cases of alloimmune hemolytic
anemia (isoerythrolysis) in calves from
vaccination of the dam with blood-
derived vaccines such as anaplasma
vaccine

® Autoimmune hemolytic anemia is
recorded in calves but is rare. 6 All
reported cases have occurred in calves
under 6 months of age
® Immune -mediated anemia can occur
in lambs that are fed cow colostrum
as a source of immunoglobulin. This is
not a common sequel to the feeding
of cows' colostrum and occurs only
with the colostrum from certain cows.
Anemia is evident at 7-20 days of age
but jaundice and hemoglobinuria are
not usually present. 7,8 The syndrome
must be differentiated from immune-
mediated thrombocytopenia, which
occurs at a younger age in some
lambs fed bovine colostrum
0 Rarely, in adults after vaccination 9
° Congenital anemia associated with
dyserythropoiesis and accompanied
by dyskeratosis and progressive
alopecia is recorded in Polled
Hereford calves. The anemia is

present at birth and the disease is,
probably inherited 10,11
® A congenital anemia with jaundice is
recorded in Murray Grey calves and it
is postulated that a defect in the red
cell membrane leads to intravascular
hemolysis. 12

Pigs

® Eperythrozoonosis is recorded but
hemolytic anemia is rare
® Isoerythrolysis, thrombocytopenia and
coagulation defects are dealt with in
the previous section
® Generalized cytomegalovirus
infection.

Horses

® Equine infectious anemia, although
the pathogenesis of the anemia is
probably multifactorial, including
hemolysis and decreased red cell
production
® Babesiosis

® Phenothiazine poisoning. This
anthelmintic is now used rarely in
horses

® Red maple leaf ( Acer rubrum ) toxicity 13
® Ingestion of dried garlic (> 0.2 g/kg
BW) results in development of Heinz
bodies and hemolytic anemia 14
° Intravenous administration of

hypotonic or hypertonic fluids (water,
20% dimethylsulfoxide)

® As a sequela to severe cutaneous
bums. 15 The severity of the hemolysis
correlates with the amount of skin
area burned. Hemolysis is due to
oxidative damage of red cell
membranes that occurs within
minutes of the bum. Prevention and
treatment include immediate
administration of polyionic fluids to
prevent hemoconcentration and to
prevent hemolytic uremia
® As a sequel to clostridial abscessation.
The anemia occurs more than 10 days
after development of the abscess and
is associated with the presence of IgG
or IgM on the surface of red cells 16
® Alloimmune hemolytic anemia
(isoerythrolysis) of foals
° Autoimmune hemolytic anemia. Not
common but several series have been
recorded 17 " 20

® Immune-mediated hemolytic anemia
and thrombocytopenia (Evans
syndrome) 21

° Penicillin-induced hemolytic anemia.
This is a rare event but can occur
when horses develop IgG
antipenicillin antibodies. These
antibodies bind to penicillin on
erythrocytes with resultant red cell
destruction. Penicillin-coated
erythrocytes agglutinate with patient
serum. 22,23 It is probable that other
immune-mediated hemolytic anemias

■52

PARTI GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

in the horse are also associated with
the development of antibody to
therapeutic agents 24
a Some snake envenomations cause
intravascular hemolysis in dogs and
cats 25 and hemolytic anemia can occur
in snakebite in horses 26 and calves
® Lead intoxication in horses causes
mild anemia, but signs of peripheral
neuropathy are the more obvious
manifestation

° Abnormalities in red cell function can
lead to increased removal of red cells
from blood (extravascular hemolysis)
and are discussed under
'Abnormalities of red cell function'.

Anemia due to decreased production
of erythrocytes or hemoglobin
(nonregenerative anemia)

The diseases in this group tend to affect
all species so that they are divided up
according to cause rather than according
to animal species.

Nutritional deficiency
Nutritional deficiencies impair produc-
tion of hemoglobin or red cells. A number
of specific deficiencies that result in
anemia are described:

o Cobalt and copper. These elements
are necessary for all animals, but
clinically occurring anemia is
observed in only ruminants. Copper
deficiency induced by zinc toxicity
causes anemia in pigs 27
° Iron, but as a clinical occurrence this
is limited to rapidly growing animals,
including baby pigs, young calves
designated for the white veal market,
housed lambs and foals. This
predilection of young animals for iron
deficiency is attributable to their rapid
growth and hence requirement for
relatively large intakes of iron (which,
in addition to production of
hemoglobin, is used in production of
myoglobin and other iron-containing
compounds), the low concentration of
iron in milk, and management
practices that deny access of the
animals to pasture or soil from which
they can obtain iron
8 Anemia in piglets can be caused by
iron deficiency. The disease occurs
in both housed piglets and those
kept on dirt, although the disease
is believed to be less common in
those kept at pasture or on dirt, in
part because of the availability of
iron ingested in dirt 28
° Iron deficiency should be

considered as a possible cause of
failure to perform well in housed
calves. Male calves up to 8 weeks
of age and on a generally suitable
diet can show less than optimum

performance in erythron levels,
and the calves with subclinical
anemia have deficits in growth rate
and resistance to diarrhea and
pneumonia. 29 Calves fed 20 mg
Fe/kg milk replacer develop
hypoferremia and mild anemia,
whereas those fed 50 mg Fe/kg
do not 30

8 Iron deficiency anemia occurs in
housed lambs and is prevented by
oral or parenteral supplementation
with iron. 31 Anemia and poor
weight gain were not prevented in
all lambs by a single administration
of 330 mg of iron once orally at
1-5 days of age, although there
was a marked increase in serum
iron concentration. Treated lambs
had higher hematocrit and greater
weight gain than did untreated
lambs

8 Microcytic anemia and
hypoferremia occur in
Standardbred foals kept at pasture
for 12 h/d. These changes are not
prevented by oral administration of
four oral doses of 248 mg of iron,
suggesting that higher levels of
supplementation are needed. 32
Conversely, hypoferremia and
anemia are reported in stabled
foals but not in a pastured cohort. 33
The stabled foals had clinical signs
of anemia (lethargy) and low
hematocrit, hemoglobin
concentration and serum iron
concentration, which were restored
to normal values by iron
supplementation (0.5 g iron sulfate
orally once daily, 3 g of iron sulfate
top dressed on cut pasture fed to
the foals and their dams, and
unlimited access to a lick block
containing iron). 33 While colostrum
of mares is rich in iron, milk has
much lower concentrations,
probably explaining the low serum
iron of some nursed foals and
demonstrating the need for access
to iron supplements or, preferably,
soil or pasture. 34 Supplementation
of foals with iron should be
undertaken cautiously because of
the documented hepatotoxicity of
large doses of iron given orally to
newborn foals. 35 Toxic hepatopathy
develops in newborn foals
administered iron fumarate at
16 mg/kg BW within 24 hours of
birth, 35 similar to the situation in
piglets. Iron supplementation of
foals should be done cautiously

o A great deal of attention is paid to
providing adequate iron to
racehorses, often by periodic
injection of iron compounds

regularly during the racing season
or provision of hematinic
supplements. Given that
strongylosis is all but unknown in
race horses in the current era of
intensive parasite control programs
and stabling of horses, anemia is
exceedingly rare in healthy race
horses. Supplementation with iron
of horses on a balanced, complete
ration is therefore unlikely to be
necessary. Moreover,
administration of excessive iron
could be dangerous, although iron
toxicity has not been documented
in race horses, as it has in foals.
Oral administration of 50 mg Fe/kg
body weight to ponies for 8 weeks
increased serum iron
concentration, did not affect
hematocrit and did not induce
signs of disease 36

8 Potassium deficiency is implicated in
causing anemia in calves
8 Pyridoxine deficiency, produced
experimentally, can contribute to the
development of anemia in calves
® Folic acid deficiency is rare in horses,
has not been reported as a
spontaneous disease in pigs, and is
unlikely to occur in ruminants
because of the constant production of
folic acid by rumen bacteria. 37 Plasma
folic acid concentrations vary in
pregnant mares kept at pasture, and
in their foals, but there is no evidence
of folate deficiency in either mares or
foals. 38 Administration of antifolate
drugs (trimethoprim, sulfonamides,
pyrimethamine, methotrexate) could,
theoretically, cause folate deficiency in
horses. Folate deficiency causing
anemia and leukopenia is reported in
a horse treated for equine protozoal
myelitis with antifolate drugs
concurrent with oral supplementation
with folic acid. 39 Intravenous
administration of folic acid
(0.055-0.11 mg/kg BW) resulted in
rapid resolution of leukopenia and
anemia. Fhradoxically, oral
administration of folic acid in
monogastric animals receiving
antifolate drugs impairs absorption of
folic acid in the small intestine and
causes folate deficiency. 39
Administration of folic acid,
sulfonamides and pyrimethamine
orally to pregnant mares results in
congenital signs of folate deficiency in
foals, including anemia and
leukopenia. 40

Chronic disease

Chronic inflammatory disease causes
mild to moderate anemia in all species of
large animals. The anemia can be difficult

to differentiate from that of mild iron-
deficiency anemia. The genesis of anemia
of chronic inflammation is multifactorial
and includes sequestration of iron stores
such that iron availability for hemato-
poiesis is reduced despite adequate body
stores of iron, reduced erythrocyte life
span and impaired bone marrow response
to anemia. The result is normocytic,
normochromic anemia in animals with
normal to increased serum ferritin con-
centrations. The clinicopathologic features
of both iron deficiency anemia and
anemia of chronic disease are detailed in
Table 9.1.

• Chronic suppurative processes can
cause severe anemia by depression of
erythropoiesis

8 Radiation injury

• Poisoning by bracken,
trichloroethylene-extracted soybean
meal, arsenic, furazolidone 41 and
phenylbutazone, cause depression of
bone marrow activity

8 A sequel to inclusion body rhinitis
infection in pigs

° Porcine dermatitis and nephropathy
syndrome 42

8 Intestinal parasitism, e.g. ostertagiasis,
trichostrongylosis in calves and sheep,
have this effect. 7

Red cell aplasia

3 Red cell hypoplasia is a fatal
syndrome of anemia,
immunodeficiency and peripheral
gangliopathy that develops at
4-8 weeks of age in some Fell pony
foals

° Anemia in some horses follows the
administration of recombinant human
erythropoietin 43j):> The anemia is due
to pure red cell aplasia and is manifest
as normocytic, normochromic anemia.
The disease is attributable to injection
of horses with recombinant human
erythropoietin with subsequent
development of substances in blood,
presumably antibodies to rhEPO, that
cross-react with and neutralize
endogenous erythropoietin in affected
horses 43,45 Not all horses administered
rhEPO develop anemia, but the
disease is reported as an outbreak in a
stable of Thoroughbred race horses
administered the compound. 45
Severely affected horses die. Treatment
of severely affected horses is futile, but
mildly affected horses can recover. 43
Whether the recovery was
spontaneous or because of
administered glucocorticoids is
unknown. Administration of
cyclophosphamide and glucocorticoids
was not effective in treatment of
several severely affected horses. Blood
transfusion provides temporary relief

Disorders of red cell number or function

453

° Pure red J cell aplasia not associated
with administration of rhEPO occurs
but rarely in horses. The disease can
be transient.

Myelophthisic anemia
Myelophthisic anemia, in which the bone
marrow cavities are occupied by other,
usually neoplastic tissues, is rare in farm
animals. Clinical signs, other than of the
anemia, which is macrocytic and normo-
chromic, include skeletal pain, pathological
fractures and paresis due to the osteolytic
lesions produced by the invading neo-
plasm. Cavitation of the bone may be
detected on radiographic examination.

® Lymphosarcoma with bone marrow
infiltration occurs in most species

• Plasma cell myelomatosis has been
observed as a cause of such anemia in
pigs, calves and horses

• Infiltration of neoplastic cells, other
than lymphoma or myeloma, such as
melanoma in horses 46

• Myelophthisic anemia due to
myelofibrosis is reported in a pony 47
and as a familial disease in pygmy
goats 48

PATHOGENESIS
Anemic hypoxia

The most important abnormality in
anemia is the hypoxemia and subsequent
tissue hypoxia that results from the
reduced hemoglobin concentration and
oxygen-carrying capacity of blood. The
anemia becomes critical when insufficient
oxygen is delivered to tissue to maintain
normal function.

Oxygen delivery is described math-
ematically by the Fick equation:

Oxygen delivery = cardiac output x
arteriovenous oxygen content
difference.

Oxygen delivery is therefore the rate at
which oxygen is delivered to the tissue -
it is a combination of the rate at which
oxygen arrives at the tissue in arterial
blood and the proportion of that oxygen
extracted from the capillary blood.

Cardiac output is determined by heart
rate and stroke volume, whereas the
arteriovenous difference in blood oxygen
content is determined by the hemoglobin
concentration, hemoglobin saturation
with oxygen in both arterial and venous
blood, and the extraction ratio. The
extraction ratio is the proportion of
oxygen that is removed from the blood
during its passage through tissues. In
animals with a normal hematocrit and
cardiac output, oxygen delivery to tissues
exceeds the oxygen requirements of the
tissue by a large margin, with the result
that the oxygen extraction ratio is small
(< 40%). However, as the oxygen-carrying

capacity per unit of blood declines (usually
expressed as mL of oxygen per 100 mL of
blood) then either blood flow to the tissue
or the extraction ratio must increase to
maintain oxygen delivery. 49,50 In reality, both
of these compensatory mechanisms occur
during the acute and chronic responses to
anemia. Heart rate increases to increase
cardiac output and therefore the delivery of
oxygen to tissue, and blood flow is
preferentially directed to those tissue beds
that are most essential for life or are most
sensitive to deprivation of oxygen (heart,
brain, gut, kidney). Extraction ratio increases
and is evident as a decrease in venous blood
hemoglobin saturation. Hemoglobin in
arterial blood is usually thoroughly
saturated with oxygen and the limitation to
oxygen delivery to tissue is the low
hemoglobin concentration and consequent
low arterial oxygen content. Assessment of
arterial blood oxygen tension and content is
discussed in Chapter 10.

Reductions in hemoglobin concentra-
tion are compensated for by increases in
cardiac output and extraction ratio so that
oxygen delivery to tissue is maintained in
mild to moderate anemia. 49 As the severity
of anemia increases, these compensatory
mechanisms are inadequate and oxygen
delivery to tissues declines. At some point
the delivery of oxygen fails to meet the
oxygen needs of the tissue and organ
function is impaired. It is important to
realize that this is not an all-or-none
phenomenon and that there is not a
particular point at which decompensation
occurs. In fact, with progressive anemia
there are progressive increases in cardiac
output and oxygen extraction ratio (evident
as a progressive decline in venous hemo-
globin saturation) until these compensatory
mechanisms are maximal. 49 Arterial pH
and lactate concentration are maintained
until the degree of anemia cannot be
compensated for by increases in cardiac
output and extraction ratio, at which
point blood lactate concentration rises
and blood pH and base excess decline.
This is the degree of anemia at which
oxygen use by tissue is entirely dependent
on blood flow - decreases in blood flow
decrease oxygen utilization and increases
in blood flow increase oxygen utilization
until the point where oxygen delivery
exceeds oxygen consumption.

Compensation for slowly developing
anemia is more complete than for rapidly
evolving anemia such that animals with
chronic anemia can tolerate a degree of
anemia that would be intolerable for
animals with acute anemia of a similar
severity. Part of this chronic compensation
includes changes in the affinity of
hemoglobin for oxygen, which is due
in part to increases in 2,3-diphospho-
glycerate concentration in red cells.

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

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f/ie changes are those expected in most species but might not occur uniformly in all species. Normal are values within the range expected for healthy animals of that species, age, and physiological status. High and low refer to values above or
below this normal range.

* Reticulocytes are detectable in blood of horses only by use of special stains and sensitive laboratory methods, t Increases in MCV in horses are slight and difficult to detect.
t Values are for adult horses. < > NK, not known.

Disorders of red cell number or function

435

When anemia is sufficiently severe
that it reduces oxygen delivery to tissue
to rates that are less than the oxygen
needs of tissue, tissue hypoxia develops
and the proportion of energy generated
by anaerobic metabolism increases.
Anaerobic metabolism cannot be sus-
tained for more than a short period of
time (minutes) before tissue function is
impaired. Impaired organ function is
evident as decreased myocardial con-
tractility, decreased cerebral function,
decreased gastrointestinal motility and
abnormal renal function, to list just a few
of many important abnormalities. The
severity of these abnormalities depends
on the metabolic activity of the tissue
with more metabolically active tissues
(e.g. the heart) being more sensitive to
hypoxia. Death usually results from acute
heart failure due to arrhythmia.

The effect of anemia is also dependent
on the metabolic state of the animal.
Exertion, even mild exertion such as
grazing or following a herd or flock, can
increase oxygen demands above that
which can be sustained by the degree of
anemia. Similarly, increases in body
temperature, such as with fever, increase
oxygen demand noticeably - an increase
in body temperature of 1°C increases
oxygen need by 12%.

Anemia induces increases in plasma
erythropoietin concentration, which
stimulates erythropoiesis in bone marrow
and, in young animals or those with
extreme anemia, in extramedullary sites.
The increase in plasma erythropoietin
concentration is prompt, occurring within
hours of the development of anemia. The
compensatory erythropoietic response is
slower, with new red cells being detect-
able in 1-2 days in most species and bone
marrow reticulocytosis detectable in less
than 1 week. 50,51

Autoimmune hemolytic anemia

The disease is believed to result from an
aberrant production of antibodies targeted
against surface antigens of the erythrocyte
as a result of an alteration in the
erythrocyte membrane from systemic
bacterial, viral or neoplastic disease. An
alternate hypothesis is the development
of immunocompetent clones that direct
antibody at the red cell membrane. 17,24
Red cells are lost by intravascular
hemolysis or removal by macrophages of
the reticuloendothelial system and
anemia occurs when the capacity of the
bone marrow to compensate for increased
red cell destruction is exceeded. Auto-
immune hemolytic anemia is considered
to be idiopathic if it cannot be associated
with an underlying disease and is con-
sidered to be secondary if associated with
another condition. Often this is neoplastic

disease. The antibodies are of the IgG or
IgM class, may be agglutinating or non-
agglutinating and can also be tempera-
ture-dependent. The antiglobulin test has
been used to confirm the diagnosis in
cases of nonagglutinating autoimmune
hemolytic anemia, but demonstration of
immunoglobulin on the surface of red
cells by immunofluorescent cell staining
and flow cytometry is much more sensi-
tive and specific. 52,53

Hemolysis

Hemolysis results from rupture of red cell
membranes as a consequence of injury to
the membrane or osmotic lysis when
serum tonicity is lower than normal.
Hemolytic disease of any cause has the
potential to overwhelm the normal
clearance mechanisms for hemoglobin,
with the result that hemoglobin concen-
trations in plasma are abnormally high.
This can result in hemoglobinuric
nephrosis (see Ch. 11).

Methemoglobinemia and oxidative
damage

Methemoglobinemia results from oxidative
damage of hemoglobin and occurs in
disease such as red maple leaf toxicosis
in horses and nitrate poisoning in
ruminants. Methemoglobinemia is rever-
sible but important as an indicator of
oxidative damage and because methe-
moglobin cannot transport oxygen.
Oxidative damage to red cells results in
denaturation of hemoglobin with subse-
quent formation of Heinz bodies. Red
cells damaged in this way are sensitive
to osmotic lysis and fragmentation.
Intravascular hemolysis and removal of
damaged red cells by the reticuloendo-
thelial system contributes to anemia.

CLINICAL FINDINGS

The clinical signs and their severity
depend on the degree of anemia. Mild
anemia in animals that are not required to
be physically active, such as veal calves or
housed lambs, might be apparent only as
failure to achieve optimal weight gain.
More severe degrees of anemia, or mild
anemia in animals required to be
physically active, such as foals at pasture
or race horses, can be evident as exercise
intolerance, failure to perform athletically,
or lethargy. Behavioral signs of anemia
include prolonged recumbency, depressed
mentation, reduced nursing, foraging
or grazing and, in extreme anemia,
belligerence.

Physical findings include pallor of the
mucosae but appreciable degrees of
anemia can occur without clinically
visible change in mucosal or skin color.
The mucous membranes, and skin in
pale- skinned, sparsely haired animals
such as pigs, can be almost white in

animals with severe anemia. Hemolytic
anemia causes jaundice in most cases.

A chart for examination of conjunctival
color in sheep and goats has been
validated as a means of assessing severity
of anemia in these species. The chart
(FAMACHA®) was developed to aid in
parasite control programs. 54 Conjunctival
color is assessed on a scale of 1-5 in
which 1 = red and 5 = white. 54 The
correlation between FAMACHA score
and hematocrit was very good (R = -0.52
in sheep and -0.30 in goats). The
sensitivity and specificity for detection of
a hematocrit below 15% for FAMACHA
scores of 4 and 5 were 83% and 89% for
sheep, and 83% and 71% for goats. This
methodology appears to be very useful for
detection of anemia in small ruminants.

The heart rate is increased, the pulse has
a large amplitude and the absolute intensity
of the heart sounds is markedly increased in
anemic animals. Tenninally the moderate
tachycardia of the compensatory phase is
replaced by a severe tachycardia, a decrease
in the intensity of the heart sounds and a
weak pulse. A hemic murmur might be
heard and is likely a result of the low
viscosity of blood in anemic animals
combined with increased ejection velocity
of blood from the heart as a consequence
of increased heart rate and cardiac output.

Dyspnea is not pronounced in anemia,
the most severe degree of respiratory
distress appearing as an increase in depth
of respiration without much increase in
rate. Labored breathing occurs only in the
terminal stages and at those times the
animals can be severely distressed.

Other signs of decompensated anemia
include anxious expression, absent
rumination, ileus, colic, anuria and cardiac
arrhythmia. Animals can appear quiet and
comfortable unless they are forced to
move or an event occurs that increases
oxygen consumption and causes decom-
pensation. An example is an animal that
has compensated for its severe anemia
but then develops a fever. Fever can
increase whole body oxygen requirement
by 12% for each 1°C increase in tem-
perature and this can cause a finely
balanced animal to decompensate.

There can be signs of the inciting disease
and these can include edema, jaundice,
petechial and ecchymotic hemorrhages in
the mucosa and hemoglobinuria.

Adjunctive examination can include
gastrointestinal, urinary or upper respi-
ratory endoscopy; radiography of the
chest or abdomen; and ultrasonographic
examination of affected regions.

CLINICAL PATHOLOGY

The clinicopathological characteristics of
the common forms of anemia are pro-
vided in Table 9.1.

;e

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

Hematology

Anemia is definitively diagnosed by
measurement of red cell indices and
demonstration of low hematocrit, red cell
count and hemoglobin concentration.
Examination of various red cell indices can
yield important information about the
cause of anemia and evidence of regener-
ation. In addition to providing the diag-
nosis, serial monitoring of the hemogram is
useful in detecting evidence of a regener-
ative response. At a minimum, repeated
measurement of hematocrit will reveal a
gradual increase when there is a regener-
ative response. Hematocrit of horses with
induced anemia increases by approximately
1% (0.01 L/L) every 3 days. 55

Red cell morphological abnormalities
include variations in size, shape, and
content:

» Red cell size

o Anisocytosis is the presence of red
cells of abnormal size. Abnormal
cells can be either macrocytes or
microcytes. See Red cell
distribution width
° Macrocytosis (high mean

corpuscular volume, MCV) usually
indicates a regenerative response.
Ruminants have a prominent
macrocytic response to anemia.

The increase in MCV in horses can
be so slight as to be undetectable,
especially in mild to moderate
regenerative anemia
° Microcytosis (low mean

corpuscular volume) is found in
classic deficiency anemias such as
iron deficiency

<> Red cell distribution width is a
measure of the variation in red cell
size in the population of red cells
in blood. It is calculated by dividing
the standard deviation of red cell
volumes by the mean red cell
volume, and multiplying the
product by 100. An increase in red
cell distribution width indicates the
presence of anisocytosis due to
macrocytosis in regenerative
anemia 51,55
0 Red cell shape

° Spherocytosis is found in diseases
that affect the red cell membrane,
such as immune-mediated anemia
and red maple toxicosis
• Schistocytes (small, irregularly
shaped cells or red cell fragments)
are found in diseases that cause
intravascular physical injury to red
blood cells, such as DIC or
vasculitis with endothelial damage
° Echinocytes are normal-sized red
cells that have uniform membrane
projects. They are of uncertain
importance

0 Eccentrocytes are cells in which
hemoglobin has been damaged
and accumulated eccentrically in
the cell, causing variation in color
density of the cell. Usually
associated with diseases causing
oxidative damage
® Red cell content

• Fblychromasia, the presence of
erythrocytes of varying staining
intensity, is usually due to the
presence of reticulocytes
0 Hypochromia can be evident as
reduced staining intensity and is
due to a reduction in red cell
hemoglobin concentration
° The amount of hemoglobin in red
cells can vary. Mean corpuscular
hemoglobin (MCH) content
increases in the presence of
reticulocytes. False increases in
MCH occur when there is free
hemoglobin in plasma, either from
in-vivo or ex-vivo hemolysis.

Mean corpuscular hemoglobin
concentration (MCHC) is reduced
in the presence of reticulocytosis
and hemolysis falsely increases
MCHC

0 Nucleated red cells appear in the
peripheral blood only in ruminants
among farm animals and only in
response to severe anemia
° Howell-Jolley bodies are nuclear
remnants that are common in the
regenerative response in ruminants
but less so in horses
° Heinz bodies are round
protrusions from the cell
membrane or intracellular
inclusions. The bodies are
denatured hemoglobin and are
found in diseases in which there is
oxidative damage to red cells.
Affected cells are fragile and
susceptible to intravascular lysis or
increased rate of removal by cells
of the reticuloendothelial system
° Parasites such as Babesia spp.,
Theileria spp., and Mycoplasma spp.
(formerly Eperythrozoon spp.) can
be detected in parasitemic animals
° Reticulocytosis

° Reticulocytes are immature red
cells released from the bone
marrow. Reticulocytes contain
remnants of nucleic acid and this
can be detected by use of
appropriate stains. Until recently,
reticulocytosis in response to
anemia was documented in
ruminants 56 and pigs, but not in
horses. This was because equine
reticulocytes do not stain with
Romanowsky and other stains
used for routine examination of
smears of peripheral blood.

However, use of oxazin, a stain
that combines with nucleic acid,
and fluorescent detection of
labeled cells has revealed the
presence of reticulocytes in
peripheral blood of horses. 51
Horses develop a reticulocytosis in
response to anemia, as do other
species

» Reticulocyte volume and

reticulocyte hemoglobin content
increase in regenerative anemia in
horses 51 but has not been
evaluated in other large animals.

Agglutination of red cells is apparent as
irregularly shaped agglomerations of red
cells. The clumps of red cells do not
dissociate when blood is diluted 1:4 with
0.9% saline, as happens with rouleaux.
Rouleaux are normal findings in blood
of horses and are apparent as rows of
erythrocytes.

Coombs testing or use of direct
immunofluorescent flow cytometry

can provide evidence of immune-mediated
hemolytic anemia. 52,53

Other hematologic changes in severe
anemia include leukocytosis and
thrombocytosis.

Bone marrow

Examination of bone marrow is useful for
demonstrating a regenerative response,
especially in horses in which a regene-
rative response can be difficult to detect in
peripheral blood, and for determining the
cause of nonregenerative anemia.

Collection of bone marrow
Samples of bone marrow can be obtained
by aspiration, with samples submitted for
cytological examination, or biopsy, with
core samples submitted for histological
examination. Bone marrow aspirates are
useful in that they provide samples in
which the relative proportions of myeloid
and eiythroid cell lines can be determined.
However, samples obtained by aspiration
do not allow examination of the over-
all cellularity of the marrow or its
architecture.

Samples of bone marrow can be
obtained from the sternebrae, proximal
aspects of the ribs or tuber coxae. The
preferred site in adult animals, and in
calves, is the cranial sternum. The
procedure is performed on standing adult
animals or laterally recumbent calves.
Animals should be adequately restrained,
which could include administration of
sedatives and analgesics. A site on the
ventral midline over the second or third
sternebra is clipped and aseptically
prepared. Local analgesia is induced
by injection of lidocaine or similar local
anesthetic (5-10 mL) . The local anesthetic
is injected subcutaneously and to the

Disorders of red cell number or function

457

surface of the sternebra. A small skin
incision is made and the aspiration needle
or biopsy instrument is introduced. Bone
marrow aspirates can be collected using a
13-15-gauge, 5-7 cm needle and stylet.
Bone marrow core biopsies are performed
using an 8-, 11- or 13-gauge 100-150 mm
bone marrow biopsy needle (Trap-
System®).

Bone marrow aspirates are collected
from adult horses by advancing the
needle approximately 2-3 cm into the
sternebra. The stylet is then removed, a
5-10 mL syringe is attached and bone
marrow is aspirated. The samples should
be placed on a clean glass slide and air-
dried, or put in a Petri dish containing
0.5-1. 0 mL of 2% EDTA.

Core samples of bone marrow are
obtained by inserting the biopsy needle
2 cm into the cortex of the sternebra. The
stylet is then removed and the needle is
advanced with a rotating motion. This can
require considerable effort in adult
animals. The needle is advanced appro-
ximately 2-3 cm and then rapidly with-
drawn. A sample of bone marrow will be
evident as pink to red bone. The sample
should be rolled on a clean, dry glass slide
(for cytological examination) and then
placed in 10% neutral buffered formalin
for histological examination.

Interpretation of bone marrow
Bone marrow is examined for overall
architecture, cellularity, the ratio of
myeloid to erythroid cells (M:E ratio) and
the presence of inflammation, necrosis or
abnormal cells. A subjective assessment
of iron stores can be made by staining
sections of marrow with Prussian blue
stain.

A regenerative response is evident as a
low M:E ratio due to erythrocyte hyper-
plasia, and the presence of erythroid
series cells in all stages of maturity. There
are increased counts of reticulocytes in
bone marrow and the number of nucleated
cells relative to the hematocrit increases.
The MCV and reticulocyte hemoglobin
content are high in regenerative bone
marrow. These responses are evident as
soon as 3 days after acute anemia and
peak at approximately 9 days. 51,57

Abnormal white cells, such as seen in
myelophthisic disease caused by myeloma
or lymphosarcoma, cause displacement of
erythroid series cells and a high M:E ratio.
Similarly, a high M:E ratio is obtained
when there is primary red cell aplasia. A
normal M:E ratio is obtained when there
is aplasia of both myeloid and erythroid
series of cells, highlighting the need to
evaluated overall cellularity of the marrow.
Normal marrow is approximately 50% fat
and 50% combined myeloid and erythroid
series cells.

Blood gas analysis, oximetry and
lactate

Arterial blood gas analysis
Arterial blood oxygen tension (mmHg,
kPa) in animals with anemia is almost
always within the reference range for
healthy animals unless there is coexisting
lung disease. Anemia does not interfere
with diffusion of oxygen from the
alveolus into capillary blood. However,
the arterial oxygen content (mL 0 2 per
100 mL blood) is reduced because of the
reduced arterial blood hemoglobin con-
centration (see Ch. 10). Arterial carbon
dioxide tension is often reduced in severe
anemia as a result of alveolar hyperventi-
lation that is a response to arterial
hypoxemia. Arterial pH and base excess
decline as the severity of anemia increases
and compensatory mechanisms are no
longer able to ensure delivery of sufficient
oxygen to tissue the, indicative of meta-
bolic acidosis resulting from tissue
anaerobiosis.

Venous blood gas analysis
The ideal sample is mixed venous blood
collected from the pulmonary artery or
right atrium. However, these sites are only
infrequently available for collection so
samples should be collected from a a major
vein (jugular vein, cranial vena cava).
Samples collected from small leg veins are
less than ideal. Measurement of venous
blood gas tensions, pH, base excess,
hemoglobin saturation and oxygen content
are useful in evaluating the physiological
effect of anemia. As discussed under
pathophysiology, reductions in oxygen
content of arterial blood cause an increase
in oxygen extraction ratio in an attempt to
maintain oxygen delivery to. tissue. The
increased extraction ratio is evident as a
reduction in venous oxygen tension,
hemoglobin saturation and oxygen
content. 49 When oxygen delivery to tissue
is less than that needed to maintain aerobic
metabolism, venous pH, bicarbonate con-
centration and base excess decline.

Methemoglobinemia
Measurement of methemoglobin con-
centration is useful in documenting the
severity of diseases such red maple leaf
toxicosis and nitrate poisoning. Methe-
moglobinemia is reversible but is a sign of
oxidative damage to red cells. Oxidative
damage to red cells causes Heinz body
formation and eventual lysis of the cell.
Methemoglobin is measured using a
co-oximeter and is combined with
measurement of oxygen saturation.
Methemoglobin concentration in blood of
healthy animals is usually less than 3%.

Lactate

Concentrations of lactate can be measured
in blood ('whole blood lactate') or

plasma. Whole blood lactate concen-
trations are lower than lactate concentra-
tions in plasma because red blood cells
have lower lactate concentration than
does plasma. Lactate concentrations can
be measured using point-of -care analyzers,
some of which have been validated for
use in animals. Lactate concentration in
blood or plasma increases when com-
pensatory mechanisms are no longer
effective and aerobic metabolism is
impaired.

Serum biochemistry

Serum biochemical abnormalities are
those of the inciting disease or reflect
damage to organs as a result of the
anemia. Severe anemia can damage many
organs, resulting in increases in serum
concentration or activity of urea nitrogen,
creatinine, sorbitol dehydrogenase,
gamma-glutamyl transpeptidase, bile
acids, bilirubin, aspartate aminotrans-
ferase, creatine kinase and troponin,
among others. Hemolytic anemia causes
increases in plasma hemoglobin con-
centration (evident grossly as pink-tinged
plasma or serum) and hyperbilirubinemia
(unconjugated).

Iron metabolism in anemic animals
is defined by measurement of serum iron
concentration, serum transferrin con-
centration (total iron-binding capacity),
transferrin saturation and serum ferritin
concentration. Serum ferritin concentra-
tion correlates closely with whole body
iron stores. Values of these variables in
anemia of differing cause are provided in
Table 9.1.

Other evaluations

Feces should be examined for the
presence of parasites (ova, larvae or adult
parasites), frank blood (hematochezia or
melena) and occult blood. Detection of
occult blood can be difficult and samples
should be collected on multiple occasions.
Samples should not be collected soon
after rectal examination, as false-positive
results can be found because of trauma to
the rectal mucosa.

Urine should be evaluated for the
presence of pigmenturia, red cells and
casts. Pigmenturia should be differen-
tiated into hemoglobinuria or myoglo-
binuria. Microscopic examination will
reveal red cells, or ghost red cells, in
animals with hematuria. Casts and
isosthenuria can be present in urine of
animals with hemoglobinuric nephrosis.

Serum erythropoietin concentration
should be evaluated in animals with
nonregenerative anemia. It is not a
readily available assay. Concentrations of
erythropoietin in adult horses are usually
less than 37 mU/mL, but values are
probably dependent on the assay used.

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune" systems

Tests for specific diseases should be
performed as appropriate:

° Measurement of bleeding time, FT,
APTT and platelet count should be
considered in animals with evidence
of excessive unexplained hemorrhage
■-> Examination for blood parasites
o Serological testing for infectious
causes of anemia
o Toxicological testing.

NECROPSY FINDINGS

Findings indicative of anemia include
pallor of tissues, thin, watery blood and
contraction of the spleen. Icterus may be
evident where there has been severe
hemolytic anemia and petechial and
ecchymotic hemorrhages with thrombo-
cytopenia. Necropsy findings specific to
individual diseases are given under those
disease headings.

TREATMENT

The principles of treatment of anemia are
ensuring adequate oxygen transport to
tissues, prevention of the deleterious
effects of anemia or hemolysis, and treat-
ment of the inciting disease. The indivi-
dual inciting diseases are discussed
elsewhere in this text.

Correction of anemia
The discussion here deals with normo-
volemic anemia. Acute anemia with
hypovolemia (hemorrhagic shock) is dealt
with in Chapter 2.

Transfusion

The oxygen- carrying capacity of blood
should be restored in the short term to at
least the level at which oxygen use by
tissue is not flow- dependent, and to
normal levels in the longer term. Short-
term restoration of the oxygen-carrying
capacity of blood is achieved by trans-
fusion of whole blood or packed red cells,
or administration of a commercial stromal
free hemoglobin solution.

The decision to transfuse an anemic
animal should not be undertaken lightly
for a number of reasons. Transfusion of
blood or packed red cells is not without
risk to the recipient, there is usually
considerable cost in identifying a suitable
donor and collecting blood, and the
process can be time-consuming. An
important concern in performing a blood
transfusion is the risk to the recipient.
Acute reactions, include anaphylaxis
and acute host versus graft reaction
(hemolysis of transfused red cells), and
graft versus host disease (hemolysis of
recipient red cells). Development of
alloantibodies in the recipient with con-
sequent problems with repeat transfusion
or development of neonatal alloimmune
hemolytic anemia in progeny of female
recipients is a concern. The incidence of

these adverse events has not been
recorded for large animals but can be
minimized by crossmatching donor and
recipient.

Crossmatching and the mechanics of
blood transfusion are discussed in
Chapter 2 and elsewhere. 58 Briefly, both
major (donor red cells and recipient
plasma) and minor (donor plasma and
recipient red cells) crossmatching should
be performed. Ideally, blood typing and
examination of plasma for alloantibodies
of both donor and recipient would be
performed before transfusion, but these
are rarely available in an appropriate time
frame.

Indications for transfusion are not
straightforward. Because of the risk to the
recipient and cost, blood transfusion
should be performed only when
indicated. Conversely, the severe adverse
effects of anemia mean that animals
should not be denied a transfusion if it is
needed. There is no one variable for which
a single value is a'transfusion trigger', and
the decision to provide a transfusion
should not be based on hematocrit,
hemoglobin concentration or red cell
count alone. Rather, the decision to pro-
vide a transfusion should be based on a
holistic evaluation of the animal, includ-
ing the history, physical abnormalities
and clinicopathological data. This infor-
mation should be considered in total
before a decision is made to provide a
transfusion. Considerations regarding
transfusion include:

0 History - animals with acutely
developing anemia are more likely to
require transfusion at a given
hematocrit than are animals with
slowly developing anemia. Similarly,
young animals with higher intrinsic
metabolic rates might require
transfusion at hematocrit values that
would be tolerated by adults
e Physical findings - these are some of
the most important indicators of the
need for transfusion and include:
c Changes in demeanor and activity
including lethargy, belligerence,
anxiousness, depressed mentation,
anorexia, intolerance of minimal
exercise (nursing, walking),
prolonged or excessive recumbency
o Tachycardia. There is no one value
that is critical, but a heart rate that
is 30-50% above the upper limit of
normal is probably important.
Progressive increases in heart rate
are indicative of the need for
transfusion

Sweating, cold extremities, and
other signs of sympathetic activation
• Absent rumination, ileus,

gastrointestinal distension, colic

® Arrhythmias, including ventricular
premature beats
® Anuria

° Clinical pathology

® Decline in hematocrit with
exacerbation of abnormalities on
physical examination. Transfusion
should be considered in any
animal with a hematocrit below
20% (0.20 L/L). Most animals do
not need a transfusion at this level,
but the proportion that requires a
transfusion increases at lower
hematocrits. Some horses with
chronic anemia and a hematocrit
of 10% (0.10 L/L) do not need a
transfusion, whereas others with
acute anemia of 15% (0.15 L/L)
need a transfusion urgently
° Venous blood hypoxemia and
declines in hemoglobin saturation.
There is no one value that is critical
as there are progressive and
gradual declines in these variables
as oxygen content of arterial blood
declines. Venous blood oxygen
tension of less than 25 mmHg is
clinically significant and values
below 20 mmHg probably
represent the need for transfusion
° Venous pH and base excess.

Development of acidosis (low base
excess) and acidemia (low pH) are
indications of tissue anaerobiosis
and the need for transfusion.
Unlike venous blood oxygen
tension and saturation, these
values are normal until
decompensation occurs
® Lactate concentration (arterial or
venous). Blood lactate
concentrations rise rapidly when
decompensation occurs. Blood
lactate concentrations above 2 and
below 4 mmol/L should be cause
for concern and prompt closer
monitoring, whereas values above
4 mmol/L probably indicate a need
for transfusion

o Evidence of organ damage,
including increases in serum
creatinine or bile acid
concentration indicators of
hepatocellular damage, and
troponin.

Transfusion to correct anemia in normo-
volemic animals should be done cau-
tiously to minimize the risk of excessive
expansion of the intravascular volume.
Ideally, packed red cells can be admin-
istered to reduced the extent of blood
volume expansion. However, preparation
of packed red cells can be difficult and
time-consuming. An alternative with
horses is simply to allow the collected
blood to sit undisturbed for 1-2 hours,

Disorders of red cell number or function

459

during which time the cells will settle to
the bottom. The red cells can then be
siphoned off and administered to the
recipient.

Details of donor selection, blood
collection and blood administration are
provided in Chapter 2.

An alternative to transfusion of whole
blood or packed red cells is the adminis-
tration of a commercial preparation of
stromal free hemoglobin. This product
is effective in increasing oxygen-carrying
capacity of blood in anemic horses and
has been used for support of a foal with
alloimmune hemolytic anemia until a
blood transfusion was available. 59,60 The
compound is stable at room temperature
and can therefore be stored for long
periods of time and be readily available
for use. However, it is expensive and its
effect is short-lived (< 48 h and probably
less). The recommended dose is 15 mL/kg
BW intravenously, but lower doses have
been used. The compound increases
oncotic pressure of plasma and causes
expansion of the plasma volume.

The efficacy of transfusion can be
assessed by examination of the animal and
measurement of venous blood oxygen
tension and saturation, and blood lactate
concentration. Venous blood oxygen ten-
sion and saturation improve promptly with
transfusion of an adequate red cell mass.

Hematinics

Hematinic preparations are used in less
severe cases and in animals with anemia
due to iron deficiency or severe external
blood loss (see Table of Drug Doses in
Appendix). Iron is administered to prevent
iron deficiency in young animals denied
access to pasture or soil. The use of
recombinant human erythropoietin in
horses has a risk of inducing anemia. 43,45
Given that there are no known causes of
low erythropoietin concentrations causing
anemia in horses, with the exception of
those horses with anemia subsequent to
rhEPO administration, the use of this
compound in horses is specifically
contraindicated.

Supportive care

The oxygen requirements of anemic
animals should be minimized. This can be
achieved by housing them individually in
quiet stalls the temperature of which is
maintained in the animal's thermoneutral
zone, minimizing the need for exercise
(such as grazing or following the mare to
nurse), and maintaining a normal body
temperature.

Animals with hemolytic anemia and
hemoglobinuria should be administered
polyionic isotonic fluids intravenously
to reduce the risk of hemoglobinuric
nephrosis.

Treatment of autoimmune hemolytic
anemia

Some animals with autoimmune hemolytic
anemia respond well to administration of
corticosteroids. 6,21,24 Compounds used
include prednisolone and dexame-
thasone. Horses with refractory aplastic
anemia or hemolytic anemia have been
administered cyclophosphamide (2 mg/kg
intravenously every 14-21 d) in addition
to glucocorticoids.

REVIEW LITERATURE

Lassen ED, Swardson CJ. Hematology and hemo-
stasis in the horse: Normal functions and com-
mon abnormalities. Vet Clin North Am Equine
Practl995; 11:351.

Durham AE. Blood and plasma transfusion in the
horse. Equine Vet Educ 1996; 8:8-12.

Knight R et al. Diagnosing anemia in horses.
Compend Contin Educ PractVet Equine Ed 2005;
October:23-33.

REFERENCES

1. Hofmann-Lehmann R etalj Clin Microbiol 2004;
42:3775.

2. Braun U etal.VetRec 2005; 157:452.

3. Lincoln SD et al. J Am Vet Med Assoc 1992;
200:1090.

4. Gilchrist F. Can Vet J 1996; 37:490.

5. Middleton JR et al. JVet Intern Med 11:1997; 382.

6. Fenger CK et al. J Am Vet Med Assoc 1992; 201:97.

7. Winter A, Clarkson M. In Pract 1992; 14:283.

8. Nappert GN et al. Can Vet J 1995; 36:104.

9. Yeruham I et al. Vet Rec2003; 153:502.

10. Steffen DJ et al.Vbt Pathol 1992; 29:203.

11. Steffan DJ et al. J Hered 1993; 84:263.

12. Nicholls TJ et al. Aust Vet J 1992; 69:39.

13. Semrad SD. Compend Contin Educ Pract Vet
1993; 15:261.

14. Pearson W et al. Am J Vet Res 2005; 66:457.

15. Norman TE et al. J Am Vet Med Assoc 2005;
226:2039.

16. Weiss DJ, Moritz A. \fet Clin Pathol 2003; 32:22.

17. Beck DJ. Equine Vbt J 1990; 22:292.

18. Messer NT, Arnold K. J Am Vet Med Assoc 1991;
198:1415.

19. Sockett D et al. J Am Vet Med Assoc 1987;
190:308.

20. MairTS et al.Vet Rec 1990; 126:51.

21. Lubas G et al. Equine Pract 1997; 19:27.

22. Step DL et al. Cornell Vet 1990; 81:13.

23. McConnico RS et al. J Am Vet Med Assoc 1992;
201:1402.

24. Morris DD. Equine Pract 1990; 11:34.

25. Meier J, Stocker K. Crit Rev Toxicol 1991; 21:171.

26. Dickinson CE et al. J Am Vet Med Assoc 1996;
208:1866.

27. Pritchard GC et al.Vet Rec 1985; 117:545.

28. Szabo P, Bilkei G. JVet Med A 2002; 49:390.

29. Lindt F, Blum JW. Zentralbl Veterinarmed A 1994;
41:333.

30. Moser M et al. Zentralbl Veterinarmed A 1994;
41:343.

31. \fotn S, FramstadT. Acta Vet Scand 2000; 41:273.

32. Kohn CW et al. Am J Vet Res 1990; 51:1198.

33. Brommer H, van Oldruitenborgh-Oosterbaan
MM. JVet Intern Med 2001; 15:482.

34. Grace ND et al. AustVet J 1999; 77:177.

35. MullaneyTP, Brown CM Equine Vet J 1988; 20:119.

36. Fbarson EG, Andreasen CB. J Am Vet Med Assoc
2001; 218:400.

37. Girard CL, Matte JJ. J Dairy Sci 1998; 81:1412.

38. Ordakowski-Burk AL et al. Am J Vet Res 2005;
66:1214.

39. Piercy RJ et al. Equine Vet J 2002; 34:311.

40. Toribio RE et al. J Am Vet Med Assoc 1998;
212:697.

41. Finnie JW. AustVet J 1992; 69:21.

42. Sipos W et al.Vet Immunol Immunopathol 2005;
107:303.

43. Piercy RJ et al. J Am Vet Med Assoc 1998; 212:244.

44. Woods Pl< et al. Equine Vet J 1997; 29:326.

45. Schwarzwald CR, Hinchcliff KW. Proc Am Assoc
Equine Pract 2004; 50:270.

46. MacGillivray KC et al. J Vet Intern Med 2002;
16:452.

47. Angel KL et al. J Am Vet Med Assoc 1991;
198:1039.

48. Cain GR et al. CompHaematol Intl994; 4:167.

49. Widness JA et al. J Appl Physiol 2000; 88:1397.

50. Malikides N et al.Vet J 2001; 162:44.

51. Cooper C et al. J Appl Physiol 2005; 99:915.

52. Wilkerson MJ et al. JVet Intern Med 2000; 14:190.

53. Davis EG et al. JVet Intern Med 2002; 16:404.

54. Kaplan RM et al. V?t Parasitol 2004; 123:105.

55. RadinMJet al.Vet Pathol 1986; 23:656.

56. Harper SB et al. ASAIO J 1994; 40:M816.

57. Malikides N et al. Res Vet Sci 1999; 67:285.

58. Durham AE. Equine Vet Educ 1996; 8:8.

59. Fbrkins GA, DiversTJ. JVet Emerg Crit Care 2001;
11:141.

60. Belgrave RL et al. JVet Intern Med 2002; 16:396.

ERYTHROCYTOSIS

Eiythrocytosis is an increase in erythrocyte
count, hemoglobin concentration and
hematocrit in blood. Polycythemia vera, a
disease of humans and rarely small
animals, and scarcely reported in cattle, 1 is
due to an increase in concentration of all
blood cellular elements (erythrocytes,
granulocytes and platelets). Eiythrocytosis,
which is due solely to an increase in red
cell count, is either relative or absolute.

Relative erythrocytosis occurs when
the total body red cell mass (i.e. the total
amount of red cells in the body) is not
elevated above normal, but the red cell
count in peripheral blood is higher than
expected. This is the most common form
of erythrocytosis. Relative erythrocytosis
occurs both as an abnormality and as a
physiological response to physical or
psychological stress in animals with a
capacious and capricious spleen. Abnormal
relative erythrocytosis results from
hemoconcentration and is evident as an
increase in concentration of red cells and
serum total protein. The cause is a
reduction in plasma volume, which is
usually associated with dehydration due
either to lack of water intake or to
excessive losses (diarrhea, vomition). The
diagnosis is usually obvious, based on the
presence of hemoconcentration and other
signs of the underlying disease. Physio-
logical relative erythrocytosis occurs most
noticeably in horse as a result of either
excitement or exercise. The blood in the
spleen of horses has a hematocrit much
higher than that of blood (70-80%) and
when relaxed the spleen contains many
liters of blood. Excitement or exercise
cause splenic contraction through an
alpha-l-mediated event and ejection of

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

the red-cell-rich blood into the peripheral
circulation, with subsequent marked
increases in hematocrit. 2 - 3 The spleen of
an adult horse can eject 5-10 L of blood
into the circulation, which, together with
a decline in plasma volume during
exercise, increases hematocrit to 55-60%
(0.55-0.60 L/L). 2

Absolute erythrocytosis occurs
because of an increase in the number of
red blood cells in the body. It is classified
as primary or secondary, and within
secondary erythrocytosis there is a further
classification of appropriate or inappro-
priate. Primary erythrocytosis is attri-
butable to proliferation of erythroid
progenitors with maturation of the red
cell series in the absence of arterial
hypoxemia or increases in plasma
erythropoietin concentration. It is a
myeloproliferative disorder. Disorders
resembling primary erythrocytosis are
described in horses. 4,5 These horses had
marked increases in red cell count
without evidence of diseases causing
arterial hypoxemia or tissue hypoxia and
without increases in serum erythropoietin
concentration. A familial erythrocytosis is
documented in cattle, but the disease
resolved as animals matured, which is not
consistent with primary erythrocytosis
due to a myeloproliferative disorder. 6

Secondary erythrocytosis is classified
as either appropriate or inappropriate.
Appropriate secondary erythrocytosis
occurs as a consequence of diseases that
cause tissue hypoxia with subsequent
increases in plasma erythropoietin
concentration. Tissue hypoxia is often
inferred from the low arterial blood
oxygen tension or content in these
diseases. Tissue hypoxia can occur in the
face of normal arterial blood oxygen
tension when there is an abnormality in
hemoglobin (such as chronic methemo-
globinemia or carboxyhemoglobinemia),
although this has not been reported as a
cause of erythrocytosis in large animals.
Diseases causing appropriate secondary
erythrocytosis include chronic lung or
respiratory disease, and congenital cardiac
anomalies in which there is right-to-left
shunting (such as Eisenmenger's complex
in cattle). Physiological appropriate
secondary erythrocytosis occurs in animals
living at high altitude.

Inappropriate secondary erythro-
cytosis occurs in animals that do not
have arterial hypoxemia or diseases
causing tissue hypoxia. Plasma erythro-
poietin concentrations are elevated
despite there being nonnal arterial oxygen
tension and content, hence the term
'inappropriate'. The disease is usually
associated with hepatic or renal neoplasia.
The disease in horses is described in foals
or young animals with hepatoblastoma 7,8

and adults with hepatic carcinoma. 9,10
Erythrocytosis is recorded in a mare with
a lymphoma that expressed the gene
for equine erythropoietin, suggesting
that anomalous production was the
cause of the secondary inappropriate
erythrocytosis. 11 Erythrocytosis also occurs
in horses with liver disease. 12 The cause is
not known, but could involve increased
production of erythropoietin or decreased
clearance because of reduced hepatic
function. Inappropriate secondary erythro-
cytosis in ruminants or pigs is not reported,
but probably occurs.

The clinical signs of secondary
erythrocytosis are those of the underlying
disease (dyspnea, congestive heart failure,
cyanosis). In addition, the erythrocytosis
can be evident as dark red or slightly
purplish mucous membranes, lethargy
and an increased propensity for throm- I
bosis. These signs occur because of the
increase in blood viscosity that results
from marked increases in red cell concen-
tration. Treatment is directed toward the
inciting disease. For animals with primary
erythrocytosis, repeated phlebotomy and
restriction of iron intake has been used to
reduce the red cell count. 5

A syndrome is described in Standard-
bred trotters in Sweden that have normal
red cell count at rest but counts during
maximal exercise that are higher than
expected. 13 The syndrome is referred to as
'red cell hypervolemia' and is associated
with poor race performance. Diagnosis is
based on a history of poor performance
and hematocrit or red cell counts during
maximal exercise or after administration
of epinephrine that are higher than
expected. Treatment is prolonged rest,
although some horses have had phleb-
otomy and therapeutic bleeding.

REFERENCES

1. Fowler ME et al. Cornell Vet 1964; 54:153.

2. McKeever KH et al. Am J Physiol 1993; 265:R404.

3. Hardy J et al. Am J Vet Res 1994; 55:1570.

4. Beech J et al. J Am Vet Med Assoc 1984; 184:986.

5. McFarlane D et al. JVet Intern Med 1998; 12:384.

6. Tennant B et al. J Am Vet Med Assoc 1967;

150:1493.

7. Cantile C et al. Equine Vet J 2001; 33:214.

8. Lennox TJ et al. J Am Vet Med Assoc 2000;

216:718.

9. Cook G et al. Equine Vet] 1995; 27:316.

10. Roby KAetal. J Am Vet Med Assoc 1990; 196:465.

11. KochTG et al. J Vet Intern Med 2006; 20:000.

12. Durham AE et al. Equine Vet J 2003; 35:542.

13. Funkquist P et al. Equine Vet J 2001; 33:417.

ABNORMAL RED CELL FUNCTION

The primary function of red blood cells is
to transport oxygen. Abnormal red cell
function that results in anemia is dealt
with under that heading. Abnormalities
of red cell function can included abnor-
malities in red cell metabolism or the
structure or function of hemoglobin.

Hemoglobinopathies are not well docu-
mented in large animals, with the excep-
tion of changes caused by ingestion of
oxidants (nitrate, onions, kale, red maple
leaves) that cause methemoglobinemia, or
the recognition that inhalation of carbon
monoxide causes carboxyhemoglo-
binemia. Both carboxyhemoglobinemia
and methemoglobinemia decrease oxygen
carriage by hemoglobin.

Reported abnormalities in red cell
metabolism include:

!? v Diminished glucose-6-phosphate
activity of red cells caused hemolytic
anemia in an American Saddlebred
colt 1

Flavine adenine dinucleotide
deficiency is reported in a Spanish
mustang with mild and variable
anemia 2

° Glutathione reductase deficiency
causing hemolytic anemia in a horse. 3
Other abnormalities of glutathione
metabolism, with minimal clinical
expression, occur in sheep 4,5 and
horses. 6

REFERENCES

1. Stockham SL et al.Vet Pathol 1994; 31:518.

2. Harvey JW et al.Vet Pathol 2003; 40:632.

3. Dixon PM, McPherson EA. Equine Vet J 1977;
9:198.

4. Fisher TJ et al. Biochim Biophys Acta 1986;
884:211.

5. Tucker EM et al. Br J Haematol 1981; 48:403.

6. Fincham DA et al. ResVet Sci 1985; 38:346.

Disorders of white cells
LEUKOPENIA

Leukopenia does not occur as a specific
disease entity but is a common mani-
festation of a number of diseases.
Neutropenia, often accompanied by
lymphopenia , occurs with a number of
acute viral diseases such as hog cholera
and equine viral arteritis. It has also been
| observed in leptospirosis in cattle,
although bacterial infections are usually
accompanied by a leukocytosis. Acute
local inflammation may cause a transient
fall in the leukocyte count because of
withdrawal of the circulating cells to the
septic focus. Neutropenia occurs as part
of the response to toxemia, and in parti-
cular endotoxemia, because of enhanced
migration of neutrophils from blood into
tissues. The emigration of neutrophils
occurs at a rate faster than their entry into
the peripheral blood from bone marrow.
Lymphopenia occurs as part of a stress
response, and as a result of adminis-
tration of glucocorticoids.

Leukopenia also occurs as part of a
pancytopenia in which all cellular elements
of the blood are depressed. Agents that

Disorders of white cells

depress the activity of the bone marrow,
spleen and lymph nodes and result in
pancytopenia occur in poisonings caused
by trichloroethylene- extracted soybean
meal, toluene, fungal toxins, e.g. fusario-
toxicosis, notably that of Stachybotrys
alternans, and bracken fern. Pancytopenia
occurs also in radiation disease and in
calves ascribed to furazolidone poisoning.
The disease is discussed under the title of
granulocytopenic calf disease. Chronic
arsenical poisoning and poisoning by
sulfonamides, chlorpromazine and
chloramphenicol cause similar blood
dyscrasias in humans but do not appear
to have this effect in animals. Leukopenia
in pigs can occur as a result of iron
deficiency . 1

Administration of glucocorticoids
causes a lymphopenia and eosinopenia in
most species. Lymphopenia is present in
animals with immune deficiency such as
severe combined immunodeficiency in
Arabian foals and Fell pony foals with
immunodeficiency.

The importance of leukopenia is that it
may reduce the resistance of the animal to
bacterial infection. Treatment of the
condition should focus on the underlying
disease, but broad-spectrum antibiotics
are often administered because of the
presumed greater risk of bacterial infec-
tion in leukopenic animals.

REFERENCE

1. Svoboda M et al. J Vet Med B 2004; 51:231.

LEU KOCYTOSIS

Leukocytosis, a white blood cell count in
peripheral blood greater than expected in
healthy animals, can be an appropriate
physiological response to an infectious or
inflammatory process, a result of white
cell dysfunction or a result of leuko-
proliferative disease. In this last instance,
a particular situation is that in which
there is neoplasia of the immune cells
with subsequent production of growth
factors or interleukins that stimulate
inappropriate proliferation of other cells
types that are detectable in the peripheral
blood. An example is horses with intes-
tinal lymphosarcoma that have peripheral
eosinophilia.The leukoproliferative diseases
are dealt with under that heading.

Leukocytosis can be a result of an
increase in concentration of all white
blood cells or a result of increases in count
of a particular subset. The changes include
lymphocytosis, neutrophilia, eosinophilia,
monocytosis and basophilia. Thrombo-
cytosis is dealt with under that heading.

Lymphocytosis not related to infection
by bovine leukemia virus is unusual.
Chronic viral or bacterial infections can
result in mild increases in lymphocyte
count in blood but these changes have

little diagnostic significance. The ratio of
T lymphocytes to B lymphocytes changes
in some disease processes, but these sub-
sets are seldom differentiated in routine
clinical practice.

Neutrophilia is almost always a
response to an inflammatory process,
with the exception of the neutrophilia
associated with stress ('stress' leukogram).
Subacute to chronic bacterial disease or
inflammation causes marked increases in
neutrophil count in peripheral blood. The
neutrophilia is variable and can reduce
even in the presence of continuing
disease, such as R. equi pneumonia. A
mature neutrophilia is evident as a high
neutrophil count in the absence of
immature forms (band cells) . A regenera-
tive neutrophilia is characterized by
normal to elevated neutrophil counts and
the presence of an excessive number of
immature neutrophils (so-called 'left
shift'). The presence of a left shift suggests
either rebound neutrophilia subsequent
to neutropenia, or ongoing severe inflam-
mation. Mature neutrophilia suggests
inflammation of longer standing but is
not definitive for this time frame. Mature
neutrophilia can occur during the
recovery stage from anemia, especially
hemolytic anemia. Profound neutrophilia
occurs in calves with bovine leukocyte
adhesion deficiency and in some septi-
cemic foals.

Eosinophilia is usually associated
with allergy or parasitism. Examples
include milk allergy in cows and intestinal
parasitism in horses. Eosinophilia can
occur in horses with intestinal lympho-
sarcoma or multisystemic eosinophilic
epitheliotropic disease.

Monocytosis and basophilia are
unusual in large animals with the excep-
tion of that occurring as part of a rebound
bone marrow response to profound
neutropenia.

ABNORMAL WHITE CELL
FU NCTION

Abnormalities of white cell function
can be either congenital or acquired.
Congenital defects include Chediak-
Higashi syndrome and bovine leukocyte
adhesion deficiency. Acquired defects
include those associated with neoplasia of
cells of the innate and adaptive immune
systems, and dysfunction induced by
disease, intoxication or deficiency (such as
iron deficiency impairing neutrophil
function). A wide variety of infectious
diseases can impair function of a white
blood cells, including phagocytosis of
microorganisms by neutrophils or macro-
phages. Intoxicants such as some of the
mycotoxins impair leukocyte function.
Malnutrition, starvation and specific

deficiencies (e.g. iron) impair leukocyte
function . 1

REFERENCE

1. Svoboda M et al. J Vet Med B 2004; 51:231.

LEUKOPROLIFERATIVE DISEASE
(LEUKEMIA, LYMPHOMA)

The leukoproliferative diseases are
neoplastic diseases of the myeloid
(hemapoietic) or lymphoid tissues. The
discussion here will be divided into those
diseases associated with abnormal
lymphoid cells (lymphoproliferative) and
those associated with abnormal myeloid
cells (myeloproliferative). The most
common leukoproliferative diseases of
large animals are lymphoma and
lymphosarcoma.

MYELOPROLIFERATIVE DISEASES

Myeloproliferative disease is rare in large
animals but granulocytic, eosinophilic,
monocytic and myelomonocytic leukemias
are reported:

° Acute (myelogenous) and chronic
granulocytic leukemia are reported in
horses 1,2

° Acute granulocytic leukemia in a
goat 3

° Systemic mastocytosis in a goat 4
° Acute myeloblastic leukemia in
cattle 5-6 and horses 7
° Myelomonocytic leukemia in a calf 8
and a horse 9

° Malignant histiocytosis in cattle 10 and
horses 11

0 Eosinophilic myeloproliferative
disease in a horse . 12

Cases manifest with nonspecific clinical
signs including weight loss, poor per-
formance, episodic ventral and lower limb
edema, petechial hemorrhage, spleno-
megaly, and some with lymph node
enlargement or palpable masses in the
abdomen in some. Thrombocytopenia
and anemia are common because of
myelophthisis. Abnormal cells are often
apparent on examination of a smear of
peripheral blood. Immunohistochemistry
and immunostaining of cells for fluor-
escent cell sorting can identify the
abnormal cells.

The diagnosis is often obtained at
necropsy examination. Antemortem diag-
nosis can be facilitated by examination of
peripheral blood smears and bone marrow
obtained by aspiration or biopsy.

There is no effective treatment, nor are
there measures to prevent the disease.

REFERENCES

1. Ringger NC et al. AustVet J 1997; 75:329.

2. Searcy GP et al. Can Vet J 1981; 22:148.

3. Pruette M et al. J Vet Diagn Invest 1997; 9:318.

4. Khan KN et al. Vet Pathol 1995; 32:719.

5. Takayama H et al. J Comp Pathol 1996; 115:95.

6. Takahashi T et al. J Vet Med Sci 2000; 62:461.

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

7. Clark P et al. Equine Vet J 1999; 31:446.

8. Woods PR et al. J Am Vet Med Assoc 1993;

203:1579.

9. MoriT et al.Vet Pathol 1991; 28:344.

10. AnjikiT et al. J Vet Med Sci 2000; 62:1235.

11. Lester DG et al. JVet Intern Med 1993; 25:471.

12. Morris DD et al. J Am Vet Med Assoc 1984;

185:993.

LYMPHOPROLIFERATIVE DISEASE

Lymphoproliferative disease occurs in all
large animal species but is common only
in cattle, where it manifests as lymphoma
or lymphosarcoma (bovine viral leukosis).
The other lymphoproliferative disease is
plasma cell myeloma, which occurs in rumi-
nants and horses. Lymphangiosarcoma is
a rare tumor of lymphoid endothelium in
horses and cattle. 1 ' 2

Plasmacytoma (multiple myeloma)

This is a tumor of plasma cells that some-
times results in production of monoclonal
globulins. The disease occurs in cattle, 3
sheep 4 and horses 5-9 and is characterized
by proliferation of lymphoid cells that
produce an immunoglobulin or immuno-
globulin fragment (often referred to as M-
protein). The disease characteristically,
but not always, involves the bone marrow,
in which case it is referred to as multiple
myeloma. The tumor cells may or may not
secrete abnormal protein.

Clinical signs are often nonspecific
and include weight loss, anorexia, limb
edema and recurrent infections. There can
be signs of excessive bleeding as a result
of minor trauma such as needle sticks.
The tumor can infiltrate many tissues,
accounting for the protean nature of the
clinical signs. Involvement of cranial
nerves can result in dysphagia 8 and
infiltration of cervical vertebrae can result
in pathological fracture and acute spinal
cord compression. 9 Involvement of the
mediastinal lymph nodes can cause signs
of an anterior thoracic mass. The clinical
signs can be sufficiently vague that the
disease is easily overlooked in its early
stages. Radiography reveals the presence of
osteolytic bone lesions in some animals. 5

Anemia is common and thrombocy-
topenia occurs in about 20% of affected
horses. 5 Plasma cells can occasionally be
seen in smears of peripheral blood.
Hypoalbuminemia and hyperglobuli-
nemia are common findings. Serum
protein electrophoresis is useful in
demonstrating the presence of a mono-
clonal proteinopathy in the alpha-2,
beta, or gamma regions. Bence-Jones
proteinuria occurs in approximately 20%
of horses with myeloma. 5 Serum concen-
trations of specific immunoglobulins are
often increased - there are two reports of
horses with myeloma and elevated con-
centrations of IgA. 6,7 Hypercalcemia
occurs in some affected horses 5-7 and can

be a result of increased concentrations of
parathyroid-hormone-related protein. 6
Examination of bone marrow obtained by
aspiration or biopsy can reveal the
presence of an excess number of plasma
cells (> 10%).

There is no effective treatment. Most
animals present with advanced disease
and die within days to weeks, but animals
detected earlier in the disease process can
live for more than 6 months. 6,7

Lymphoma and lymphosarcoma

Bovine leukosis virus causes lymphoma in
cattle and sheep, but with these excep-
tions the etiology of lymphoma in large
animal species is unknown.

Ruminants and pigs

Lymphosarcoma occurs as four distinct
clinical entities in cattle:

° Juvenile multicentric lymphosarcoma
occurs at birth or in early life. It is
multicentric and commonly involves
the bone marrow and most lymph
nodes

8 Thymic lymphosarcoma develops in
cattle from 3 months to 2 years of age
and involves the thymus, occasionally
spreads to other lymph nodes and
rarely infiltrates other organs
° Cutaneous lymphosarcoma occurs
primarily in cattle at 1-3 years of age
° Adult multicentric lymphosarcoma,
bovine viral leukosis.

Lymphosarcoma in cattle is discussed in
detail under the headings of bovine viral
leukosis and sporadic bovine leukosis.

° Lymphoma associated with infection
by bovine leukosis virus occurs in
sheep. 10 The sporadic form of the
disease can have a variety of
presentations, including involvement
of the brain, skin and joints in
addition to the expected localization
in lymphoid tissue 11-13
c Goats develop sporadic lymphoma
including a multicentric form 14-16
0 Pigs develop lymphosarcoma

sporadically, with most forms being of
B cells, although disease due to T cells
is described. 17,18 There is also an
inherited form of the disease. 19,20

The clinical signs of lymphosarcoma are
similar to those described for the disease
associated with bovine leukosis virus in
cattle. Lymphadenopathy and clinical
abnormalities arising as a result of lymph-
adenopathy (dysphagia, bloat, respiratory
distress) are common presentations.
Radiography or ultrasonography are use-
ful diagnostic aids. 15 Biopsy of lymph
nodes can yield a diagnosis. Necropsy
examination reveals lymphadenopathy
and infiltration by neoplastic lymphocytes.
There is no documented effective treat-

ment. Administration of glucocorticoids
might cause transient improvement
because of lympholysis. Radiotherapy is
feasible in small ruminants or pigs of
sufficient monetary or emotional value,
but has not been reported.

Horses

Etiology and epidemiology
There is no recognized etiology of
lymphoma or lymphosarcoma in horses.
The disorder is more accurately described
as neoplasia of one of many lymphoid cell
lines, and with increasing sophistication of
immunohistochemical staining it is
possible to differentiate lymphoma by the
particular cell line that is affected. Both
immunohistochemistry of fixed tissue
sections and fluorescent cell sorting of cells
in body fluids have been used to determine
the abnormal cell type. 21,22 An additional
advantage of advanced testing is that
tumors of uncertain origin (lymphoid,
myeloid) can sometimes be characterized. 22

The tumors in horses are most
commonly ofT-cell or B-cell lines. Equine
B-cell lymphoma accounts for approxi-
mately 70% of equine lymphomas. 21
B-cell lymphomas that do not contain
large numbers of T cells (which are not
neoplastic) account for 40% of equine
lymphoma and are characteristically
tumors of the spleen and thoracic and
mediastinal lymph nodes. B-cell tumors
that contain large numbers of T cells
(T-cell-rich B-cell lymphoma) account for
approximately one third of equine
lymphoma. These latter are typically
tumors of the skin and subcutis. 21 T-cell
lymphomas account for approximately
20% of equine lymphomas and typically
cause disease involving mediastinal
lymph nodes. Approximately 50% of
equine fymphomas have cells that express
progesterone receptors, but none express
the estrogen receptor. 23

The disease occurs in all ages of horse
but there is no information on age-
specific incidence. One study has reported
cases in horses ranging from 4 months to
22 years of age 24 and the mean age of
cases in this, and other case reviews,
suggests that there is some increase in
risk with increasing age. Limited slaughter
surveys show a prevalence that varies from
0.7 to 3.2 cases per 100 000 animals. 25

Clinical signs

The clinical manifestation of lympho-
sarcoma in horses is probably best
described by the statement that the
disease can manifest in a protean manner.
Lymphosarcoma can exert an influence
on the function of any organ system and
this is determined by where it occurs
in the body. Most cases, certainly over
50% of cases, are multicentric although
they may present with signs that are

Disorders of white cells

organ-specific and the multicentricity
may not be recognized until further, more
complete, clinical or postmortem examin-
ation. 24 External lymphadenopathy is
usually a reflection of multicentric disease. 26

Common presenting histories for
other cases include chronic wasting and
chronic diarrhea, upper respiratory distress
with stertorous breathing or inspiratory
dyspnea, lower respiratory abnormality,
subcutaneous edema, anemia and fever of
unknown origin.

Lymphosarcoma is the single most
common cause of neoplasia in the thorax
of the horse. 27,28 A common syndrome is
that of weight loss, ventral edema of the
neck and thorax, sometimes accompanied
by pleural or peritoneal effusion, anemia,
dyspnea, cough and abdominal masses
palpable per rectum. 24,25 In cases where the
lesions are predominantly in the thorax the
syndrome is that produced by a space-
occupying lesion, 28 manifested by pectoral
edema, jugular vein engorgement but an
absence of the jugular pulse and dyspnea.
The heart may be displaced and there may
be cardiac murmurs. If there is compression
of the esophagus, dysphagia is present.

Another relatively common syndrome
is chronic weight loss, with or without
diarrhea, associated with infiltration of
the intestine . 29,30 A case review of chronic
diarrhea in horses found alimentary
lymphosarcoma to be the cause in five of
51 cases. 31 Oral glucose tolerance tests are
adversely affected by the intestinal infil-
tration of lymphosarcoma but an abnor-
mal test is not pathognomonic for this
disease. 32 Lymphosarcoma is also a cause
of recurrent colic in horses. 33

Cutaneous lymphosarcoma is a
common disease in horses and might be
the most common form of lymphoma in
horses. The tumors can be solitary or
multiple and are usually discrete, firm,
nonpainful swellings. The swellings are
often haired, but in the more severe
disease there is loss of hair. The lesions
tend to be on the head, neck and dorsal
trunk, but can be anywhere on the body.
The tumors sometimes metastasize but
horses affected with a mild or waxing and
waning disease can live for years. The
tumor is usually a T-cell-rich B-cell
lymphoma. Diagnosis is by excisional
biopsy. Another variation is mycosis-
fungoides, aT-cell lymphoma of the skin
that appears to have a more aggressive
course. 34 Pruritus with alopecia can occur
as part of a paraneoplastic syndrome in
horses with diffuse lymphoma. 35

Lymphosarcoma is the final diagnosis
in a significant proportion of horses with
fever of unknown origin 36 and also
should be considered in the differential
diagnosis of horses with signs of ataxia or
other signs of neurological disease. 37,38

The organ systems affected by lympho-
sarcoma in the horse are not restricted to
those mentioned above and individual
horses may show involvement of virtually
any body system.

Ultrasound can aid in the location of
tumor masses or accumulation of pleural
or peritoneal fluid, and in aspiration of
material from these sites. Radiography is
useful for detecting mediastinal disease.
Rhinolaryngoscopy permits detection and
assessment of disease of the pharynx.

Clinical pathology

A specific diagnosis can be obtained by
cytology and needle aspirates or biopsy
with cytological examination of affected
lymph nodes is diagnostic. Samples can
be obtained from enlarged lymph nodes
or from bone marrow. Cytological exam-
ination of fluid obtained by thoraco-
centesis or abdominocentesis where there
is thoracic or abdominal involvement is
also frequently diagnostic.

Anemia is a consistent finding in
horses with advanced lymphosarcoma.
The anemia can be due to tumor cells
occupying bone marrow, 39 but this is not a
usual manifestation of the disease. More
commonly, anemia is probably due to
increased destruction of red cells or
anemia of chronic disease. Only a small
proportion of horses with lymphade-
nopathy due to lymphosarcoma have
concurrent leukemic blood changes.
Sezary-like cells have been detected
in the blood of a horse with B-cell
lymphoma. 40 Thrombocytopenia occurs
in approximately 30% of cases. 24

Immunophenotyping cells obtained
at necropsy examination, by biopsy of
affected organs or lymph nodes, or from
peripheral blood can aid in determining
the cell type involved. 21,22

Hypergammaglobulinemia and hypo-
albuminemia occur in some horses.
Hypergammaglobulinemia in horses
with lymphosarcoma is almost always
due to a polyclonal globulinopathy - in
contrast to horses with plasma cell
myeloma - and is probably attributable to
the inflammatory response to the tumor.
Plasma fibrinogen concentrations can be
elevated in horses with lymphosarcoma
for the same reason.

Low serum immunoglobulin concen-
trations have been reported in horses
with lymphosarcoma 41 but this finding is
not specific for lymphosarcoma. Detection
of low serum IgM concentration has poor
sensitivity and specificity for diagnosis of
lymphosarcoma. 42 The sensitivity and
specificity of serum IgM below 60mg/dL
for diagnosis of lymphosarcoma in horses
are 50% and 35 %, respectively. This is not
a good screening or diagnostic test for
lymphosarcoma in horses.

Abnormalities in serum calciunT con-
centration are uncommon and variable,
with both hypocalcemia and hypercalcemia
being reported. Hypercalcemia can be
associated with elevated serum concen-
trations of parathyroid hormone related
peptide.

Treatment

Treatment of lymphoma in horses is
scarcely reported. Immunotherapy with
cyclophosphamide and vaccinia-virus-
infected autologous tumor cells resulted
in some remission of disease in a stallion
with cutaneous lymphosarcoma and the
animal remained clinically stable for 19
months without tumor progression. 43
Removal of an ovarian granulosa theca
cell tumor in a mare with waxing and
waning cutaneous lymphosarcoma was
associated with regression of the tumor. 44
Radiotherapy of localized disease of the
head and pharynx might be effective in
treatment of the lymphoma in horses, 45 as
lymphoma in other species is radio-
sensitive. Surgical removal of isolated
masses in the skin is appropriate in some
cases of cutaneous lymphosarcoma.

Administration of oncolytic agents
has resulted in remission of disease in
some horses. Drugs used include predni-
solone, vincristine, cyclophosphamide
and cytarabine. The glucocorticoids cause
lysis of abnormal lymphocytes and can
result in some improvement in clinical
signs. A protocol that has met with some
success involves administration of cyclo-
phosphamide (2 mg/kg, intravenously)
once weekly for 4-6 weeks, and then
once every 2-3 weeks, combined with
oral administration of prednisolone
(0.5-1.5 mg/kg every 24-48 h). Another
protocol involves administration of
vincristine (0.008 mg/kg intravenously)
and cyclophosphamide (2 mg/kg intrave-
nously) once every 2 weeks for four to
six treatments, combined with daily
administration of prednisolone. The aim
of all these treatments is to induce
remission or to reduce clinical signs of the
disease when these signs are due to
lymphadenopathy (such as dysphagia,
dyspnea). An example could be the treat-
ment of a pregnant mare with retro-
pharyngeal tumor that causes dysphagia,
with a view to prolonging the mare's life
until parturition.

REVIEW LITERATURE

McClure JT. Leukoproliferative disorders of horses. Vet

Clin North Am Equine Pract 2000; 16:165-181.

REFERENCES

1. Ijzer J, van den Ingh TSGAM. J Comp Pathol

2000; 122:312.

2. Ruggles RG et al. J Am Vet Med Assoc 1992;

200:1987.

3. Kameyama M et al. J Vet Diagn Invest 2003;

15:166.

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

4. Perez J et al.Vet Pathol 2000; 37:479.

5. Edwards DF et al. J Vet Intern Med 1993; 7:169.

6. Barton MH et al. J Am Vet Med Assoc 2004;
225:409.

7. Pusterla N et al.Vet Rec 2004; 155:19.

8. McConkey S et al. JVet Diagn Invest 2000; 12:282.

9. Drew RA et al. Equine Vet J 1974; 6:131.

10. Dimmock CK et al. Immunol Cell Biol 1990;
68:45.

11. Da Silva DL. J S Afr Vet Assoc 2002; 73:90.

12. Roels S, Vanopdenbosch E. Vet Rec 2001; 149:392.

13. Pearson GR et al. J Comp Pathol 1999; 120:295.

14. Guedes RM et al.Vet Rec 1998; 143:51.

15. Rozear L et al. Vet Radiol Ultrasound 1998;
39:528.

16. DiGrassieWA et al. Can Vet J 1997; 38:383.

17. Vo TDetal. JVet Med A 2004; 51:348.

18. Hejazi R, Danyluk AJ. Can Vet J 2005; 46:179.

19. Head KW et al.Vet Rec 1974; 95:523.

20. McTaggart HS et al.Vet Rec 1979; 105:36.

21. Kelley LC, Mahaffey EA.Vet Pathol 1998; 35:241.

22. McClure JT et al. JVet Intern Med 2001; 15:144.

23. Henson KL et al.Vet Pathol 2000; 29:40.

24. Rebhun WC, Bertone A. J Am Vet Med Assoc
1984; 184:720.

25. \&n der Hoven R, Franken P. Equine Vet J 1983;
15:49.

26. Kofler J et al. JVet Med A 1998; 45:11.

27. Sweeney CR, Gillette DM. J Am Vet Med Assoc
1989; 195:374.

28. MairTS et al. Equine Vet J 1985; 17:428.

29. Wilson RG et al. Equine Vet J 1985; 17:148.

30. Platt H. J Comp Pathol 1987; 97:1.

31. Love S et al.Vet Rec 1992; 130:217.

32. MairTS et al. Equine Vet J 1991; 23:344.

33. MairTS, Hillyer MH. Equine Vet J 1997; 29:415.

34. Potter K, Anez D. J Am Vet Med Assoc 1998;
212:550.

35. Finley MR et al. J Am Vet Med Assoc 1998;
213:102.

36. MairTS et al. EquineVet J 1989; 21:260.

37. Zeman DH et al. JVet Diagn Invest 1989; 1:187.

38. Williams MA et al. ProgVet Neurol 1992; 3:51.

39. Lester GD et al. JVet Intern Med 1993; 7:360.

40. Polk AC et al. JVet Intern Med 1999; 13:620.

41. Furr MO et al. J Am Vet Med Assoc 1992; 201:307.

42. Perkins GA et al. JVbt Intern Med 2003; 17:337.

43. Gollagher RD et al. Can Vet J 1993; 34:371.

44. Henson KL et al. J Am Vet Med Assoc 1998;
212:1419.

45. Weaver MP et al. EquineVet J 1996; 28:245.

Lymphadenopathy

(lymphadenitis)

Lymph nodes can be enlarged because of
inflammation (lymphadenitis) or infil-
tration with neoplastic cells. Enlargement
of peripheral nodes causes visible and
palpable swellings and in some cases
obstruction to lymphatic drainage and
subsequent local edema, as in sporadic
lymphangitis of horses. Enlargement of
internal nodes may cause obstruction of
the esophagus or pharynx, trachea or
bronchi. Enlargement of the lymph nodes
can occur as a result of infection or of
neoplastic invasion. lymphadenopathy as
part of lymphoma and lymphosarcoma
are discussed under 'Leukoproliferative
diseases'.

Lymphadenitis occurs most commonly
in response to infection or inflammation in

the region of the body distal to, and
drained by, the lymph node. Lymph-
adenitis also accompanies other signs in
many other diseases, including bovine
malignant catarrh, sporadic bovine
encephalomyelitis, the porcine repro-
ductive and respiratory syndrome, East
Coast fever, Ondiri disease and ephemeral
fever.

Infection and enlargement of lymph
nodes is the major presenting sign in a
small number of diseases, which include:

e Caseous lymphadenitis of sheep and
ulcerative lymphangitis in horses and
cattle due to infection with
Corynebacterium pseudotuberculosis
® Internal abscessation associated with
C. pseudotuberculosis in horses 1
° Anthrax, especially in the pig but also
in the horse, which may initially
manifest as cervical lymphadenopathy
with considerable inflammation and
swelling in the pharyngeal region and
neck

° Strangles in horses associated with
S. equi and lymphadenitis produced
by Streptococcus zooepidemicus.
Lymphadenopathy that causes
enlargement of abdominal lymph
nodes is a characteristic of infection
with S. equi in the burro
° Anorectal lymphadenopathy in young
horses, causing extraluminal rectal
obstruction with colic and sometimes
urinary dysfunction 2
° Cervical adenitis (jowl abscess) of
pigs, caused principally by group
E type IV Streptococcus sp. but also by
Actinomyces pyogenes and Pasteurella
multocida

° Granulomatous cervical adenitis,
which also occurs in pigs and is a
common finding at slaughter. The
lesions rarely cause clinical illness but
are a public health concern because
they may be tuberculosis. Most
commonly they are associated with
R. equi or atypical mycobacteria but
Mycobacterium tuberculosis,
Mycobacterium avium and
Mycobacterium bovis are also causes
° Tularemia, infection with Francisella
tularensis, in tick-infested sheep
0 Melioidosis associated with infection
with Pseudomonas (Malleomyces)
pseudomallei

° Tick pyemia associated with

Staphylococcus aureus in sheep infested
with the tick Ixodes ricinus
° Retropharyngeal lymph node

enlargement up to three or four times
normal, and colored bright green,
have been identified in cattle as
resulting from infection with the algae
Prototheca spp. 3
° Tuberculosis

° lymphadenitis in lambs associated
with P. multocida, and in some cases of
actinobacillosis

■> Morel's disease of sheep associated
with a micrococcus
0 Bovine farcy and atypical skin
tuberculosis, the latter involving the
lymphatics but not associated with
lymph node enlargement.

In acute lymphadenitis there may be pain
and heat on palpation but the nodes are
for the most part painless. Obstructions
produced by enlarged lymph nodes can
result in secondary signs such as
respiratory difficulty with enlargement of
the retropharyngeal lymph nodes and
esophageal obstruction by enlarged
mediastinal lymph nodes. Needle biopsy
for cytology and culture can aid in the
determination of the cause of lympha-
denitis and can allow the differentiation
between lymphadenitis and neoplastic
enlargement. Ultrasound may also aid
in diagnosis. 4 The diseases above are
discussed in more detail under their
specific headings.

Absence of lymphoid tissue occurs
as a congenital defect in Arabian foals
with severe combined immunodeficiency
and is recorded in an Angus calf.

REFERENCES

1. Pratt SM et al. J Am Vet Med Assoc 2005; 227:441

2. Magee AA et al. J Am Vet Med Assoc 1997;
210:804.

3. Rogers RJ et al. J Comp Pathol 1980; 90:1.

4. Kofler J et al.Vet Rec 1998; 14:425.

Diseases of the spleen and
thymus

The spleen serves a number of functions -
it is a storage organ for blood, a source of
extramedullary erythropoiesis in some
species, a major component of the reticulo-
endothelial system, and an important
component of the immune system. Its
function is most evident in the horse, in
which an intact and functioning spleen is
necessary for normal work capacity. Blood
in the spleen of horses has a hematocrit
much higher than that of blood (70-80%)
and when relaxed the spleen contains
many liters of blood. Excitement or
exercise cause splenic contraction
through an alpha-l-mediated event and
ejection of the red-cell-rich blood into the
peripheral circulation, with subsequent
marked increases in hematocrit. 1,2 The
spleen of an adult horse can eject 5-10 L
of blood into the circulation and, together
with declines in plasma volume during
exercise, increase hematocrit to 55-60%
(0.55-0.60 L/L). 1

Diseases of the spleen and thymus

465

Splenectomy is performed as part of
treatment of idiopathic refractory thrombo-
cytopenia, or as a consequence of splenic
infarction. Removal of the spleen
(splenectomy) impairs the oxygen-carrying
capacity of blood during exercise, by
preventing the normal increase in
hematocrit, and prevents the normal
cardiovascular responses to exercise, includ-
ing increases in right atrial pressure. 3,4

SPLENOMEGALY

Diffuse diseases of the spleen that result
in enlargement are usually secondary to
diseases in other organs. Splenomegaly
with complete destruction of splenic
function is virtually symptomless, especially
if the involvement occurs gradually, and
in most cases clinical signs are restricted
to those caused by involvement of other
organs. An enlarged spleen may be
palpable on rectal examination in the
horse and careful percussion may detect
enlargement of the spleen in cattle, but in
most instances involvement of the organ
is not diagnosed at antemortem exam-
ination unless laparotomy is performed.

Left dorsal displacement of the colon in
the horse is a colic in which the spleen is
displaced medially and this may give the
impression that the organ is enlarged.
Rupture of a grossly enlarged spleen may
cause sudden death due to internal
hemorrhage. This is sometimes the cause of
death in bovine viral leukosis or equine
amyloidosis. 5 Moderate degrees of
splenomegaly occur in many infectious
diseases, especially salmonellosis, anthrax,
babesiosis, equine infectious anemia and
diplococcus septicemias in calves, and in
some noninfectious diseases such as copper
toxicity in sheep. Animals that die suddenly
because of lightning stroke, electrocution
and euthanasia may also show a moderate
degree of splenomegaly but the enlarge-
ment is minor compared to that observed
in congestive heart failure, portal obstruc-
tion or neoplastic change.

Neoplasms of the spleen are not
common in large animals but may
include lymphosarcoma, hemangiosar-
coma, myelocytic leukemia or malignant
melanoma in horses. 6 " 8 Metastasis of
hepatic carcinoma to the spleen of a dairy
cow is reported. 9 The abnormality is
usually readily detected by ultrasono-
graphic examination of the spleen. They
may be discovered incidentally during
rectal examination or because of colic
resulting from displacement of the bowel
by the enlarged spleen.

SPLENIC ABSCESS

Splenic abscess may result when a septic
embolus lodges in the spleen, but is more
commonly caused by extension of infection

from a neighboring organ. Perforation by a
foreign body in the reticulum of cattle is the
commonest cause of the disease in large
animals and gastric penetration by sharp
metal have caused splenitis in the horse.
Perforation of a gastric ulcer or an erosion of
the gastric wall caused by Gasterophilus
intestinalis 10 or extension of a granuloma
caused by larvae of Habronema sp. in horses
may lead, by extension, to development
of a suppurative lesion in the spleen.
In those occasional cases of strangles
in horses in which systemic spread occurs,
splenic abscess occasionally occurs.

Splenic abscesses associated with
C. pseudotuberculosis infection are diag-
nosed in horses in those parts of the
world where the infection is endemic. The
most common clinical signs are concurrent
external abscesses, anorexia, fever, lethargy,
weight loss and signs of respiratory tract
disease or abdominal pain. Clinico-
pathological abnormalities included serum
synergistic hemolysin inhibition titer of
512 or more, and leukocytosis with
neutrophilia, hypergiobulinemia, hyper-
fibrinogenemia and anemia. Diagnosis is
based on the presence of appropriate
clinical signs and ultrasonographic exam-
ination of the spleen. Prolonged treat-
ment with antimicrobials is successful in
most cases. 11

If the abscess is extensive and acute
there are systemic signs of fever, anorexia
and increased heart rate. Fhin is evidenced
on palpation over the area of the spleen
and hematological examination reveals a
marked increase in the total white cell
count and a distinct shift to the left in the
differential count.

Abdominocentesis usually provides
evidence of chronic peritonitis by the
presence of a large amount of inflammatory
exudate. Peritonitis is often coexistent and
produces signs of mild abdominal pain with
arching of the back and disinclination to
move. Mild recurrent colic may also occur.
Anemia, with marked pallor of mucosae,
and terminal ventral edema are also
recorded. The spleen may be sufficiently
enlarged to be palpable per rectum. 12

Treatment of splenic abscess is often
unrewarding because of the extensive
nature of the lesion before clinical signs
appear. The systemic signs can usually be
brought under control by treatment with
sulfonamides or antibiotics over a period
of about 7 days but relapses are common
and death is the almost certain outcome.
Splenectomy is recommended if adhesions
and associated peritonitis are absent.

SPLENIC HEMATOMA, RUPTURE
OR INFARCT ION

Formation of a hematoma in the spleen
or, in the more severe instance, splenic

rupture usually occurs as a result of
trauma. The syndrome is best described in
horses, occurring as a result of falling on
to a stirrup or blunt trauma to the left side
of the rib cage. 7,13,14 The clinical signs
include colic, tachycardia, cold extremities
and pallor of the mucous membranes - all,
of which are suggestive of hemorrhagic
shock. If a hematoma is present ultra-
sonographic examination of the abdomen
will reveal an abnormally shaped spleen
containing a hypoechoic mass. Rupture of
the spleen with be apparent as accumu-
lation of a large quantity of fluid within
the abdomen. The fluid will have the
ultrasonographic characteristics of blood
(a swirling echodensity) . Laparoscopy can
be used to confirm the diagnosis.
Hematology can reveal leukocytosis and
low hematocrit. Peritoneal fluid can be
serosanguinous if the hematoma has not
ruptured, or bloody if the spleen is ruptured.

Infarction of the spleen is reported
rarely in horses and so predisposing
factors are not identified. 15 In other
species splenomegaly predisposes to
infarction. The clinical signs are mild to
moderate colic, tachycardia and signs of
hemorrhagic shock. Ultrasonography and
exploratory laparotomy are diagnostic.
The spleen is enlarged and has numerous
zones of varying echogenicity, which is in
marked contrast to the usual homo-
genous echogenicity of normal spleen.
There can be excessive, echogenic fluid in
the abdomen consistent with blood.
Treatment is surgical, although technically
challenging because of the splenomegaly
and risk of rupture of the spleen.

Treatment of a splenic hematoma is
conservative, with enforced rest for a
period of up to 3 months. Resolution of
the hematoma can be monitored by
periodic ultrasonographic examination.
Horses with a ruptured spleen usually die
within a short period of time. Theore-
tically, emergency splenectomy might be
useful, but timely diagnosis and surgery is
difficult to achieve because of the short
time course of the disease.

REFERENCES

1. McKeever KH et al. Am J Physiol 1993; 265:R404.

2. Hardy J et al. Am J Vet Res 1994; 55:1570.

3. McKeever KH et al. Am J Physiol 1993; 265:R409.

4. Kunugiyama I et al. JVet Med Sci 1997; 59:733.

5. Pusterla N et al. J Vet Intern Med 2005; 19:344.

6. Chaffin MK et al. J Am Vet Med Assoc 1992;

201:743.

7. Geelen SNJ et al. Tijdschr Diergeneeskd 1996;

121:544.

8. MacGilli vray KC e t al . JVet Intern Med 2002; 16:452.

9. Jeong WI et al. Vet Pathol 2005; 42:230.

10. Dart AJ et al. AustVet J 1987; 64:155.

11. Pratt SM et al. J Am Vet Med Assoc 2005; 227:441.

12. Spier S et al. J Am Vet Med Assoc 1986; 189:557.

13. Dyke TM, Friend SCE Equine Vet J 1998; 20:138.

14. Ayala I et al. AustVet J 2004; 82:479.

15. RoyMF et al. Equine Vet J 2000; 32:174.

16

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

CONGENITAL ANOMALIES

Abdominal situs inversus is reported in a
calf. 1 The calf had a rumen that was on
the right side of its abdomen, and two
spleens, among other abnormalities. The
clinical presentation was chronic bloat.

REFERENCE

1. Fisher KR et al. Anat Rec 2002; 267:47.

THYMUS

The thymus is the source of T cells in
animals and is essential for development
of normal immune responses. These
functions occur during late gestation and
in the neonate. Primary diseases of the
thymus are rare in farm animals. The
thymus is largest, relative to body size, in
neonates and atrophies in adults to the
extent that it can be difficult to identify.
Aplasia or thymic hypoplasia occurs as
part of severe combined immuno-
deficiency in Arabian foals. Aplasia of the
thymus is reported in a Holstein calf. 1 The
congenital condition results in increased
susceptibility to infection. Extrathoracic
thymus tissue occurs in lambs and can be
mistaken for enlargement of the thyroid
glands. 2 Neoplasia of the thymus occurs
in most species. Thymic lymphomas are
reported in horses, 3 pigs 4 and calves. 5
Thymoma and thymic carcinoma are
reported in horses and cattle. 6 " 8 The
clinical syndrome is that of a cranial
thoracic mass. There can be compression
of the cranial vena cava with obstructed
blood flow and signs of congestive heart
failure. The jugular veins are distended
and there can be submandibular edema.
There can be accumulation of excessive
pleural fluid. Esophageal obstruction
evident as bloat in cattle or dysphagia in
cattle and horses occurs. Radiography or
ultrasonography of the chest demonstrate
the mass, and histological diagnosis can
be achieved at necropsy or in samples
obtained by fine-needle biopsy.

REFERENCES

1. Yeruham 1 et al. J Vet Med B 2000; 47:315.

2. Kock ND et al. Vet Rec 1989; 124:635.

3. Van den Hoven R, Franken P. Equine Vet J 1983;
15:49.

4. Kadota K et al. Zentralbl Veterinarmed A 1990;
37:592.

5. Angel KL et al. J Am Vet Med Assoc 1991; 198:1771.

6. Whitely LO et al. Vet Pathol 1986; 23:627.

7. NorrfinRW. Cornell Vet 1970; 60:617.

8. Oda S et al. J Vet Med Sci 1999; 61:561.

Immune deficiency
disorders (lowered
resistance to infection)

Increasingly, animals are encountered
that are much more susceptible to infec-
tion than their cohorts. These animals

may be suffering because of a reduction in
their immune function and need to be
identified as such. The history and signs
that should suggest the possible presence
of compromised immune function are:

• Infections developing in the first
6 weeks of life

° Repeated or continuous infections
that respond poorly to treatment

• Increased susceptibility to low-grade
pathogens and organisms not usually
encountered in immunocompetent
animals

0 Administration of attenuated vaccines
leading to systemic illness
0 Low leukocyte counts, either
generally or as lymphopenia or
neutropenia, perhaps within an
associated low platelet count.

It is not proposed to detail the mechan-
isms of humoral and cellular immunity
here because there is a large literature
based on the subject in immunology.
However, it is necessary to remember that
the normal immune response is a very
complicated process, including many
sequential steps, and there are various
sites at which defective development or
function can occur.

The disorders of immunity may be
primary, in which the animal is born with
a congenital defect of one of the immune
processes, or secondary, in which the
animal has a normal complement of
immunological processes at birth but
suffers a dysfunction of one of them, often
temporarily, during later life. Toxicological
and microbiological agents can have this
effect.

Immunosuppression is a state of
temporary or permanent dysfunction
of the immune response resulting from
damage to the immune system and lead-
ing to increased susceptibility to disease
agents. 1 In immunosuppression there is
decreased immune responsiveness to all
foreign antigens, whereas in immune
tolerance there is a state of decreased or
nonresponsiveness to one particular
antigen. Immunosuppression may be
associated with infectious and non-
j infectious agents. A review of the general
i aspects of immunosuppression and the
: various agents responsible is available. 1
; Infectious agents include bacteria, viruses,
j protozoa and helminths; noninfectious
. causes include chemicals, hormones and
i some antimicrobials such as chlortetra-
i cyclines and toxins. Environmental factors
: such as extremes of temperature, humidity,
j high population density and mixing
j animals from different origins, and pro-
I longed transportation have also been
j implicated as causes of immuno-
j suppression but the pathogenesis of these
| has not been well explained.

Various laboratory methods can be
used to evaluate immunosuppression.
The criteria which can be used to evaluate
immune functions include:

° Gross and microscopic changes in the
morphology of central or peripheral
lymphoid tissues

0 Changes in the concentration or ratios
of different classes of immunoglobulin
° Changes in serum complement
concentration

° Changes in the functional activity of
immunoglobulins

3 Changes in functional activity of the
immune response
3 Interference with the results of
vaccination

3 Exacerbation in the course of disease
associated with other agents
° Changes in the number and viability
of cells from lymphoid organs. 1

The development of monoclonal antibody
reagents has allowed new approaches to
veterinary immunopathology, particularly
the identification and analysis of leukocyte
subpopulations in health and disease. 2

Most of the diseases associated with
immunological deficiency states are dealt
with in systems or other categories of
disease throughout this book and only a
checklist is provided here.

PRIMARY IMMUNE DEFICIENCIES

The primary immunodeficiencies can be
in either innate immunity or adaptive im-
munity. Deficiencies of innate immunity
include:

Chediak-Higashi syndrome, an
inherited defect of many animal
species, including cattle. This is a
defect of phagocytic capacity via the
neutrophils and monocytes
c Bovine leukocyte adhesion deficiency
of Holstein calves, which results from
a deficiency in CD18 and
accumulation of profound numbers of
neutrophils in circulation but not in
tissue.

Deficiencies of adaptive immunity

include:

Combined immunodeficiency (CID)
of Arabian horses due to an inherited
failure to produce and differentiate
lymphoid precursor cells into B and
T lymphocytes. See Table 34.2 for a
listing of immunodeficiencies of
horses. A similar disease is reported in
an Angus calf
Agammaglobulinemia of
Standardbred and Thoroughbred
horses, a probably inherited failure to
produce B lymphocytes. These horses
live much longer than those affected
with CID

Amyloidoses

467

° Selective deficiencies of one or more
globulins. A deficiency of IgM in
Arabian horses and Quarter horses is
listed. 3 IgM and IgA combined
deficiencies with diminished but
discernible levels of IgG are observed
occasionally in horses. A transient
hypogammaglobulinemia (absence of
IgG) has been reported in one
Arabian foal, which was
immunodeficient until it was
3 months old and then became normal

° Selective IgG 2 deficiency in Red
Danish cattle

° A syndrome of immunodeficiency in
Fell ponies

° Common variable immunodeficiency
is described in adult horses 4-5

0 Lethal trait A46 (inherited

parakeratosis) of cattle is a primary
immunodeficiency influencing T
lymphocytes, with impairment of
cellular immunity

® Selective IgG 2 deficiency of cattle
causes increased susceptibility to
gangrenous mastitis and other
infections. It is a primary deficiency of
IgG 2 synthesis, and is recorded in the
Red Danish milk breed

° Sheep and pigs - there are as yet no
recognized primary
immunodeficiencies in these species.

SECONDARY IMMUNE
DEFICIENCIES

These are as follows:

° Failure of transfer of passive
immunity, i.e. of antibodies from
colostrum to the offspring, is well
known as the commonest cause of
deficient immunity in the newborn
and is discussed in Chapter 3

° Atrophy of lymphoid tissue and
resulting lymphopenia associated
with:

o Viral infections such as equine
herpes virus in newborn foals,
rinderpest, bovine virus diarrhea,
swine fever, porcine circovirus 6 and
hog cholera. All these cause
lymphatic tissue suppression and a
diminished

immunoresponsiveness. The
pathogenesis of the
immunodeficiency associated with
the bovine viral diarrhea (BVD)
virus may be due to impairment of
the function of polymorphonuclear
cells

Bacterial infections such as
Mycoplasma spp. and
Mycobacterium paratuberculosis
have approximately the same effect
as the above

* Physiological stress such as birth
may cause immunosuppression in

the fetus, making it very
susceptible to infection in the
period immediately after birth.
There is a similar depression of
immunological efficiency in the
dam immediately after parturition,
which, for example, leads to
periparturient rise of worm
infestation in ewes. Psychological
stress in experimental animals does
increase susceptibility to infection,
but the practical importance of this
to animal production is not clear
° Toxins such as bracken,
tetrachlorethylene- extracted
soybean meal, T 2 mycotoxin and
atomic irradiation suppress
leukopoiesis. Immunosuppression
is also attributed to many
environmental pollutants,
including polychlorinated
biphenyls, 2,4,5-T contaminants,
DDT, aflatoxin and the heavy
metals

° General suppression of immune
system responsiveness, e.g.:

° Glucocorticoids administered in
large doses or over long periods
reduce the activity of neutrophils
and the number of circulating
lymphocytes, although the
reduction varies widely between
species. The production of
antibodies is also reduced
° Nutritional deficiency, especially of
zinc, pantothenic acid, calcium and
vitamin E, cause general
suppression. A total caloric
deficiency has a similar effect.
Addition of certain trace elements
such as copper, iron, zinc and
selenium in animal feeds is
necessary for an adequate
immunity. Selenium, alone or in
combination with vitamin E, can
enhance antibody responses,
whereas its deficiency results in
immunosuppression. Selenium
supplementation in animal feeds is
important to enhance both
antibody production and
phagocytic activity of neutrophils.

In cattle, copper deficiency induced
by molybdenum or iron can cause
an impairment in the ability of
neutrophils to kill ingested Candida
albicans. 1 A review of the influence
of immunoenhancing vitamins in
cattle is available. Nutrients that
stimulate disease resistance include
carotenoids, vitamins A, E, and C,
zinc, manganese, copper and
selenium. Neonatal calves may
have low reserves of carotene and
vitamins A and E and are
dependent upon obtaining them
from colostrum, which contains

highly variable quantities.
Administration of drugs that
impair folate metabolism can
induce anemia and depletion of
white blood cells, with subsequent
bacterial infection 7

0 Experimentally, a protein-energy .
malnutrition in neonatal calves
results in loss of body weight, and
decreased lymphocyte interleukin-2
activity and lymphocyte
proliferation when compared to
calves of similar age

° Exposure to cold and heat stress
for periods of several weeks
duration

° Events associated with parturition,
in particular glucocorticoid release,
that impair innate immunity. 8

REFERENCES

1. Muneer MA etal.BrVet J 1988; 144:288.

2. MacKay CR, MacKay IR. Br Vet J 1989; 145:185.

3. Perryman LE et al. J Am Vet Med Assoc 1977;

170:212.

4. Flaminio J et al. J Am Vet Med Assoc 2002;

221:1296.

5. Pellegrini-Masini A et al. J Am Vet Med Assoc

2005; 227:114.

6. ShibaharaT et al. J Vet Med Sci 2000; 62:1125.

7. Piercy RJ et al. Equine Vet J 2002; 34:311.

8. Burton JL et al.Vet Immunol Immunopathol 2005;

105:197.

Amyloidoses

The amyloidoses are a group of diseases
characterized by the deposition of an
extracellular proteinaceous substance,
amyloid, in the tissues with subsequent
disruption of normal tissue architecture
leading eventually to organ dysfunction.
Amyloidosis in farm animals usually
occurs in association with a chronic
suppurative process elsewhere in the
body and is due to accumulation of AA
amyloid. Another form of the disease
involves accumulation of AL amyloid,
especially as localized disease in horses.

ETIOLOGY AND EPIDEMIOLOGY

Amyloidosis occurs rarely and when it
does occur it is most common in animals
exposed systemically and repeatedly to
antigenic substances. Examples include
repeated injections of antigenic material
for commercial production of hyper-
immune serum and long-standing sup-
purative diseases or recurrent infection as
in Chediak-Higashi syndrome. Severe
strongylid parasitism in the horse has
been reported as a cause. Holstein calves
with bovine leukocyte adhesion deficiency
have accumulation of amyloid in tissue,
although this is not the primary disease.
Many cases of amyloidosis in large
animals are without apparent cause.

The incidence of visceral AA amyloi-
dosis in slaughtered cattle in a group of

468

PART 1 GENERAL MEDICINE ■ Chapter 9: Diseases of the hemolymphatic and immune systems

302 cattle older than 4 years of age in
Japan was 5.0% compared with those
previously reported from Japan and other
countries ranging from Q.4-2.7%. 1
Systemic AA-amyloidosis associated with
tuberculosis has been described in a
European wild boar. 2 Systemic amyloi-
dosis in goat kids with chronic arthritis
associated with seroconversion to
Erysipelothrix rhusiopathiae has been
described. 3

Out of 16 000 horses referred for
clinical examination into a veterinary
teaching hospital over a period of 13 years,
nine horses were identified with
amyloidosis. 4 Cutaneous amyloidosis has
been associated with malignant histiocytic
lymphoma in the horse. 5

A case of cardiac amyloidosis causing
heart failure in a 16-year-old Thorough-
bred gelding has been described. 6 The
disease was due to accumulation of AL
amyloid. 6

The AL form of amyloidosis is charac-
teristically associated with unstable
monoclonal immunoglobulin light chains
produced by plasma cell dyscrasia and
resulting in deposition of AL fibrils. 6

PATHOGENESIS

How amyloid is formed is uncertain but a
hyperglobulinemia is commonly present
and this, together with the circumstances
under which it occurs, suggest an abnor-
mality of the antigen-antibody reaction.
Amyloidoses are classified by the types of
amyloid protein deposited. AA amyloid is
derived from serum amyloid-A protein
(SAA), which is an acute-phase reactant
produced by hepatocytes. 7 However, j
increased concentrations of SAA alone I
are not sufficient to cause amyloidosis, j
AA (secondary) amyloidosis is associated |
with recurrent acute or chronic infections, j
inflammatory disease or neoplasia. i

Extensive amyloid deposits may occur j
in the spleen, liver or kidneys and cause j
major enlargement of these organs and j
serious depression of their functions, j
The commonest form that is clinically I
recognizable in animals is renal amyloi- j
dosis. This presents as a nephrotic j
syndrome with massive proteinuria and a j
consequent hypoproteinemia and edema, j
Terminally, the animal is uremic, becoming
comatose and recumbent. The edema of
the gut wall and its infiltration with
amyloid create the conditions necessary '
for the development of diarrhea. In horses, j
cases of multiple cutaneous lesions are
recorded. The amyloid is present in j
5-25 mm diameter nodes in the skin of i
the head, neck and pectoral regions.

Rare cases of involvement of the upper
respiratory tract (nasal cavities, pharynx,
larynx, guttural pouch and lymph nodes
of the head and neck, and conjunctiva)

are also recorded in horses. The amyloid
material deposited in the tissues is usually
of the AL form, whereas systemic disease
is almost always the AA form.

AL amyloidosis is also reported in an
adult cow with bo vine leukocyte adhesion
deficiency. 8

CLINICAL FINDINGS

Many cases of amyloidosis are detected
incidentally at necropsy. The cutaneous
form in horses is characterized by the
presence of hard, nonpainful, chronic
plaques in the skin. 5 Most of the lesions,
which can be widespread and severe, are
on the sides of the neck, shoulders and
head. Respiratory tract involvement in the
horse is usually limited to the nasal
cavities, and this may cause dyspnea. 4

Chronic heart failure due to cardiac
amyloidosis secondary to systemic amy-
loidosis in a 16-year-old gelding was
characterized clinically by weight loss,
dysphagia, recurrent episodes of eso-
phageal obstruction and anorexia of a few
weeks duration. 1 Ventral edema, tachycardia
and irregular heart rate associated with
atrial fibrillation were present. The clinical
findings were consistent with biventricular
heart failure from ventricular dysfunction,
atrial fibrillation and pulmonary hyper-
tension. The amyloid was of the AL form.

A case of systemic AL amyloidosis
associated with multiple myeloma in a
horse was characterized clinically by rapid
weight loss, muscle atrophy, soft unformed
feces and ventral edema. 9

Hemoperitoneum and acute death
secondary to splenic or hepatic rupture in
horses with systemic amyloidosis is
reported. 10

Clinical cases in cattle are characterized
by emaciation and enlargement of the
spleen, liver or kidneys; involvement of
the kidney causes proteinuria and is often
accompanied by profuse, chronic diarrhea,
polydipsia and anasarca. In cattle the
grossly enlarged left kidney is usually
palpable per rectum. Cases may occur with-
in 2 weeks of calving.They are characterized
by anorexia, watery diarrhea, anasarca,
rapid emaciation and death in 2-5 weeks.

Corpora amylacea are small, round
concretions of amyloid material found in
mammary tissue of cows. They are usually
inert but may cause blockage of the teat
canal.

CLINICAL PATHOLOGY

An extreme, persistent proteinuria should
suggest the presence of renal amyloidosis.
Electrophoretic studies of serum may be
of value in determining the presence of
hyperglobulinemia. Alpha-globulin levels
are usually elevated and albumin levels
depressed. Horses with hepatic amyloi-
dosis have elevated activities of gamma-
glutamyltransferase and, to a lesser extent.

bile acids. 11 In cattle there is hypocalcemia,
hyperfibrinogenemia, hypomagnesemia,
high serum urea and creatinine con-
centration, low-specific-gravity urine and
prolongation of the bromsulfalein clear-
ance time. Biopsy of cutaneous plaques is
an accurate diagnostic technique.

NECROPSY FINDINGS

Affected organs are grossly enlarged and
have a pale, waxy appearance. In the
spleen, the deposits are circumscribed; in
the liver and kidneys they are diffuse. In a
horse with systemic AL amyloidosis
associated with multiple myeloma, diffuse
gastrointestinal hemorrhage, thickened
jejunal mucosa and splenomegaly were
present. 9

The pathology of AA amyloidosis in
domestic sheep and goats has been
described. 12 Most sheep had pneumonia
and other sites of chronic inflammation.
Amyloid was detected in all grossly
affected kidneys using Congo red staining.

Deposits of amyloid in tissues may be
made visible by staining with aqueous
iodine. Amyloid is detected as green
birefringence of Congo-Red-stained
tissues viewed under polarized light. AA
and AL amyloidosis can be differentiated
by treatment of tissue sections with
potassium permanganate. Tissue contain-
ing AA will lose its green birefringence
after treatment with potassium perman-
ganate whereas tissue containing AL will
continue to appear green after Congo Red
staining and viewing under polarized
light.

The Shtrasburg method is now avail-
able for the identification of AA amyloid
and to distinguish it from amyloid types
in a large number of domestic and wild
animals. 13

DIFFERENTIAL DIAGNOSIS

Enlargement of parenchymatous organs
associated with chronic suppurative
processes should arouse suspicion of
amyloidosis, especially if there is
emaciation and marked proteinuria.

Pyelonephritis, nonspecific nephritis and
nephrosis bear a clinical similarity to
amyloidosis.

TREATMENT

I There is no effective treatment of the
j systemic disease. The localized disease as
! occurs in the upper respiratory tract of
j horses can be treated by surgical excision,

: but the results are not encouraging.

REVIEW LITERATURE

Gruys E. Amyloidosis in the bovine kidney. Vet Sci
Commun 1977; 1:265.

REFERENCES

1. Tojo K et al. Amyloid 2005; 12:103.

2. Segales J et al. J Vet Med A Physiol Pathol Clin
Med 2005; 52:135.

Porphyrias

469

3. Wessels M.Vet Rec 2003; 152:302.

4. Van Andel ACJ et al. Equine Vet J 1988; 20:277.

5. GliattoJM, AlroyJ. Vet Rec 1995; 137:68.

6. NoutYS et al. J Vet Intern Med 2005; 17:588.

7. Vanhooser SL et al. EquineVet J 1988; 20:274.

8. Taniyama H et al.Vet Pathol 2000; 37:98.

9. Kim DY et al.Vet Pathol 2005; 42:81.

10. Pusterla N et al. J Vet Intern Med 2005; 19:344.

11. Abdelkader SV et al. J Comp Pathol 1991;
105:203.

12. Mensua C et al.Vet Pathol 2003; 40:71.

13. Shtrasburg S et al.Vet Pathol 2005; 42:132.

Porphyrias

Porphyria is not common in farm
animals. 1 The congential disease in cattle
is discussed in Chapter 34.

REFERENCE

1. Rimington D, Moore MR. Clio Dermatol 1985;
3:144.

PART 1 GENERAL MEDICINE

Diseases of the respiratory system

PRINCIPLES OF RESPIRATORY
INSUFFICIENCY 471

Definitions 471
Hypoxia 472

Compensatory mechanisms 473
Carbon dioxide retention
(hypercapnia) 473
Respiratory failure 473

PRINCIPAL MANIFESTATIONS OF
RESPIRATORY INSUFFICIENCY 473

Abnormalities in rate, depth and ease
of breathing 474
Abnormal posture 475
Normal and abnormal breath
sounds 475
Respiratory noises 478
Coughing 478
Cyanosis 479
Nasal discharge 479
Epistaxis and hemoptysis 480
Thoracic pain 480

SPECIAL EXAMINATION OF THE
RESPIRATORY SYSTEM 480

Auscultation and percussion 481
Endoscopic examination of the airways
(rhinolaryngoscopy,
tracheobronchoscopy) 481
Radiography 482

Scintigraphy (nuclear imaging) 483
Ultrasonography 483
Laboratory evaluation of respiratory
secretions 484

Principles of respiratory
insufficiency

The principal function of the respiratory
system is gas exchange in which oxygen is
transferred from the environment to the
blood and carbon dioxide is moved in
the opposite direction. Other important
functions include a role in thermoregulation
in most species, acid-base regulation in
concert with the kidney, as an endocrine
organ (e.g. angiotensin-converting
enzyme), in the metabolism of meta-
bolically active substances, including
eicosanoids and nitric oxide, and in the
immune response to inhaled immunogens
and pathogens. Capillaries in the lungs of
the farm animal species and horses also
possess intravascular macrophages, which
are important as a reticuloendothelial organ
in the processing of antigens - an action
achieved by similar cells in the liver of dogs,
cats, and humans. Interference with these
functions can occur in a number of ways
and can have a variety of manifestations

Pulmonary function tests 489
Arterial blood gas analysis 490
Venous blood gas analysis 491
Pulse oximetry 492
Blood lactate concentration 492
Collection and analysis of exhaled
breath condensate 492
Lung biopsy 492

Respiratory sound spectrum analysis 493
Exercise testing 493

PRINCIPLES OF TREATMENT AND
CONTROL OF RESPIRATORY TRACT
DISEASE 493

Treatment of respiratory disease 493
Control of respiratory disease 496

DISEASES OF THE LUNGS 498

Pulmonary congestion and edema 498
Pulmonary hypertension 500
Atelectasis 500

Acute respiratory distress syndrome 501
Pulmonary hemorrhage 501
Pulmonary emphysema 507
Pneumonia 508
Aspiration pneumonia 515
Caudal vena caval thrombosis (posterior
vena caval thrombosis) and embolic
pneumonia in cattle 516
Cranial vena caval thrombosis 517
Pulmonary abscess 517
Pulmonary and pleural neoplasms 518

that are apparent during disease. The
most readily apparent failure of the respir-
atory system is failure of gas exchange
with resultant hypoxemia and hypercapnia.
However, failure of other functions of the
respiratory system can also result in
clinically apparent disease.

Failure of gas exchange, and the result-
ant hypoxia and hypercapnia, is responsible
for most of the clinical signs of respiratory
disease and for respiratory failure, the
terminal event of fatal cases. Death due to
respiratory failure is due to hypoxia. An
understanding of hypoxia, hypercapnia
and respiratory failure is essential to the
study of clinical respiratory disease.

DEFINITIONS

A number of terms are used to describe
the function of the respiratory tract, or
abnormalities that arise because of a
variety of diseases. Many of these terms
are described in more detail in the text
that follows, but a brief definition of each
is provided here:

10

DISEASES OF THE PLEURA AND
DIAPHRAGM 519

Hydrothorax and hemothorax 519
Pneumothorax 519
Diaphragmatic hernia 521
Synchronous diaphragmatic flutter in
horses (thumps) 521
Pleuritis (pleurisy) 522
Equine pleuropneumonia (pleuritis,
pleurisy) 525

DISEASES OF THE UPPER
RESPIRATORY TRACT 530

Rhinitis 530

Obstruction of the nasal cavities 531
Laryngitis, tracheitis, bronchitis 533
Traumatic laryngotracheitis, tracheal
compression and tracheal
collapse 534
Pharyngitis 534

Upper airway obstruction in horses:
laryngeal hemiplegia ('roarers') 535
Dorsal displacement of the soft palate
(soft palate paresis) 536
Other conditions of the upper
airway of horses 537
Diseases of the guttural pouches
(auditory tube diverticulum,
eustachian tube diverticulum) 538
Guttural pouch empyema 538
Guttural pouch mycosis 540
Guttural pouch tympany 541
Other guttural pouch diseases 541
Congenital defects 541

° Hypoxia is a broad term meaning
diminished availability of oxygen to
tissues

° Hypoxemia is deficient oxygenation of
blood, usually assessed by
measurement of blood oxygen tension,
or by measurement of blood
hemoglobin saturation and hemoglobin
concentration, and subsequent
calculation of blood oxygen content
° Hypercapnia is an abnormally high
carbon dioxide tension in blood
o P a o 2 is the oxygen tension (partial
pressure) in arterial blood
■ P A o 2 ' s the oxygen partial pressure in
alveolar gas

-> P„ co 2 is the carbon dioxide tension in
arterial blood

° P A C0 2 is the carbon dioxide partial
pressure in alveolar air
o C a o 2 is the arterial oxygen content
(milliliters of 0 2 per 100 mL of blood)
o P v o 2 is the oxygen tension (partial
pressure) in venous blood
•j P v co 2 is the carbon dioxide tension in
i venous blood

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

° C v 0 2 is the venous oxygen content
(milliliters of 0 2 per 100 mL of blood)

0 Respiratory failure is the inability of
an animal to maintain arterial blood
oxygenation and carbon dioxide
tension within the normal range
0 Dyspnea refers to signs of respiratory
distress in animals (in humans it
describes the sensation of air hunger,
which is a symptom and not a sign)

° Polypnea is an excessively high rate of
breathing

0 Tachypnea is an excessively high rate
of breathing, with the implication that
the breathing is shallow
° Hyperpnea is an increased minute
ventilation.

HYPOXIA

Failure of the tissues to receive an adequate
supply of oxygen occurs in a number of
ways and the differences are clinically
relevant, in that they are associated with
failure of different organ systems, different
diseases, and have fundamentally different
pathophysiological mechanisms

Hypoxic (or hypoxemic) hypoxia

Hypoxic (or hypoxemic) hypoxia occurs
when there is inadequate oxygenation of
blood (hypoxemia) and is usually asso-
ciated with disease of the respiratory tract
or other causes of hypoventilation. Situ-
ations in which there is inadequate
oxygenation of blood in the lungs include
hypoventilation, ventilation/perfusion
mismatches, diffusion impairment, low
inspired oxygen tension and extrapul-
monary right-to-left shunting.

Hypoventilation occurs in animals
with depressed consciousness, such as
occurs with general anesthesia and heavy
sedation, or in newborns, in which the
central respiratory drive is suppressed.
Airway obstruction caused by the pre-
sence of foreign bodies in the airway,
luminal obstruction by masses, such as
retropharyngeal abscesses in horses with
strangles, laryngeal spasm or broncho-
constriction can cause inadequate alveolar
ventilation and hypoxemia. Diseases that
prevent adequate inflation of lungs cause
alveolar hypoventilation and the conse-
quent hypoxemia. These diseases include
pneumothorax, pleural effusion or respir-
atory muscle weakness, such as can occur
with botulism, tick paralysis, tetanus,
strychnine poisoning or severe white
muscle disease.

Ventilation/perfusion (WQ) mis-
matches occur when the distribution of
blood flow in the lungs does not match
the distribution of alveolar ventilation,
with the result that areas of lung that are
well ventilated are not adequately perfused
and those areas that are well perfused by
blood are not well ventilated. Ventilation/

perfusion mismatches are the most
important cause of hypoxemia in many
lung diseases, including pneumonia.

Diffusion impairment occurs when
there is decreased transfer of oxygen from
alveolar air that has a normal P A o 2 to red
blood cells in alveolar capillaries because of:
increased distance of diffusion through the
alveolar membranes, such as might occur
with pulmonary edema; decreased surface
area available for diffusion, such as occurs
with positional atelectasis or pulmonary
embolism; or decreased transit time of red
cells through the alveolar capillaries, such as
occurs in horses during heavy exercise.

Low inspired oxygen tension occurs
naturally only in animals at high altitude.
It can also occur during anesthesia if there
are defects in the ventilator causing low
oxygen tension in the gases delivered to
the animal.

Extrapulmonary right-to-left shunt-
ing occurs most commonly as a vascular
defect (see Ch. 8).

The actual cause of hypoxemia in an
individual animal or disease is often
multifactorial and not simply a result of
one of the mechanisms described above.
For instance, cows placed in dorsal recum-
bency during general anesthesia become
hypoxemic because of compression of the
thorax by the abdominal viscera, thereby
causing hypoventilation and compression
atelectasis with diffusion impairment,
ventilation/perfusion mismatching and
reduced cardiac output because of reduced
venous return. 1

Anemic hypoxia

Anemic hypoxia occurs when there is a
deficiency of hemoglobin per unit volume
of blood (anemia). The percentage
saturation of the available hemoglobin
and the oxygen tension of arterial blood
are normal but as a result of the low
hemoglobin concentration the oxygen -
carrying capacity of the blood is reduced.
Anemia due to any cause has these
characteristics. The decrease in oxygen-
cariying capacity caused by a 50% reduc-
tion in hemoglobin concentration from
normal values (from 20 g/dL to 10 g/dL) is
much greater than the decrease that
results from a 50% reduction in arterial
oxygen tension from normal (e.g. a reduc-
tion from 100 mmHg to 50mmHg).

Alteration of hemoglobin to pigments,
such as methemoglobin or carboxy-
hemoglobin, that are not capable of carry-
ing oxygen has the same effect on oxygen
content as anemia. Thus in poisoning
caused by nitrite, in which hemoglobin is
converted to methemoglobin, and in that
due to carbon monoxide, when the hemo-
globin is converted to carboxyhemoglobin,
there is hypoxia due to inadequate oxygen-
ation of blood.

Circulatory hypoxia

Circulatory hypoxia occurs as a result of
inadequate delivery of oxygen to tissue
because of inadequate perfusion of
tissues by blood. The blood is usually
adequately oxygenated but blood flow
rate to tissues is not, and therefore the
rate at which it delivers oxygen to tissue is
less than the amount of oxygen required
to support the metabolic function of that
tissue. In other words, the rate of delivery
of oxygen to tissue does not match the
metabolic requirements of that tissue. A
common cause of this is low cardiac
output, such as occurs with congestive
heart failure or hypovolemic shock. It also
occurs with local interruption to arterial
flow such as the thrombotic emboli of
thromboembolic colic of horses or com-
pression of vessels, such as in right dis-
placement and torsion of the abomasum.

Histotoxic anoxia

Histotoxic anoxia occurs when oxygen
delivery to tissue is adequate because
both oxygen content of arterial blood and
blood flow are appropriate, but the tissue
is unable to utilize oxygen. Cyanide
poisoning is the only common cause of
this form of anoxia.

Consequences of hypoxia

Consequences of inadequate delivery of
oxygen include changes in almost all
body systems. The central nervous system
and heart are most susceptible to the
immediate and acute effects of hypoxia,
whereas clinical signs related to hypoxic
damage to the gastrointestinal tract and
kidneys are somewhat delayed. Central
nervous system hypoxia is evident as mild
changes in mentation, such as de-
pression, progressing through decreased
alertness to coma and death. Cardiac
changes include a reduction in the force
and efficiency of contraction due to
impaired myocardial contractility, and an
increased susceptibility to arrhythmia.
The kidney, gut and liver are all
metabolically active tissues and therefore
susceptible to hypoxia. Renal function is
reduced during hypoxia, with the renal
medulla being most sensitive to decreases
in oxygen delivery. Signs of gastrointestinal
dysfunction during hypoxia include ileus,
abdominal pain and abdominal distension
due to accumulation of gas and liquid in
the gastrointestinal tract. Liver dysfunction
can be evident as decreases in blood
glucose concentration and increases in
serum activity of liver- derived enzymes
(alkaline phosphatase, gamma- glutamyl
transpeptidase, sorbitol (inositol) dehydro-
genase) and metabolites (bile acids,
bilirubin).

Some metabolically active tissues,
when deprived of oxygen, use anaerobic
metabolism to sustain energy supply for

short periods of time (depending on the
tissue, but the brain cannot survive
without oxygen for more than 2-3 min).
Use of anaerobic glycolysis for energy
causes metabolic acidosis. Animals in
respiratory failure therefore often have a
mixed acid-base disturbance characterized
by metabolic and respiratory acidosis.

COMPENSATORY MECHANISMS

Compensation of respiratory insufficiency
occurs as both short-term and long-term
events. Short-term compensatory mech-
anisms for low arterial oxygen tension or
oxygen delivery to tissues occur within
seconds to minutes and include respi-
ratory, cardiovascular and behavioral
responses. Stimulation of respiratory
centers in the medulla oblongata by low
arterial oxygen tension (P a Oj) and high
arterial carbon dioxide tension (P a coj
causes an increase in respiratory minute
volume mediated by an increase in tidal
volume and respiratory frequency. Both
low oxygen tension and high carbon
dioxide tension in arterial blood, together
or separately, are potent stimulators of
these events. Inadequate tissue oxygena-
tion also stimulates an increase in cardiac
output, mainly as a result of increased
heart rate and to a lesser extent by an
increase in stroke volume. Splenic con-
traction, in those species such as the
horse in which the spleen is an important
reservoir of red blood cells, increases both
blood volume and hemoglobin concen-
tration, thereby increasing the oxygen-
carrying capacity of blood. Hypoxemia also
causes animals to attempt to decrease their
oxygen requirement by decreasing physical
activity, including moving and eating.

Longer-term compensatory mechan-
isms include an increase in erythropoietin
secretion by the kidney with subsequent
increases in bone marrow production of
red blood cells and an increase in
hemoglobin concentration in blood. This
polycythemia increases the oxygen-
carrying capacity of blood. Severe poly-
cythemia, such as occurs with congenital
cardiac anomalies causing chronic right-
to-left shunting, increases the viscosity
of blood and impairs tissue perfusion,
increases the workload of the heart and
the risk of thromboembolism. Longer-
term compensatory mechanisms also
include changes in ventilatory pattern,
such as in horses with heaves, and
behavior.

CARBON DIOXIDE RETENTION
(HYPERCAPNIA)

Respiratory insufficiency results in
decreased elimination of carbon dioxide
and its accumulation in blood and tissues.
Animals breathing room air that are

Principal manifestations of respiratory insufficiency

hypercapnic are always hypoxemic.
Increasing the oxygen tension of inspired
air can alleviate the hypoxemia but, by
reducing hypoxic stimulation of the respir-
atory center, can cause further increments
in arterial Pco 2 .

Acute hypercapnia causes a respiratory
acidosis that reduces both blood and
cerebrospinal fluid pH. 2 The clinical signs
of acute hypercapnia are initial anxiety
followed by central nervous system
depression and eventual coma and death.
These clinical abnormalities are attri-
butable to declines in the pH of cerebro-
spinal fluid (CSF), a consequence of the
ease with which carbon dioxide crosses
the blood-brain barrier. Decreases in CSF
pH are greater for respiratory acidosis
than for a similar degree of metabolic
acidosis. Severe hypercapnia also causes
peripheral vasodilation, which can contri-
bute to arterial hypotension, and cardiac
arrhythmia. The acid-base effects of
chronic hypercapnia are compensated by
renal mechanisms that return the arterial
and CSF pH to almost normal and there-
fore do not cause more than mild clinical
disease in most instances. So long as
oxygen delivery to tissue is maintained,
animals can tolerate quite high arterial
carbon dioxide tensions for a number of
days or longer - this is referred to as
'permissive hypercapnia' and is sometimes
an alternative to artificial or mechanical
ventilation of animals with respiratory
insufficiency.

RESPIRATORY FAILURE

Respiratory movements are involuntary
and are stimulated and modified by the
respiratory centers in the medulla. The
centers appear, at least in some species,
to have spontaneous activity that is
modified by afferent impulses to higher
centers, including: cerebral cortex and the
heat-regulating center in the hypo-
thalamus; from the stretch receptors in the
lungs via the pulmonary vagus nerves; and
from the chemoreceptors in the carotid
bodies. The activity of the center is also
regulated directly by the pH and oxygen
and carbon dioxide tensions of the cranial
arterial blood supply. Stimulation of almost
all afferent nerves may also cause reflex
change in respiration, stimulation of pain
fibers being particularly effective.

Respiratory failure is the terminal stage
of respiratory insufficiency in which the
activity of the respiratory centers diminishes
to the point where movements of respir-
atory muscles cease. Respiratory failure
can be paralytic, dyspneic or asphyxial, or
tachypneic, depending on the primary
disease.

The respiratory failure that occurs in
animals with pneumonia, pulmonary

edema and upper respiratory tract
obstruction is caused by combinations of
hypoventilation, ventilation/perfusion
mismatch and diffusion impairment,
which leads to hypercapnia and hypox-
emia. Hypercapnia and hypoxia stimulate
the respiratory center and there is a
potent respiratory drive evident as
markedly increased respiratory rate and
effort. As the disease progresses these
changes become more marked until
death occurs as a result of central nervous
system or cardiac failure. Animals that die
of the central nervous system effects of
respiratory failure typically have dyspnea
followed by periods of gasping and apnea
just before death.

Paralytic respiratory failure is caused
by depression of the respiratory centers or
paralysis of the muscles of respiration.
Depression of the respiratory center
occurs with poisoning by respiratory
center depressants, such as general anes-
thetics, or damage to the respiratory
center, such as might occur with brain-
stem injury. Fhralysis of respiratory muscles
occurs in disease such as botulism,
tetanus, strychnine poisoning, white
muscle disease, severe hypocalcemia and
tick paralysis. The signs of paralytic
respiratory failure are a gradual or abrupt
cessation of respiratory movements with-
out preceding signs of increased respiratory
effort or dyspnea. The animal is often
unconscious, or unable to move, during
the later stages of the disease.

The differentiation of these types of
failure is of some importance in deter-
mining the type of treatment necessary. In
the paralytic form of respiratory failure
the optimal treatment is mechanical
ventilation, along with removal of the
inciting cause. Administration of respira-
tory stimulants is seldom effective as sole
therapy. The more complex pathogenesis
of respiratory failure in most diseases
requires a therapeutic approach that
removes each of the underlying defects.
In most cases this is achieved by treating
the inciting disease, for example adminis-
tering antimicrobials to an animal with
pneumonia or furosemide to an animal
with pulmonary edema, in addition to
supportive care including, potentially,
nasal or pharyngeal insufflation with
oxygen, or mechanical ventilation.

Principal manifestations of
respiratory insufficiency

Respiratory disease is evident as one or
more of a variety of signs detectable on
clinical examination. The signs vary with
the etiology of the disease and its
anatomic location. Diseases that impair

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PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

ventilation or gas exchange have hypox-
emia and hypercapnia as prominent life-
threatening abnormalities. Infectious and
inflammatory diseases can cause prominent
clinical abnormalities as a result of a
systemic inflammatory response and
toxemia. The toxemia may be so severe (e.g.
in calf diphtheria, aspiration pneumonia
and equine pleuritis) as to cause death
even though oxygen and carbon dioxide
exchange are not greatly impaired. The
common signs of respiratory disease are:

° Abnormalities in the rate, depth, or

ease of breathing

° Lethargy or exercise intolerance
° Abnormal posture
° Abnormal lung sounds
° Abnormal respiratory noises
° Coughing
° Cyanosis
0 Nasal discharge
° Epistaxis and hemoptysis.

ABNORMALITIES IN RATE, DEPTH
AND EASE OF BREATHING

Polypnea is a rate of breathing that is
faster than observed in clinically normal
animals of the same species, breed, age,
sex and reproductive status in a similar
environment.

Tachypnea also describes an increased
rate of breathing, although with the
implication that breathing is shallow (i.e.
of a reduced tidal volume).

Hyperpnea is an abnormal increase in
the rate and depth of breathing (an
abnormally high minute volume) but the
breathing is not labored and is not associ-
ated with signs from which one could
infer represent distress on the part of the
animal (i.e. the animal is not dyspneic).
This assessment requires measurement of
minute ventilation or arterial blood gas
tensions.

Dyspnea is a term borrowed from
human medicine, in which it refers to the
sensation of shortness of breath or air
hunger. It is used in veterinary medicine
to describe labored or difficult breathing
in animals that also display some signs of
distress, such as anxious expression,
unusual posture or stance, or unusual
behavior.

Dyspnea is a physiological occurrence
after strenuous exercise and is abnormal
only when it occurs at rest or with little
exercise. It is usually caused by hypoxia
with or without hypercapnia, arising most
commonly from diseases of the respi-
ratory tract. In pulmonary dyspnea one
other factor may be of contributory
importance; there may be an abnormally
sensitive Hering-Breuer reflex. This is
most likely to occur when there is
inflammation or congestion of the lungs
or pleura. Rapid, shallow breathing results.

Expiratory dyspnea is prolonged and
forceful expiration, usually associated with
diffuse or advanced obstructive lower
airway disease. The dyspnea of pulmonary
emphysema is characteristically expi-
ratory in form and is caused by ano>*c
anoxia and the need for forced expiration
to achieve successful expulsion of the
tidal air. It is commonly accompanied by
an audible expiratory grunt in ruminants
but less so in pigs and almost never in
horses.

Inspiratory dyspnea is prolonged
and forceful inspiration due to obstruc-
tion of the extrathoracic airways, such as
with laryngeal obstruction or collapse of
the cervical trachea. It may also be associ-
ated with abnormalities that restrict
thoracic expansion, such as restrictive
lung diseases and space-occupying lesions
of the thorax. It is accompanied by a
stridor or loud harsh sound on inspiration
when the cause is obstruction of the

extrathoracic airways, such as is typical of
laryngeal or tracheal disease.

Open-mouth breathing is labored
breathing with the mouth held open,
commonly with the tongue protruded in
ruminants and most commonly asso-
ciated with advanced pulmonary disease
or obstruction of the nasal cavities.

DISEASES CAUSING DYSPNEA AT
REST OR LACK OF EXERCISE
TOLERANCE

Dyspnea, along with hypoxemia and
hypercapnia, are the clinical and labo-
ratory findings most likely to attract
attention to the possible presence of
disease in the respiratory system. A brief
summary of the causes of dyspnea is
outlined in Figure 10.1. It is most
important, when attempting to differen-
tiate diseases that cause dyspnea, to
include diseases of systems other than the
respiratory system that can result in
dyspnea. Dyspnea at rest is usually, but
not always, caused by respiratory tract
disease, whereas exercise intolerance can
be caused by disease in the respiratory,
cardiovascular, musculoskeletal and other
body systems.

Respiratory tract disease

Respiratory tract diseases interfere with
normal gas transfer, through the mechan-
isms discussed above. Characteristics of
respiratory disease that lead to dyspnea
or lack of exercise tolerance include:

° Flooding of alveoli with

inflammatory cells and/or protein-
rich fluid - pneumonia and
pulmonary edema

° Atelectasis (collapsed alveoli and
small airways) - pleural effusion,
hemothorax, hydrothorax,
pneumothorax, chylothorax,
pyothorax, prolonged recumbency of

Fig. 10.1 The causes of dyspnea.

Principal manifestations of respiratory insufficiency

large animals and diaphragmatic
hernia

8 Airway obstruction -

nasal obstruction, pharyngeal/
laryngeal obstruction, tracheal/
bronchial obstruction,
bronchoconstriction and bronchiolar
obstruction.

Cardiovascular disease

This causes inadequate perfusion of tissues
including the lungs. There is reduced
oxygen delivery to tissues, even in the pre-
sence of normal arterial oxygenation:

• Cardiac disease. Cardiac dyspnea
results from heart failure and is
multifactorial. In animals with
dyspnea attributable to cardiac
disease there are other readily evident
signs of heart failure

• Peripheral circulatory failure -
usually due to hypovolemic shock,
although shock associated with
toxemia, including endotoxemia, can
cause dyspnea. There are always other
prominent signs of disease.

Diseases of the blood

These cause inadequate delivery of oxygen
to tissues because of anemia or presence
of hemoglobin that is unable to carry
oxygen.

o Anemia - an abnormally low
concentration of hemoglobin
® Altered hemoglobin -

methemoglobinemia (e.g. in nitrite
poisoning of cattle, red maple
toxicosis of horses),
carboxyhemoglobinemia.

Nervous system diseases

Diseases of the nervous system affect
respiratory function by one of several
mechanisms:

0 Paralysis of respiratory muscles

occurs in tick paralysis or botulism.
Tetanic spasm of respiratory muscles,
such as in tetanus or strychnine
toxicosis, also impairs or prevents
alveolar ventilation. Both flaccid and
tetanic paralysis cause hypercapnia
and hypoxemia and, in extreme
situations, death by suffocation
Paralysis of the respiratory center,
as in poisoning by nicotine sulfate, or
overall central nervous system
depression, causes hypoventilation
because of impaired ventilatory drive
° Stimulation of the respiratory
center, so-called neurogenic dyspnea,
occurs as a result of stimulation of the
center by a small irritative lesion, such
as in animals with encephalitis, or
administration of drugs, such as
lobeline, that increase sensitivity of
the respiratory center to hypoxemia or
hypercapnia.

Musculoskeletal diseases
0 Muscle diseases. Diseases of the
respiratory muscles can impair
ventilation. These include white
muscle disease in lambs, calves, and
foals, and some congenital diseases
(such as glycogen branching enzyme
deficiency in foals)

• Fatigue. Animals with primary severe
respiratory disease can develop
fatigue of the respiratory muscles
(intercostal, diaphragm, accessory
muscles of respiration), which can
further impair ventilation

• Trauma. Fractured ribs can impair
ventilation both because of the pain
of breathing and because of
mechanical disruption to respiration
(flail chest).

General systemic states

Tachypnea can occur in a number of
systemic states in which there is no lesion
of the respiratory tract or nervous system.
These include:

0 Pain - such as in horses with colic

• Hyperthermia - as can occur with
intense or strenuous exercise

8 Acidosis - as a metabolic disturbance
associated with any of a number of
diseases but notably gastrointestinal
disease that causes excessive loss of
cationic electrolytes in feces.

Environmental causes

3 Low inspired oxygen tension, such as
in animals at high altitude
® Exposure to toxic gases.

Miscellaneous poisons

A number of poisons cause dyspnea as a
prominent sign, but in most cases the
pathogenesis has not been identified.

° Farm chemicals, including

metaldehyde and dinitrophenols
(probable mechanism is stimulation of
respiratory center)

° Organophosphates and carbamates
(probable mechanism is alteration of
pulmonary epithelium), urea
(probably effective as ammonia
poisoning)

° Nicotine depressing the respiratory
center

° Poisonous plants, including/ast-draf/;
factor of algae, the weeds Albizia,
Helenium, Eupatorium, lpomoea, Taxus
spp. and Laburnum and ironwood
(Erythrophleum spp.); all appear to act
at least in part by central stimulation.

ABNORM AL POS TURE

Animals with respiratory disease, and
especially those in respiratory distress,
often adopt an unusual posture and are
rarely recumbent except in the terminal
stages of the disease. Animals in severe

respiratory distress will stand with the
head and neck held low and extended.
Animals, except horses, will often have
open-mouthed breathing. Horses, except
in extreme and unusual circumstances,
are unable to breath through the mouth
because of the anatomical arrangement of
the soft palate, which effectively provides
an airtight barrier between the oropharynx
and nasopharynx. Cattle with severe
respiratory distress and open-mouthed
breathing will often drool large quantities
of saliva - probably a consequence of
decreased frequency of swallowing as the
animal labors to breath.

The positioning of the legs is often
abnormal. Severely affected animals, and
those with pleuritic pain (horses or cattle
with pleuritis) or severe respiratory
distress, will usually stand with elbows
(humeroradial joint) abducted. The animals
are reluctant to move but when forced to
do so can react violently. They are resistant
to diagnostic or therapeutic interventions
that interfere even transiently with their
ability to breath.

NORMAL AND ABNORMAL
BREATH SOUNDS

Auscultation of the lungs and air passages
is the most critical of the physical exam-
inations made of the respiratory system.
The examination should be performed in
as quiet an environment as possible,
though it is often difficult to achieve a
silent listening environment in large
animal practice. The animal should be
adequately restrained so that the examiner
can concentrate on the lung sounds, and
should not be sedated or anesthetized
because of the depression in lung sounds
that can occur in these instances. To be
effective and diagnostically reliable,
auscultation must be systematic. Both the
upper and lower parts of the respiratory
tract must be examined in every case. It is
preferable to begin the examination by
auscultating the larynx, trachea and the
area of the tracheal bifurcation in order to
assess the rate of air flow and the volume
of air sound to be heard over the lungs.

GENERATION OF BREATH SOUNDS

The animal must be breathing to generate
lung sounds. The lung sounds are
generated by movement of air in the large
and mid-sized airways, including the
trachea and bronchi. The greater the
velocity of air in the airways, the louder
the noise, explaining the loud sounds that
are generated in the trachea. Air move-
ment in the bronchioles, terminal airways
and alveoli is silent because of the large
combined cross-sectional area of these
airways and consequent low velocity
of air movement and laminar character
of the airflow. Sound is generated by

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PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

turbulent airflow and the degree of
turbulence is affected by the velocity
of airflow and the diameter of the airway.
This sound is then transmitted through
the lung and chest wall to the surface of
the thorax, where it can be detected by
use of a stethoscope.

Quiet breath sounds can be a result
of low tidal volume with resultant low
velocity of airflow, or impaired trans-
mission of sounds to the surface of the
chest. Sound is transmitted most readily
through dense liquids such as water. Most
tissue, except fat, is approximately 70%
water and transmits sounds readily.
Sound is reflected at the interface of two
media of markedly different densities -
such as air and tissue - and less sound is
transmitted. Thus, in the normal lung
there is marked attenuation (softening) of
breath sounds because of the extensive
air-tissue interfaces. This is evident by
comparing the intensity of breath sounds
heard over the trachea to those heard
over the chest wall. However, lung sounds
are more readily transmitted when areas
of the lung do not contain air, such as
occurs with atelectasis, pulmonary edema
or infiltration of lung by inflammatory
exudates. Sounds generated in the large
airways are more readily transmitted
through this consolidated tissue and are
evident at the chest wall as louder
bronchial breath sounds. The presence of
bronchial breath sounds that are audible
on the chest surface is dependent upon
the presence of a patent bronchus with
airflow to generate the lung sounds and
of tissue that readily transmits the sounds
generated in the bronchus. Lung sounds
will not be heard if they are not generated
(as a result of lack of airflow in bronchi) or
are muffled by extensive accumulations of
fluid or fat between the lung and the
chest wall. Lung sounds are reduced in
animals with airflow of low velocity in
large airways, such as occurs in animals
with low tidal volumes, or in which there
is obliteration of the bronchial lumen by
fluid or tissue. Low tidal volumes occur in
animals at rest or in those in which there
is rapid but shallow (low tidal volume)
breathing. Obliteration of the bronchial
lumen occurs in many diseases, including
pneumonia.

REBREATHING ('BAGGING')
EXAMINATION

Detection of abnormal lungs sounds is
optimized by increasing the animal's tidal
volume, and thereby the velocity of air-
flow in large airways. An expeditious
means of temporarily increasing the
animal's tidal volume is to occlude the
nostrils for a brief period (30-60 s). When
the animal is again allowed to breath it
will take several large, deep breaths,

during which lung sounds can be
ausculted. However, the increase in tidal
volume is transient and does not permit
time for detailed auscultation of the chest.
A preferred technique is to place an air-
tight bag over the animal's muzzle such
that all the air that it inhales is contained
within the bag. The volume of air in the
bag should exceed the anticipated
stimulated tidal volume of the animal. As
a rule of thumb, the volume of the bag
should be sufficient to allow the animal a
tidal volume of 10-15 mL of air per
kilogram of body weight (BW). A 500 kg
horse or cow therefore needs a bag that
contains 10 L of air. Hyperventilation is
stimulated by an increase in carbon
dioxide content of inspired air with
subsequent hypercapnia and stimulation
of the respiratory center. A more refined
technique has the animal inhaling gas
that is 5% carbon dioxide and 95%
oxygen, thereby preventing hypoxemia
due to the examination. Rebreathing
examinations (or 'bagging') are not indi-
cated if abnormal lung sounds are
detected on initial examination as the
results of the rebreathing examination
will not add any additional information.
Animals in respiratory distress should not
be subjected to a rebreathing examination
because it might worsen the hypoxemia
or hypercapnia already present, and is
inhumane. Rebreathing examinations are
indicated when respiratory disease is
suspected but initial auscultation of the
thorax does not reveal abnormal lung
sounds.

INTERPRETATION OF BREATH
SOUNDS

Terminology used to describe normal
and abnormal lung sounds is now well
established and should be used consis-
tently so that it is a useful diagnostic
aid. 3-4 Associations between abnormal
respiratory sounds and diseases and
abnormalities of respiratory function are
well established. Correct identification of
lung sounds, and consistency in terms
used to describe them, therefore permits
greater diagnostic accuracy and provides
the ability to accurately and precisely
describe diseases. The identification and
clinical significance of respiratory sounds
are summarized in Table 10.1. The clini-
cian must carefully auscultate both the
upper respiratory tract (larynx, trachea)
and the entire aspects of both lung fields
and interpret the sounds that are audible
or not audible. The variables that must
be interpreted include:

° The nature of the sounds (increased
or decreased breath sounds, crackles
or wheezes)

° The timing of the sounds in the
respiratory cycle

° Their anatomical location.

The questions that should be asked are:

° Are breath sounds audible?

0 Are the breath sounds of normal
intensity?

° Are the breath sounds normal or
abnormal?

° If abnormal sounds are present, what
are they (crackles, wheezes, stridor,
stertor, etc.; see Table 10.1)?

° Are breath sounds audible over all
lung fields?

Interpretation of these variables should
indicate the nature of the lesion. Examples
are summarized in Table 10.1. Lung sounds
can be divided into normal breath sounds
and abnormal breath sounds.

Breath sounds are produced by air
movement through the tracheobronchial
tree. The terms 'bronchial sounds' and
vesicular sounds are not anatomically
accurate or based on physiological prin-
ciples and should not be used. The term
'breath sounds' should be used. These are
the sounds which are audible clearly over
the trachea and which are attenuated
over the lungs. Breath sounds are of
normal, increased or decreased intensity.
Abnormally loud or soft breath sounds
can be attributed to either changes in
sound production in the airways by
changes in flow rate or altered transmission
of sound through various normal or
abnormal tissues or fluids in the thorax, as
discussed above.

Normal breath sounds

Normal breath sounds vary in quality
depending on where the stethoscope is
placed over the respiratory tract. They are
loudest over the trachea and base of the
lung and quietest over the diaphragmatic
lobes of the lung. Normal breath sounds
are louder on inspiration than on expiration
because inspiration is active with more
rapid airflow, whereas expiration is
passive in normal animals and associated
with lower rates of airflow. Breath sounds
may be barely audible in obese animals or
in the noisy surroundings common in
field conditions.

Increased loudness of breath sounds
is heard in normal animals with increased
respiratory rate and depth of respiration.
This can occur for physiological reasons
such as exercise, excitement or a high
environmental temperature. They can also
occur in abnormal states such as fever,
acidosis or pulmonary congestion in early
pneumonia or myocardial disease.

Decreased loudness or an almost
complete absence of breath sounds
occurs in pleural effusion or pneumo-
thorax because of almost complete reflec-
tion of the breath sounds at the pleural
surface due to the mismatching of the

Principal manifestations of respiratory insufficiency

Sounds

Acoustic characteristics

Significance and examples

Normal breath sounds

Increased audibility
of breath sounds

Soft blowing sounds, longer and louder on
inspiration than on expiration, audible over
the trachea and lungs

Mild to moderate increase in loudness of breath
sounds audible on inspiration and expiration
over the trachea and lungs

Decreased audibility Decreased audibility of breath sounds on

of breath sounds inspiration and/or expiration over the lungs

Crackles Short duration, interrupted, nonmusical breath

sounds. Coarse crackles are loud and most
commonly heard over large airways in animals
with pulmonary disease and may be heard during
inspiration and expiration. Fine crackles are of
short duration, less intense and higher pitched

Wheezes

Continuous musical-type squeaking and whistling
sounds audible over the lungs

Pleuritic friction
sounds

Stridor

Stertor

Expiratory grunting

Transmitted upper
respiratory tract
breath sounds

'Sandpapery' sound; grating; sound close to the
surface; on inspiration and expiration; tend to be
jerky and not influenced by coughing
A harsh, high-pitched sound on inspiration audible
with or without stethoscope over the larynx and
trachea

Snoring sound (low-pitched, coarse and raspy)
audible without a stethoscope on inspiration and
expiration over the pharyngeal and laryngeal areas
Loud grunting on expiration, which is usually forced
against a closed glottis with sudden release, audible
on auscultation of the thorax, over the trachea and
often audible without the aid of a stethoscope
Abnormal tracheal breath sounds (crackles and
wheezes) audible by auscultation over the
extrathoracic trachea during inspiration

Extraneous sounds heard on auscultation of respiratory tract

Crepitations in Loud superficial crackling sounds induced by

subcutaneous tissues movement of stethoscope over the skin

Peristaltic sounds

Gurgling, grating, rumbling, squishing sounds
audible over the lungs

Normal respiratory tract

Any factor that increases respiratory rate or depth of respirations,
including fever, excitement, exercise, high environmental
temperatures, lung disease. Harsh loud breath sounds are audible
over the lungs with any disease resulting in collapse or filling of
alveoli and leaving bronchial lumina open; pulmonary
consolidation and atelectasis

Obese animal, pleural effusion, space-occupying mass of lung or
pleural cavity, pneumothorax, diaphragmatic hernia, occlusive
(lung) airway disease as in bronchial lumen filled with exudate
Coarse crackles are caused by air bubbling through, and causing
vibrations in, secretions in large airways. Fine crackles are caused
by sudden explosive popping open of a series of airways closed
during expiration. May be detected in early or late inspiration.
Suggest the presence of secretions and exudate in airways and
edematous bronchial mucosa as in exudative bronchopneumonia,
tracheobronchitis, aspiration pneumonia and obstructive
pulmonary disease. Loud crackles may be audible in animals
with interstitial pulmonary emphysema
Narrowing of large airways; expiratory polyphonic wheezing
common in equine reactive airway disease
bronchopneumonia, any species; inspiratory monophonic
wheezing occurs when upper extrathoracic airways are
constricted, such as in laryngeal disease
Pleuritis; diminish or disappear with pleural effusion

Obstruction of upper airways, especially the larynx (due to
edema, laryngitis, paralysis of vocal cord); prime example is calf
diphtheria or retropharyngeal abscessation in strangles in horses
or tracheal collapse in horses

Partial obstruction of the upper respiratory tract commonly due
to abnormalities of soft palate and nasopharynx

Severe diffuse pulmonary emphysema; pleuropneumonia and
pericarditis; extensive consolidation; in acute pleurisy and
peritonitis; a groan indicating pain may occur

Indicates presence of abnormalities of the upper respiratory tract
(larynx, nasopharynx, nasal cavities and upper trachea) resulting
in accumulation of respiratory secretions causing constriction of
airways. Laryngitis is an excellent example

Subcutaneous emphysema from pulmonary emphysema in
cattle; trauma to any part of respiratory tract that results in
penetration of airway, allowing accumulation of air
subcutaneously; gas-forming bacteria in subcutaneous tissues
Gastrointestinal sounds transmitted from the abdomen: ruminal
sounds in cattle; stomach and intestinal sounds in horse. Does
not indicate diaphragmatic hernia unless other evidence such as
an absence of breath sounds is present

acoustic properties of the pleural tissues
and fluids. Space-occupying masses
between the lung and the thoracic wall also
cause a relative absence of breath sounds
over the site as do areas of lung that are not
ventilated, such as a pulmonary abscess.

Increased loudness of breath sounds
The normal breath sounds heard over the
trachea may sound abnormally loud over
the lungs because of changes in the trans-
mission properties of the respiratory
system . 5 This is because, when sound
waves pass through structures of different

physical properties, the amount of sound
transmitted depends on the matching of
acoustic properties of the different struc-
tures. Consolidation results in less
reflection of sound at the thoracic wall
and consequently more transmission to
the stethoscope. Thus, in consolidation,
the breath sounds are much louder than
normal. These are harsh breath sounds
that approximate those heard over the
trachea. They are audible on inspiration
and expiration but become louder on
expiration in abnormal states such as I
consolidation or atelectasis. Any disease ]

in which the bronchial lumen remains
open and the surrounding lung tissue has
been replaced by cells, exudate or tissues
(consolidation) that transmit sound with-
out reflection will result in increased
bronchial sounds.

Abnormal breath sounds

Abnormal breath sounds include crackles
and wheezes. Crackles are discontinuous
sounds and wheezes are continuous
sounds . 6

j Crackles are abnormal lung sounds
] described as clicking, popping or bubbling

’8

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

sounds. They are caused by airways that
remain closed for a portion of inspiration
and then suddenly open. The crackling is
caused by the sudden equalization of
pressure between the proximal and distal
part of the airway . 6 Crackles may thus be
caused by the presence of exudate and
secretions in the airways, and edematous
bronchial mucosa. Crackling lung sounds
are also audible in cattle with interstitial
pulmonary emphysema. Crackling sounds
may move their point of maximum
intensity following coughing, presumably
as a result of movement of exudate.

Wheezes are continuous whistling,
squeaking sounds caused by vibrations of
airways or air passing through a narrowed
airway. They can be characterized as
monophonic (single tone) or polyphonic
(multiple tones) and by the timing of their
occurrence in the respiratory cycle.
Inspiratory wheezing suggests obstruction
of the upper airways, usually extra-
thoracic. Expiratory wheezing usually
indicates intrathoracic airway obstruction
such as bronchoconstriction with or
without distal airways that are narrowed
because of tenacious exudate.

Pleuritic friction sounds are a com-
bination of continuous and discontinuous
sounds produced by the rubbing together
of inflamed parietal and visceral pleura.
The sound is loud, coarse and usually not
influenced by coughing. Pleuritic friction
sounds are not common and their
absence does not preclude the presence
of pleuritis, particularly in the horse.
Pleuritic friction rubs may also occur in
cattle with severe diffuse pulmonary
emphysema as: the relatively dry parietal
and visceral surfaces rub together during
the respiratory cycle.

Absence of lung sounds occurs when
the breath sounds are reflected at the
interface between the lung and thoracic
wall by the presence of a medium such as
a space-occupying mass, fluid or air. The
common causes of the 'silent lung'include
pleural effusion, space- occupying masses
of the thorax, large pulmonary abscess,
complete destruction of a lobe of lung
including the terminal airways, such as can
occur with bronchial lumen occlusion by a
foreign body or tumor, and diaphragmatic
hernia . 6

Extraneous sounds. Miscellaneous
unexpected sounds that are occasionally
audible over the thorax include peristaltic
sounds, skin and hair sounds caused by
the stethoscope, crepitating sounds due
to subcutaneous emphysema and muscular
contractions. Subcutaneous emphysema
occurs in diseases in which there is
leakage of air from the lungs or airways
into the subcutaneous space. This occurs
with bullous lung disease in cattle, rib
fractures and pneumothorax, and after

percutaneous tracheal aspirate in animals
that cough. Coughing in these animals
causes air to be forced out of the trachea
through the hole through which the
tracheal aspirate was obtained. This
occurs in the period of coughing when
intratracheal pressures are markedly
increased just prior to the opening of the
glottis.

RESPIRATORY NOISES

Respiration may be accompanied by
audible noises that indicate certain normal
or abnormal occurrences in the respiratory
tract such as sneezing, snorting, stridor,
stertor or snoring, wheezing, roaring,
expiratory grunting and snuffling,
bubbling and rattling sounds

Sneezing is a sudden, involuntary,
noisy expiration through the nasal cavities
caused reflexly by irritation of the nasal
mucosae. Sneezing occurs in rhinitis and
obstruction of the nasal cavities, and
digital manipulation and examination of
the nasal mucosae.

Snorting is a forceful expiration of air
through the nostrils as in a sneeze, but a
snort is a voluntary act used by horses
and cattle as a device to intimidate
potential predators.

Stridor is an inspiratory stenotic sound
originating from a reduction in the caliber
of the larynx, as occurs in laryngeal edema
and abscess.

Stertor or snoring is a deep guttural
sound on inspiration originating from
vibrations of pharyngeal mucosa. Snoring
is often intermittent, depending on the
animal's posture. For example, a fat young
bull will often snore when he is dozing
half asleep, with his head hung down,
but the snore will disappear when he is
alert and his head is held up in a more
normal position. Stertor can occur during
expiration in horses with dorsal displace-
ment of the soft palate.

Wheezing is a high-pitched sound
made by air flowing through a narrow
lumen, such as a stenotic or inflamed nasal
cavity.

Roaring may occur during exercise
and is caused by air passing through a
larynx with a reduced lumen, e.g. laryngeal
hemiplegia in horses.

Expiratory grunting is a clearly audible
grunting noise synchronous with expir-
ation. It is most common in cattle with
diffuse pulmonary disease. A painful
grunt may occur in painful diseases of
the thorax such as fibrinous pleuritis
and is unassociated with inspiration or
expiration.

Snuffling, bubbling or rattling
sounds may be audible over the trachea
or base of the lungs when there is an
accumulation of secretion, or exudate, in

the nasal cavities, larynx or trachea. These •
are most clearly audible on inspiration.

COUGHING

A cough is an explosive expiration of air
from the lungs. It is initiated by reflex
stimulation of the cough center in the
medulla oblongata by irritation of sensory
receptors in one of various organs,
especially the respiratory tract.The stimulus
may originate in the pharynx, larynx,
trachea or bronchi. Coughing may also be
initiated by irritation of the esophagus, as
in choking. The act of coughing consists
of several stages:

0 Deep inspiration followed by closure
of the arytenoid cartilages (glottis)

° Compression of the air in the lungs
and large increase in pressure in the
thorax and airways by a forced
expiratory effort against a closed
glottis

° A sudden relaxation of the arytenoid
adductor muscles, resulting in
opening of the larynx and abrupt,
vigorous and forced expiration.
Coughing in horses is associated with
transient dorsal displacement of the
soft palate so that material in the
airways caudal to the larynx is
expelled through the mouth
0 The sudden opening of the glottis
allows an explosive expiration, during
which the linear velocity attains a
speed of several hundred kilometers
per hour. The intrathoracic airways
collapse after opening of the glottis
during the forced expiration, whereas
the extrathoracic airways are
momentarily dilated.

The purpose of coughing is to remove the
excess mucus, inflammatory products or
foreign material from the respiratory tract
distal to the larynx. Coughing indicates
the existence of primary or secondary
respiratory disease.

Coughing can be assessed according
to several characteristics. Coughing is
infrequent in the early stages of respi-
ratory tract disease but can become
frequent as the degree of inflammation in
the larynx, trachea and bronchi becomes
more severe. Assessment of the severity
of coughing, at least in horses, requires
prolonged observation (preferably for an
hour ). 7 Coughing is a fairly specific but
not very sensitive indicator of pulmonary
inflammation . 8 If coughing is detected
then it is quite likely that the animal has
inflammation of the airways, whereas
failure to detect coughing does not
reliably rule out the presence of clinically
significant airway inflammation . 8 The
severity of coughing in horses is closely
linked to the severity of inflammation

Principal manifestations of respiratory insufficiency

479

and accumulation of mucopus in the
airways. 7,8 Race horses that cough are
10 times more likely to have more than
20% neutrophils in a tracheal aspirate, and
more than 100 times more likely
to have more than 80% neutrophils. 8
The frequency of coughing correlates well
with maximal changes in pleural pressure,
extent of mucus accumulation and propor-
tion of neutrophils in bronchoalveolar
lavage fluid of horses with heaves
(recurrent airway obstruction). 7 Coughing is
therefore a specific indicator of the
presence of respiratory inflammation.

The frequency of coughing is an indi-
cator of the severity of lung disease in
horses 7 and presumably in other species.
Horses that cough more than four times per
hour have increased likelihood of mucus
accumulation and higher pleural pressure
changes during breathing than do horses
that cough fewer than four times per hour. 7

A cough cannot be induced in normal
adult cattle and horses by manual ma-
nipulation of the larynx or trachea. If a
cough can be induced in an adult horse by
manual manipulation of the larynx or
trachea, then this indicates airway inflam-
mation and is a reason for further exam-
ination of the respiratory tract.

The most common causes of coughing
in farm animals are due to diseases of the
larynx, trachea, bronchi and lungs, which
are presented under the headings of
diseases of those parts of the respiratory
tract later in this chapter.

CYANOSIS

Cyanosis is a bluish discoloration of the
skin, conjunctivae and visible mucosae
caused by an increase in the absolute
amount of reduced hemoglobin in the
blood. It can occur only when the hemo-
globin concentration of the blood is
normal or nearly so, and when there
is incomplete oxygenation of the hemo-
globin. Cyanosis is apparent when the
concentration of deoxygenated hemoglobin
in blood is greater than 5 g/dL (50g/L). 9
Cyanosis does not occur in anemic
animals. The bluish discoloration should
disappear when pressure is exerted on the
skin or mucosa. In most cases, the oral
mucous membranes are examined for
evidence of cyanosis, although the skin of
the pinna and the urogenital mucous
membranes will suffice. Examination of
vaginal mucosa is preferred in horses that
have severe congestion of the oral and
nasal mucosa as a result of disease
affecting the head, such as cellulitis or
bilateral jugular thrombophlebitis. Artificial
lighting and skin pigmentation affect the
ability to detect cyanosis.

Methemoglobinemia is accompanied
by discoloration of the skin and mucosae

but the color is more brown than blue
and cannot be accurately described as
cyanosis.

Cyanosis is classified as central or
peripheral. Central cyanosis is present
when arterial oxygen saturation is below
normal with concentration of deoxy-
genated hemoglobin exceeding 4-5 g/dL.
Peripheral cyanosis occurs when there
is localized desaturation of blood despite
arterial oxygen saturation being normal.
This usually occurs because there is
diminished blood flow to tissue, with a
resulting increase in oxygen extraction by
the ischemic tissues and low end-capillary
and venous hemoglobin saturation.

Central diseases include:

° Congenital cardiac diseases that cause
right-to-left shunting
° Pulmonary diseases that cause
hypoemia. Cyanosis is not usually
marked in pulmonary disease unless
the degree of ventilation/perfusion
mismatch is severe
° Upper airway obstruction causing
hypoxemia. Cyanosis is common and
is a sign of life-threatening disease in
severe cases of laryngeal obstruction,
as occurs in severe laryngitis in calves
with necrotic laryngitis or horses with
bilateral laryngeal paralysis (lead
poisoning, after tracheal intubation
during anesthesia, idiopathic)

° Abnormalities in hemoglobin
function.

Peripheral causes of cyanosis include:

0 Arterial obstruction, such as is seen in
horses with aortoiliac thrombosis
('saddle thrombus') or thrombosis of
distal limbs (such as can occur with
severe septicemia) 10
° Venous obstruction
° Severe vasoconstriction.

Central cyanosis is characterized by
decreased arterial oxygen saturation due
to right-to-left shunting of blood or
impaired pulmonary function. Central
cyanosis due to congenital heart disease
or pulmonary disease characteristically
worsens during exercise. Central cyanosis
usually becomes apparent at a mean
capillary concentration of 4-5 g/dL reduced
hemoglobin (or 0.5 g/dL methemoglobin).
Since it is the absolute quantity of reduced
hemoglobin in the blood that is responsible
for cyanosis, the higher the total hemo-
globin content the greater the tendency
toward cyanosis. Thus cyanosis is detect-
able in patients with marked polycythemia
at higher levels of arterial oxygen saturation
than in patients with normal hematocrit
values, and cyanosis may be absent in
patients with anemia despite marked
arterial desaturation. Patients with con-
genital heart disease often have a history

of cyanosis that is intensified 'during
exertion because of the lower saturation of
blood returning to the right side of the heart
and the augmented right-to-left shunt. The
inspiration of pure oxygen (100% FjOj will
not resolve central cyanosis when a right-
to-left shunt is present, but can resolve
when primary lung disease or polycythemia
is causing the cyanosis.

Peripheral cyanosis is caused by
obstruction of blood flow to an area. This
can occur as a result of arterial or venous
obstruction, although it is usually more
severe when arterial blood flow is
obstructed. Obstruction of arterial blood
flow also causes the limb to be cold
and muscle and nerve function in the
ischemic area to be impaired. Cyanosis
can also occur as a result of cutaneous
vasoconstriction due to low cardiac out-
put or exposure to cold air or water. It
usually indicates stasis of blood flow
in the periphery. If peripheral cyanosis
is localized to an extremity, arterial
or venous obstruction should be sus-
pected. Peripheral cyanosis due to vaso-
constriction is usually relieved by warming
the affected area.

Heart failure can cause cyanosis that is
restricted to the extremities, probably
because of reduced blood flow to
extremities during this disease and the
consequent markedly lower end-capillary
oxygen content. Blood in the venous end
of the capillaries, and in the venous bed
draining these tissues, is therefore
deoxygenated and cyanosis is observed.
While this type of cyanosis has a
peripheral distribution, its underlying
cause is central.

NASAL DISCHARGE

Excessive or abnormal nasal discharge is
usually an indication of respiratory tract
disease. Nasal discharges are common in
all the farm animal species. Cattle can
remove some or all of the nasal discharge
by licking with their tongue, while horses
do not remove any.

Origin

The nasal discharge is usually obvious but
the determination of its origin and
significance can be difficult and elusive.
The history should determine the duration
of the nasal discharge and if it has been
unilateral or bilateral.

Nasal discharges may originate from
lesions in the nasal cavities, congenital
defects of the hard palate such as cleft
palate in the newborn, paranasal sinuses,
guttural pouch in the horse, pharynx,
larynx, trachea and lungs. Diseases of the
esophagus and stomach that cause
dysphagia and regurgitation or vomition
can also cause a nasal discharge stained
with feed material.

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

The origin of a nasal discharge is
sometimes determined by close inspec-
tion of the external nares and the visible
aspects of the nasal cavities using a
pointed source of light. Some important
infectious diseases of the respiratory tract
characterized by lesions of the nasal
mucosae can be identified by examination
of the external nares for the origin of a
nasal discharge. If the source of the dis-
charge is not apparent on this examin-
ation, then more detailed investigation is
warranted.

Examination

The characteristics of the discharge are
noted carefully by inspection. It may be
copious, serous, mucoid, purulent, caseous,
streaked with blood, foul-smelling (ozena)
or contain feed particles.

° A copious bilateral serous nasal
discharge is characteristic of early
inflammation of the nasal cavities
such as in viral rhinitis
° A bilateral mucoid discharge suggests
inflammation of a few days duration
° A bilateral purulent discharge can
indicate inflammation in the upper or
lower respiratory tract
o A copious bilateral caseous discharge
suggests an allergic or bacterial rhinitis
° Foul-smelling nasal discharges are
usually associated with necrosis of
tissues anywhere in the nasal cavities,
the guttural pouch in the horse, or
severe necrotic and gangrenous
pneumonia

° A bilateral foul-smelling discharge
containing feed particles suggests
dysphagia, regurgitation or vomition
° In most cases, a chronic unilateral
nasal discharge suggests a lesion of
one nasal cavity

<' A bilateral nasal discharge suggests a
lesion posterior to the nasal system.

Examination of the paranasal sinuses
for evidence of pain and facial deformity
will assist in the diagnosis of sinusitis.
Percussion is useful in identifying para-
nasal sinuses that are filled with fluid or
tissue as sinuses affected in this way do
not produce a resonant sound when the
skin overlying the sinus is tapped. The
pharynx and larynx of cattle can be
examined through the oral cavity whereas
a flexible endoscope is necessary for
close examination of the upper and lower
respiratory tract of horses or cattle of
almost any age to determine the origin of
a nasal discharge. The examination should
include both nares, the region of the
opening of the nasomaxillary sinus (this
opening cannot be seen), the nasopharynx
(in horses) or the pharynx (in other
species), the guttural pouches in horses,
the larynx and the trachea, preferably to

the level of the carina, although this
might not be possible in large animals or
when short endoscopes are used. !

Radiography of the structures of the j
head and pharynx is also useful to locate j
lesions of the nasal cavities and paranasal j
sinuses that might be the origin of a nasal j
discharge. j

Nasal discharge and location of
lesion

There is not necessarily a correlation j
| between the characteristics of a nasal
discharge and the nature of any pulmonary
lesions. In exudative pneumonias in cattle,
mucopus is produced and is moved up the
| trachea and into the pharynx by the
j mucociliary mechanism or by coughing.

| Some of it is then swallowed and some
[ may be deposited in the nasal cavities and
| moved forward to the external nares by
ciliary action. In the horse, with its long
soft palate, most purulent material from the |
lungs will be deposited in the nasal cavities
and appear as a nasal discharge.

Sampling of nasal discharge

When infectious disease is suspected,
nasal swabs can be collected and sub-
mitted for microbiological examination.
Nasal swabs are useful only when a
specific etiological agent is suspected and
demonstration of its presence will con-
firm the cause of the disease. Examples of
this include strangles ( Streptococcus equi),
influenza (equine or porcine), infectious
bovine rhinotracheitis and Mycoplasma
bovis. Submission of nasal swabs for
culture yields mixed flora and the results
are impossible to interpret, with the
exception noted above. Organisms
cultured from nasal or nasopharyngeal
swabs are not representative of those
! cultured from lungs in individual animals
j but might be somewhat useful in herd
| outbreaks of disease . 11,12 Culture of trans-
j tracheal aspirates or, in cattle but not
j horses, bronchoalveolar lavage fluid, is
| representative of organisms causing
j pulmonary disease . 12,13 Cytological exam-
ination of the nasal discharge can reveal
exfoliated cells in the case of nasal tumors
or eosinophils when allergic rhinitis is
present.

EPI STAXIS AND HEMOPTYSIS

° Epistaxis (blood from the nostril) is
in most instances a result of disease of
the mucosae of the upper respiratory
tract but it may originate anywhere in
the upper or lower respiratory tract.
Epistaxis occurring during or within
several hours of intense exercise by
horses is due to exercise-induced
pulmonary hemorrhage
° Hemoptysis is the coughing up of
blood. The blood usually originates

from hemorrhage in the lower
respiratory tract. The presence of
hemoptysis is difficult to detect in
animals. Hemoptysis occurs in horses,
which is perhaps unexpected given
the anatomic separation of the
nasopharynx and oropharynx.

Pulmonary hemorrhage, particularly in
the horse, may be manifested as epistaxis.
Pulmonary hemorrhage in cattle is com-
monly manifested as hemoptysis and
epistaxis. These are described in more
detail later in this chapter.

A small amount of serosanguineous
fluid in the nostrils, as occurs in equine
infectious anemia and infectious equine
pneumonia, does not represent epistaxis,
which must also be differentiated from
the passage of blood-stained froth caused
by acute pulmonary edema. In this
instance the bubbles in the froth are very
small in size and passage of the froth is
accompanied by severe dyspnea, cough-
ing and auscultatory evidence of pulmon-
ary edema.

THORACIC PAIN

Spontaneous pain, evidenced by grunting
with each respiratory cycle, usually
indicates pleural pain, such as from a frac-
tured rib, torn intercostal muscle or
traumatic injury, including hematoma of
the pleura, or pleurisy. A similar grunt
may be obtained by deep palpation or
gentle thumping over the affected area of
the thoracic wall, with a closed fist or a
percussion hammer. Fhin due to a chronic
deep-seated lesion cannot be detected
in this way. The use of a pole under the
sternum, as described under traumatic
reticuloperitonitis, provides a useful
alternative.

Special examination of the
respiratory system

In addition to the routine clinical
examination of the respiratory tract, there
are a number of diagnostic techniques
that can be used to aid in making a specific
diagnosis, providing a reliable prognosis
and formulating the most rational treat-
ment. These techniques are being used
more commonly by species specialists,
particularly on valuable animals. Most
equine practices have flexible endoscopes
for the examination of the upper respir-
atory tract of horses. Medical imaging
using thoracic radiography and ultra-
sonography of animals with suspected
lung disease is now common, and the
laboratory evaluation of respiratory tract
secretions and exudates are common-
place. All these techniques increase the

Special examination of the respiratory system

481

costs of making a diagnosis, and it is
therefore important to consider whether
the additional diagnostic testing will
improve the final outcome of the case.
Techniques for advanced evaluation of the
respiratory system include:

° Auscultation and percussion of the
thorax

° Endoscopy of the upper airways,
guttural pouch (in Equidae), trachea,
bronchi and larger bronchioles
° Invasive endoscopic examination of
the sinuses using rigid endoscopes
° Pleuroscopy using either rigid or
flexible endoscopes
° Radiographic examination of the
skull, pharynx, larynx, guttural pouch
(in Equidae), trachea and thorax
• Computed tomographic and magnetic
resonance imaging
° Scintigraphic examination of
respiratory function

° Ultrasonographic examination of the
soft tissue of the pharynx and larynx,
and thorax

° Collection and evaluation of
respiratory tract secretions:

° Nasal

° Paranasal sinus
0 Guttural pouch
0 Pharyngeal

0 Tracheobronchial (tracheal

aspirates, bronchoalveolar lavage)

0 Pleural (thoracocentesis)

0 Pulmonary function testing, including
measurement of tidal and minute
volumes, pleural pressure, forced
expiratory volume, flow-volume
loops, forced oscillometry, and C0 2
breathing

° Arterial blood gas analysis
° Venous blood gas analysis
° Blood lactate concentration
0 Pulse oximetry

° Collection and analysis of exhaled
breath condensate
Lung biopsy

Respiratory sound spectrum analysis
Exercise testing.

AUSCULTATION AND
PE RCUSSI ON

The techniques of auscultation and per-
cussion used in examination of the thorax
are discussed in Chapter 1 and references
on percussion of the thorax are available. 14,15
Percussion of the thorax is a useful means
of determining lung margins and there-
fore of detecting the presence of over-
inflation, as occurs with heaves in
horses, 16 or areas of consolidation. Con-
solidation is evident as a loss of resonance,
and detection of this abnormality can
reveal the presence of excessive pleural
fluid or pulmonary consolidation. There is
excellent agreement in the assessment of

lung margins determined by percussion
and by ultrasonographic examination. 16
Percussion is therefore a valuable diag-
nostic tool, especially when ultra-
sonographic examination is not available.

ENDOSCOPIC EXAMINATION OF
THE AIRWAYS
(RHINOLARYNGOSCOPY,
TRACHEOBRONCHOSCOPY)

Horses

Flexible endoscopes allow examination of
the upper respiratory tract of horses
including the nasal cavities, nasopharynx,
auditory tube diverticula (guttural
pouches), palatal arch, epiglottis, larynx,
trachea and major bronchi. For examin-
ation to the level of the rostral trachea an
endoscope of 1 m in length is suitable.
However, an endoscope of 1.5 m in length
is useful for examining to the level of the
thoracic inlet. The endoscope is usually
less than 1.5 cm in diameter. Endoscopic
examinations are tolerated by most
horses with the minimum of restraint
(application of a nose or ear twitch).
Sedation should be avoided if a purpose
of the examination is to determine the
functional integrity of the pharynx and
larynx. Sedation depresses laryngeal
function and impairs assessment of the
symmetry and abductor function of the
arytenoid cartilages. Sedated horses are
more likely to displace the soft palate and
to fail to return it to its normal position.

Rhinolaryngoscopic examination of
horses should include a careful exam-
ination of the ventral and middle meatuses,
turbinates, region of the nasomaxillary
sinus opening (this cannot be visualized
directly but discharge from it can be
detected), ethmoidal turbinates, naso-
pharynx, soft palate, guttural pouches,
dorsal pharyngeal recess, epiglottis and
larynx. The endoscope should be used to
examine both left and right nasal cavities
and ethmoid turbinates. Both guttural
pouches should be examined. Fhssage of
the endoscope into the guttural pouch is
best achieved by passing the endoscope
through the ipsilateral nasal cavity. The
guttural pouch is then entered by first
introducing a thin, stiff tube, such as an
endoscopic biopsy instrument, through
the biopsy port of the endoscope into the
guttural pouch. The endoscope is then
rotated so that the entrance to the guttural
pouch is opened and the endoscope is
carefully advanced into the pouch. An
alternative technique involves insertion of a
stiff catheter, such as a Chambers mare
uterine catheter, into the guttural pouch
such that the entrance is dilated to enable
passage of the endoscope.

Many disorders of the equine pharynx
and larynx manifest only during strenuous

exercise because of the high pressures
generated in the airways by the large
minute ventilation of exercising horses.
Pressures in the pharynx and larynx that
are of similar magnitude to those occur-
ring during intense exercise can be
induced in resting horses by 60 seconds of
nasal occlusion . 4 The respiratory efforts
of horses during nasal occlusion can
therefore be used to simulate those
during exercise, thereby permitting detec-
tion of disorders of the pharynx (displace-
ment of the soft palate) and larynx (mild
laryngeal hemiplegia) that would not
otherwise be apparent in a resting horse.
Rhinolaryngoscopic examination can also
be performed on horses running on a
treadmill (see Exercise testing, below).

Bronchoscopic examination requires
an endoscope that is at least 2 m in length
and less than 1.5 cm in diameter. Horses
must be sedated for bronchoscopic
examination (a combination of xylazine,
0.25-0.5 mg/kg intravenously, and butor-
phanol, 1 mg per 40 kg intravenously,
works well). Instillation of lidocaine
(20 mL of 2% lidocaine diluted with
40 mL of isotonic saline or similar)
minimizes coughing. The lidocaine is
instilled into the trachea through the
biopsy channel of the endoscope. The
airways are examined in a systematic
fashion and results are recorded using a
system that has been described for
identifying the major airways. 17,18 Lobar
bronchi are identified on the basis of the
side of the bronchial tree on which they
are found and the order in which they
originate from the primary bronchus. 17
On the right side, RBI, RB2 and RB3 refer
to the right cranial lobar bronchus and
subsequent right bronchi, respectively.
On the left side, LB1 and LB2 refer to the
left cranial lobar bronchus and the left
caudal lobar bronchus, respectively.
Segmental bronchi are identified by
consecutive numbers in the order of origin
from the lobar bronchus. The direction
of the segmental bronchus is denoted by
the capital letters D (dorsal), V (ventral),
L (lateral), M (medial), R (rostral) and
C (caudal). Subsegmental bronchi are
identified in the order of origin from the
segmental bronchi, using lower case letters.

Cattle

The nasopharynx, pharynx and larynx of
cattle can be examined by endoscopy 19
and this should be done without sedation
if possible. 20 Xylazine is not recommended
because it commonly interferes with
normal laryngeal function. Acepromazine is
recommended if necessary. 20

The anatomy of the proximal portion
of the respiratory tract of cattle differs
from that of horses. The nasal septum
does not completely separate the left and

482

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

right aspects of the nasopharynx. In
cattle, the nasal septum tapers caudo-
dorsally, allowing both ethmoturbinates
to be observed from one side. The phar-
yngeal septum is contiguous with the
nasal septum and merges with the caudo-
dorsal wall of the pharynx. The naso-
pharyngeal openings of the auditory
tubes are visible. The appearance of the
vocal cords is similar to that observed in
the horse. Cattle do not have a laryngeal
saccule and a laryngeal ventricle is not
visible rostral to the vocal cords. During
endoscopy, the arytenoid cartilages are
maintained in fully abducted position.
Constriction of the pharynx during
swallowing is accompanied by rostroventral
movement of the pharyngeal septum,
completely occluding the nasopharynx,
which differs from the situation in the
horse.

ENDOSCOPY OF PARANASAL
SINUSES

The paranasal sinuses of the mature horse
can be examined with a 4 mm arthro-
scope while standing and sedated or
under general anesthesia. 21 The pro-
cedure is technically challenging and is
usually performed by surgeons experienced
in the use of arthroscopic equipment
inserted through portals created by
trephining holes in the sinus. The side to be
examined is determined by physical, radio-
graphic and rhinoscopic examination of the
animal. Endoscopic examination is indi-
cated in animals in which diagnosis of the
disease requires collection of tissue from
the sinus. Therapeutic interventions that
can be performed during endoscopic exam-
ination of the paranasal sinuses include
lavage, removal of accretions of inflam-
matory material, drainage of cysts and
creation or enlargement of drainage holes.

PLEUROSCOPY

Pleuroscopy using a rigid or flexible
endoscope enables direct visual inspec-
tion of the pleural cavity for the diagnosis
of pleural disease. 22 The technique is
particularly valuable in diagnosis of
diseases of the thorax that extend to the
pleural surface and do not exfoliate large
quantities of cells, thereby making diag-
nosis by examination of fluid obtained by
pleurocentesis unlikely. The procedure is
useful in collection of tissue samples, such
as from suspected thoracic neoplasia, 23 or
in therapeutic procedures including relief
of pleural adhesions and resection of lung
sections. 24

The procedure is performed in stand-
ing, sedated horses restrained in stocks.
Strict aseptic technique is used. The portal
for insertion of the endoscope is at the
level of the eighth to 12th intercostal
space with optimal examination of intra-
thoracic structures obtained via the 10th

or 12th intercostal space. Either a rigid
endoscope (10 mm diameter, 57 cm
length) or flexible endoscope (10 mm
diameter, 1 m length) can be used. The
endoscope is inserted through a small
incision in the intercostal space made
under local anesthesia. The ipsilateral
lung is partially collapsed by induced
pneumothorax to permit visualization of
intrathoracic structures. The mediastinum
is intact in most horses. Inadequate
collapse of the lung increases the likeli-
hood of it being damaged during the
procedure. The lung is reinflated by
removal of air in the pleural space
at the end of the procedure. Potential
complications of the procedure include
pneumothorax, hemothorax, damage to
intrathoracic structures and infection.

RADIOGRAPHY

Radiography of the head, neck and thorax
is valuable in the diagnosis of diseases of
the respiratory tract of animals. Examina-
tion is hindered by the large size of adult
horses and cattle through the need for
specialized, high-capacity equipment for
obtaining radiographs, and the need
for adequate restraint. Radiographic exam-
ination of adult animals in the field using
portable radiographic units is very limited.
However, large practices with fixed radio-
graphic units capable of generating suffi-
cient voltage and amperage can obtain
diagnostic radiographs of the thorax of
adult horses and cattle. Diagnostic films
of smaller animals, including adult sheep
and goats and foals and calves, can be
obtained using portable units capable of
generating 80-100 kVp and 15-20 mA..

Examination of the thorax of large
animals is restricted to lateral radiographs
because the large amount of tissue
prevents adequate exposure for ventro-
dorsal views. Multiple films are required
for complete examination of the thorax,
and the exposure needed for optimal
quality films varies among anatomical
sites. Localization of focal lesions can be
achieved by examining sets of radiographs
that include images collected with the
horse or cow standing first with one side
to the plate and then with the other side
toward the plate. The lesion will appear
larger in views obtained with the lesion
closer to the source of X-rays.

Radiographs of calves and foals can
be recorded with them standing or
recumbent. Images obtained with the foal
or calf in lateral recumbency with the
forelimbs pulled forward permit optimal
examination of the cranial thorax. How-
ever, calves or foals that are recumbent for
prolonged periods of time (e.g. > 30 min)
can develop atelectasis of the down lung
that can mimic pneumonia radiographi-

cally. Ventrodorsal views assist with
localizing lesions in foals and calves.
Radiographic evidence of lung disease is
common in ill neonatal foals (74% having
such lesions in one study), 25 and is not
related to clinical evidence of respiratory
disease or dyspnea. 26 The characteristics
of lung lesions detected in neonatal foals
are associated with likelihood of survival.
Guidelines for recognition of pulmonary
patterns in foals have been proposed
(Table 10. 2) 26 and these guidelines are
likely to be useful aids for interpretation
and description of pulmonary patterns in
neonates of other species.

Radiography can assist in the recogni-
tion and differentiation of atelectasis and
consolidation, interstitial and exudative
pneumonias, the alveolar pattern of pul-
monary disease, neoplasms, pleural
effusions, pneumothorax, hydroperi-
cardium and space-occupying lesions of
the thorax. Cardiomegaly, abnormalities
of the cranial mediastinum, fractures of
ribs and diaphragmatic hernia can also be
detected.

Many pulmonary diseases do not have
lesions that are readily detected on radio-
graphic examination. Failure to detect
abnormalities on radiographic examination
of the thorax does not eliminate pulmon-
ary disease. Furthermore, radiographically
detectable signs of lung disease can
persist after the animal has clinical and
clinicopathological signs of recovery or
improvement.

Bronchography utilizing contrast
agents is of value in determining the
patency of the trachea and bronchi, but
general anesthesia is required to over-
come the coughing stimulated by the
passage of the tracheal catheter. Using a
fluoroscope to determine the location of
the catheter tip, the contrast agent can be
deposited in each dependent lobe in turn.
This technique is used infrequently.
Computed tomographic (CT) examin-
ation of the lung is very sensitive and
specific for lung disease in companion
animals and is technically feasible in
calves, foals and small ruminants. The
technique is useful in the diagnosis of
mediastinal disease in foals. 27

Radiographic examination of the trachea
can reveal the presence of abnormalities
in shape, such as occur with tracheal
collapse, or the presence of foreign bodies
or exudate.

Radiographic examination of the head
can identify diseases of the paranasal
sinuses, ethmoids and pharynx. Radio-
graphic examination is useful in defining
diseases of the guttural pouches and in
detecting retropharyngeal abscesses or
abnormalities, such as the presence of
foreign bodies. The CT anatomy of the
head of horses and foals has been

Special examination of the respiratory system

Alveolar lung pattern (Vessels not visualized. There is displacement of air from the distal air spaces
of the lung leading to a relatively homogeneous increase in soft tissue opacity. Formation of air
bronchograms is usually associated with the pattern but is not always present)

Absent

Minimal alveolar component
(< 10%)

Focal (> 10% to 30%)

Localized (> 30% to 50%)

Extensive (> 50%)

The pulmonary vessels are easily seen
No visualization of vessels in < 10% of the lung field. Usually
occurs in conjunction with a moderate or severe interstitial
lung pattern

No visualization of vessels in 1 1 -30% of lung fields. Air
bronchograms might or might not be present within < 30% of
lung fields

No visualization of vessels in 31-50% of lung fields. Air
bronchograms might or might not be present within < 50% of
lung fields

No visualization of vessels in > 50% of lung fields. Air
bronchograms might or might not be present throughout the
entire section of lung field

Interstitial lung pattern (Characterization of the non-air-containing elements of the lungs
including blood vessels and bronchi)

Normal Clear visualization of vessels. Borders are well defined

Mild increase The pulmonary vessels appear slightly ill defined (hazy borders

with loss of visualization of the fine vascular structures). Mildly
lacy appearance to lung field

Moderate increase The vessels are ill defined, resulting in moderately lacy

appearance and increased opacity of the lung field
Marked increase Significantly increased opacity; vessel borders are barely

recognizable

Bronchial pattern (Characterized by alterations in bronchial wall thickness and density, or in
bronchial lumen diameter. Note that periobronchial cuffing is a feature of interstitial not bronchial
pattern)

Bronchial structures seen in cross section appear as small,
thin-walled hollow rings between paired vessels. The bronchial
walls are barely distinguishable when viewed side-on and are
not clearly visualized at the periphery of the lung field
A few thickened bronchial walls evident in cross section
('doughnuts') at the periphery of the lung fields. Longitudinal
sections appear as tram lines reaching two-thirds of the way
to the lung periphery

Extensive bronchial thickening might be observed, extending
far into the periphery of the visible lung field

Normal

Moderate increase

Marked increase

described. 28-30 CT imaging of the nasal
cavities and paranasal sinuses of horses is
useful in the detection of diseases of these
structures, 31,32 and of the teeth, 33 pharynx,
larynx and guttural pouches. 34 The tech-
nique is technically feasible in ruminants
and pigs, although there are few reports
of its use in these species. 35

Magnetic resonance (MR) imaging
is useful in diagnosis of diseases of the
head, and the anatomy as visualized on
MR imaging of the head of horses has
been reported. 36 Unfortunately, the lack
of units suitable for examination of large
animals precludes routine use of this
imaging modality.

SCINTIGRAPHY (NUCLEAR
IM AGIN G)

The basis of pulmonary scintigraphy is
detection at the body surface of radiation
emitted from the lungs after injection or
inhalation of radioactive substances. 37 The
technique has been described in both
horses and calves. 37,38 The technique has
limited diagnostic usefulness in large
animals because of the need for avail-

ability of appropriate isotopes and detec-
tion equipment. Furthermore, the large
size of adult cattle and horses limits the
sensitivity of the technique. The tech-
nique has been used to determine the
distribution of pharmaceuticals adminis-
tered by aerosolization and the presence
of ventilation/perfusion mismatches.
Alveolar clearance can be detected using
scintigraphic examination. Currently pul-
monary scintigraphy is largely a research
tool.

ULTRASONOGRAPHY

Ultrasonographic examination of the
thorax of farm animals and horses is a
very useful diagnostic tool. Ultrasono-
graphic examination of the thorax provides
diagnostic information that is not obtained
by radiographic examination. The wide-
spread availability of portable ultrasound
units and the ability to image parts of the
thorax using ultrasound probes intended
for examination of the reproductive tract
of mares and cows makes this a poten-
tially valuable diagnostic aid for both field
and hospital-based practitioners. Further-

more, the absence of radiation exposure
and the 'real-time' nature of images
obtained by ultrasonography aid in
frequent assessment and monitoring
of abnormalities and performance of
diagnostic or therapeutic procedures
such as thoracocentesis or aspiration of
masses.

There are limitations to imaging
imposed by aerated lung and the bones of
the ribcage. Examination of the thorax is
limited by the presence of ribs and
aerated lungs because the sound waves
used to create ultrasound images are
reflected from these surfaces. Ultra-
sonography cannot reveal lesions of the
lungs that are not confluent with the
visceral pleura. Imaging windows are
restricted to the intercostal spaces but this
impediment can be overcome by scan-
ning through adjacent intercostal spaces
and angling of the ultrasound beam.

Ultrasonographic examination of the
thorax should be performed in a con-
sistent manner that ensures thorough
examination of the thorax. Preferences for
the pattern of examination differ some-
what among examiners, but one common
and successful technique is to scan each
intercostal space from dorsal to ventral
starting at the 17th intercostal space in
horses and the 12th intercostal space in
cattle. The ultrasound probe is slowly
moved from dorsal to ventral while the
examiner studies the images. When one
scanning of one intercostal space is
completed, the probe is moved to the
most dorsal aspect of the next intercostal
space and the examination is repeated.
Each side of the chest is examined in this
manner. This consistent and thorough
examination ensures that no important or
localized abnormalities are missed. The
examination is performed in adult horses
and cattle with the animal standing. The
rostral thorax is scanned by pulling the
ipsilateral forelimb forward. This is more
readily achieved in horses than in cattle.
Thorough examination of the rostral
thorax might require placing the animal
in lateral recumbency. Calves and foals
can be examined either standing or in
lateral recumbency.

Ultrasound examination of the thorax
is particularly useful for detecting diseases
of the pleura, pleural space or lung surface.
This is in addition to the well-documented
utility of ultrasonographic examination of
the heart and great vessels (see Ch. 8).
The normal ultrasonographic anatomy of
the thorax of cattle, horses and calves has
been determined. 39-41 The following is a
partial list of disorders or abnormalities
detectable by percutaneous ultra-
sonographic examination of the thorax of
farm animals or horses (excluding cardiac
abnormalities);

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

8 Excess pleural fluid
8 Characteristics of pleural fluid
(flocculent, bubbles, fibrin)

8 Extent of pleural fluid accumulation
° Localized areas of pleural fluid
accumulation

° Nonaerated lung (atelectatic,
consolidated)

8 Pulmonary abscesses (must be
confluent with visceral pleura)

8 Intrathoracic masses (thymic
lymphoma, cranial thoracic mass,
gastric squamous cell carcinoma)

0 Pleural roughening ('comet- tail' lesions)
8 Pneumothorax
8 Pulmonary hematoma 42
8 Exercise-induced pulmonary
hemorrhage
8 Hemothorax
° Diaphragmatic hernia
° Fractured ribs (especially in neonates).

Ultrasonographic examination is more
sensitive and specific than radiographic
examination in detecting the presence of
pleural fluid 42 and is particularly useful in
the diagnosis and management of pleuritis
in horses and cattle 43,44 and pneumonia in
calves. 45 The extent of pulmonary lesions
detected at necropsy correlates closely
with the results of ultrasonographic
examination of calves with pasteurellosis. 46
Ultrasonographic examination is useful in
diagnosis of thoracic diseases of cattle. 47
Ultrasonography can identify pulmonary
lesions in horses with infectious viral
pneumonia 48 and is a viable alternative,
though not as sensitive, to radiology in
the evaluation of foals with Rhodococcus
equi pneumonia. 49 Ultrasonography is
very useful in identifying the presence of
pleural fluid and guiding thoracocentesis
to sample and drain this fluid.

LABORATORY EVALUATION OF
RESPIRATORY SECRETIONS

SAMPLING RESPIRATORY
SECRETIONS

When an inflammatory disease process of
the respiratory tract is suspected, the
collection of samples of secretions and
exudate for microbiological and cyto-
logical examination can be considered.
The objective is to obtain a sample
uncontaminated with environmental
flora, which are common in the upper
respiratory tract, and to isolate the
pathogen (s) or demonstrate inflammatory
cells which may be associated with the
lesion. This can be done by:

° Swabbing the nasal cavities or the
pharynx

0 Collection of fluid from the
paranasal sinus
8 Collection of fluid from the
guttural pouch of Equidae

8 Transtracheal aspirate
8 Tracheal lavage
° Bronchoalveolar lavage
8 Thoracocentesis.

NASAL SWAB

A swab of the nasal cavities is a reliable
method for the evaluation of the
secretions associated with disease of the
upper respiratory tract such as infectious
bovine rhinotracheitis and allergic rhinitis.
However, when attempting to assess the
health status of the lungs the nasal swab
can be unsatisfactory because micro-
biological examination usually yields a
large population of mixed flora, consisting
of pathogens and nonpathogens, which is
difficult to interpret.

NASOPHARYNGEAL SWABS

For more reliable results and to lessen the
contamination that occurs with nasal
cavity samples, swabs of the laryngeal-
pharyngeal area can be collected. A swab
in a long covered sheath, of the type used
for collecting cervical swabs from mares,
is easily passed through the nasal cavities
to the pharyngeal area. Significant differ-
ences may exist between the microbial
isolates from nasopharyngeal swabs and
those from lung tissues, which makes
nasal swabs unreliable for diagnosis. For
example, at the individual animal level,
nasopharyngeal swabs and broncho-
alveolar lavage show only moderate
agreement; at the group or herd level the
isolation rates of various organisms are
similar. 50

For isolation of viruses associated with
disease of the upper respiratory tract, nasal
swabs are satisfactory provided a copious
amount of nasal discharge is collected and
the swabs are kept moist during transport
to the laboratory. Nasal swabs sometimes
contain an insufficient amount of secretion,
and certain viral pathogens can become
inactivated in transit.

NASAL LAVAGE

When larger quantities of nasal discharge
are required for research purposes, nasal
washings are usually collected, the simplest
technique being irrigation of the nasal
cavities and collection into an open dish.
From these samples, it is possible to
isolate bacteria and viruses, and identify
immunoglobulins. The development of
immunofluorescent and enzyme-linked
immunosorbent assay (ELISA) tests for
agents of infectious disease has provided
reliable systems for the diagnosis of a
variety of virus diseases in the early stages
of infection. A technique and apparatus
are available that obtain much better
samples than the conventional cotton-
wool swab provides. A vacuum pump
aspirates epithelial cells and secretion
from the nasal passage and pharynx. Cell

smears are then prepared for microscopic
examination and the mucus and cells are
used for conventional microbiological
isolation.

PARANASAL SINUS FLUID

Fluid can be collected from the frontal
and paranasal sinuses of most of the
domestic large animals. Indications for
collection of fluid include the presence
or suspected presence of disease of the
paranasal sinus. Medications can be
administered and infected sinuses lavaged
using this approach. 51,52 Absolute contra-
indications are few but include failure to
be able to adequately restrain the animal.
Demonstration of fluid in the paranasal
sinuses is aided by radiographic examin-
ation of the skull. Fluid is collected by
percutaneous centesis of the frontal or
maxillary sinus and submitted for cytolo-
gical and bacteriological examination
(Gram stain, culture). The procedure is:
restraint of the animal, which can include
the induction of moderate sedation by
administration of alpha-2 agonists and
narcotics, or in cattle restraint in a head
gate with the head secured with a halter.
The area over the centesis site is prepared
aseptically and the skin and subcuta-
neous tissues are anesthetized with local
anesthetic. 51 A stab incision (< 1 cm) is
made in the skin and subcutaneous
tissues. A hole is then drilled into the
sinus using a Jacob's chuck with a
Steinmann pin (2-4 mm diameter). Only
a short (5 mm) length of the Steinmann
pin should be exposed by the chuck. The
hole is drilled by applying steady pressure
and making alternating clockwise and
counterclockwise movements with the
chuck. Entry into the sinus cavity is
evident as a sudden release of tension
and easy passage of the Steinmann pin.
The pin is then withdrawn and sterile
polyethylene tubing is inserted into the
sinus cavity. Fluid can be aspirated at this
time or, if none is forthcoming, 10-20 mL
of sterile 0.9% saline or similar fluid can
be instilled to the sinus cavity. Some of
this fluid may run out the nostril if the
animal's muzzle is lower than the sinus.
Complications include injury to adjacent
structures, including the infraorbital nerve
(trigeminal nerve), nasolacrimal duct or
parotid salivary duct near its entrance to
the oral cavity at the level of the upper
cheek teeth. Hemorrhage is usually
minor and self-limiting. Subcutaneous
emphysema resolves within days. Cellulitis
is a risk, especially for animals with septic
processes in the paranasal sinuses.
Prophylactic administration of antibiotics
should be considered in these cases.

GUTTURAL POUCH FLUID

Indications for collection of fluid from
the guttural pouches of equids include

Special examination of the respiratory system

bacteriological or polymerase chain
reaction (PCR) examination to determine
if the horse is infected by S. equi (the
etiological agent of strangles) or to inves-
tigate the suspected presence of other
inflammatory or neoplastic disease. The
preferred method of collection is during
endoscopic examination of the guttural
pouch. During this examination, fluid can
be collected through a polyethylene tube
inserted through the biopsy port of the
endoscope. Fluid collected in this manner
is potentially contaminated by organisms
in the upper respiratory tract, and results
of bacteriological examination should
be interpreted with caution. Usually,
bacteriological examination is for the
presence of S. equi and demonstration of
its presence is all that is required for a
diagnosis of infection. Fluid can also be
obtained from the guttural pouch by blind
passage of a firm catheter, such as a
Chambers mare catheter or 10 French dog
urinary catheter, into the guttural pouch.
This procedure requires some skill and
there is always the uncertainty that one
might not have actually manipulated the
catheter into the guttural pouch. A third
technique involves percutaneous puncture
of the guttural pouch just posterior to the
ramus of the mandible and ventral to the
ear. This technique has the potential to
yield fluid that is uncontaminated by
organisms from the upper respiratory
tract, but carries with it a high risk of
injury to the important vascular and
neural structures in and around the
guttural pouch (internal and external
carotid arteries, pharyngeal branch of the
vagus nerve, hypoglossal nerve, and
others). Percutaneous sampling of guttural
pouch fluid should not be undertaken
without careful consideration of the risks
and benefits of the procedure.

TRACHEOBRONCHIAL SECRETIONS

The collection and evaluation of tracheo-
bronchial secretions is a useful method
for assessing lower airway disease and is
widely used in the determination of the
etiology of infectious pneumonia (viral,
mycoplasmal, fungal, and parasitic) or the
severity of disease (bronchoalveolar
lavage fluid cytology in horses with
heaves, exercise-induced pulmonary
hemorrhage in athletic horses). It is also
used as a tool in evaluating respiratory
health of intensively housed animals, such
as in piggeries. 33 Cytological examination
of recovered fluid can provide valuable
information about the severity, extent and
etiology of disease of the lower airway.
There are two methods of sampling
tracheobronchial secretions - aspiration
of tracheal fluid or lavage of bronchioles
and distal airways. Each sampling method
yields fluid of differing characteristics and

source and interpretation of the results of
examination of these fluids depends on
their source and the method of collection.

Comparison of tracheal aspirates and
bronchoalveolar lavage fluid

Examination of tracheal aspirates and
bronchoalveolar lavage fluid yields differ-
ent, but often complementary, information
about the lower respiratory tract. The dif-
ferences between tracheal aspirates and
bronchoalveolar lavage fluid arise because
cell populations, and types of cell, differ
markedly among segments of airways.
There is no correlation between cytological
features of tracheal aspirates and
bronchoalveolar lavage fluid of horses,
and this is probably the case in other
species. 54 Tracheal aspirates are represen-
tative of cell and bacterial populations of
the large conducting airways (trachea and
mainstem bronchi), which can originate
in both the large and small conducting
airways and the alveoli. 54 Secretions of
more distal airways can be modified
during rostrad movement, such that fluid
in a tracheal aspirate is not representative
of processes deeper within the lung.
Furthermore, disease localized to one
region of the lung can alter tracheal fluid.
Examination of tracheal aspirates is useful
for detecting inflammation of the large
airways and for isolation of microorganisms
causing disease in these structures. There
is no good evidence that findings on
examination of tracheal aspirates correlate
with abnormalities in pulmonary func-
tion, and tracheal aspirates do not
accurately reflect lesions in the lungs of
horses. 33

Bronchoalveolar lavage is useful for
sampling secretions in the more distal
airways. It provides a sample of secretions
that have not been contaminated by
upper respiratory tract organisms or
secretions before collection and the
sample is therefore assumed to be more
representative of small airway and, to a
lesser extent, pulmonary parenchymal
and alveolar secretions or exudates.
Bronchoalveolar lavage is useful in the
detection of widespread lung disease but
not necessarily in the detection of
localized disease. Tracheal aspirates,
because they in theory represent a
composite sample of secretions from all
regions of the lung, are likely to be more
sensitive in detecting focal disease, such
as a pulmonary abscess. Bronchoalveolar
lavage fluid composition correlates well
with pulmonary function in horses. 56 ' 37

There is little agreement in cytological
examination of tracheal aspirates and
bronchoalveolar lavage fluid of sick and
healthy horses, and this difference prob-
ably exists in other species. Typically, the
proportion of cells that are neutrophils is

much higher in tracheal aspirates than in
bronchoalveolar lavage fluid of both horses
with heaves and normal horses. 54 ' 58 Mast
cells are detected more frequently, and
eosinophils less frequently, in broncho-
alveolar lavage fluid than in tracheal fluid
of normal horses. 59

Tracheal aspirates

Indications for collection of tracheal
aspirates include the need for micro-
biological and cytological assessment of
tracheal fluids. The primary indication is
collection of samples for microbiological
diagnosis of infectious respiratory disease.
Other indications include detection and
characterization of inflammation of the
conducting airways. Contraindications
include severe respiratory distress,
although this is not an absolute contra-
indication, inability to adequately restrain
the animal, and severe, spontaneous
coughing. Percutaneous tracheal aspirate
collection performed in animals with
severe coughing can result in develop-
ment of severe subcutaneous emphysema
as a result of the high intratracheal
pressures associated with the early phase
of coughing. Most animals in which per-
cutaneous tracheal aspirates are collected
subsequently have radiographic evidence
of pneumomediastinum.

Tracheal aspirates can be collected
either by percutaneous puncture of the
trachea or through an endoscope passed
through the upper airways. The advantage
of percutaneous collection of tracheal
aspirates is that there is minimal risk of
contamination of the sample by upper
respiratory tract or oropharyngeal secre-
tions. Microbiological examination of the
samples is therefore likely to accurately
reflect microbes present in tracheal fluid.
Collection of tracheal aspirates through
an endoscope markedly increases the risk
of contamination of the sample with
oropharyngeal fluids, and compromises
the diagnostic utility of culture of the
sample. This disadvantage is partially
alleviated by the use of guarded catheters
inserted through the endoscope. 60,61 The
disadvantage of percutaneous collection
of tracheal fluid is that it is invasive and
there is a risk of localized cellulitis and
emphysema at the site of puncture.
Endoscopic collection is relatively non-
invasive and readily accomplished. 5 We
prefer use of the percutaneous method
when accurate microbiological assess-
ment of samples is desired.

Percutaneous transtracheal
aspiration

This is a practical method that has been
used extensively in the horse 60 and is
adaptable to cattle, 62 sheep and goats. For
the horse, a 60 cm no. 240-280 polyethylene
tube is passed through a 9-14-gauge

486

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

needle inserted into the trachea between
two rings. Commercially prepared kits for
performing tracheal aspirates in horses
are available that include all catheters and
needles required. An alternative to poly-
ethylene tubing is to use an 8-10 French
male dog urinary catheter inserted through
an appropriately sized cannula. The site
for insertion of the needle or cannula is at
the junction of the proximal and middle
one-thirds of the ventral neck. The horse
is usually sedated prior to insertion of the
needle or cannula. The skin site is prepared
aseptically and a short stab incision is
made after the area has been anesthetized.
The cannula is removed to avoid cutting
the tube and the tube is pushed in as far
as the thoracic inlet. Fluid typically pools
in the trachea at the thoracic inlet in
horses with lung disease (the tracheal
lake or pool) and it is this fluid that is
aspirated. Thirty to 50 mL of sterile saline
(not bacteriostatic saline) is rapidly
infused.The catheter or tubing should be
rotated until tension is felt on aspiration
by a syringe. Fluid is aspirated and
submitted for cytological, microbiological
or other examination.

Complications such as subcutaneous
emphysema, pneumomediastinum and
cellulitis can occur, which necessitates
care and asepsis during the procedure.
Sudden movement of the cannula during
insertion of the tubing may cause part of
the tube to be cut off and to fall into the
bronchi, but without exception this is
immediately coughed up through the
nose or mouth.

Endoscopic sampling of tracheal
secretions

The flexible fiberoptic endoscope can be
used to obtain tracheal lavage samples
and at the same time visualize the state of
the airways. 13,60 The process is as for
rhinolaryngoscopic examination with the
addition of passage of a catheter through
the biopsy port of the endoscope. Tracheal
fluid is then visualized and aspirated
through the catheter. The clinical advan-
tages of the endoscopic collection include
noninvasiveness, visual inspection of the
airways, guidance of the catheter, and
speed. 60 The use of an endoscope with a
guarded tracheal swab minimizes con-
tamination by oropharyngeal secretions
but does not eliminate it. 5,61

Assessment of results

Microbiological examination can yield
any one or more of a variety of bacteria,
depending on the species examined, the
animal's age and its clinical condition.
Tracheal aspirates of normal animals
rarely yield any bacterial growth on
culture. Growth of unusual organisms or
known oropharyngeal commensal bacteria
from samples obtained by endoscopic

examination should not be given undue
clinical significance as they probably
result from contamination of the tracheal
aspirate during collection. Pseudomonas
spp. and anaerobes isolated from tracheal
aspirates collected by endoscopy are
almost always contaminants and of no
clinical significance. 5 The extent of con-
tamination of tracheal aspirate samples
by oropharyngeal bacteria can be estimated
from the number of squamous epithelial
cells in the sample. 59 There is an apparent
approximate linear relationship between
the number of squamous cells per milliliter
of fluid and the number of colony-forming
bacterial units in tracheal aspirates.
Samples containing over approximately
10 squamous epithelial cells per milliliter
of tracheal aspirate had markedly greater
bacterial contamination. 59 Examination of
Gram-stained smears of tracheal fluid is
j specific but not very sensitive for detec-
tion of bacteria, compared with culture. 63
In other words, if examination of a Gram-
stained smear of tracheal fluid reveals
bacteria, then the sample is likely to yield
bacteria on culture, whereas failure to
detect bacteria predicts poorly the likeli-
hood of growth of bacteria on culture of
the sample. This indicates that exam-
ination of Gram-stained samples of
tracheal fluid does not reliably predict
bacterial isolation, and if an infectious
etiology is suspected the fluid should be
cultured. Results of the microbiological
examination of the tracheal fluid should
be consistent with the animal's clinical
condition and expected isolates.

Cytological examination of tracheal
fluid is an important diagnostic tool.
Various stains are available to aid identifi-
cation of cell types and numbers in
tracheal aspirates. Neutrophils, macro-
phages, lymphocytes and epithelial cells
are readily identified on the basis of their
classical morphology and staining using
fast Romanowsky stain (Diff-Quik®), but
this stain is not suitable for identifying
mast cells in equine tracheal fluid and
probably that of other species. 59 Leishman's
stain is useful to identify mast cells. 59
Clinically norma! horses typically have
fewer than 20-30% of cells as neutrophils
with the majority of remaining cells being
I macrophages, lymphocytes and epithelial
j cells. 54,61 Animals with inflammation of
j the airways typically have increased cell
j counts and proportion of neutrophils, and
I large amounts of mucus. Horses with
j inflammatory airway disease such as
heaves typically have more than 20% of
the cells as neutrophils (see Heaves,
below), and those with infectious pneu-
monia often have 50-90% of cells as
neutrophils. The presence of eosinophils
is considered abnormal and is consistent
with parasite migration ( Parascaris equorum

in foals, Dictyocaulus viviparus in calves).
The presence of hemosiderin-laden macro-
phages is evidence of prior pulmonary
hemorrhage. 64

Bronchoalveolar lavage

Bronchoalveolar lavage provides a sample
of secretions and cells of the distal air-
ways and alveoli, referred to as broncho-
alveolar lavage fluid. It is a widely used
procedure in horses and, to a lesser
extent, cattle and calves, 65 ' 67 sheep 68 and
pigs. 53,69 Analyses performed on broncho-
alveolar lavage fluid include measurement
of cell number and type, culture (usually
in pigs and cattle) and analysis of immune
proteins and surfactant. It is a relatively
noninvasive procedure that allows cyto-
logical and biochemical evaluations of the
lower airways and alveoli, which are
useful diagnostic aids when evaluating
animals with lung disease. While fiberoptic
bronchoscopy and tracheal aspirates
permit assessment of the major bronchi
and upper airways, bronchoalveolar lavage
offers an extension of the diagnostic
potential by sampling the terminal air-
ways and alveolar spaces.

The primary indication for collection
of bronchoalveolar lavage fluid is acute or
chronic lung disease. This includes both
infectious and noninfectious diseases,
although interpretation of samples
collected by passage of the collection tube
through the nostrils or mouth is
complicated by the inevitable contami-
nation of the sample by oropharyngeal
commensal bacteria. Despite this short-
coming, the technique has been used to
detect pneumonia associated with
Mycoplasma sp. in cattle. 70 Contra-
indications are few, with respiratory
distress being an obvious one. Compli-
cations of bronchoalveolar lavage are also
few, and include a mild neutrophilia in
lavaged sections of lungs and changes
in phagocytic function of pulmonary
macrophages, and microbial content, for
several days after the procedure. 31,71

A shortcoming of bronchoalveolar
lavage is that it lavages only a small
region of the lung, with the risk that focal
lung disease is not detected. This is best
exemplified in pneumonia in horses, in
which bronchoalveolar lavage fluid from
pneumonic horses can contain large num-
bers and a high proportion of neutrophils
or can be normal, depending on the area
of lung lavaged. Therefore, the broncho-
alveolar lavage procedure is a very specific
but not very sensitive test for pneumonia in
horses. 72 Abnormal lavage fluid is helpful
diagnostically, whereas normal results do
not exclude the presence of foci of
pulmonary disease. The lavage samples may
be normal in horses affected with pneu-
monia or pleuropneumonia and, because

of these false-negative results, this is not
the best diagnostic technique to evaluate
a horse with pneumonia. 13 In contrast,
the tracheobronchial aspirates are more
sensitive and most horses with pneu-
monia have cytological abnormalities. 13

Endoscopic bronchoalveolar lavage
Endoscopic bronchoalveolar lavage has
the advantage of permitting visual exam-
ination of the airways during the pro-
cedure and selection of the region of the
lung to be lavaged. This technique does
require access to sophisticated endoscopic
equipment. The technique described
below for horses can be modified for use
in other species. 73

Horses for bronchoalveolar lavage
should be appropriately restrained. Sed-
ation is usually essential and is achieved
by administration of alpha-2-agonists.
Coadministration of narcotics is rec-
ommended by some authorities to reduce
the frequency and severity of coughing.
Butorphanol tartrate 10 mg for a 400 kg
horse is recommended, although this
drug is not as effective as intratracheal
lidocaine at reducing the frequency or
severity of coughing when combined with
detomidine for collection of broncho-
alveolar lavage fluid. 74 Effective sup-
pression of coughing during collection of
bronchoalveolar lavage fluid can be
achieved by instillation of lidocaine
(60 mL of a 0.7% solution - made by
diluting 20 mL of 2% lidocaine solution
by addition of 40 mL of isotonic saline).
The lidocaine solution is administered as
the endoscope enters the rostral trachea.
A twitch can be applied to the nares. The
endoscope must be at least 2 m in length
and the external diameter should be
10-15 mm. Endoscopes of 10 mm diameter
will pass to about the fifth- generation
bronchi, whereas endoscopes of larger
diameter will not pass quite as far into the
lung. The endoscope is passed until it
wedges and then 300 mL of warmed (to
reduced bronchospasm) isotonic saline is
introduced in 5 x 60 mL aliquots. Air is
infused after the last aliquot to ensure
that all fluid is instilled. After the horse
has taken between one and three breaths
the fluid is withdrawn and the aliquots
are mixed. There is no difference in the
cytological composition of the first and
subsequent aliquots. 75

Blind bronchoalveolar lavage
Commercial bronchoalveolar lavage tubes
are available for use in horses, and are
suitable for use in adult cattle and
calves. 67 The tubes are made of silicone
and are therefore considerably more
pliable than stomach tubes (which are not
suitable for this procedure). The tubes
are 2 m in length and have an external
diameter of about 8 mm. The horse is

Special examination of the respiratory system

487

restrained and sedated as for endoscopic
bronchoalveolar lavage and the tube is
passed through one nostril into the
trachea. The tube is then advanced until it
wedges, evident as no further insertion of
the tube with mild pressure. Continued
vigorous attempts to pass the tube can
result in the tube flexing in the pharynx
and a loop of the tube entering the
mouth. After the tube wedges, the cuff on
the tube is inflated to prevent leakage of
fluid around it, 300 mL of warm isotonic
saline is instilled, the tube is flushed with
air and fluid is aspirated. The fluid should
be foamy and, if cell counts are high,
slightly cloudy.

Bronchoalveolar lavage can be per-
formed in conscious sheep by insertion of
1.7 mm external diameter polyethylene
tubing through a cannula inserted per-
cutaneously in the trachea. 68 The tubing is
inserted until resistance is detected
(about 40-45 cm in an adult sheep) and
the lung is lavaged with 30 mL of sterile
isotonic saline.

Laboratory assessment of
tracheobronchial secretions

A problem with comparison of cell counts
of bronchoalveolar lavage fluid reported
by different authors is the use of
inconsistent quantities of fluid to perform
the lavage. The use of different volumes
alters the extent of dilution of the fluid.
There is a need for uniformity in tech-
nique. 76 An approach to this problem has
been to measure substances in the
bronchoalveolar lavage fluid that can
provide an indication of the extent of
dilution of the sample. Both endogenous
(urea, albumin) and exogenous (inulin,
methylene blue) markers have been used.
Dilution factors using urea concentration
in plasma and in bronchoalveolar lavage
fluid appear to be useful. 77 The assumption
is that urea concentrations in bronchial
and alveolar secretions will be identical to
that in plasma. The formula for correcting
for dilution that occurs during collection
of bronchoalveolar lavage fluid is:

Dilution factor = Urea concentration

in bronchoalveolar lavage fluid/Urea

concentration in plasma,

where urea concentration in broncho- j
alveolar lavage fluid and in plasma is j
expressed in the same units. The volume I
of the pulmonary epithelial lining fluid
can then be calculated:

Pulmonary epithelial lining fluid

volume = dilution factor x volume of

bronchoalveolar lavage fluid.

Samples for cytology are submitted for
preparation involving centrifugation of
the sample to concentrate cells for prep-
aration of slides for staining and micro-

scopic examination. At least for samples
from horses, examination of smears made
directly from the sample, without centri-
fugation, is diagnostically useful. 78 As for
tracheal fluid, the proportion of mast cells
in equine bronchoalveolar lavage fluid is
underestimated if cells are stained with
fast Romanowsky stain (Diff-Quik®). 79

Diagnostic value

The aspirates from normal animals con-
tain ciliated columnar epithelial cells,
mononuclear cells and a few neutrophils
with some mucus. The concentration of
the cells depends on the volume of fluid
infused and the disease status of the
animal. Representative values for various
species are listed in Table 10.3. The
general pattern is that animals with
inflammatory airway disease, either infec-
tious or noninfectious, have a higher
proportion of neutrophils than do disease-
free animals. However, ranges of normal
values vary considerably depending on
the species, the age of the animal and its
management (primarily housing con-
ditions). Care should be taken not to
overinterpret findings on examination of
tracheal aspirates or bronchoalveolar
lavage fluid. While there is good correlation
between microbiological results and cell
counts in bronchoalveolar lavage fluid of
calves with pneumonia 65 and Thorough-
bred race horses with inflammatory air-
way disease, 80 this association might not
hold for all diseases or species.

Thoracocentesis (pleurocentesis)

Paracentesis of the pleural cavity is of
value when the presence of pleural fluid is
suspected and, in the absence of ultra-
sonographic examination, needs to be
confirmed, and when sampling of pleural
fluid for cytological and bacteriological
examination is indicated. The primary
indication for sampling pleural fluid is the
presence of excess pleural fluid. Sampling
of pleural fluid is usually accompanied by
therapeutic drainage, in which case the
cannula used for sampling is larger than if
only collection of pleural fluid is desired.
Contraindications are minimal, especially
if the procedure can be performed under
ultrasonographic guidance. The principal
contraindication is the inability to restrain
an unruly animal, as this increases the
risk of laceration of the lung or a coronary
vessel, or cardiac puncture. Complications
include hemorrhage from lacerated
intercostal or pleural vessels, pneumothorax
secondary to laceration of the lung or
introduction of air through the cannula,
cardiac puncture and sudden death,
irritation of the myocardium and ven-
tricular arrhythmia (premature ventricular
contractions), or coronary artery laceration
and subsequent cardiac tamponade and
death. There is a risk of cellulitis at the site

488

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

Special examination of the respiratory system

of centesis, especially if indwelling
cannulas are maintained for more than
a day.

The procedure is performed with the
animal standing. Sedation or systemic
analgesia is usually not needed, unless it
is medically indicated or the animal is not
easily restrained. The equipment for
sampling of pleural fluid from adult
horses or cattle is a blunt 10-15 cm
cannula of approximately 3 mm diameter
(such as a bovine teat cannula) or a 7.5 cm
spinal needle. The blunt- tipped cannula is
preferred because use of it reduces the
risk of laceration of vital structures. A
three-way stopcock or similar device
should be attached to the hub of the
needle or cannula and closed to prevent
aspiration of air when the pleural cavity is
entered. The site for centesis is best
identified by ultrasonographic examin-
ation of the thorax or, if that is not
available, by percussion and auscultation
of the chest to identify the fluid level. A
commonly used site is the seventh
intercostal space on the left side and the
sixth intercostal space on the right side.
The skin should be clipped of hair and
aseptically prepared. The region can be
anesthetized with approximately 10 mL
of 2% lidocaine, mepiricaine or similar
product. The cannula or needle should be
introduced over the rib and then directed
cranial to the rib (the intercostal vessels
and nerves course along the caudal edge
of the rib). If a cannula is used then a
slight 'popping' sensation is felt as the
cannula perforates the parietal pleura. A
syringe is attached to the cannula or
needle and fluid is aspirated from the
pleural space.

Collected fluid should be examined
visually. Normal pleural fluid, which is
present in small quantities in normal
animals, is clear and slightly yellow.
Abnormal fluid can be bloody, thick and
yellow, suggestive of purulent material, or
flocculent. The material should be smelled
- a foul odor is usually present when the
pleural fluid is infected by anaerobic
bacteria and is a sign of a poor prognosis.
Cytological examination should be per-
formed, including white cell count and
measurement of total protein concen-
tration. Ancillary measurements on pleural
fluid include pH, Pco 2 , Po 2 , bicarbonate,
glucose and lactate. Sterile pleural fluid
has a pH, Po 2 and Pco 2 and lactate,
glucose and bicarbonate concentrations
similar to those of venous blood. 81 Infected
pleural fluid is acidic, hypercarbic and has
an increased concentration of lactate and
decreased concentrations of bicarbonate
and glucose compared to venous blood. 81
Pleural fluid should be cultured for
aerobic and anaerobic bacteria and
mycoplasmas . Antimicrobial susceptibility

should be determined for isolated organ-
isms. Fungal cultures are rarely indicated.

Ultrasound-guided needle puncture of
a suspected lung abscess to determine the
species of bacteria present is sometimes
practiced but there is the risk that
infection will be spread to the pleura by
this technique. This technique is not
recommended as a routine procedure as
microbiological examination of tracheal
aspirates will probably yield the offending
bacteria.

PULMON ARY FUNCTION TE S TS

Pulmonary function tests provide quanti-
tative assessment of pulmonary ventilatory
function through measurement of expired
and inspired gas volumes, intrathoracic
pressures and derivations of these vari-
ables - sometimes referred to as pulmon-
ary mechanics. The techniques are widely
used in research into pulmonary diseases,
especially heaves, in horses, and have
been adapted for use in ruminants. 82 A
relatively simple assessment of pulmonary
function is measurement of pleural
pressure changes during respiration.
This can be achieved by either insertion of
a blunt cannula through the intercostal
space or passage of a balloon catheter
into the thoracic esophagus. The pressure
changes during respiration are then
recorded and the maximal pressure change
between inspiration and expiration is
calculated. The pressure change is closely
correlated with airway resistance to
airflow and is an excellent indicator of the
severity of bronchoconstrictive diseases.

More complex measurements are
made by application of an airtight face
mask containing a flow meter to the
animal. Combined with measures of air-
way pressure, air flow during tidal breath-
ing yields measures of tidal volume, minute
volume, respiratory rate, pulmonary
resistance and pulmonary dynamic
compliance. Measurements made with the
animal at rest are relatively insensitive to
small changes in pulmonary function and
the sensitivity of these tests to detect
heaves is low. 57 The sensitivity of changes
in maximal pleural pressure and resist-
ance of the lower airways are 44% and
22%, respectively. 57 The sensitivity of the
test can be increased by measuring these
variables during exercise. Measurement of
pulmonary mechanics in horses with
heaves is reproducible over both short
(hours) and long (months) periods of
time, indicating the usefulness of these
techniques for monitoring of disease pro-
gression and response to therapy. 83

Measurement of flow-volume loops
has been performed for both stationary
and exercising horses. 84-85 A number of
variables are derived from these measures

and used as indicators of pulmonary
function. However, the large variability in
these measures in stationary horses
(16-32%) severely limits the utility of this
test to detect mild or subclinical respiratory
disease. Similarly, flow-volume loops in
exercising horses with obstructive lung
disease of moderate severity do not differ
markedly from those of the same horses
when they do not have lung disease.
Flow-volume loops have limited use in
evaluation of lung function in animals.

Other tests of pulmonary function
include the nitrogen dilution test and the
single-breath diagram for C0 2 . For the
nitrogen dilution test concentrations of
nitrogen in exhaled air are measured
while the animal breathes 100% oxygen.
A number of variables are calculated from
the decay curve of nitrogen concentration
in exhaled air, including the functional
residual capacity. 86 There are clinically
significant differences between animals
with normal respiratory function and
those with pulmonary disease. However,
this test is not readily adapted for routine
clinical use. Volumetric capnography is
the graphic examination of expired breath
C0 2 concentrations versus expired volume
to create a single-breath diagram for
C0 2 . 87 The results are divided into phase
I, which represents the relatively carbon-
dioxide-free air from the proximal or orad
conducting airways, phase II, which is the
transitional phase, and phase III, which is
the carbon -dioxide-rich air from the
alveoli. Measures of pulmonary function
obtained include estimates of dead space
ratio, physiological dead space volume
and alveolar efficiency. 87 The clinical
utility of this test and its ability to detect
mild or subclinical disease in animals
have not been demonstrated.

Impulse oscillometry offers the
potential of being a potentially clinically
useful test of respiratory function in both
horses and cattle. 46-88-89 The test measures
impedance of the respiratory system and
provides estimates of respiratory resistance
and reactance. 46 The technique has the
advantage of being more sensitive to
changes in pulmonary function than
measurement of pleural pressure changes, 90
is minimally influenced by respiratory rate
and tidal volume 91 and is relatively easier
i to perform than more complex measures
| of respiratory mechanics. The test involves
j fitting an airtight facemask containing a
| pneumotachograph for measurement of
1 respiratory volumes and tubing to a
| horse. The tubing is attached to a loud-
| speaker, which is used to generated square-
j wave signals containing harmonics
| between 0 and 10 Hz. Information from
i the system is analyzed using a computer
program and indices of pulmonary
I resistance and reactance are determined.

490

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

The forced oscillation technique in feedlot
cattle with naturally occurring shipping
fever indicates the presence of a large
increase in pulmonary resistance and a
decrease in dynamic compliance with
obstructive lung disease located mainly at
the level of large airways but also in small
airways. 92 The clinical utility of the
technique remains to be determined.

The sensitivity of these tests can be
increased by provocative tests in which
animals are administered agents, such as
histamine or methacholine, that cause
bronchoconstriction in animals with
reactive airways. 90

Measurement of forced expiratory
flow-volume curves and forced vital
capacity in horses is a sensitive indicator
of bronchoconstriction. 57-93 The test
involves the heavilysedated horse having
a nasotracheal tube inserted. The naso-
tracheal tube is then attached to a large
vacuum reservoir and a valve is opened
abruptly. The maximum rate of forced
expiratory airflow is measured and various
variables indicative of pulmonary func-
tion are calculated, including forced
expiratory volume in one second (FEV!). 93
The clinical utility of this test of pulmon-
ary function is limited by the extensive
instrumentation of the animal and the
need for sophisticated electronics.

A portable system for monitoring
cardiovascular and respiratory function in
large animals is available. Pulmonary
function testing of cattle is also being
examined and may provide some under-
standing of the pathophysiology of
respiratory tract disease. Calves between
1 and 8 months of age with chronic
respiratory disease have: 82

° Significantly reduced inspiratory and
expiratory times and tidal volume
° Significantly increased respiratory
frequency and airway resistance
More negative transpulmonary
pressure values when compared to
predicted values for the same calves.

Arterial oxygen and carbon dioxide ten-
sions are the only variables which correlate
with clinical scores.

ARTERIAL BLOOD GAS ANALYSIS

Measurement of P a 0 2 , P a C 0 2 and arterial
oxygen content (QoJ provides valuable
information about pulmonary function
and oxygen delivery to tissues. The
arterial oxygen tension and arterial
oxygen content are not equivalent. The
arterial oxygen tension (P a 0 2 ) is a
measure of the partial pressure of oxygen
in arterial blood determined by the
amount of oxygen dissolved in the blood
(not the amount bound to hemoglobin)
and the temperature of the blood - it is

not a direct measure of arterial oxygen
content. Arterial oxygen content is the
amount of oxygen per unit of blood and
includes both dissolved oxygen and that
bound to hemoglobin. The oxygen
tension can be viewed as the driving force
for diffusion of oxygen from capillaries
into mitochondria (in which the oxygen
tension is about 2 mmHg), whereas the
oxygen content is the amount of oxygen
delivered to tissue. Both are important
measures of pulmonary function and
oxygen delivery to tissue.

Measurement of oxygen tension in
blood is achieved by analysis of an
appropriately collected sample of arterial
blood using a blood gas analyzer (oxygen
electrode). Instruments designed for
medical or veterinary clinical use measure
pH, Po 2 and Pco 2 at a temperature of
37°C. Depending on the software included
with the instrument, various derived
values are also reported, including bicar-
bonate concentration, base excess and
oxygen saturation.lt is important to under-
stand that oxygen saturation reported by
blood gas instruments is a calculated value
and might not be correct. Oxygen satu-
ration is measured by a co-oximeter, which
is different from a blood gas machine, and
the amount of oxygen carried by
hemoglobin is then calculated from this
value and the assumption that each gram
of hemoglobin, when fully saturated,
carries approximately 1.34-1.39 mL of
oxygen. The total oxygen content of
blood is calculated by adding the amount
carried by hemoglobin to the amount of
oxygen dissolved in the aqueous phase of
the blood. The formula is:

0 2 content = (S„o 2 xl.34x [Hb]) +

(0.003 x P„o 2 ),

where 0 2 content is in mL/100 mL, S„o 2 is
the arterial oxygen saturation (%), 1.34 is
the amount of oxygen carried by fully
saturated hemoglobin (mL/g), [Hb] is the
concentration of hemoglobin in blood
(g/100 mL), 0.003 is the amount of oxygen
dissolved in the aqueous phase of 100 mL
of blood for each 1 mmHg increase in Po 2 ,
and P a O z is the oxygen tension in arterial
blood. The appropriate substitutions can
be made to calculate the oxygen content
of venous blood.

The oxygen content of arterial blood is
! the critical factor (with cardiac output) in
determining oxygen delivery to tissues.
However, measurement of arterial oxygen
content is not as readily accomplished as
measurement of arterial oxygen tension.
Therefore, in animals with normal hemo-
globin concentration and function the
arterial oxygen tension is used as a
surrogate measure of arterial oxygen
content. In doing so, it must be recognized
that the extent of hemoglobin saturation

with oxygen is dependent on both the
affinity of hemoglobin for oxygen and the
oxygen tension of the blood. The oxygen
tension/percentage saturation relationship
is sigmoidal, with 50% saturation occur-
ring at about 30 mmHg in most species
(there are minor variations) and 80%
saturation at a Po 2 of 45-55 mmHg. 94
The sigmoidal shape of the oxygen-
hemoglobin saturation curve has import-
ant clinical consequences. Small decrements
in P a 0 2 from normal values (usually
95-105 mmHg in animals breathing
ambient air at sea level) have a minimal
effect on oxygen content of blood. Many
modern blood gas analyzers have soft-
ware that calculates oxygen content of
blood, but it must be recognized that
these calculations often use an assumed,
not measured, hemoglobin concentration
(usually 15 g/dL) and values for the
human So 2 -Po 2 relationship. These
assumed values may not be correct for
animals and one should always check the
assumptions used to calculate oxygen
content of blood before accepting and
acting on those values. Direct measure-
ment of blood oxygen content is restricted
to research laboratories - indirect esti-
mates gained from oxygen saturation and
hemoglobin concentration are usually
sufficiently accurate for clinical use.

The oxygen tension in blood is pro-
portional to the amount of oxygen
dissolved in the aqueous phase of the
blood and the temperature of the blood.
For a given amount of oxygen dissolved in
blood, the tension varies according to the
temperature of the animal. Almost all
blood gas analyzers measure the Po 2 at
37°C. If the animal's body temperature is
markedly different from that then the
reported Po 2 can be erroneous. For
instance, the P a 0 2 of a horse with a body
temperature of 40°C measured using an
analyzer with a temperature of 37°C
would be 80 mmHg (the Pco 2 would be
35 mmHg). If the P a 0 2 was adjusted for
the difference between the horse's body
! temperature and that of the analyzer,
i then the reported P a 0 2 would be
| 100 mmHg (and the P a C 0 2 would be
I 44 mmHg). Failure to make the appro-
priate temperature corrections can result
in errors of 6-7% per °C. 95 When inter-
preting blood gas values, attention should
be paid to the temperature of the animal
and consideration given to adjusting gas
tension values according to the animal's
body temperature. This is probably only
clinically important when there are
extreme deviations from normal tempera-
ture and oxygen tension. Most blood gas
analyzers include software that makes the
appropriate corrections.

The arterial oxygen tension is deter-
mined in the alveolus by the alveolar

Special examination of the respiratory system

491

oxygen tension and the alveolar-arterial
difference. The alveolar oxygen tension
(PaOJ can be calculated from:

P A o 2 = F,0 2 (P b - Ph 2 o) - (PfioJRQ),

where Fp 2 is the inspired oxygen fraction
(21% for ambient air), P B is the barometric
pressure (760 mmHg at sea level), Ph 2 0 is
the partial pressure of water vapor in the
alveolar air (47 mmHgat37°C), and RQ is
the respiratory quotient (usually assumed
to be 0.8 for resting animals). The
alveolar-arterial Po 2 difference (A-a PO 2 )
is calculated:

A-a Po 2 = P A o 2 - P„o 2 .

The A-a Po 2 difference has clinical
significance in that it is an indicator of
pulmonary function that is somewhat
independent of inspired oxygen fraction
and is therefore useful in animals being
supplemented with oxygen (there is a
small increase in A-a difference with
marked increases in FjOj. Increases in
A-a Po 2 difference are indicative
of ventilation/perfusion mismatches,
with the A-a Po 2 difference increasing
with worsening ventilation/perfusion
abnormalities.

Normal values

Values obtained from clinically normal
animals breathing room air at sea level
vary slightly between species, with
most animals having an arterial P a 0 2
of 95-105 mmHg and a P a C0 2 of
35-45 mmHg. Oxygen saturation in
clinically normal animals breathing air at
sea level is above 98% and oxygen
content of arterial blood is 16-24 mL/dL
of blood (this depends on the hemo-
globin concentration in blood). The
difference in oxygen content of arterial
and mixed venous blood is usually
4-8 mL/dL of blood. Values can be
influenced substantially by changes in
physiological state (exercise, hyperpnea),
positioning, pulmonary disease and
altitude (Fable 10.4). Positioning of the
animal can be important, especially in
neonatal foals, in which the compliant
chest wall can impair ventilation in

laterally recumbent foals - foals have
lower arterial oxygen tension when in
lateral recumbency than when in sternal
recumbency. 96

Collection of arterial blood gas
samples

Arterial samples can be collected from
any of the appropriate peripheral arteries,
which vary depending on species. An
arterial sample is representative of aortic
blood in almost all instances. Samples can
be collected from the carotid, transverse
facial, metacarpal and metatarsal arteries
in horses and foals, and from the carotid,
radial and coccygeal arteries in cattle and
calves. Minimally invasive arterial access
is difficult in pigs.

Samples should be collected in glass or
plastic syringes in which the dead space
has been filled with heparin solution.
Typically, a 3 mL plastic syringe contain-
ing approximately 0.1 mL of sodium
heparin and attached to a 22-25-gauge
needle is used. All air should be expelled
from the syringe before collection of the
sample, and care should be taken to not
introduce air into the syringe until blood
gas tensions are measured. Air in the
syringe will increase the measured
oxygen tension of blood from normal
animals. The sample should be measured
as soon after collection as possible (within
minutes). If immediate analysis is not
available, the sample should be stored in
iced water until analysis to prevent
consumption of oxygen, production of
carbon dioxide and a decrease in pH.
Storage of arterial samples in plastic
syringes in iced water can increase the
oxygen tension from 100 mmHg to 109
mmHg in as little as 30 minutes. 97 This
does not occur when samples are stored
in glass syringes in iced water. The pH a
and P a C0 2 are not affected by the type of
syringe.

VENOUS BLOOD GAS ANALYSIS

Measurement of gas tensions in venous
blood is of limited value in assessing
pulmonary function because of the exten-
sive and variable effects of passage through

the capillary beds on gas tensions. How-
ever, measurement of venous oxygen
tension, saturation or content can be
useful in assessment of the adequacy of
oxygen delivery to tissue. The oxygen
tension, saturation and content of venous
blood depends on the extent of oxygenation
of arterial blood, the blood flow to the
tissues, the metabolic rate of the tissues
drained by the veins from which blood is
sampled, and the transit time of blood
through capillaries. The multiplicity of
these factors means that determining the
precise reasons for abnormalities in
venous blood gas tensions is not possible.
However, some generalizations can be
made about venous oxygen tension,
saturation and content.

In normal, resting animals, oxygen
delivery to tissues exceeds oxygen needs
(demand) of the tissue, with the result
that venous blood draining these tissues
is only partially desaturated. Hence,
venous blood from the pulmonary artery
(mixed venous blood) has oxygen ten-
sion, saturation and content of approxi-
mately 35-45 mmHg, 80-90% and
12-18 mL/100 mL (the latter depending
on hemoglobin concentration in addition
to hemoglobin saturation). However, in
situations in which oxygen delivery to
tissue is decreased to levels that only just
meet or do not meet the oxygen needs of
tissue, there is extraction of a greater
proportion of the oxygen in blood and
venous oxygen tension, saturation and
content decline and the arterial-venous
difference in oxygen content increases.
Reasons for oxygen delivery to tissue not
meeting the oxygen needs of that tissue
are decreased perfusion of tissue, such as
can occur with shock or circulatory failure,
anemia or decreased P a o 2 . Additionally,
tissues with a high metabolic rate, such as
exercising muscle, have high oxygen
demands that can outstrip delivery.

Ideally, whole body assessment of
oxygen delivery by measurement of venous
blood gas tensions is best achieved by
examination of mixed venous blood. Mixed
venous blood represents an admixture of
blood draining all tissues and is collected

; T'tM) pit

Arterial oxygen tension
(P a o 2 , mmHg)

Arterial carbon dioxide tension
(P a co 2 , mmHg)

i r u(0; fiffil InScsJ

Alveolar-arterial oxygen
difference (mmHg)

Physiological state or disease

t

i

<->

Hyperventilation (excitement, panting)

fjorl

i

Low inspired 0 2 (altitude)

i

T

<->

Hypoventilation

l

T

Diffusion impairment (rarely encountered)

i

0 or T

T

Ventilation/perfusion mismatch. T P a co 2 with
this disorder is uncommon

J-

t

T

Strenuous exercise by horses

T, above value in normal animal breathing ambient air at sea level; i, below value in normal animal breathing ambient air at sea level; <->, unchanged from value in
normal animal breathing ambient air at sea level

492

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

from the pulmonary artery (although
samples collected from the right ventricle
or atrium are also appropriate in most
instances). While this blood is optimal for
assessment of oxygen delivery to tissue,
collection of mixed venous samples is not
routine because of the need for catheter-
ization of the pulmonary artery. Samples
from peripheral veins are therefore used,
but care should be taken when interpreting
these values as venous blood gas tensions
can vary considerably among veins. 98 For
animals with normal circulatory status,
blood gas tensions in jugular vein blood
are likely to be reasonable estimates of
mixed venous gas tensions. However, if
circulatory function is not normal, then
samples from peripheral veins may not be
indicative of values in mixed venous blood.

Samples for venous blood gas analysis
should be collected into syringes in which
the dead space is filled with sodium or
lithium heparin solution. The volume of
heparin should not be more than 2% of
the amount of blood. Samples should be
processed promptly. If samples cannot
be processed within an hour they should
be stored in iced water. Samples stored in
iced water for 24 hours have values that
are minimally different from those before
storage, while samples stored at 25°C
change markedly in 2-3 hours. 99,100

PULSE OXIM ETRY

Pulse oximeters are devices for measure-
ment of blood oxygen saturation that
attach to skin or mucous membranes and
sense the absorption spectrum of light by
hemoglobin (the same principle is used in
bench top co-oximeters) in the under-
lying tissues. The devices are widely used
for noninvasive monitoring of oxygenation
in humans and have been adopted for use
in animals. However, important challenges
to their use exist in animals, not least of
which is the presence of hair and densely
pigmented skin in most farm animals. The
devices have important deficiencies when
used in foals and adult horses but those
applied to the ear, lip or tongue of foals
have good sensitivity and specificity
for detecting arterial So 2 of less than
90mmHg (12 kPa). 101,102 The devices
consistently underestimate arterial So 2 at
low saturations. 101,102 Care should be taken
when using these devices to monitor
arterial hemoglobin saturation in animals.

BLOOD LACTATE
CONCENTR ATION

Measurement of blood lactate concen-
tration is useful in assessing the adequacy
of oxygen delivery to tissues. Hypoxia
causes a shift to anaerobic metabolism
and the production of lactate. Lactate
production is related to the severity and

duration of hypoxia, with more severe
hypoxia resulting in greater accumulation
of lactate in tissues and its subsequent
diffusion or transport into blood. Hypoxia
also reduces the rate of removal of lactate
from blood. The combination of increased
production and decreased removal causes
lactate to accumulate in blood. Measure-
ment of blood lactate concentrations
(which are usually lower than plasma
lactate concentrations) is gaining increasing
clinical usefulness as 'point-of-care'
analyzers become more readily available
and testing more affordable.

Samples for measurement of blood
lactate can be collected into syringes
containing heparin solution (as used
for measurement of blood gas tensions) if
the sample is to be analyzed within
30 minutes. 103 Samples should be stored
in iced water until analysis. Prolonged
storage at room temperature results in
increases in blood lactate concentration. If
sample collection is anticipated to be
delayed, then samples should be collected
into evacuated tubes containing sodium
fluoride and potassium ethylenediamine
tetraacetic acid (EDTA) - the sodium
fluoride inhibits glycolysis. However,
plasma lactate concentrations collected in
these tubes are approximately 10% lower
than in samples collected into tubes
containing heparin - probably because of
the osmotic effect of sodium fluoride/
potassium EDTA on red cells. Samples for
clinical analysis should be collected into
syringes containing a heparin solution
and analyzed within 30 minutes of
collection. Measurement of blood or
plasma lactate concentrations can be
made using 'point-of-care' analyzers,
although these can yield results that differ
markedly from traditional analyzers,
especially in animals with extreme values
for hematocrit (severe anemia or poly-
cythemia). Ideally, blood and plasma
lactate concentrations should be measured
only on analyzers that have been validated
for the species and clinical situation being
studied. 104

Blood lactate and plasma lactate
concentrations are not equal, with blood
lactate concentration being lower because
of the dilutional effect of red blood cells,
which have a lower lactate concentration
than plasma. However, most clinical
assessments are based on blood lactate
concentrations. Mixed venous or arterial
blood lactate concentrations in most farm
animal species are less than 2 mmol/L in
normal, healthy animals. Tissue hypoxia,
in addition to other conditions such as
toxemia and septic shock, can increase
blood lactate concentration. Blood lactate
concentrations between 2 and 4 mmol/L
should be interpreted with caution
whereas values above 4 mmol/L are indi-

cative of clinically important disruption of
oxygen transport and cellular metabolism.
Repeated measurements over time can be
useful for assessing progression of disease
or efficacy of treatment. For instance,
plasma lactate concentrations above
4 mmol/L in cattle with pneumonia are
predictive of death within 24 hours. 105

COLLECTION AND ANALYSIS OF
EXHALED BREATH CONDENSATE

Collection and analysis of exhaled breath
condensate has use primarily in research
studies at the current time. Breath con-
densate is collected and analyzed for
markers of pulmonary or systemic
disease. Induction of pneumonia in calves
by infection with Pasteurella multocida
causes increases in concentration of
leukotriene B 4 in breath condensate. 106
Horses with heaves have higher concen-
trations of hydrogen peroxide than normal
horses - probably a result of the airway
neutrophilia in affected animals. 107

LUNG BIOPSY

Percutaneous biopsy of the lung is useful
in confirming diagnosis of lung disease by
providing tissue for histological and
microbiological examination. The pro-
cedure in cattle, sheep and horses is
described. 108-110 Indications for the pro-
cedure include the presence of diseases of
the lungs in which a diagnosis cannot be
arrived at through other forms of
examination, including tracheal aspiration
or bronchoalveolar lavage. It can also
be used for assessing the severity of
histological changes and response to
therapy. The procedure is best suited for
widespread diseases of the lung, but can
be used for diseases that produce focal
lesions if the biopsy is performed with
ultrasonographic guidance. Contra-
indications include abnormalities in
clotting function, pneumothorax and
severe respiratory distress. The danger in
performing lung biopsy in animals in
severe respiratory distress is that compli-
cations of biopsy, such as pneumothorax,
hemothorax or hemorrhage into airways,
could further impair lung function and
cause the death of the animal.

Complications include pneumothorax,
hemothorax, hemorrhage into airways
with subsequent hemoptysis or epistaxis,
pulmonary hematoma and dissemination
of infection from infected lung to the
pleural space. Pneumothorax, which is
usually not clinically apparent, occurs in
most horses in which the procedure is
performed. 108 Coughing and epistaxis
occur in about 20% and 10% of horses,
respectively. 108 Life-threatening hemor-
rhage occurs uncommonly (=2% of
cases). Bleeding into the airways, detected

Principles of treatment and control of respiratory tract disease

493

by tracheobronchoscopic examination,
occurred in 16 of 50 horses after use of the
manually discharged biopsy needle and
in five of 50 horses after use of the
automatically discharged needle. 108 Two
of 60 cows collapsed immediately after
the procedure, but subsequently stood
and recovered. 109 The remaining cows had
no clinical abnormalities detected after
biopsy, although necropsy examination
24 hours later revealed small lesions in
the pulmonary parenchyma at the site of
biopsy. 109 One of 10 healthy sheep had
coughing and bloody nasal discharge
after lung biopsy. 110

The procedure is performed in adult
horses and cattle using a 14-gauge biopsy
needle, either manually operated or one
that discharges automatically. Such
instruments yield tissue in over 95% of
attempts in cattle. 109 The area for exam-
ination is best determined by radiographic
or ultrasonographic examination of the
thorax. A common site for biopsy is at the
junction of the dorsal and middle thirds of
the thorax at the ninth intercostal space in
cattle and sheep 109,110 and the 13th
intercostal space in horses. The procedure
is best performed with the animal
standing. The skin over the area should be
clipped of hair and aseptically prepared and
local anesthesia induced by injection of 2%
lidocaine or a similar compound into the
intercostal space. A 0.5 cm incision is made
through the skin and the biopsy instrument
is advanced through the caudal intercostal
space (intercostal vessels and nerves course
along the caudal aspect of the ribs) and into
the lung perpendicular to the skin surface.
The instrument is advanced approximately
2 cm into the lung and tissue is collected at
the end of inspiration. The procedure is
repeated as necessary for collection of
samples for histological and microbiological
examination. The skin incision is closed
with a single suture if necessary. The animal
is then monitored closely for 12-24 hours
for signs of coughing, epistaxis, hemoptysis,
fever or respiratory distress. Hemorrhage
into the airways is usually evident, often
within minutes of completing the pro-
cedure, by the animal coughing. Hemor-
rhage into the airways is often evident as
hemoptysis, even in horses. Respiratory
distress can be caused by pneumothorax,
hemothorax or hemorrhage into airways.
Treatment includes percutaneous aspir-
ation of pleural air, administration of
oxygen by insufflation or, in extreme
instances, mechanical ventilation.

RESPIRATORY SOUND SPECTRUM
ANALYSIS

Analysis of respiratory sounds has utility
in the diagnosis of disorders of the upper
respiratory tract of horses. Respiratory

sounds can be detected by a small
microphone near the horse's nostril with
the recording made by a tape recorder or
similar device worn on the saddle or girth
strap. 111,112 Studies can be performed with
horses running on either a treadmill or
outside over ground. Dorsal displacement
of the soft palate produces broad-fre-
quency expiratory noises with rapid
periodicity (rattling), whereas dynamic
unilateral collapse of the arytenoid causes
an increase in inspiratory broad band
high-frequency noise. 111-113 The tech-
nique correctly identifies more than 90%
of horses with dynamic collapse of the left
arytenoid cartilage ('roarers'). 113

EXERCISE TESTING

Exercise testing for assessment of respir-
atory tract function is essentially limited
to horses. Such tests are usually conducted
on a treadmill, although some are amen-
able to use in the field. Tests available for
use on horses running on a treadmill
include endoscopic examination of the
upper airway, respiratory noise analysis,
blood gas analysis and measurement of
respiratory mechanics. The most import-
ant of these in a clinical setting is video-
endoscopy, during exercise on a treadmill,
to detect dysfunction of the upper airway
of horses. 114 Some disorders of the upper
respiratory tract, such as progressive
weakness of the laryngeal abductor
muscles, axial deviation of the aryepiglottic
fold and epiglottic retroversion, can only
be diagnosed by endoscopic examination
performed during strenuous exercise. 113
The interested reader is referred to texts
devoted to this topic. 116

Principles of treatment and
control of respiratory tract
disease

TREATMENT OF RESPIRATORY
DISEASE

Treatment of diseases of the lower
respiratory tract depends on the cause of
the disease. However, the common
principles are:

° Ensure adequate oxygenation of
blood and excretion of carbon dioxide
® Relieve pulmonary inflammation
° Effectively treat infectious causes of
respiratory disease
° Relieve bronchoconstriction
° Supportive care to minimize demands
for respiratory gas transport.

Respiratory gas transport

Cause of acute death in animals with
respiratory disease is usually failure of
transport of respiratory gases with sub-

sequent hypoxemia and hypercapnia.
Treatment of failure of oxygenation of
blood and excretion of carbon dioxide can
be achieved through administration of
supplemental oxygen or mechanical venti-
lation. The reasons for failure of respiratory
gas transport are discussed above, and
should be considered when therapy of an
animal with respiratory disease and
hypoxemia with or without hypercarbia is
planned. Animals with hypercarbia and
hypoxemia are probably hypoventilating
and consideration should be given to
increasing the animal's minute ventilation
through relief of airway obstruction (e.g. by
foreign bodies or bronchoconstriction),
improvement in function of the respiratory
muscles (restore hydration, maintain
normal blood concentrations of electro-
lytes, including calcium), and positional
adjustments (foals have better respiratory
function when in sternal recumbency 33 ).
Artificial ventilation should be considered,
but is impractical for long-term treatment
in animals other than those housed in
referral centers. Ventilation/perfusion
abnormalities cause hypoxemia with
normal to only slightly elevated P a Co 2 in
most affected animals. Oxygen therapy can
be useful in ameliorating or attenuating
the hypoxemia due to ventilation/perfusion
abnormalities.

OXYGEN THERAPY

The principal treatment for hypoxemia
caused by diseases of the lungs is the
administration of oxygen. Oxygen therapy
is not often used in large animals in field
situations but the use of a portable
oxygen cylinder may find a place in tiding
animals over a period of critical hypoxia
until inflammatory lesions of the lungs
subside. It has been used most often in
valuable calves and foals. 117 Oxygen
therapy must be given continuously,
requires constant or frequent attendance
on the animal, and can be expensive.
Supplemental oxygen is usually adminis-
tered through a nasal cannula with the tip
placed in the nasopharynx, through a
mask or through a cannula inserted
percutaneously in the trachea. The use of
an oxygen tent is impractical.

Oxygen therapy is useful only when
hypoxemia is attributable to failure of
oxygen transport in the respiratory system.
It is of no value when the hypoxia is due
to toxins that interfere with oxygen meta-
bolism in tissues (e.g. cyanide). Oxygen
therapy will only minimally increase
oxygen transport in animals with anemia,
abnormal hemoglobin (methemo-
globinemia) or cardiovascular shock
(stagnant hypoxia). Cases of pneumonia,
pleurisy, and edema and congestion of
the lungs are most likely to benefit from
provision of supplemental oxygen.

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

Oxygen is often administered to new-
born animals, either during resuscitation
after birth or in those animals with
respiratory disease. The value of supple-
mental oxygen in increasing P a o 2 has been
examined in foals, but the recommen-
dations probably apply to newborns of
other species as well. Both a facemask
and nasopharyngeal tube are effective
in increasing P a o 2 when oxygen is
administered at 10 L/min. 96 The ability to
elevate arterial oxygen increases with age
from birth to 7 days of age because of
the existence of right-to-left shunts in the
newborn foal. 96 Maximal changes in
arterial oxygen tension occur within
2 minutes of the start of supplementation.
In normal foals a flow rate of 4 L/min
increases arterial oxygen tension, but
responses in sick foals are often attenuated
as a result of positional effects on gas
exchange (recumbency) and other causes
of hypoventilation. Nasal insufflation
improves arterial oxygen tensions and
acid-base status in mild to moderately
affected foals but may not be sufficient for
oxygenation of foals with severe impair-
ment of gas exchange. Intranasal catheters
are also difficult to maintain in active
sucking foals and require the use of
higher oxygen flow rates to achieve
beneficial effects. Oxygen should be
delivered through a system that includes
a humidifier so the insufflated gas is
humidified and therefore drying of the
respiratory mucosa is minimized.

A transtracheal oxygen delivery
system has been used in foals with
pneumonia and rapidly progressive
dyspnea and hypoxemia despite intra-
nasal oxygen therapy. 117 A catheter is
inserted into the midcervical trachea and
directly distally in the tracheal lumen for
approximately 25 cm. The catheter is
attached to about 6 m of oxygen tubing
and suspended above the foal, allowing it
to move around the stall and suck the
mare for up to 6 days without dislodging
the catheter. This system was more effec-
tive than nasal insufflation in increasing
arterial oxygen tension, probably because
the catheter tip is in the distal trachea and
bypasses a significant length of dead
space that would not be oxygenated were
the oxygen delivered into the nasopharynx.

In foals with neonatal respiratory
distress, signs of respiratory failure may
be evident at birth or several hours after
birth. Tachypnea, shallow and paradoxic
respiration, an expiratory grunt with
accentuated abdominal effort, and cyanosis
are all common. Management of foals
with respiratory distress includes oxygen
therapy but, when the distress is severe,
oxygen insufflation alone is insufficient
to improve the P a o 2 , which is usually
45-60 mmHg (6.0-8. OkFh). The atelectasis

and alveolar hypoventilation worsen,
resulting in progressive hypoxemia and
respiratory acidosis, which requires
ventilatory assistance by the use of
continuous positive airway pressure.

In cattle and adult horses the nasal
tube must be inserted to the nasopharynx
because passage short of this causes
excessive waste of oxygen. The length of
tube inserted should equal the distance
from the nostril to a point one-third of the
way from the lateral canthus of the eye to
the base of the ear. Insertion of a nebulizer
in the system permits the simultaneous
administration of antibiotics and moisture
to prevent drying of the pharyngeal
mucosa. The volume of oxygen used
should be about 10-20 mL of oxygen per
min per kg of body weight. Repeated
measurement of arterial oxygen tension,
if available, is useful for determining the
flow rate. Arterial oxygen tension responds
to changes in the rate of administration of
oxygen within several minutes.

Oxygen toxicity is a risk in animals
breathing pure oxygen for periods exceed-
ing 1-2 days, but this rarely occurs in
veterinary medicine because supplemen-
tation with oxygen does not result in the
animal breathing pure oxygen (except for
animals under general anesthesia).

RESPIRATORY STIMULANTS

Use of respiratory stimulants, including
doxapram, picrotoxin, leptazol (Metrazol),
nikethamide (Coramine), caffeine and
amfetamine sulfate, which has been
advocated in the past, is not useful or
recommended in animals with hypoxemia
due to respiratory disease. In these animals
there is already maximal stimulation of
the respiratory center and administration
of drugs such as caffeine or doxapram is
at best useless and at worst harmful, in
that they can increase oxygen demand, in
particular myocardial oxygen demand,
thus exacerbating any oxygen deficit. The
drugs might be useful in stimulating
respiration in animals with pharmacological
depression of the respiratory center by
general anesthetics and sedatives.

MECHANICAL VENTILATION

Short-term mechanical ventilation can be
achieved in neonates and small adults by
use of a nasotracheal tube and a hand-
operated bellows, which is usually in the
form of a resilient bag equipped with a
one-way valve. The animal's trachea is
intubated and the bag is connected and
squeezed to supply a tidal volume of
approximately 5-10 mL/kgBW at a rate of
approximately 20 breaths per minute.
Commercial bags (Ambubag®) are avail-
able in a variety of sizes suitable for
neonates and small ruminants. There is a
simple device for respiratory resuscitation
of newborn calves and lambs consisting

of a mouthpiece, a nonreturn valve, a
flange and an oral tube. 118 Ventilation of
larger animals requires use of compressed
gases and appropriate valving systems,
including a Hudson demand valve. 119 In
an emergency situation, artificial venti-
lation of neonates and small ruminants
can be achieved by mouth-to-nose
ventilation by the veterinarian. This
should be done only with an awareness of
the risks of disease transmission (e.g. a
weak newborn calf could be infected by
Brucella sp. or Leptospira sp.).

Prolonged mechanical ventilation is an
activity requiring special equipment and
expertise. It is indicated for the treatment
of diseases of neonates, and perhaps
adults, 120 that cause hypoxemia and
hypercarbia. There is usually a significant
component of hypoventilation in these
diseases and this is a prime indication for
use of mechanical ventilation. An excellent
example is the use of mechanical venti-
lation to treat foals with botulism. 121 In
experienced hands, this technique is
effective. Because of the highly technical
and demanding requirements for mech-
anical ventilation, the interested reader is
referred to more detailed sources for
descriptions of the methodology. 122

ANTI-INFLAMMATORY THERAPY

Many infectious and noninfectious
diseases of the lower respiratory tract
have inflammation as a major component
of the tissue response to the initial insult.
Primarily inflammatory diseases include
heave and inflammatory airway disease
of horses. Inflammation is an important
component of pneumonia and some
of the allergic or toxic lung diseases.
Suppression of the inflammatory response
is indicated when the inflammatory
response is exacerbating clinical signs of
the disease through obliteration of alveoli
(inflammatory atelectasis), blockage of
airways by inflammatory exudates and
infiltration of bronchial walls, and broncho-
constriction as a consequence of inflam-
mation increasing airway reactivity.
Administration of anti-inflammatory
drugs is indicated as the definitive
therapy in noninfectious inflammatory
airway diseases (with control achieved by
environmental controls, see below). Care
must be taken that suppression of the
inflammatory response does not impair
innate and adaptive immune responses to
infectious agents.

Anti-inflammatory drugs used in the
treatment of diseases of the respiratory
tract include glucocorticoids and non-
steroidal anti-inflammatory drugs
(NSAIDs), with other agents such as
leukotriene antagonists, interferon and
cromolyn sodium used in particular
situations.

Principles of treatment and control of respiratory tract disease

Nonsteroidal anti-inflammatory
drugs are useful in the treatment of
infectious respiratory disease of cattle and
horses, and likely other species. The drugs
act by inhibiting the inflammatory
response induced by the infecting organism
and tissue necrosis. Meloxicam (0.5 mg/kg
subcutaneously, once), when administered
with tetracycline, improves weight gain
and reduces the size of lesions in lungs of
cattle with bovine respiratory disease
complex over those of animals treated
with tetracycline alone. 123 NSAIDs also
improve the clinical signs of cattle with
respiratory disease. 124 Use of these drugs
is routine in horses with pneumonia or
pleuritis.

Glucocorticoids are administered for
control of inflammation in a variety of
inflammatory lung diseases but notably
heaves of horses and interstitial pneumonia
of foals. Treatment can be administered
orally, by intravenous or intramuscular
injection, or by inhalation. Oral, intra-
muscular or intravenous administration
results in systemic effects of the agents.
Inhalation of glucocorticoids provides
therapy directed to the site of the disease
and minimizes, but does not always
prevent, the systemic effects of the
drugs. Drugs for inhalation are usually
human preparations of fluticasone,
beclomethasone and flunisolide that are
available as metered-dose inhalers. The
compounds are administered through a
mask adapted so that a large proportion
of the drug is inhaled. Anti-inflammatory
responses in the airways are pronounced
and result in marked improvement in
respirator)' function in horses with
heaves (see Heaves, Recurrent airway
obstruction).

IMMUNOMODULATORS

Interferon is used for the treatment of
inflammatory airway disease in race
horses and feedlot cattle with respiratory
disease. 125,126 A dose of 50-150IU of
interferon-alpha administered orally once
daily for 5 days reduced signs of airway
inflammation in young Standardbred
race horses. 127 Immune stimulation by
injection of a suspension of Propioni-
bacterium acne s has been investigated for
treatment of chronic inflammatory airway
disease in horses. The compound enhances
expression of interferon-gamma and NK-
lysin in peripheral blood mononuclear
cells, increases the proportion of CD4 +
cells in peripheral blood and increases
phagocytic activity of cells in peripheral
blood. 128,129 Similar changes were detected
in bronchoalveolar lavage fluid. 129 The
effect on respiratory disease has yet to be
definitively determined.

ANTIMICROBIAL THERAPY

Bacterial infections of the respiratory tract

of all species are treated with anti-
microbial agents given parenterally or, less
commonly, orally. Individual treatment is
usually necessary and the duration of
treatment will depend on the causative
agent and the severity when treatment
was begun. In outbreaks of infectious
respiratory disease the use of mass
medication of the feed and water supplies
may be advisable for the treatment of
subacute cases and for convalescent
therapy. The response to mass medication
will depend on the total amount of the
drug ingested by the animal and this is a
reflection of the appetite or thirst of the
animal, the palatability of the drug and its
concentration in the feed or water. The
choice of drug used will depend on its
cost, previous experience on similar cases
and the results of drug sensitivity tests if
available. The individual treatment of all
in -contact animals in an affected group
may be useful in controlling an outbreak
of respiratory disease such as shipping
fever in feedlot cattle.

Selection of antimicrobials is based
on the principles detailed in Chapter 4.
Briefly, antimicrobials for treatment of
bacterial respiratory disease should be
active against the causative agent, should
be able to achieve therapeutic concen-
trations in diseased lung and should be
convenient to administer. The anti-
microbials should be affordable and, if
used in animals intended as human food,
must be approved for use in such animals.

Antimicrobials for treatment of lung
disease are preferably those that achieve
therapeutic concentrations in diseased lung
tissue after administration of conventional
doses. This has been convincingly demon-
strated for the macrolide (azithromycin,
erythromycin, clarithromycin), 130 triamilide
(tulathromycin) 131,132 and fluoroquinolone
(danofloxacin, enrofloxacin) 133,134 anti-
microbials, and fluorfenicol 135 in a variety of
species. The beta-lactam antimicrobials
(penicillin, ceftiofur) are effective in
treatment of pneumonia in horses, pigs,
and ruminants despite having chemical
properties that do not favor their accumu-
lation in lung tissue.

Routes of administration include oral
(either individually or in medicated feed
or water), parenteral (subcutaneous, intra-
muscular, intravenous) or by inhalation.
Intratracheal administration of anti-
microbials to animals with respiratory
disease is not an effective means of
achieving therapeutic drug concentrations
in diseased tissue. Aerosolization and
inhalation of antimicrobials has the
theoretic advantage of targeting therapy
to the lungs and minimizing systemic
exposure to the drug. However, while
administration by inhalation achieves
good concentrations of drug in bronchial

lining fluid, it does not penetrate
unventilated regions of the lungs, in
which case parenteral or oral adminis-
tration of antimicrobials is indicated.
Aerosol administration of gentamicin to
horses and ceftiofur sodium to calves with
pneumonia has been investigated. Aerosol
administration of gentamicin to normal
horses results in gentamicin concen-
trations in bronchial lavage fluid 12 times
that achieved after intravenous adminis-
tration. 136 Aerosolized ceftiofur sodium
(1 mg/kg) is superior to intramuscular
administration in treatment of calves with
Pasteurella (Mannheimia) haemolyticaP 7

BRONCHODILATOR DRUGS

Bronchoconstriction is an important
component of the increased airway
resistance present in many animals with
disease of the lower respiratory tract.
Administration of bronchodilators can
relieve respiratory distress and improve
arterial blood oxygenation. Bronchodilatory
drugs are beta-2-agonists (clenbuterol,
albuterol/salbutamol, terbutaline), para-
sympatholytic drugs (ipratropium, atropine)
and methylxanthines (aminophylline,
theophylline).

The indication for the use of bron-
chodilators is relief of bronchoconstriction.
Bronchoconstriction is an important
component of the pathophysiology of
many diseases of the lungs and airways.
Bronchodilators are used extensively in
horses with heaves and inflammatory
airway disease, and less so in animals
with infectious diseases. Contra-
indications are few but caution should
be exercised when using these drugs in
animals that are severely hypoxemic as
the beta-2-agonists can transiently worsen
gas exchange by increasing perfusion of
nonventilated sections of the lung, and in
pregnant animals, in which the tocolytic
effect of the beta-2-agonists can delay
parturition. The use of beta-2-adrenergic
agonist bronchodilator drugs in food
animals is not permitted in most
countries because of the risk of contami-
nation of foodstuffs intended for
consumption by people. This is parti-
cularly the case with clenbuterol, a drug
approved in many countries for use in
horses that is administered to cattle
illicitly as a growth promoter. People can
be poisoned by clenbuterol in tissues of
treated cattle. 138

The beta-2-adrenergic agonists are

potent and effective bronchodilators that
can be administered orally, intravenously
or by inhalation. These drugs also
enhance mucociliary clearance of material
from the lungs. Most administration is
oral or by inhalation. Use of these drugs is
restricted to horses and the drugs are
discussed in the section on Heaves.

6

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

Parasympatholytic (anticholinergic)
drugs relieve vagally mediated broncho-
constriction. Again, their use is restricted
to horses. These drugs can cause tachy-
cardia and gastrointestinal dysfunction,
including ileus.

The methylxanthines are used in
horses and have been investigated for use
in cattle with respiratory disease. Their
use in horses is mainly of historical
interest because the availability of the
more efficacious beta-2-adrenergic agonists
and parasympatholytic drugs has super-
seded the use of methylxanthines. The
use of theophylline in feedlot cattle with
respiratory disease in field conditions is
associated with accumulation of toxic
concentrations in blood and an excessive
mortality rate. 139

MUCOLYTICS, MUCOKINETIC AND
ANTITUSSIVE DRUGS

Many groups of drugs are used in the
therapy of respiratory diseases with
the objective of improving mucokinesis
or effective mucociliary clearance . 140
Mucokinetic agents have been divided
into six groups according to their mode of
action.

° Diluents, surface acting agents and
mucolytics are supposed to reduce the
viscosity of the respiratory secretions
0 Bronchomucotropic agents, formerly
called expectorants, are supposed to
increase the production of a less
viscous mucus

° Other agents, such as beta-adrenergic
agonists and methylxanthine
derivatives, promote more effective
clearance of mucus and act as ciliary
augmentors or bronchodilators.

The aim of mucokinetic agents is to
decrease the viscosity of the respiratory
secretions but in some animals with
respiratory disease the excessive secre-
tions are of low viscosity and the use of a
mucolytic agent in such cases would
further decrease mucokinesis. There is
little or no evidence that administration of
mucolytic or mucokinetic agents, with the
possible exception of clenbuterol and
dembrexine, relieves signs of respiratory
disease or hastens recovery.

Inflammation of the lower respiratory
tract results in production of mucus and
immigration of inflammatory cells. This
accumulation of material is cleared by
rostral movement into the pharynx,
where it is discharged through the
nostrils or swallowed. Clearance is by the
mucociliary apparatus or coughing.
Mucolytics are agents that alter the
constituents of mucoid or purulent respir-
atory secretions and make them less
viscous. Bromhexine (Bisolvon: Boehringer
Ingelheim) is a popular mucolytic with

horse owners. It is said to reduce the
viscosity of airway mucus and increase
mucus production, although its clinical
efficacy has not been determined. It may
be of some value in cattle to increase
mucociliary clearance. Dembrexine
(Sputolosin: Boehringer Ingelheim) alters
the carbohydrate side chains of mucin
and improves its flow properties and is
reported to decrease coughing and hasten
recovery in horses with respiratory
disease. 141

Hyperhydration, the administration of
large quantities of fluids intravenously,
has been suggested as being useful in the
treatment of horses with accumulation of
excessive amounts of mucus or mucopus
in the lower airways. However, experi-
mental trials have demonstrated that this
approach is not effective in horses with
heaves. 142

Bronchomucotropic agents (expec-
torants) are administered with the
intention of augmenting the volume of
respiratory secretions by stimulating
the mucus-producing cells and glands.
Formerly called expectorants, they are
supposed to increase the production of a
less viscous mucus. These compounds
include the iodides, and ammonium and
glycerol guaiacolate, which are commonly
found in cough mixtures. These are com-
monly used in farm animals, especially
horses, although their efficacy is unknown.

Coughing is a common sign in animals
with respiratory disease, and it is an
important pulmonary defense mechan-
ism, allowing the expulsion of mucus and
foreign bodies. Antitussive (cough
suppressant) drugs are infrequently used
in large-animal medicine. These drugs
should only be used when definitive
therapy has been implemented for the
underlying disease. Control of the under-
lying disease will in almost all instances
resolve the coughing. It is not appropriate
to use antitussive agents (butorphanol,
codeine, diphenhydramine) to suppress a
cough when the underlying cause is
unknown or untreated.

SURFACTANT

Surfactant is critical to normal alveolar
function and a lack of this complex
phospholipid results in progressive
alveolar collapse. 143 Lack of surfactant is
an important cause of respiratory disease
in newborn animals, with those born
prematurely being at increased risk.
Attempts have been made to prevent acute
respiratory disease in premature newborn
foals, such as those delivered by cesarian
section because of maternal disease, but
the results have been disappointing. 144

SURGERY

Many conditions of the upper respiratory
tract of horses are amenable to surgical

correction. Tracheostomy is often used in
the emergency or urgent relief of acute
upper airway obstruction, and in the
removal of large amounts of tracheal
debris, such as occurs in animals with
smoke inhalation. Drainage of excessive
or infected pleural fluid can be therapeutic
in animals with pleuritis.

GENERAL NURSING CARE

Animals with respiratory disease should
have minimal or no enforced activity and
environmental stressors should be
minimized. One of the most important
aspects of the treatment of respiratory
tract disease in farm animals is the pro-
vision of a comfortable, well-ventilated
environment during and after the disease
episode. Affected animals should be
placed in a draft-free area that is ade-
quately ventilated and supplied with an
abundance of bedding for comfort and
warmth, particularly during convalescence.
Feed and water should be readily avail-
able and dusty feeds avoided.

CONTROL OF RESPIRATORY
DISEASE

Infectious diseases of the respiratory tract
of farm animals are caused by a combi-
nation of infectious agents and pre-
disposing causes such as inclement
weather, the stress of weaning or
transportation and poorly ventilated
housing, each of which can weaken the
defense mechanisms of the animal.
Prevention and control of these diseases
include:

0 Minimizing exposure to inciting
agents (infectious or physical)

° Maximizing innate resistance by
ensuring that the animals are in
excellent general health through
attention to nutrition, housing and
animal welfare

° Maximizing adaptive resistance by the
administration of effective vaccines
such that maximal resistance is
produced to coincide with the time of
greatest risk of the disease.

IMPORTANCE OF DIAGNOSIS

For some complex respiratory diseases of
food animals it is becoming increasingly
more difficult to obtain a definitive
etiological diagnosis because some of the
common diseases appear to be caused by
multiple infections rather than a single
one. Most of the infective agents that
cause respiratory disease are ubiquitous
in the environment and are present as
normal residents in the nasal cavities of
normal animals. This often creates diffi-
culty with the interpretation of the
microbiological findings in outbreaks of
respiratory disease because the infectious
agents can commonly be isolated from

Principles of treatment and control of respiratory tract disease

both sick and well animals. Thus there
may be no well-defined cause-and-effect
relationship and the predisposing causes
begin to assume major importance in any
control program.

MANAGEMENT TECHNIQUES

Most of the common respiratory diseases
occur at certain times under certain
conditions and successful control will
depend on the use of management
techniques before the disease is likely
to occur. For example, in beef cattle,
pneumonic pasteurellosis can be kept to a
minimum with the use of certain
management procedures that minimize
stress at weaning. The incidence of
pneumonia can be minimized in young
bulls destined for a performance testing
station if they are weaned well in advance
of movement to the test center. In North
America, bovine respiratory disease is
most common in feedlots where young
cattle from several different backgrounds
have been mingled after having been
transported long distances. Outbreaks of
equine respiratory disease occur in young
horses that are assembled at the racetrack
for training or at horse shows.

HOUSING FACILITIES

Cattle and pig barns that are over-
crowded, damp and cold during the cold
winter months and hot and stuffy during
the summer months can predispose to
a high incidence of pneumonia. The
morbidity and mortality from pneumonia
may be much higher when the ammonia
concentration of the air is high or if it is
dusty.

The incidence of pulmonary inflam-
mation and coughing (heaves) in horses
is much higher in those that are housed in
barns that are dusty and not ventilated
compared to horses kept outdoors. Bad
stabling management as a major cause of
coughing in horses was described almost
200 years ago but there is still a major
emphasis on the clinical management of
chronic coughing in housed horses using
a wide spectrum of antibiotics, expectorants
and other drugs. More consideration of
good housing and ventilation is necessary.

In pigs, enzootic pneumonia is wide-
spread but the effects of the pneumonia
can be maintained at an insignificant level
with adequate housing, ventilation and
nutrition. Too much emphasis has been
placed on the attempted eradication of
Mycoplasma spp., which is extremely diffi-
cult, and insufficient emphasis on build-
ing design and ventilation methods.

VACCINES

\&ccines are available for the immunization
of farm animals against some of the com-
mon infectious diseases of the respiratory
tract. Their advantages and disadvantages

are discussed under each specific disease.
The general principles underlying use of
vaccines for control of respiratory disease
are that:

~ The disease must be caused by a
disease that is infectious
There must be an effective vaccine
suitable for use in the species and age
group of animals at most risk of the
disease. Ideally, this will be known
from published, appropriately
designed trials testing the vaccine in a
group of animals identical to those in
which the vaccine will be used in
practice

> The vaccine must be administered to
animals in such a manner (route,
timing, frequency) as to optimize the
immunization (adaptive immunity)
o The timing of the vaccination

program should be such that maximal
resistance to the anticipated diseases
is achieved at the time of greatest risk
of the disease

■ Vaccination should be part of an on-
going program of disease control and
should not be regarded as a panacea
with which to rectify other
shortcomings in management of the
animals.

ENVIRONMENTAL CONTROL

In effect, the principles of control and
! prevention of airborne respiratory disease
are based largely on keeping the levels of
pathogens in the air at a low level. This
can be accomplished by a combination of
the following practices:

° The use of filtered-air positive
pressure ventilation systems
• The removal of affected animals from
the group

n Increasing the ventilation rate of the
building unit

° Subdivision of the unit into small
units, each with its own ventilation
system

° A continual disinfection system where
appropriate and practicable
° The provision of supplemental heat so
that during cold weather the
ventilation can be maintained and
animals will not huddle together to
keep warm and thereby increase the
exposure rate of infection
° The use of vaccines for specific
diseases of the respiratory tract
° Effective dust control.

REVIEW LITERATURE

Roudebush P Lung sounds. J Am Vet Med Assoc 1982;
181:122-126.

Kotlikoff MI, Gillespie JR. Lung sounds in veterinary
medicine. Part 1: Terminology and mechanisms of
sound production. Compend Contin Educ Pract
Vet 1983; 5:634-639.

Kotlikoff MI, Gillespie JR. Lung sounds in veterinary
medicine. Part 2: Deriving clinical information

from lung sounds. Compend Contin EdUc Pract
Vet 1983; 6:462-467.

Curtis RA et al. Lung sounds in cattle, horses, sheep,
and goats. Can Vet J 1986; 27:170-172.

| McGorum BC et al. Clinical examination of the
j respiratory tract. In: Radostits OM et al. (eds)

Veterinary Clinical Examination and Diagnosis
Philadelphia, PA: WB Saunders, 2000:299-348.

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Diseases of the lungs

PULMONARY CONGESTION AND
EDEM A

Pulmonary congestion is caused by an
increase in the amount of blood in the
lungs due to engorgement of the pul-
monary vascular bed. It is sometimes
followed by pulmonary edema when intra-
vascular fluid escapes into the parenchyma
and alveoli. The various stages of the
vascular disturbance are characterized by
respiratory compromise, the degree
depending upon the amount of alveolar
air space which is lost.

ETIOLOGY

Pulmonary congestion and edema is a
common terminal event in many diseases
but is frequently overshadowed by other
disturbances. Congestion that is clinically
apparent may be primary when the basic
lesion is in the lungs or secondary when it
is in some other organ, most commonly
the heart.

Pulmonary edema occurs because of
imbalances in the Starling forces across

the pulmonary capillary. From a clinical
perspective, the common proximate
causes of pulmonary edema are injury to
the endothelium of the pulmonary
capillary with subsequent leakage of
protein-rich fluid into the interstitial
spaces, elevated blood pressure in the
alveolar capillaries, or low plasma oncotic
pressure. Damage to pulmonary vascular
endothelium can occur in infectious
diseases (e.g. African horse sickness) or
intoxications (endotoxemia). Physical
injury, including inhalation of excessively
hot air or smoke, can damage the alveolar
epithelium with secondary damage to
capillary endothelium. Elevated pulmon-
ary capillary pressure occurs in left-sided
heart failure (ruptured chordae tendineae
of the mitral valve) and during strenuous
exercise by horses. Low plasma oncotic
pressure occurs in diseases causing
hypoproteinemia but is rarely a cause for
pulmonary edema by itself, although it
contributes to the pulmonary edema in
hypoproteinemic animals administered
large volumes of fluids intravenously.

Primary pulmonary congestion

° Early stages of most cases of
pneumonia

° Inhalation of smoke and fumes 1
° Anaphylactic reactions
° Hypostasis in recumbent animals
° Yew (Taxus sp.) intoxication 2
° Race horses with acute severe
exercise-induced pulmonary
hemorrhage . 3

Secondary pulmonary congestion

° Congestive heart failure (cardiogenic
pulmonary edema), including
ruptured chordae tendineae of the
mitral valve, and left-sided heart
failure.

Pulmonary edema

Pulmonary edema as a sequel to pulmon-
ary capillary hypertension or pulmonary
microvascular damage 4 occurs in:

° Acute anaphylaxis
° Acute pneumonia - Pasteurella

haemolytica produces several virulence
factors that induce direct or
leukocyte-mediated pulmonary
endothelial cell injury 4
° Gram-negative sepsis in ruminants
and pigs 4

o Congestive heart failure and acute
heart failure, e.g. the myocardial form
of enzootic muscular dystrophy in
inherited myocardiopathy of Hereford
calves; ruptured mitral valve or
chordae tendonae

° Inhalation of smoke or manure gas 1
° Transient upper airway obstruction in
the horse (negative pressure
pulmonary edema ) 5
° After general anesthesia in horses 6

Diseases of the lungs

c Yew ( Taxus sp.) intoxication 2
0 Exercise-induced pulmonary edema
in race horses 3

° Fumonisin intoxication in pigs 7
0 Specific diseases, including: mulberry
heart disease of swine; East Coast
fever in cattle; the pulmonary form of
African horse sickness; Hendra virus
infection of horses; poisoning with
organophosphates, alpha-naphthyl
thiourea (ANTU) or ionophore
antibiotics (monensin, salinomycin);
plant poisonings by oleander,
Hymenoxis spp. and Phenosciadium
spp.

0 Doxycycline intoxication of calves 8
0 Clostridium perfringens type D epsilon
toxin in calves and sheep 9-10
0 The Barker syndrome in young pigs
• Semen embolism. 11

PATHOGENESIS

In pulmonary congestion, ventilation is
reduced and oxygenation of the blood is
impaired. Oxygenation is reduced by the
decreased rate of blood flow through the
pulmonary vascular bed. Hypoxemic
anoxia develops and is the cause of most
of the clinical signs that appear.

Hypoxemia occurs in pulmonary
edema because of ventilation/perfusion
abnormalities, diffusion abnormalities
(although this is usually a minor contri-
butor to the hypoxemia), and hypo-
ventilation caused by the physical
obstruction of airflow by fluid and foam in
the airways. The edema is caused by
damage to the capillary walls by toxins or
anoxia or by transudation of fluid due to
increased hydrostatic pressure in the
capillaries. Filling of the alveoli, and in
severe cases the bronchi, effectively pre-
vents gaseous exchange.

Smoke inhalation in horses results in
decreased oxygen content of inspired air
and exposure of the respiratory tract
tissues to various noxious gases. 1 Follow-
ing smoke inhalation, diffuse tracheo-
bronchial mucosal sloughing occurs,
which, if progressive, causes separation of
the epithelium and development of
pseudomembranous casts, which may
cause partial or complete airway obstruc-
tion. Pulmonary edema is also extensive.

CLINICAL FINDINGS

All degrees of severity of pulmonary
congestion and edema occur commonly
in farm animals and only the most severe
form is described here. The depth of
respiration is increased to the point of
extreme dyspnea with the head extended,
the nostrils flared and mouth-breathing.
Breathing movements are greatly exag-
gerated and can be best described as
heaving; there is marked abdominal and
thoracic movement during inspiration
and expiration. A typical stance is usually

adopted, with the front legs spread wide
apart, the elbows abducted and the head
hung low. The respiratory rate is usually
increased especially if there is hyper-
thermia, which occurs in acute anaphylaxis
and after violent exercise as well as in the
early stages of pneumonia. The heart rate
is usually elevated (up to 100/min) and
the nasal mucosa is bright red or cyanotic
in terminal cases.

In acute pulmonary congestion there
are harsh breath sounds but no crackles
are present on auscultation.

When pulmonary edema develops,
loud breath sounds and crackles are
audible over the ventral aspects of
the lungs. In long-standing cases there
may be emphysema with crackles and
wheezes of the dorsal parts of the lungs,
especially if the lesion is caused by
anaphylaxis.

Coughing is usually present but the
cough is soft and moist and is not painful.
A slight to moderate serous nasal dis-
charge occurs in the early stage of con-
gestion but in severe pulmonary edema
this increases to a voluminous, frothy
nasal discharge, which is often pink-
colored due to blood.

The primary importance of pulmonary
congestion is as an indicator of early
pathological changes in the lung or heart.
Spontaneous recovery occurs quickly
unless there is damage to alveolar epi-
thelium, or myocardial asthenia develops.
Severe pulmonary edema has much greater
significance and usually indicates a stage
of irreversibility. Death in cases of pul-
monary edema is accompanied by asphyxial
respiratory failure.

Smoke inhalation in horses is charac-
terized by:

° Fblypnea and dyspnea
° Diffuse wheezes throughout the lungs

Coughing

° A bronchointerstitial pattern

radiographically

° The horse may expectorate large

proteinaceous tracheobronchial casts. 1

The prognosis is good if affected animals
can survive the initial stages of pulmonary
damage and secondary organ involvement.

CLINICAL PATHOLOGY

Laboratory examinations are of value only
in differentiating the causes of the
congestion or edema. Bacteriological
examination of nasal swabs and a complete
hematological examination, looking
particularlyfor the presence of eosinophilia,
are the standard examinations that are
carried out.

NECROPSY FINDINGS

In acute pulmonary congestion the lungs
are dark red in color. Excessive quantities
of venous blood exude from the cut

surface. Similar but less marked changes
occur in milder forms of congestion but
are only seen in those animals that die
from intercurrent disease. Histologically
the pulmonary capillaries are markedly
engorged and some transudation and
hemorrhage into alveoli is evident.

Macroscopic findings in pulmonary
edema include swelling and loss of
elasticity of the lungs, which pit on
pressure. They are usually paler than
normal. Excessive quantities of serous
fluid exude from the cut surface of the
lung. Histologically there are accumu-
lations of fluid in the alveoli and
parenchyma.

DIFFERENTIAL DIAGNOSIS

The diagnosis of pulmonary congestion
and edema is always difficult unless there
is a history of a precipitating cause such as
an infectious disease, strenuous exercise,
ingestion of toxicants, or inhalation of
smoke or fumes. Pneumonia usually
presents itself as an alternative diagnosis
and a decision cannot be based entirely on
the presence or absence of pyrexia. The
best indication is usually the presence of
toxemia but this again is not entirely
dependable. Bacterial pneumonia is usually
accompanied by some toxemia but cases
of viral pneumonia are often free of it.
Response to antibacterial treatment is one
of the best indications, the only variable
being the tendency for congestion and
edema of allergic origin to recover
spontaneously. In many instances there will
be doubt and it is then advisable to treat
the animal for both conditions.

TREATMENT

The principles of treatment of pulmonary
congestion and edema are one or more
of: reduction of pulmonary capillary
pressure (by reduction either of pulmon-
ary venous or pulmonary arterial pressure);
alleviation of pulmonary microvascular
damage; and correction of low plasma
oncotic pressure. The treatment of pul-
monary congestion and edema must first
be directed at correction of the primary
cause as listed under etiology. Affected
animals should be confined at rest in a
clean, dry environment and exercise
avoided.

Pulmonary capillary pressure can be

reduced in animals with left-sided heart
failure by reduction of cardiac preload,
improvement in cardiac pump function or
a combination of these factors. These
topics are dealt with in detail in Chapter
8. Briefly, preload can be reduced by
administration of furosemide and pump
function improved by administration of
drugs that improve myocardial function
(digoxin) or decrease afterload (arterial
vasodilators). The usual first step is the

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

administration of furosemide (1-2 mg/kg
intravenously).

Alleviation of pulmonary micro-
vascular damage is more difficult.
Administration of anti-inflammatory
drugs including NSAIDs or glucocorticoids
is indicated in animals in which micro-
vascular damage is suspected. These
drugs are used to treat, among other
diseases, smoke inhalation of horses. 1

Plasma oncotic pressure can be
increased by intravenous infusion of
plasma (10—40 mL/kg) or synthetic colloids
such as hetastarch. Administration of
crystalloid solutions should be judicious
and the amount of fluid administered
must be monitored carefully to ensure
that only sufficient fluids to meet the
needs of the animal are given.

Oxygen should be administered to
hypoxemic animals in conjunction with
other specific treatments.

Special diseases

When edema is due to organophosphate
poisoning prompt administration of
atropine may reduce fluid transudation.
In these cases the animal is in consider-
able danger and repeated injections may
be necessary. Details of the recommended
treatment regimen are given in the
section on treatment of poisoning by
organophosphorus compounds.

Epinephrine is recommended in
pulmonary edema due to anaphylaxis.
It will have an immediate pharmacological
effect, which may be followed by the use
of a corticosteroid to maintain vascular
integrity and to decrease permeability of
pulmonary vessels. Antihistamines are
commonly used in conjunction with
epinephrine for the treatment of acute
pulmonary edema due to anaphylaxis.
However, recent studies of experimental
anaphylaxis in cattle and horses have
shown that the antihistamines may be of
limited value because histamine and
serotonin arc of relatively limited signi-
ficance as mediating substances. On the
other hand, the kinins, prostaglandins
and slow-release substances may be more
important.

Studies in cattle have found that anti-
histamines and 5-hydroxytryptamine
(5-HT) antagonists failed to protect cattle
in experimental hypersensitivity. Sodium
meclofenamate has been more successful
in antagonizing experimental anaphylaxis
in cattle and horses. Acetylsalicylic acid
was more effective than antihistamines or
antiserotonin agents in providing symp-
tomatic relief in experimental acute
interstitial pneumonia of calves.

It is difficult, however, to extrapolate
the results of these studies in which the
drugs were usually given before or at the
same time as the experimental disease

was produced.There is a need for develop-
ment of more effective antianaphylactic
drugs for the treatment of acute anaphylaxis
in farm animals, which invariably results
in pulmonary edema and emphysema.
Thus epinephrine is the drug of choice for
the emergency treatment of pulmonary
edema due to anaphylaxis.

REFERENCES

1. KemperT et al. J Am Vet Med Assoc 1993; 202:91.

2. Cope RB et al.Vet Hum Toxicol 2004; 46:279.

3. Boden LA et al. EquineVet J 2005; 37:269.

4. BreiderMA.J Am Vet Med Assoc 1993; 203:300.

5. Kollias-Baker CA et al. J AmVet Med Assoc 1993;
202:1116.

6. Senior M. Vet Anesth Analg 2005; 32:193.

7. Gumprecht LA et al. Toxicology 2001; 160:71.

8. Yeruham I et al JVet Med B 2002; 49:406.

9. Uzal FA et al. J Comp Pathol 2002; 126:71.

10. Uzal F A et al. JVet Diagn Invest 2004; 16:403.

11. Dukes TW, Balachandran V. Can Vet J 1994;
35:709.

PULMONARY HYP ERTENSION

Pulmonary hypertension is an increase in
pulmonary arterial pressure above normal
values due to structural or functional
changes in the pulmonary vasculature.
Primary pulmonary hypertension occurs
in cattle with high-altitude disease.
Chronic pulmonary hypertension results
in right-side congestive heart failure
due to right ventricular hypertrophy or
cor pulmonale.

Causes

Hypoxemia is a potent stimulus of pul-
monary arterial pressure through increased
pulmonary vascular resistance induced by
pulmonary vasoconstriction. 1 Pulmonary
artery pressure can also increase in
response to increases in cardiac output
that are not matched by pulmonary
vasodilation - the most extreme example
of this being the large increase in
pulmonary artery pressure of strenuously
exercising horses. Alveolar hypoxia causes
constriction of the precapillary pulmonary
vessels, resulting in pulmonary hyper-
tension. Conditions which may induce
hypoxia include:

° Exposure to high altitude

Respiratory impairment secondary to
thoracic wall abnormalities
■ Airway obstruction
° Pneumonia
° Pulmonary edema
° Emphysema

° Pulmonary vascular disease
r > Heaves.

At high altitudes, the low inspired oxygen
tension causes hypoxic pulmonary vaso-
constriction and hypertension that are
common causes of cor pulmonale (brisket
disease) in cattle. Susceptible cattle can be
identified by measurement of pulmonary
artery pressure before clinical disease

develops. This test is used to select bulls
for use in high-altitude pastures. Cattle
grazing pastures that contain locoweed
have an increased incidence of brisket
disease but the pathogenesis is unknown.
Although uncommon, right-sided con-
gestive heart failure and pulmonary
hypertension can occur in cows at low
altitudes with primary lung disease. 1

Pulmonary hypertension occurs in
neonates and is a consequence of per-
sistent fetal circulation (see Ch. 8). This is
particularly a problem of cloned calves. 2

An outbreak of pulmonary hyper-
tension in a group of dairy calves
5-6 months of age has been described. 3
Some affected calves died suddenly.
Clinical findings included lethargy, anor-
exia, pale mucous membranes, tachypnea,
tachycardia, weakness, engorged jugular
veins and loss of body condition. 3 Right-
side cardiac catheterization revealed pul-
monary hypertension. Necropsy findings
revealed evidence of right-sided congestive
heart failure, and periarteritis and fibrosis
of the pulmonary and bronchial arteries.
Lesions were characterized by variable
stages of vasculitis; the airways were free
of pathological changes. Ingestion of
monocrotaline, a pyrrolizidine alkaloid,
can cause similar pulmonary vascular
lesions in rats but no evidence of such
ingestion was found in affected calves.

Pulmonary hypertension occurs second-
ary to left-sided heart disease in horses,
although the hypertension has been
mistakenly identified as the primary lesion. 4

REFERENCES

1. Angel KL, Tyler JW. JVet Intern Med 1992; 6:214.

2. Hill JR et al. Theriogenology 1999; 51:1451.

3. Pringle JK et al. J Am Vet Med Assoc 1991;

198:857.

4. Gelberg HH et al. J Am Vet Med Assoc 1991;

198:679.

ATELECTASIS

Atelectasis is collapse of the alveoli due to
failure of the alveoli to inflate or because
of compression of the alveoli. Atelectasis
is therefore classified as obstruction
(resorption), compression or contraction.
Obstruction atelectasis occurs secondary
to obstruction of the airways, with
subsequent resorption of alveolar gases
and collapse of the alveoli. This disease is
usually caused by obstruction of small
bronchioles by fluid and exudate. It is
common in animals with pneumonia or
aspiration of a foreign body. Compression
atelectasis occurs when intrathoracic
(intrapleural) pressure exceeds alveolar
pressure, thereby deflating alveoli. This
occurs when there is excessive pleural
fluid or the animal has a pneumothorax.
In large animals it also occurs in
the dependent lung or portions of lung
in recumbent animals. Compression

Diseases of the lungs

5G1

atelectasis is the explanation for the large
shunt fraction and hypoxemia that occurs
in anesthetized horses. 1 Compression
atelectasis and secondary broncho-
pneumonia can occur in horses kept in
flotation tanks for up to several weeks for
treatment of skeletal injuries. 2 Contraction
atelectasis occurs when there is com-
pression of parts of the lung by fibrotic
changes in the pleura. Patchy atelectasis
occurs in the absence of surfactant, such as
can occur in newborns. Failure of the lung
to inflate, or development of atelectasis of
the lungs of the newborn, usually those
bom prematurely, occurs because of lack of
pulmonary surfactant. The disorder can
progress to hyaline membrane disease.
Affected newborn animals are severely
dyspneic, hypoxemic, cyanotic, weak and
commonly die in a few hours.

The clinical signs of atelectasis are not
apparent until there is extensive involve-
ment of the lungs. Animals develop
respiratory distress, tachypnea, tachycardia
and cyanosis. Blood gas analysis reveals
hypoxemia, with or without hypercapnia.
Thoracic radiographs reveal pulmonary
consolidation. Ultrasonographic examin-
ation of the thorax demonstrates conso-
lidated lung.

Atelectasis is reversible if the primary
obstruction or compression is relieved
quickly before secondary consolidation
and fibrosis occur.

REFERENCES

1. Nyman G et al. Equine Vet J 1990; 22:317.

2. McClintock SA ct al. Equine Vet J 1986; 18:462.

ACUTE RESPIRATORY DISTRESS
SYNDROME

This is a well-recognized clinical syndrome
of humans characterized by acute onset of
hypoxemia and pulmonary infiltrates
without increases in left atrial pressure
(i.e. without evidence of cardiogenic pul-
monary edema). Precipitating causes
include both direct and indirect lung
injury, including sepsis, multiple trans-
fusions, trauma, near-drowning, smoke
inhalation, pancreatitis and more. The
underlying lesion is diffuse alveolar
capillary damage with secondary severe
pulmonary edema. The disease occurs
spontaneously in domestic animals 1 and,
although the spontaneous disease is not
extensively documented, the disease
produced experimentally as a model of
the human disease is better described. 2

Acute respiratory distress syndrome
(ARDS) in animals occurs in newborns and
in adult animals. The disease in some
newborn farm animals is related to lack of
surfactant but except for animals born
prematurely this is more the exception than
the rule. Most young animals and all adult
animals with ARDS have some inciting

acute lung injury that then progresses to
ARDS. 1,3,4 The causes can be infectious
(eg. influenza virus infection), physical
(smoke inhalation) or toxic (endotoxin).

The pathophysiology of the disease
involves a common final pathway that
results in damage to alveolar capillaries.
The initial injury can be to either the
endothelium of pulmonary capillaries or
to alveolar epithelium. Damage to these
structures leads to extravasation of
protein-rich fluid and fibrin with sub-
sequent deposition of hyaline membranes.
The capillary injury is attributed to
activated leukocytes (macrophages and
neutrophils) and cytokines. Accumulation
of hyaline membranes and ventilation/
perfusion mismatches impair respiratory
gas exchange and cause hypoxemia.

The clinical signs are characteristic of
acute, progressive pneumonia. Animals
are anxious, tachycardic, tachypneic and
have crackles and wheezes on thoracic
auscultation. Severely affected animals
can be cyanotic. Thoracic radiographs
reveal diffuse pulmonary infiltrates.
Hematologic changes are characteristic of
the inciting disease but usually include
leukopenia. There is arterial hypoxemia.

Treatment includes administration of
anti-inflammatory drugs (NSAIDs with
or without glucocorticoids), colloids,
antimicrobials and oxygen. The arterial
blood gas response to oxygen therapy is
often minimal in severely affected animals.
If it is available, mechanical ventilation
can be useful, although the prognosis is
grave. Inhalation of nitric o>«de is beneficial
in some humans with the disease, and
there are anecdotal reports that it has
been used to treat foals with ARDS.

REVIEW LITERATURE

Wilkins PA, Seahorn T. Acute respiratory distress
syndrome. Vet Clin North Am Equine Pract 2004;
20:253-273.

REFERENCES

1. Dunkel B et al. Equine Vet J 2005; 37:435.

2. Steinberg J et al. Shock 2005; 23:129.

3. Peek SF et al. JVet Intern Med 2004; 18:132.

4. Sharp MW et al. Vbt Rec 1993; 132:467.

PULMONARY HEMORRHAGE

Pulmonary hemorrhage is uncommon in
farm animals but does occur occasionally
in cattle, and exercise-induced pulmon-
ary hemorrhage (EIPH) occurs in
45-75% of exercised horses. Pulmonary
hemorrhage also occurs in horses with
pulmonary abscesses, tumors or foreign
bodies. Tracheobronchoscopic, radio-
graphic and ultrasonographic examin-
ations are useful in identifying the site
and cause of the hemorrhage.

Cattle

In cattle the most common cause is
erosion of pulmonary vessels adjacent to

lesions of embolic pneumonia associated
with vena caval thrombosis and hepatic
abscessation. The onset of hemorrhage
may be sudden and affected animals
hemorrhage profusely and die after a
short course of less than 1 hour. Marked
epistaxis and hemoptysis, severe dyspnea,
muscular weakness and pallor of the
mucous membranes are characteristic. In
other cases, episodes of epistaxis and
hemoptysis may occur over a period of
several days or a few weeks along with a
history of dyspnea.

EXERCISE-INDUCED PULMONARY
HEMORRHAGE OF HORSES (EIPH,
BLEEDERS)

Etiology Pulmonary hemorrhage during
exercise

Epidemiology Present in most (> 80%)
Thoroughbred and Standardbred
racehorses, although clinical signs are less
common. Occurs worldwide in any horse
that performs strenuous exercise. Rarely
causes death

Pathogenesis Probably associated with
rupture of pulmonary capillaries by the
high pulmonary vascular pressures
generated during exercise. There may be a
contributory role for inflammation and
obstruction of small airways, and tissue
damage caused by large and rapid changes
in intrathoracic pressure
Clinical signs Epistaxis is an uncommon
but very specific sign of EIPH in horses that
have just exercised. Affected horses may
cough or suddenly slow during a race.
Endoscopic examination of the trachea and
bronchi reveals blood
Clinical pathology Presence of
hemosiderin-laden macrophages in
tracheal aspirates or bronchial lavage fluid
Lesions Fibrosis and discoloration of the
caudodorsal regions of the lungs. Fibrosis,
accumulation of hemosiderin-laden
macrophages in interstitial tissue,
inflammation and bronchial artery
angiogenesis. Horses dying acutely have
blood-filled airways and heavy, wet lungs
Diagnostic confirmation
Demonstration of blood in the trachea or
bronchi by endoscopic examination, or
cytological examination of tracheal
aspirates or bronchoalveolar lavage fluid
Treatment None of demonstrated
efficacy. Furosemide is used as prophylaxis
Control There are no specific control
measures, however, prevention of
environmental and infectious respiratory
disease may reduce the incidence of the
disease

Etiology

EIPH occurs in horses during strenuous
exercise.

Epidemiology

EIPH is primarily a disease of horses,
although it has been reported in racing
camels. 1 EIPH occurs in horses worldwide

12

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

and there does not appear to be any
geographical distribution. It is a disorder
of horses that run at high speed, such as
Thoroughbred or Standardbred racehorses.
The disorder is uncommon in endurance
horses or draft breeds, although it does
occur in horses used for these activities.
As a general rule, the more intense the
exercise or the higher the speed attained,
the greater the proportion of horses
with EIPH.

The prevalence of EIPH varies with the
method used to detect it and the frequency
with which horses are examined, as
discussed later in this section. Epistaxis
associated with exercise is almost always
attributable to pulmonary hemorrhage
and occurs only in a small proportion of
racehorses. 2-5 Epistaxis occurs in only 3%
of horses that have blood detected in the
trachea by endoscopic examination per-
formed within 2 hours of racing. 5 The
prevalence of epistaxis in racehorses
varies between 0.1 and 9.0%, with the
frequency depending on the breed, age
and sex of horses selected for study, the
type of racing and the timing and
frequency of observation of horses after
racing. Epistaxis is more common in older
horses. 2,3 There are conflicting reports of a
sex predisposition, although epistaxis
may be more common in female
Thoroughbreds. 2,3 Epistaxis is more
common after races of less than 1600 m
than in longer races, 2 although not all
sources agree on this point. 3,6 However,
horses in steeplechase races, which are
typically longer than 2000 m, are at
greater risk of epistaxis than are horses
in flat races. 2,6 Epistaxis is relatively
uncommon and most horses with EIPH do
not have epistaxis.

There are a variety of other methods of
detecting EIPH, including endoscopic
examination of the airways and micro-
scopic examination of tracheal aspirates
or bronchoalveolar lavage fluid.

Almost all Thoroughbred racehorses in
active training have hemosiderophages in
bronchoalveolar lavage fluid, indicating
that all have some degree of EIPH.' The
prevalence of EIPH decreases when
diagnosis is based on endoscopic exam-
ination of horses after exercise or racing.

Exercise-induced pulmonary hemor-
rhage is very common in Thoroughbred
racehorses, with estimates of prevalence,
based on a single endoscopic examination
of the trachea and bronchi, of 43-75%. 6,8-10
The prevalence increases with the
frequency of examination, with over 80%
of horses having evidence of EIPH on at
least one occasion after examination after
each of three consecutive races. 11 The
prevalence of EIPH in Standardbred
racehorses is assumed to be lower, with
26-34% of horses reported to have blood

in the trachea after racing. 12,13 However,
these studies were based on a single
examination and one 12 only reported as
positive those horses with blood covering
more than one half the tracheobronchial
tree. When examined after each of three
races, 87% of Standardbred racehorses
have evidence of EIPH on at least one
occasion, 14 suggesting that EIPH is as
common in Standardbred racehorses as it
is in Thoroughbred racehorses.

Exercise-induced pulmonary hemor-
rhage occurs in approximately 62% of
racing Quarter horses, and has been
observed in Quarter horses used for
barrel racing. 13 The disorder occurs in
racing Appaloosa horses , 16 Approximately
11% of polo ponies are affected with
EIPH. 17 The disease occurs in draft horses
but is not well documented.

Age is considered a risk factor for
EIPH, with the prevalence of the disorder
being higher in older horses. 8-10 There
is no consistent association of sex
with prevalence of EIPH. 8-10,13 Among
Thoroughbred racehorses the prevalence
of EIPH increases with increasing
speed, 10,18 being greater in Thorough-
breds after racing than after breezing
(galloping). Lesions of EIPH are not
detected in young Thoroughbred race-
horses that have trained at speeds of less
than 7 m/s. 10,18

Pathogenesis

The cause of EIPH is rupture of alveolar
capillary membranes with subsequent
extravasation of blood into interstitial and
alveolar spaces. 19 The source of blood in
such instances is the pulmonary circu-
lation. Bleeding from bronchial circulation
during exercise has been suggested, based
on histological evidence of bronchial
angiogenesis in horses that have experi-
enced previous episodes of EIPH, 20 but
contribution of the bronchial circulation to
EIPH has not been demonstrated. Regard-
less of the contribution of bronchial circu-
lation to blood in the airways, the likely
initial lesion is in capillaries associated
with the pulmonary circulation. Hemor-
rhage into the interstitial space and
alveoli, with subsequent rostral move-
ment of blood in the airways, results in
blood in the trachea and bronchi.

Rupture of alveolar capillaries occurs
secondary to an exercise-induced increase
in transmural pressure (pressure differ-
ence between the inside of the capillary
and the alveolar lumen) . If the transmural
stress exceeds the tensile strength of the
capillary wall, the capillary ruptures. 19 The
proximate cause of alveolar capillary
rupture is the high transmural pressure
generated by positive intracapillary press-
ures, which are largely attributable to
capillary blood pressure, and the lower

intra- alveolar pressure generated by the
negative pleural pressures associated with
inspiration.

During exercise, the absolute magni-
tudes of both pulmonary capillary press-
ure and alveolar pressure increase, with a
consequent increase in transmural press-
ure. Strenuous exercise is associated with
marked increases in pulmonary artery
pressure in horses. 22-24 Values for mean
pulmonary arterial pressure at rest of
20-25 mmHg increase to more than
90 mmHg during intense exercise because
of the large cardiac output achieved by
exercising horses. The increases in pul-
monary artery pressure, combined with
an increase in left atrial pressure during
exercise, probably result in an increase in
pulmonary capillary pressure. Combined
with the increase in pulmonary capillary
pressure is a marked decrease (more
negative) in pleural, and therefore
alveolar, pressure during exercise. The
pleural pressure of normal horses during
inspiration decreases from approximately
-0.7 kPa (-5.3 mmHg) at rest to as low as
-8.5 kPa (64 mmHg) during strenuous
exercise. 23 Together, the increase in pul-
monary capillary pressure and decrease
(more negative) in intrapleural (alveolar)
pressure contribute to a marked increase
in stress in the alveolar wall. Although the
alveolar wall and pulmonary capillaries of
horses are stronger than those of other
species, rupture may occur because the
wall stress in the alveolus exceeds the
mechanical strength of the capillary 26

Other theories of the pathogenesis of
EIPH include: small-airway disease, upper
airway obstruction, hemostatic abnor-
malities, changes in blood viscosity and
erythrocyte shape, intrathoracic sheer
forces associated with gait, and bronchial
artery angiogenesis. 20,27 It is likely that the
pathogenesis of EIPH involves several
processes, including pulmonary hyper-
tension, lower alveolar pressure and
changes in lung structure, that summate
to induce stress failure of pulmonary
capillaries.

Obstruction of either the upper or lower
airways has been proposed as a cause of
EIPH. Inspiratory airway obstruction
results in more negative intrapleural, and
therefore alveolar, pressures. This effect is
exacerbated by exercise, with the result
that alveolar transmural pressure is
greater in horses with airway obstruc-
tion. 28,29 The higher transmural pressure
in such horses may increase the severity
of EIPH, although this has not been
demonstrated. Moreover, while inspiratory
airway obstruction may predispose to
EIPH, the prevalence of this condition is
much less than that of EIPH, indicating
that it is not the sole factor inducing EIPH
in most horses.

Diseases of the lungs

503

Horses with moderate to severe EIPH
have histological evidence of inflam-
mation of the small airways, 18 ' 30 and there
is a clear association between the
presence of EIPH and inflammatory
changes in bronchoalveolar or tracheal
aspirate fluid. 6 However, instillation of
autologous blood into the airways
induces a marked inflammatory response
in normal horses, 31 and it is therefore
unclear whether inflammation alone
induces or predisposes to EIPH or whether
the inflammation is a result of EIPH.
Theoretically, small- airway inflammation
and bronchoconstriction have the poten-
tial to produce intrathoracic airway
obstruction and, therefore, a more nega-
tive alveolar pressure. Given that small-
airway disease is common in horses, there
is the potential for an important effect of
factors, such as viral infections, air
pollution and allergic airway disease, to
contribute to the initiation or propagation
of EIPH.

The characteristic location of lesions of
EIPH in the caudodorsal lung fields has
led to the proposal that hemorrhage is a
result of tissue damage occurring when
waves of stress, generated by forelimb
foot strike, are focused and amplified into
the narrowing cross-sectional area of the
caudal lung lobes. 27 According to the theory,
the locomotor impact of the forelimbs
results in transmission of forces through
the scapula to the body wall, from where
they pass into the lungs and caudally and
dorsally. As the wave of pressure passes
into the narrower caudodorsal regions of
the lungs it generates progressively
greater shearing forces that disrupt tissue
and cause EIPH. However, studies of
intrapleural pressures have not demon-
strated the presence of a systemic press-
ure wave passing through the lung and do
not provide support for this hypothesis. 32

Horses with EIPH have been suspected
of having defects in either hemostasis or
fibrinolysis. However, while exercise
induces substantial changes in blood
coagulation and fibrinolysis, these is no
evidence that horses with EIPH have
defective coagulation or increased
fibrinolysis. 33,31

Regardless of the cause, rupture of
pulmonary capillaries and subsequent
hemorrhage into airways and interstitium
causes inflammation of both airways and
interstitium with subsequent develop-
ment of fibrosis and alteration of tissue
compliance. Heterogeneity of compliance
within the lungs, and particularly at the
junction of normal and diseased tissue,
results in the development of abnormal
shear stress with subsequent tissue
damage. These changes are exacerbated
by inflammation and obstruction of small
airways, with resulting uneven inflation of

the lungs. 35 Tire structural abnormalities,
combined with pulmonary hypertension
and the large intrathoracic forces associ-
ated with respiration during strenuous
exercise, cause repetitive damage at the
boundary of normal and diseased tissue
with further hemorrhage and inflam-
mation. The process, once started, is life-
long and continues for as long as the

horse continues to perform strenuous
20

exercise.

Clinical findings

Poor athletic performance or epistaxis are
the most common presenting complaints
for horses with EIPH. While poor per-
fonnance may be attributable to any of a
large number of causes, epistaxis associated
with exercise is almost always secondary to
EIPH.

Epistaxis due to EIPH occurs during or
shortly after exercise and is usually first
noticed at the end of a race, particularly
when the horse is returned to the
paddock or winner's circle and is allowed
to lower its head. It is usually bilateral and
resolves within hours of the end of the
race. Epistaxis may occur on more than
one occasion, especially when horses are
raced or exercised at high speed soon
after an initial episode.

Exercise-induced pulmonary hemorrhage
and performance

Failure of racehorses to perform to the
expected standard (poor performance) is
often, accurately or not, attributed to
EIPH. Many horses with poor perform-
ance have cytological evidence of EIPH
on microscopic examination of tracheo-
bronchial aspirates or bronchoalveolar
lavage fluid or have blood evident on endo-
scopic examination of the tracheobronchial
tree performed 30-90 minutes after stre-
nuous exercise or racing/' 31 ' However, it is
important to recognize that EIPH is very
common in racehorses and it should be
considered the cause of poor performance
only after other causes have been elimi-
nated. Severe EIPH undoubtedly results
in poor performance and, on rare occasions,
death of Thoroughbred racehorses. 37
Thoroughbred horses with EIPH racing in
Victoria, Australia have impaired
performance compared to unaffected
horses. Affected horses have a lower
likelihood of finishing in the first three
places, are less likely to be elite money
earners and finish further behind the
winner than do unaffected horses/

Results of studies in Standardbred
racehorses indicate either a lack of effect
of EIPH on performance or an association
between EIPH and superior performance.
There was no relationship between
presence of EIPH and finishing position
in 29 Standardbred racehorses with inter-
mittent EIPH examined on at least two

occasions, 14 nor in 92 Standardbred
racehorses examined on one occasion 13
However, of 965 Standardbred racehorses
examined after racing, those finishing first
or second were 1.4 times more likely (95%
confidence interval 0. 9-2.2) to have
evidence of EIPH on tracheobronchoscopic
examination than were horses that finished
in seventh or eighth position. 38

Physical examination

Apart from epistaxis in a small proportion
of affected horses, there are few abnor-
malities detectable on routine physical
examination of horses with EIPH. Rectal
temperature and heart and breathing
rates may be elevated as a consequence of
exercise in horses examined soon after
exercise, but values of these variables in
horses with EIPH at rest are not notice-
ably different from horses with no
evidence of EIPH. Affected horses may
swallow more frequently during recovery
from exercise than do unaffected horses,
probably as a result of blood in the larynx
and pharynx. Coughing is common in
horses recovering from strenuous exercise
and after recovery from exercise; horses
with EIPH are no more likely to cough
than are unaffected horses. Other clinical
signs related to respiratory abnormalities
are uncommon in horses with EIPH.
Respiratory distress is rare in horses with
EIPH and, when present, indicates severe
hemorrhage or other serious lung disease
such as pneumonia, pneumothorax or
rupture of a pulmonary abscess. Lung
sounds are abnormal in a small number
of EIPH- affected horses and when pre-
sent are characterized by increased
intensity of normal breath sounds during
rebreathing examination. Tracheal rales
may be present in horses with EIPH but
are also heard in unaffected horses.

Tracheobronchoscopy
Observation of blood in the trachea or
large bronchi of horses 30-120 minutes
after racing or strenuous exercise provides
a definitive diagnosis of EIPH. The
amount of blood in the large airways
varies from a few small specks on the
airway walls to a stream of blood
occupying the ventral one-third of the
trachea. Blood may also be present in the
larynx and nasopharynx. If there is a
strong suspicion of EIPH and blood is not
present on a single examination con-
ducted soon after exercise, the examin-
ation should be repeated in 60-90 minutes.
Some horses with EIPH do not have
blood present in the rostral airways
immediately after exercise, but do so
when examined 1-2 hours later. Blood is
detectable by tracheobronchoscopic
examination for 1-3 days in most horses,
with some horses having blood detectable
for up to 7 days.

504

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

Bronchoscopic examination can be
used to estimate the severity of EIPH
through the use of a grading system. 39,40
The interobserver repeatability of tracheo-
bronchoscopic assessment of severity of
EIPH using a 0-4 grading scale is
excellent: 40

0 Grade 0: No blood detected in the
pharynx, larynx, trachea or main stem
bronchi

0 Grade 1: Presence of one or more
flecks of blood or < 2 short (< quarter
the length of the trachea) narrow
(< 10% of the tracheal surface area)
streams of blood in the trachea or
main stem bronchi visible from the
tracheal bifurcation
° Grade 2: One long stream of blood
(> half the length of the trachea) or
> 2 short streams occupying less than
one- third of the tracheal
circumference

0 Grade 3: Multiple, distinct streams of
blood covering more than one-third
of the tracheal circumference. No
blood pooling at the thoracic inlet
° Grade 4. Multiple, coalescing streams
of blood covering > 90% of the
tracheal surface with pooling of blood
at the thoracic inlet.

It is assumed that a higher score repre-
sents more severe hemorrhage, but while
the repeatability of this scoring system
has been established, the relationship
between the amount of blood in the large
airways and the actual amount of
hemorrhage has not been established.

Radiography

Thoracic radiography is of limited use in
detecting horses with EIPH. Radiographs
may demonstrate the presence of
densities in the caudodorsal lung fields of
some horses but many affected horses
have minimal to undetectable radio-
graphic abnormalities. 41 Examination of
thoracic radiographs of horses with EIPH
may be useful in ruling out the presence
of another disease process, such as a
pulmonary abscess, contributing to the
horse's pulmonary hemorrhage or poor
athletic performance.

Prognosis

Horses that have experienced one
episode of epistaxis are more likely to
have a second episode. For this reason
most racing jurisdictions do not permit
horses with epistaxis to race for a period
of weeks to months after the initial
instance, with more prolonged enforced
rest after a subsequent episode of
epistaxis and retirement from racing after
a third bout. The recurrence rate after one
episode of epistaxis in Thoroughbred
horses is approximately 13.5% despite
affected horses not being permitted to

race for 1 month after the initial episode. 2
This high rate of recurrence suggests that
the inciting pulmonary lesions have not
healed.

Clinical pathology

Examination of airway secretions or
lavage fluid

The presence of red cells or macrophages
containing either effete red cells or the
breakdown products of hemoglobin
(hemosiderophages) in tracheal or
bronchoalveolar lavage fluid provides
evidence of EIPH. Detection of red cells or
hemosiderophages in tracheal aspirates
or bronchoalveolar lavage fluid is believed
to be both sensitive and specific in the
diagnosis of EIPH. 7 Examination of air-
way fluids indicates the presence of EIPH
in a greater proportion of horses than
does tracheobronchoscopic examination
after strenuous exercise or racing. The
greater sensitivity of examination of air-
way fluid is probably attributable to the
ability of this examination to detect the
presence of small amounts of blood or its
residual products and the longevity of
these products in the airways. While
endoscopic examination may detect
blood in occasional horses up to 7 days
after an episode of EIPH, cellular evidence
of pulmonary hemorrhage persists for
weeks after a single episode. 42 Red blood
cells and macrophages containing red
cells are present in bronchoalveolar
lavage fluid or tracheal aspirates for at
least 1 week after strenuous exercise or
instillation of autologous blood into air-
ways and hemosiderophages are present
for at least 21 days and possibly longer. 42

Recent studies have reported on the
use of red cell numbers in broncho-
alveolar lavage fluid as a quantitative
indicator of EIPH. However, this indicator
of EIPH severity has not been validated
nor demonstrated to be more reliable or
repeatable than tracheobronchoscopic
examination and visual scoring. Further-
more, considerable concern exists over
the suitability of red cell counts in broncho-
alveolar lavage fluid for assessment of
severity of EIPH given that an unknown
area, although presumably small, of the
lung is examined by lavage and that there
is a risk that this area of lung may not be
representative of the lung as a whole,
similar to the situation of examination of
bronchoalveolar lavage fluid of horses
with pneumonia. Bronchoalveolar lavage
of sections of both lungs, achieved using
an endoscope, may obviate some of these
concerns.

Tracheal aspirates may be obtained any
time after exercise by aspiration either
during tracheobronchoscopic examin-
ation or through a percutaneous intra-
tracheal needle. Aspirates obtained through

an endoscope may not be sterile, depend-
ing on the collection technique. Broncho-
alveolar lavage fluid can be obtained
through either an endoscope wedged in
the distal airway or a cuffed tube inserted
blindly into a distal airway. Collection of
fluid through an endoscope has the
advantage of permitting examination of
the distal airways and selection of the
area of lung to be lavaged. However, it
does require the use of an endoscope that
is longer (2 m) than those readily avail-
able in most equine practices. Use of
a commercial bronchoalveolar lavage
catheter does not require use of an endo-
scope and this procedure can be readily
performed in field situations.

DIFFERENTIAL DIAGNOSIS

Epistaxis and hemorrhage into airways can
occur as a result of a number of diseases
(Table 10.5).

Necropsy

Exercise-induced pulmonary hemorrhage
is a rare cause of death of racehorses, but
among race horses that die during racing
for reasons other than musculoskeletal
injuries, EIPH is common. 37 Necropsy
examination of horses is usually incidental
to examination for another cause of
death. Pertinent abnormalities in horses
with EIPH are restricted to the respiratory
tract. Grossly, horses examined within
hours of strenuous exercise, such as
horses examined because of catastrophic
musculoskeletal injuries incurred during
racing, may have severe petechiation in
the caudodorsal lung fields. Horses with
chronic disease have blue/gray or blue/
brown discoloration of the visceral pleural
surfaces of the caudodorsal lung fields
that is often sharply demarcated, especially
on the diaphragmatic surface. The dis-
coloration affects both lungs equally with
30-50% of the lung fields being dis-
I colored in severe cases. Affected areas do
not collapse to the same extent as
unaffected areas and, in the deflated lung,
have a spleen-like consistency. On cut
surface, the discolored areas of lung are
predominantly contiguous with the dorsal
pleural surface and extend ventrally into
the lung parenchyma. Areas of affected
lung may be separated by normal lung.
There is proliferation of bronchial vessels,
predominantly arteries and arterioles, in
affected areas. Histologically, affected areas
exhibit bronchiolitis, hemosiderophages in
the alveolar lumen and interstitial spaces,
and fibrosis of interlobular septa, pleural
and around vessels and bronchioles.

Treatment

Therapy of EIPH is usually a combination
of attempts to reduce the severity of

Diseases of the lungs

505

• • r,_.. /• •• :

• \v. -- - ••MVV'.V

1 ' * " * - ' ** ' ■**- ‘ '*•***

Disease

Epidemiology

Clinical signs and diagnosis

Treatment and control

Hemorrhage into trachea or bronchi, sometimes with epistaxis

Exercise-induced pulmonary

Horses after strenuous exercise.

Epistaxis is a rare but very specific sign

Efficacy of various drugs used for

hemorrhage (EIPH)

Most common in Thoroughbred

of EIPH. Only occurs after exercise.

treatment and control is debated.

and Standardbred racehorses

Endoscopic examination of the airways

Furosemide is used extensively'

is diagnostic

before racing

Trauma

Sporadic. Associated with trauma

Physical examination reveals site and

Symptomatic treatment

to head, neck, or chest

nature of the trauma. Can require
endoscopic examination of upper airways

Pneumonia

Recent shipping or respiratory

Fever, tachypnea, abnormal lung sounds,

Antimicrobials, NSAIDs, oxygen.

disease. Can occur as outbreaks

leukocytosis, radiography demonstrates

Control by vaccination and

though usually individual animals

lung lesions. Cytological and microbiological
examination of tracheal aspirate

prevention of respiratory disease

Lung abscess

Sporadic. Hemorrhage can occur

Sometimes no premonitory signs. Fever,

Antibiotics

after exercise

depression, anorexia, cough. Hemogram
demonstrates leukocytosis.
Hyperfibrinogenemia. Ultrasonography or
radiography demonstrates lesion. Tracheal
aspirates

Intrabronchial foreign body

Sporadic

Cough, hemoptysis, fever. Endoscopy or

Removal of foreign body - often

radiography reveals foreign body

not readily achieved

Pulmonary neoplasia

Sporadic. Often older horse, but

Cough, hemoptysis. Demonstrate mass on

None

not always. Hemangiosarcoma

ultrasonographic or radiographic examination

Epistaxis (in addition to the above diseases)

Guttural pouch mycosis

Sporadic. Acute onset epistaxis

Severe, life-threatening epistaxis. Tachycardia,

Surgical ligation or occlusion of

anemia, hemorrhagic shock

arteries in the guttural pouch

Ethmoidal hematoma

Sporadic

Epistaxis not associated with exercise.

Surgery or injection of mass

Usually unilateral

with formaldehyde

Thrombocytopenia

Sporadic

Epistaxis, mild, intermittent. Petechiation and
ecchymotic hemorrhages. Thrombocytopenia

Glucocorticoids

Neoplasia

Sporadic

Neoplasia of upper airways

None

Trauma

Sporadic

Injury to head or pharynx

Symptomatic

Sinusitis

Sporadic

Endoscopic or radiographic examination
of sinus

Drainage. Antimicrobials

subsequent hemorrhage and efforts to
minimize the effect of recent hemorrhage.
Treatment of EIPH is problematic for a
number of reasons. Firstly, the pathogenesis
of EIPH has not been determined although
the available evidence supports a role for
stress failure of pulmonary capillaries
secondary to exercise-induced pulmonary
hypertension. Secondly, there is a lack of
information using large numbers of horses
under field conditions that demonstrates an
effect of any medication or management
practice (with the exception of bedding) on
EIPH. There are numerous studies of small
numbers of horses (< 40) under experi-
mental conditions but these studies often
lacked the statistical power to detect
treatment effects and, furthermore, the
relevance of studies conducted on a tread-
mill to horses racing competitively is
questionable. Treatments for EIPH are
usually intended to address a specific aspect
of the pathogenesis of the disease and
will be discussed in that context.

Prevention of stress failure of the
pulmonary capillaries
There is interest in reducing the pressure
difference across the pulmonary capillary
membrane in an effort to reduce EIPH.
Theoretically, this can be achieved by
reducing the pressure within the capillary

or increasing (making less negative) the
pressure within the intrathoracic airways
and alveolus.

Reducing pulmonary capillary pressure
Furosemide administration as prophylaxis
of EIPH is permitted in a number of
racing jurisdictions worldwide, most
notably Canada, the USA, Mexico and
most of the South American countries.
Within the USA and Canada, almost all
Thoroughbred, Standardbred and Quarter
horse racing jurisdictions permit adminis-
tration of furosemide before racing.

The efficacy of furosemide in treat-
ment of EIPH is uncertain. While field
studies of large numbers of horses do not
demonstrate an effect of furosemide on
the prevalence of EIPH, 43 studies of
Thoroughbred horses running on a tread-
mill provide evidence that furosemide
reduces the severity of EIPH. 44 Under
field conditions, based on tracheo-
bronchoscopic evaluation of the severity
of bleeding, furosemide has been reported
to reduce or have no influence on the
severity of bleeding. 43,45 This apparent
inconsistency may be attributable to
measurement of red blood cell counts in
bronchoalveolar lavage fluid of horses
that have run on a treadmill not being
representative of effects of furosemide

under field conditions. The weight of
evidence, albeit unconvincing, from field
studies does not support a role for
furosemide in preventing or reducing the
severity of EIPH.

The mechanism by which furosemide
may reduce the severity of EIPH is
unknown, although it is speculated that
furosemide, by attenuating the exercise -
induced increase in pulmonary artery and
pulmonary capillary pressure of horses,
reduces the frequency or severity of
pulmonary capillary rupture.

Furosemide is associated with superior
performance in both Thoroughbred and
Standardbred racehorses, 46,47 which
further complicates assessment of its
efficacy in treating EIPH.

An increase in pulmonary capillary
pressure secondary to altered rheostatic
properties of blood during exercise has
been suggested as a possible contributing
factor for EIPH. 48

Increasing alveolar inspiratory pressure
Airway obstruction, either intrathoracic or
extrathoracic, increases airway resistance
and results in a more negative intra-
thoracic (pleural) pressure during inspir-
ation to maintain tidal volume and alveolar
ventilation. Causes of extrathoracic airway
obstruction include laryngeal hemiplegia

506

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

and other abnormalities of the upper
airway, whereas intrathoracic obstruction
is usually a result of bronchoconstriction
and inflammatory airway disease. Horses
with partial extrathoracic inspiratory
obstruction or bronchoconstriction and
airway inflammation associated with
recurrent airway obstructive disease
(heaves) have pleural (and hence alveolar)
pressures that are lower (more negative)
than those in unaffected horses or in
horses after effective treatment.

Partial inspiratory obstruction, such as
produced by laryngeal hemiplegia,
exacerbates the exercise-induced decrease
in intrapleural pressures with a con-
sequent increase in transmural capillary
pressures . 28-29 These changes may
exacerbate the severity of EIPH although
an association between upper airway
obstructive disease and EIPH has not
been demonstrated. Surgical correction of
airway obstruction is expected to resolve
the more negative intrapleural pressure,
but its effect on EIPH is unknown.

Recently, the role of the nares in
contributing to upper airway resistance,
and hence lowering inspiratory intra-
pleural pressure during intense exercise,
has attracted the attention of some
investigators. Application of nasal dilator
bands (Flair® strips) reduces nasal resist-
ance by dilating the nasal valve and
reduces red cell count of bronchoalveolar
lavage fluid collected from horses after
intense exercise on a treadmill . 44 Further-
more, application of the nasal dilator
strips to horses in simulated races reduces
red cell count in bronchoalveolar lavage
fluid of some, but not all, horses . 49

The role of small-airway inflammation
and bronchoconstriction in the patho-
genesis of EIPH is unclear. However,
horses with EIPH are often treated with
drugs intended to decrease lower airway
inflammation and relieve broncho-
constriction. Beta-adrenergic broncho-
dilatory drugs such as clenbuterol and
albuterol (salbutamol) are effective in
inducing bronchodilation in horses with
bronchoconstriction, but their efficacy in
preventing EIPH is either unknown or, in
very small studies, is not evident. Corti-
costeroids, including dexamethasone,
fluticasone and beclomethasone adminis-
tered bv inhalation, parenterally or
enterally reduce airway inflammation and
obstruction but have no demonstrated
efficacy in preventing EIPH. Cromolyn
sodium (sodium cromoglycate) has no
efficacy in preventing EIPH.

Water vapor treatment (inhalation of
water-saturated air) has been proposed as
a treatment for EIPH because of its
putative effect on small-airway disease.
However, water vapor treatment has no
effect on EIPH.

The use of bedding of low allergenic
potential (shredded paper) to prevent
EIPH has no apparent effect on prevalence
of the condition . 50 While it is suggested
that preventing or minimizing small-
airway disease may reduce the severity of
EIPH, studies to demonstrate such an
effect have not been reported. However,
optimizing the air quality in barns and
stables and preventing infectious respir-
atory disease appear sensible precautions.

Interstitial inflammation and bronchial
angiogenesis

Hemorrhage into interstitial tissues
induces inflammation with subsequent
development of fibrosis and bronchial
artery angiogenesis . 30,42 The role of these
changes in perpetuating EIPH in horses is
unclear but is probably of some import-
ance. Treatments to reduce inflammation
and promote healing with minimal
fibrosis have been proposed. Rest is an
obvious recommendation and many
racing jurisdictions have rules regarding
enforced rest for horses with epistaxis.
While the recommendation for rest is
intuitive, there is no information that rest
reduces the severity or incidence of EIPH
in horses with prior evidence of this
disorder.

Similarly, corticosteroids are often
administered, either by inhalation,
enterally or parenterally, in an attempt to
reduce pulmonary inflammation and
minimize fibrosis. Again, the efficacy of this
intervention in preventing or minimizing
severity of EIPH has not been documented.

Excessive bleeding
Coagulopathy and fibrinolysis
Exercise induces substantial changes in
blood coagulation and fibrinolysis. How-
ever, there is no evidence that horses with
EIPH have defective coagulation or
increased fibrinolysis 33,34 Regardless,
aminocaproic acid, a potent inhibitor of
fibrin degradation, has been administered
to horses to prevent EIPH. The efficacy of
aminocaproic acid in preventing EIPH
has not been demonstrated. Similarly,
estrogens are given to horses with the
expectation of improving hemostasis,
although the effect of estrogens on
coagulation in any species is unclear.
There is no evidence that estrogens
prevent EIPH in horses.

Vitamin K is administered to horses
with EIPH, presumably in the expectation
that it will decrease coagulation times.
However, as EIPH is not associated with
prolonged bleeding times, it is unlikely
that this intervention will affect the
prevalence or severity of EIPH.

Platelet function

Aspirin inhibits platelet aggregation in
horses and increases bleeding time.

Seemingly paradoxically, aspirin is some-
times administered to horses with EIPH
because of concerns that increased platelet
aggregation contributes to EIPH. There is
no evidence that aspirin either exacerbates
or prevents EIPH.

Capillary integrity

Capillary fragility increases the risk of
hemorrhage in many species. Various
bioflavonoids have been suggested to
increase capillary integrity and prevent
bleeding. However, hesperidin and citrus
bioflavonoids have no efficacy in pre-
vention of EIPH in horses. Similarly,
vitamin C is administered to horses with
EIPH without scientific evidence of any
beneficial effect.

Summary of treatment options
Selection of therapy for horses with EIPH
is problematic. Given that most horses
have some degree of pulmonary hemor-
rhage during most bouts of intense
exercise, the decision must be made not
only as to the type of treatment and its
timing but also which horses to treat.
Moreover, the apparently progressive
nature of the disease with continued work
highlights the importance of early and
effective prophylaxis and emphasizes the
need for studies of factors such as air
quality and respiratory infections in
inciting the disorder.

The currently favored treatment for
EIPH is administration of furosemide
before intense exercise. Its use is per-
mitted in racehorses in a number of
countries. Increasingly persuasive labor-
atory evidence of an effect of furosemide
in reducing red cell count in broncho-
alveolar lavage fluid collected from horses
soon after intense exercise supports the
contention that furosemide is effective in
reducing the severity of EIPH in race
horses. However, it should be borne in
mind that neither the relationship
between severity of EIPH and red cell
count in bronchoalveolar lavage fluid nor
the efficacy of furosemide in reducing
severity of EIPH in race horses in the field
has been demonstrated. In fact, there is
evidence that furosemide does not reduce
the prevalence of EIPH and other
evidence that it does not reduce the
severity of EIPH under field conditions.
The association between furosemide
administration and superior performance
in Standardbred and Thoroughbred
racehorses should be borne in mind when
recommending use of this drug.

Prevention and control

There are no documented preventive
strategies. Rest is an obvious recommen-
dation for horses with EIPH, but the
hemorrhage is likely to recur when
the horse is next strenuously exercised.

Diseases of the lungs

507

The duration of rest and the optimal
exercise program to return horses to
racing after EIPH is unknown, although
some jurisdictions require exercise no
more intense than trotting for 2 months.
Firm recommendations cannot be made
on duration of rest because of a lack of
objective information.

Although aroleforlower airway disease
(either infectious or allergic) in the
genesis of EIPH has not been demon-
strated, control of infectious diseases and
minimization of noninfectious lower
airway inflammation appears prudent.

Concern about the role of impact waves
in the genesis of EIPH has led to discussion
of low-stress' training protocols, but these
have not been adequately evaluated.

REFERENCES

1. Akbar SJ et al. Vet Rec 1994; 135:624.

2. Takahashi T et al. J Am Vet Med Assoc 2001; 218
1462.

3. Weideman H et al. J S AfrVet Assoc 2003; 74:127.

4. Williams R et al. Equine Vet J 2001; 33:478.

5. Hinchcliff KW et al. J Am Vet Med Assoc 2005;
227:768.

6. Newton JR, Wood JLN. Equine Vet J Suppl 2002;
34:417.

7. McKane SA et al. AustVet J 1993; 70:401.

8. Mason DK et al. In: Snow DH, Fbrsson SGB, Rose
RJ, eds. Equine exercise physiology. Cambridge:
Granta, 1983:57.

9. Riscoe J et al. Am J Vet Res 1981; 42:703.

10. Raphel CF, Soma LR. Am J Vet Res 1982;
43:11237.

11. Sweeney CR et al. Am J Vet Res 1990; 51:772.

12. MacNamara B et al. J Am Vet Med Assoc 1990;
196:443.

13. Speirs VC et al. Aust\fet J 1982; 59:38.

14. Lapointe JM et al. Equine Vet J 1994; 26:482.

15. Hillidge Q et al. J Equine Vet Sci 1984; 4.

16. Hillidge CJ et al. J EquincVet Sci 1986; 5:351.

17. Voynick BT, Sweeney CR. J Am Vet Med Assoc
1986; 188:301.

18. Oikawa M. J Comp Pathol 1999; 121:339.

19. West JB et al. J Appl Physiol 1993; 75:1097.

20. Riscoe JR. Proc Am Assoc Equine Pract 1996;
42:220.

21. West JB, Mathicu-Costello O. Equine Vet J 1994;
26:441.

22. Birks EK et al. J Appl Physiol 1997; 82:1584.

23. Langsetmo I et al. Equine Vet J 2000; 37:379.

24. Manohar M et al. BrVet J 1993; 149:419.

25. ArtT et al. Rcspir Physiol 1990; 82:279.

26. Birks EK et al. Respir Physiol 1994; 97:235.

27. Schroter RC et al. Equine Vet J 1998; 30:186.

28. Hackett RP et al. Am J Vet Res 1999; 60:485.

29. Ducharme NG et al. Equine Vet J Suppl 1999;
30:27.

30. O'Callaghan MW et al. Equine Vet J 1987; 19:411.

31. McKane SA, Slocombe RF. EquincVet J Suppl
2002; 34:451.

32. Jones JH et al. EquincVet J Suppl 2002; 34:391.

33. Bayly WM et al, In: Snow DH, Persson SGB, Rose
RJ, eds. Equine exercise physiology. Cambridge:
Granta, 1983:64.

34. Johnstone IB et al. Can JVet Res 1991; 55:101.

35. Robinson NE, Derksen FJ. Proc Am Assoc Equine
Pract 1980; 26:421.

36. Martin BB. Jr et al. J Am Vet Med Assoc 1999;
214:673.

37. Boden LA et al. EquincVet J 2005; 37:269.

38. Rohrbach BW. J Am Vet Med Assoc 1990;
196:1563.

39. Pascoe JR et al. Am JVet Res 1981; 42:703.

40. Hinchcliff KW et al. Am JVet Res 2005; 66:596.

41. Pascoe JR et al.Vet Rad 1983; 24:85.

42. McKane S, Slocombe R. Equine Vet J 1999; 30:126.

43. Birks EK et al. Equine Vet J Suppl 2002; 34:375.

44. Geor RJ et al. Equine Vet J 2001; 33:577.

45. Pascoe JR et al. Am JVet Res 1985; 46:2000.

46. Gross DK et al. J Am Vet Med Assoc 1999; 215:670.

47. Soma LR et al. Equine Vet J 2000. 32:334.

48. Fedde MR, Erickson HH. Equine Vet J 1998;
30:329.

49. \faldez S et al. J Am Vet Med Assoc 2004; 224:558.

50. Mason DK et al.Vet Rec 1984; 115:268.

PULMONARY EMPHYSEMA

Pulmonary emphysema is distension of
the lung caused by overdistension of
alveoli with rupture of alveolar walls with
or without escape of air into the inter-
stitial spaces. Overinflation describes the
situation in which there is enlargement of
airspaces without tissue destruction. Pul-
monary emphysema is always secondary
to some primary lesion which effectively
traps an excessive amount of air in the
alveoli. It is a common clinicopathological
finding in many diseases of the lungs of
all species and is characterized clinically
by dyspnea, hyperpnea, poor exercise
tolerance and forced expiration.

ETIOLOGY

Pulmonary emphysema is an important
lesion only in cattle, although occasional
cases occur in pigs. The bovine lung is
highly susceptible to the development of
emphysema from many different causes,
not all of them respiratory in origin. In
those of respiratory origin it is common to
find pulmonary emphysema when the
primary lesion in the lung causes trapping
of air in alveoli or terminal bronchioles.
Endotoxemia, for example, can result in
diffuse alveolar damage associated with
thromboangiitis resulting in pulmonary
edema and emphysema. Some causes of
emphysema are as follows:

Cattle

■ Acute interstitial pneumonia

Parasitic pneumonia with pulmonary
edema in acute anaphylaxis
Perforation of the lung by foreign
body as in traumatic
reticuloperitonitis
Poisoning by the plants Senecio
quadridentatus, rape, Zieria arborescens,
Perilla frutescens and the fungus
Periconia spp. are recorded as causing
pulmonary emphysema in cattle
Pulmonary abscess.

Horses

Bronchiolitis due to viral infection of
the respiratory tract in young horses.

All species

Secondary to bronchopneumonia
Poisoning by oleander, Bryophyllum
pinnatum and moldy sweet potatoes 1 "’

° Acute chemical injury - as in
inhalation of welding fumes
0 Chlorine gas poisoning
0 Local or perifocal emphysema is also
a common necropsy finding around
local pulmonary lesions, especially
atelectasis, often with no respiratory
dysfunction. In calves and pigs the
emphysema is sometimes sufficiently
extensive to kill the animal.

PATHOGENESIS

Emphysema occurs because of destruction
of the connective tissues of the lung,
including the supporting and elastic
tissue of the pulmonary parenchyma.
Tissue damage resulting in emphysema
in humans is caused by the action of
proteases in the lung. Whether this occurs
in the farm animal species is unknown
but is a consideration. An initial lesion
probably leads to an area of weakness
from which emphysema spreads during
coughing or exertion. In interstitial
emphysema there is the additional factor
of distension of the connective tissue with
air and compression collapse of the
alveoli.

The development of interstitial emphy-
sema depends largely upon the amount
of interstitial tissue that is present and is
most common in cattle and pigs. Whether
there is simple overdistension of alveoli or
whether their walls are also ruptured is
very important in prognosis and treat-
ment. Excellent recoveries occur in simple
alveolar emphysema, especially those
occurring acutely at pasture. This suggests
that the lesion is functional and that the
alveoli are not substantially damaged.

The pathophysiological conse-
quences of emphysema depend upon
the inefficiency of evacuation of pulmon-
ary air-space and failure of normal
gaseous exchange in the lungs. The elastic
recoil of the tissue is diminished, and
when the thorax subsides during expiration
incomplete evacuation occurs. Because of
the increase in residual volume, the tidal
volume must be increased to maintain
normal gaseous exchange. Retention of
carbon dioxide stimulates an increase in
; the depth of respiration but maximum
respiratory effort necessitated by exercise
cannot be achieved. Anoxia develops and
metabolism of all body tissues is reduced.
The characteristic effect of emphysema is
j to produce an increase in expiratory effort
j necessitated by the failure of normal
| elastic recoil.

; Interference with the pulmonary circu-
j lation results from collapse of much of the
I alveolar wall area and a consequent
j diminution of the capillary bed. The
j decreased negative pressure in the chest
1 and the abnormally wide respiratory
j excursion also cause a general restriction

508

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

of the rate of blood flow into the thorax.
The combined effect of these factors may
be sufficient to cause failure of the right
ventricle especially if there is a primary
defect of the myocardium. Acidosis may
also result because of the retention of
carbon dioxide.

CLINICAL FINDINGS

Characteristically, diffuse pulmonary
emphysema causes severe expiratory
dyspnea with a grunt on expiration and
loud crackling lung sounds on auscultation
over the emphysematous lungs. In severe
cases in cattle, the emphysema is com-
monly interstitial and dissection of the
mediastinum and fascial planes results in
subcutaneous emphysema over the
withers. In severe cases in cattle, open-
mouth breathing is common.

In cattle and pigs the presence of pul-
monary emphysema in pulmonary disease
is often not detectable clinically.

CLINICAL PATHOLOGY

There is hypoxemia and, often, hyper-
capnia. Compensatory polycythemia may
develop. There are no characteristic
hematological findings but, if there is a
significant secondary bronchopneumonia, a
leukocytosis and left shift may be evident.
In the appropriate location, an exam-
ination of feces for lungworm larvae may
be desirable. In cases suspected of having
an allergic origin, swabs of nasal secretion
may reveal a high proportion of eosinophils
and a hematological examination may
show eosinophilia.

NECROPSY FINDINGS

The lungs are distended and pale in color
and may bear imprints of the ribs. In
interstitial emphysema the interalveolar
septae are distended with air, which may
spread to beneath the pleura, to the
mediastinum and under the parietal
pleura. There may be evidence of con-
gestive heart failure. On histopathological
examination a bronchiolitis is present in
most cases. This may be diffuse and
apparently primary or originate by spread
from a nearby pneumonia.

TREATMENT

The treatment of pulmonary emphysema
will depend on the species affected, the
cause of the emphysema and the stage of
the disease.

There is no known specific treatment
for the pulmonary emphysema associated
with acute interstitial pneumonia in
cattle, which is discussed under that
heading. The emphysema secondary to
the infectious pneumonias will usually
resolve spontaneously if the primary
lesion of the lung is treated effectively. In
valuable animals, the administration of
oxygen may be warranted if the hypoxia is
severe and life-threatening. Antihistamines,

DIFFERENTIAL DIAGNOSIS

Acute emphysema in cattle is often
accompanied by pulmonary edema with
the presence of consolidation and crackles
in the ventral parts of the lungs. It may be
similar to acute pulmonary congestion and
edema caused by anaphylaxis but forced
expiration is not a characteristic of these
latter conditions.

Acute pneumonia in cattle or horses is
characterized by fever and localization of
abnormal respiratory sounds, which are
not as marked nor as widely distributed as
those of emphysema.

Chronic pneumonia is characterized by
dyspnea, chronic toxemia, crackles and
wheezes and poor response to therapy.
Pneumothorax is accompanied by
forced inspiration and an absence of
normal breath sounds.

atropine and corticosteroids have been
used for the treatment of pulmonary
emphysema secondary to interstitial
pneumonia in cattle but their efficacy has
been difficult to evaluate.

REFERENCES

1. Oryan A et al. Zentralbl Vet A 1996; 43:625.

2. Reppas GP. AustVet J 1995; 72:425.

3. Medeiros RM et al. Vet Hum Toxicol 2001; 43:205.

PNEUMONIA

Pneumonia is inflammation of the pul-
monary parenchyma usually accompanied
by inflammation of the bronchioles and
often by pleuritis. It is manifested clinically
by an increase in the respiratory rate,
changes in the depth and character of
respirations, coughing, abnormal breath
sounds on auscultation and, in most
bacterial pneumonias, evidence of toxemia.

ETIOLOGY

Pneumonia may be associated with
viruses, bacteria, or a combination of
both, fungi, metazoan parasites and
physical and chemical agents. Most of the
pneumonias in animals are bronchogenic
(inhalation) in origin but some originate
by the hematogenous route, such as
pneumonia of foals and calves with
septicemia. The pneumonias which occur
in farm animals are grouped here accord-
ing to species.

Cattle

Pneumonic pasteurellosis (shipping
fever) - M. haemolytica, P. multocida
with or without parainfluenza-3 virus
Histophilus somnus in feedlot cattle is
not necessarily associated with the
septicemic form of the disease. The
role of the organism as a primary
pathogen in acute bovine respiratory
disease is uncertain
Enzootic pneumonia of calves -
parainfluenza-3, adenovirus-1, -2 and

-3, rhinovirus, bovine respiratory
syncytial virus, reovirus, bovid
herpesvirus-1 (the IBR virus), plus
Chlamydia spp.. Mycoplasma spp.,
Pasteurella spp., Mannheimia spp.,
Actinomyces pyogenes, Streptococcus spp.,
Bedsonia sp. and Actinobacillus actinoides
° Pneumonia and arthritis in beef calves
associated with Mycoplasma bovis and
Mycoplasma califomicum
° Viral interstitial pneumonia in
recently weaned beef calves
associated with bovine respiratory
syncytial virus; it may also occur in
yearling and adult cattle
c Contagious bovine pleuropneumonia
- Mycoplasma mycoides
° Acute and chronic interstitial
pneumonia associated with D, L-
tryptophane, moldy hay and other
pneumotoxic agents
Atypical interstitial pneumonia
associated with ryegrass staggers in
calves 2

Massive infestation with pig ascarid
larvae

° Lungworm pneumonia - Dictyocaulus
viviparus

Klebsiella pneumoniae infection in
calves and nursing cows with mastitis
associated with this organism
Sporadically in tuberculosis associated
with M. bovis

Fusobacterium necrophorus as a
complication of calf diphtheria, and
sporadically in feedlot cattle
There is a preliminary report of
circovirus in adult cattle with
pneumonia 3

Mycotic pneumonia associated with
Mortierella wolfii in adult cattle. 4

Pigs

Enzootic pneumonia - Mycoplasma sp.
with Pasteurella sp. secondarily
Pneumonic pasteurellosis -
P. multocida

Pleuropneumonia - Actinobacillus
pleuropneumoniae

Interstitial pneumonia - septicemic
salmonellosis

Bordetella bronchiseptica, Salmonella

choleraesuis

Influenza virus 5

Porcine reproductive and respiratory
syndrome virus 5
Haemophilus parasuis 5
Actinobacillus pyogenes 5
Paramyxovirus causing respiratory and
central nervous system disease in
pigs 6

Uncommonly, lungworm pneumonia
Anthrax by inhalation, causing
pulmonary anthrax.

Horses

Pleuropneumonia in mature horses
due to aerobic and anaerobic

Diseases of the lungs

51

i

bacteria. 7 " 9 The aerobic bacteria most
commonly isolated are alpha-hemolytic
Streptococcus spp., Pasteurella spp.,
Escherichia coli and Enterobacter spp.

The anaerobic bacteria most frequently
isolated are Bacteroides spp., Prevotella
spp., Fusobacterium spp. and Clostridium
spp. 9 ' 10

° Newborn foals -Streptococcus spp.,

£. coli, Actinobacillus equuli and other
agents causing septicemia in this age
group

° In immunodeficient foals, pneumonia
associated with adenovirus or
Pneumocystis jiroveci (formerly
P. carinii) n

° Immunosuppression following
corticosteroid therapy for other
diseases 12

° Older foals - R. equi, equine

herpesvirus-1 (the EVR virus), equine
influenza virus 13

0 Bronchointerstitial pneumonia in foals
1-8 months of age - etiology
uncertain 14,15

Eosinophilic pneumonia secondary to
parasite migration ( Parascaris
equorum ) or Dictyocaulus amfieldi
infection

° Interstitial proliferative pneumonia in
foals from 6 days to 6 months of age,
and the adult form in horses 2 years
of age and older 16

Nicoletella semolina in adult horses 17
Bordetella bronchiseptica in adult
horses 18

Pleuropneumonia associated with
pulmonary hydatidosis in a horse 19
As a sequel to strangles
Influenza 20

Rarely, as a sequel to equine viral
arteritis or equine viral
rhinopneumonitis in adult animals
Glanders and epizootic lymphangitis
(. Histomonas farcinicus) usually include
pneumonic lesions
Paecilomyces spp. in foals 21
Mycotic pneumonia associated with
Emmonsia crescens (adiaspiromycosis)
in adult horses 22
Strenuous exercise in very cold
conditions can cause damage to the
airways of horses (and probably other
species). 23

Sheep

Pneumonic pasteurellosis
(. Mannheimia spp.) as acute primary
pneumonia in feedlot lambs, or
secondary to parainfluenza-3 or
Chlamydia sp. infection
Newborn lambs - uncommonly
Streptococcus zooepidemicus, Salmonella
abortus-ovis

Severe pneumonia due to Mycoplasma
sp. in lambs - kageda in Iceland and
Switzerland

° Symptomless pneumonias without
secondary infection - adenovirus,
respiratory syncytial virus, reovirus,
Mycoplasma spp. (including M.
ovipneumoniae, M. dispar) 2i
0 Corynebacterium pseudotuberculosis -
sporadic cases only
° Melioidosis ( Pseudomonas
pseudomallei)

° Lungworm ( Dictyocaulus filaria)

° Ovine herpesvirus-2 25
0 Progressive interstitial pneumonia
(maedi) and pulmonary adenomatosis
(jaagsiekte)

° Carbolic dip toxicity.

Goats

° Pleuropneumonia associated with
Mycoplasma strain F 38 or Mycoplasma
capri, a devastating disease
0 Chronic interstitial pneumonia with
cor pulmonale as a common sequel
may be associated with a number of
Mycoplasma spp., but M. mycoides var.
mycoides appears to be the most
commonly recorded
Parainfluenza type 3 26
'■ Contagious ecthyma virus 27
Retrovirus infection.

All species

- Toxoplasmosis - rare, sporadic cases
Systemic mycoses

Aspiration pneumonia is dealt with as
a separate entity
Sporadic secondary pneumonia
associated with Streptococcus sp.,
Corynebacterium sp., Dermatophilus sp.
Interstitial pneumonia, pulmonary
consolidation and fibrosis by toxins in
plants - Eupatorium glandulosum in
horses, Zieria arborescens (stinkwood)
in cattle, Astragalus spp. in all
species.

EPIDEMIOLOGY

In addition to the infectious agents which
cause the pneumonia, there are risk factors
which contribute to the susceptibility of
the animal. Three risk factors interact in
the pathogenesis of specific pneumonias:

Animal

Environmental and management
Pathogen.

These are of paramount importance in
any consideration of pneumonia and the
details of the epidemiology of each specific
pneumonia are presented with each
specific disease in this book. As examples,
some of the commonly recognized risk
factors include:

The weaning of beef calves in
northern climates

The long transportation of beef cattle
to feedlots

The collection and mixing of animals
at auction marts where they might be

deprived of feed and water for
prolonged periods

° The transportation of Thoroughbred
horses farther than 500 miles and
viral respiratory tract disease or
exposure to horses with respiratory
tract disease 12,28

° Housing dairy calves in poorly
ventilated overcrowded barns
° Marked changes in weather.

Susceptibility to pneumonia is deter-
mined by the animal's resistance to
infection by agents that cause or pre-
dispose to pneumonia. Factors that impair
innate resistance or adaptive resistance
(immunity) increase the animal's suscept-
ibility to pneumonia. For instance, shipping
not only increases the risk of exposure of
animals to pathogens to which they have
not been exposed but also can impair
innate resistance through damage to the
respiratory tract by airborne irritants,
dehydration, food deprivation and the
effects of stress. There is a distinct trend
evident since 1994 of increasing mortality
from respiratory disease among cattle in
feedlots, 29 although the reasons have not
been identified.

PATHOGENESIS

Pulmonary defense mechanisms

I Under normal conditions the major
airways and the lung parenchyma prevent
the entry of and neutralize or remove
injurious agents, so that the lung contains
very few, if any, organisms beyond the
large airways. Many infections of the
; respiratory tract originate from aerosolized
particles carrying infectious agents that
arise external to or within the respiratory
tract. In order to induce an infection by
the aerosol route, an etiological agent
must be aerosolized, survive in the aerosol,
be deposited at a vulnerable site in the
respiratory tract of a susceptible host, and
then multiply. Thus the pathogenesis of
these respiratory infections is related to
the deposition of particles and infectious
agents within the respiratory tract.

Under normal conditions a complex of
biochemical, physiological and immuno-
logical defense mechanisms protects the
respiratory tract from inhaled particles
that could be injurious or infectious. The
major defense mechanisms of the respir-
atory tract include:

Aerodynamic filtration by the nasal

cavities

Sneezing

Local nasal antibody
The laryngeal reflex
The cough reflex

Mucociliary transport mechanisms

Alveolar macrophages

Systemic and local antibody systems.

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

Most of the research on defense mechan-
isms has been done in man and in
laboratory animals.

Respiratory mucociliary clearance
The mucociliary escalator has important
functions in the lung's physical defenses
against the constant challenge of inhaled
pathogens. 30 By various physical mechan-
isms, mucus traps and subsequently
transports inhaled particles to the pharynx,
where they are normally swallowed.
Mucus also protects the airways by
absorbing inhaled chemicals and gases,
by humidifying the inspired air and by
keeping the underlying mucosa hydrated.
Mucus contains antibodies, especially
IgA, which together with lactoferrin and
lysozyme provide immunological defense.

Airway secretions consist of two
layers. An underlying liquid layer, known
as the periciliary fluid, in which the cilia
beat, originates largely from trans-
epithelial osmosis. An overlying gel or
mucus layer is composed of intertwined
mucin strands. Airway mucus is secreted
in small globules, which expand several
hundredfold within seconds and are later
drawn into strands and transported
rostrally by ciliary activity.

The secretion of respiratory mucus is a
protective mechanism by which inhaled
particles touching the airway mucosa
stimulate local mucus production, which
then traps and transports the particle
from the lung. Airway mucus is produced
mainly by submucosal glands and goblet
cells, also known as mucus-producing cells.
Airway secretions also contain alveolar
fluid, surfactant and alveolar cells, includ-
ing macrophages, which are drawn into
the mucociliary ladder by surface tension.

Airway mucus is a complex substance
consisting of 95% water and a 5% combi-
nation of glycoproteins, proteoglycans,
lipids, carbohydrates and minerals. Mucin is
the main nonaqueous component. Effective
mucociliary clearance or mucokinesis can
occur over a range of mucus viscosity but
very-low-viscosity mucus is poorly trans-
ported and tends to gravitate toward the
alveoli, while excessively viscous mucus,
which is also poorly transported,
may lodge in the airways and become
inspissated.

In respiratory disease mucociliary
clearance is impaired through disruption
of effective ciliary activity, or changes in
the quantity or quality of the mucus or
periciliary fluid, or all three factors. In viral
pulmonary disease, ciliary activity can be
disrupted because of temporary deciliation
or lesions of the respiratory mucosa. The
defective mucociliary clearance may also
last for several weeks. In chronic obstruc-
tive pulmonary disease in the horse,
metaplasia of ciliated epithelium to a

nonciliated epithelium may occur in the
smaller airways.

Changes in the quality of mucus are

common in respiratory tract disease,
especially increases in viscosity with
pulmonary disease. The destruction of
leukocytes and respiratory epithelial cells
and the release of DNA increases the
viscosity. Large increases in the glyco-
protein content of mucus also occur,
which affects the mucokinetic properties.
Purulent respiratory secretions have
reduced elasticity and together with the
increased viscosity affect the mucociliary
clearance. Acute inflammation also results
in the production of serum proteins from
the airway exudate, which alters the
viscoelasticity of mucus and further reduces
mucokinesis.

Yellow or green respiratory secretions

are due to the enzyme myeloperoxidase,
released from leukocytes in the static secre-
tion, or to high numbers of eosinophils.

The quantity of mucus increases in
most cases of respiratory disease as a
result of stimulation of goblet cells and
submucosal glands by inflammatory
mediators. The abnormal production can
also exacerbate the original pulmonary
dysfunction. Tracheal mucociliary clearance
can be assessed endoscopically, in vivo, by
dropping dye or small markers on the
tracheal mucosa and measuring their rate
of transit visually or using radioactive
particles detected by scintigraphy. 30

Large particles in upper respiratory tract
Large aerosolized particles that are
inhaled are removed by the nasal cavities
and only small ones are able to get into
the lung. In the upper respiratory tract,
essentially 100% of particles more than
j 10 pm in diameter and 80% of particles of
the 5 pm size are removed by gravitational
| settling on mucosal surfaces. Particles
: deposited between the posterior two-
thirds of the nasal cavity and the
. nasopharynx and from the larynx to the
terminal bronchioles land on airways lined
by mucus-covered, ciliated epithelium and
are removed by means of the mucociliary
transport mechanism. The nasopharyngeal
and tracheobronchial portions of the
ciliated airways transport mucus toward
1 the pharynx, where it can be eliminated by
swallowing. The cilia beat most effectively
in mucus at a certain elasticity, viscosity and
chemical composition. Anything that
interferes with the secretion and main-
: tenance of normal mucus will interfere
with the clearance of particles from the
upper respiratory tract. The damaging effect
j of viruses on mucociliary clearance has
j been demonstrated in laboratory animals
and in humans.

Mycoplasma pneumoniae infection
; slows tracheobronchial clearance for as

long as 1 year, suggesting a possible
explanation for the predisposition to
bacterial pneumonia commonly observed
after these infections. Viral diseases of the
upper respiratory tract of farm animals are
common and a similar interference in the
mucociliary transport mechanism may
explain the occurrence of secondary
bacterial pneumonia.

Cough reflex

The cough reflex provides an important
mechanism by which excess secretions
and inflammatory exudates from the
lungs and major airways can be removed
from the airways and disposed of by
expectoration or swallowing. In animals
with relatively normal lungs, coughing
represents a very effective means of
expelling inhaled foreign bodies, or
excessive or abnormal respiratory secre-
tions, down to the level of the fourth- or
fifth-generation bronchi. If the airways
become deciliated, the cough reflex is the
main and only mucus-clearance mechan-
ism remaining. The cough reflex is valu-
able for transporting the increased secre-
tions present in equine pulmonary disease
and antitussive agents should therefore
not be used in horses.

In the presence of severe tracheitis and
pneumonia, coughing may result in
retrograde movement of infected material
to the terminal respiratory bronchioles
and actually promote spread of the
infection to distal parts of the lung. Any
process that causes airway obstruction
can predispose the lung to secondary
bacterial infections. Experimental obstruc-
tion of the bronchi supplying a lobe of
lung in sheep allows the development of
secondary bacterial pneumonia. It has
been postulated that damage to small
airways following viral infections may
allow the accumulation of exudate and
cellular debris, which may facilitate
; secondary bacterial infections.

Small particles into lower respiratory
. tract

Particles of 1-2 pm size settle in the lungs
through the action of gravity in the
alveolar spaces and particles below
0-2 pm settle through diffusion of air. The
alveolar macrophage plays a major role in
clearing inhaled particles from the lung.

. Under normal conditions, bacteria that
gain entry into the alveoli are cleared
quickly and effectively in a matter of
I hours. Experimental parainfluenza-3
(PI-3) virus infection has the greatest
adverse effect on the pulmonary clearance
of M. haemolytica administered by intra-
nasal aerosol on the seventh day follow-
ing viral infection. The effect on pulmonary
clearance is much less when the bacteria
are given on the third or 11th day follow-
ing the initial viral infection.

Diseases of the lungs

511

The presence of pre-existing antibody
to M. haemolytica eliminates the effect of
the viral infection on pulmonary clearance.
Thus there is some evidence that in
domestic animals lung clearance mechan-
ism may be affected by a concurrent viral
infection. This may have major impli-
cations in the control of some of the
common infectious respiratory diseases of
farm animals.

Species susceptibility

The anatomical and physiological features
of the respiratory system of cattle may
predispose them to the development of
pulmonary lesions much more than other
farm animal species. Cattle have a small
physiological gaseous exchange capacity
and greater resultant basal ventilatory
activity. The small gaseous exchange
capacity may predispose cattle to low
bronchiolar or alveolar oxygen levels
during exposure to high altitudes and
during periods of active physical or
metabolic activity. During these times,
low oxygen tension or hypoxia may slow
mucociliary and alveolar macrophage
activity and decrease pulmonary clearance
rates. The basal ventilatory activity is
comparatively greater than other mammals,
which results in the inspired air becoming
progressively more contaminated with
infectious, allergenic or noxious substances.

The bovine lung also has a higher
degree of compartmentalization than
other species. This may predispose to
airway hypoxia peripheral to airways that
become occluded. This results in reduced
phagocytic activity and the retention or
multiplication of infectious agents. In
addition, because of the low numbers of
alveolar macrophages in the bovine lung
the pulmonary clearance mechanism may
not be as effective as in other species.
There is also a low level or atypical bio-
activity of lysozyme in bovine respiratory
mucus, which may make cattle more
susceptible to infection of the respiratory
tract than other species.

Development of pneumonia

The process by which pneumonia develops
varies with the causative agent and its
virulence and with the portal by which it
is introduced into the lung.

Bacteria are introduced largely by way
of the respiratory passages and cause a
primary bronchiolitis that spreads to involve
surrounding pulmonary parenchyma. The
reaction of the lung tissue may be in the
fonn of an acute fibrinous process as in
pasteurellosis and contagious bovine
pleuropneumonia, a necrotizing lesion as
in infection with F. necrophorum or as a
more chronic caseous or granulomatous
lesion in mycobacterial or mycotic
infections. Spread of the lesion through
the lung occurs by extension but also by

passage of infective material along
bronchioles and lymphatics. Spread along
the air passages is facilitated by the
normal movements of the bronchiolar
epithelium and by coughing. Bronchiectasis
and pulmonary abscesses are complications
and common causes of failure to respond
to therapy. Hematogenous infection by
bacteria results in a varying number of
septic foci, which may enlarge to form lung
abscesses. Pneumonia occurs when these
abscesses rupture into air passages and
spread as a secondary bronchopneumonia.

Viral infections are also introduced
chiefly by inhalation and cause a primary
bronchiolitis, but there is an absence of
the acute inflammatory reaction that
occurs in bacterial pneumonia. Spread
to the alveoli causes enlargement and
proliferation of the alveolar epithelial cells
and the development of alveolar edema.
Consolidation of the affected tissue
results but again there is an absence of
acute inflammation and tissue necrosis so
that toxemia is not a characteristic
development. Histologically the reaction
is manifested by enlargement and pro-
liferation of the alveolar epithelium,
alveolar edema, thickening of the interstitial
tissue and lymphocytic aggregations
around the alveoli, blood vessels and
bronchioles. This interstitial type of reaction
is characteristic of viral pneumonias.

The pathophysiology of all pneu-
monias, regardless of the way in which
lesions develop, is based upon interference
with gaseous exchange between the
alveolar air and the blood. Anoxia and
hypercapnia develop, which results in
polypnea, dyspnea or tachypnea. Con-
solidation results in louder than normal
breath sounds, especially over the antero-
ventral aspects of the lungs, unless a
pleural effusion is present to muffle the
sounds. In bacterial pneumonias there is
the added effect of toxins produced by the
bacteria and necrotic tissue; the accumu-
lation of inflammatory exudate in the
bronchi is manifested by abnormal lung
sounds such as crackles and wheezes on
auscultation. Interstitial pneumonia results
in consolidation of pulmonary parenchyma
without involvement of the bronchi, and
on auscultation loud breath sounds pre-
dominate in the early stages.

Extension of the pneumonia to the
visceral surface of the pleura results in
pleuritis, pleuropneumonia, pleural effu-
sion and thoracic pain. Fibrinous pleuritis
is a common complication of pneumonic
pasteurellosis in cattle. Pleuritis and
pleural effusion secondary to pneumonia
and pulmonary abscess are commonly
recognized in adult horses with the
pleuropneumonia complex associated
with aerobic and anaerobic bacteria . 10
Anaerobic bacterial pleuropneumonia in

the horse is accompanied by a putrid odor
of the breath, the sputum or the pleural
fluid . 8 It is suggested that most anaerobic
bacterial pulmonary infections in the
horse are the result of aspiration of
oropharyngeal contents, and are most
commonly located in the right Tung
because of the proximity of the right
main stem bronchus. Some horses with
pleuropneumonia may develop acute
hemorrhagic pulmonary infarction and
necrotizing pneumonia . 31

Restriction of gaseous exchange occurs
because of the obliteration of alveolar
spaces and obstruction of air passages. In
the stage before blood flow through the
affected part ceases, the reduction in
oxygenation of the blood is made more
severe by failure of part of the circulating
blood to come into contact with oxygen.
Cyanosis is most likely to develop at this
stage and to be less pronounced when
hepatization is complete and blood flow
through the part ceases. An additional
factor in the production of anoxia is the
shallow breathing that occurs. Pleuritic
pain causes reduction in the respiratory
excursion of the chest wall but when no
pleurisy is present the explanation of the
shallow breathing probably lies in the
increased sensitivity of the Hering-Breuer
reflex. Retention of carbon dioxide with
resulting acidosis is most likely to occur in
the early stages of pneumonia because of
this shallow breathing.

CLINICAL FINDINGS

° Rapid, shallow breathing is the

cardinal sign of early pneumonia
° Dyspnea occurs in the later stages
when much of the lung tissue is
nonfunctional

o Polypnea may be quite marked with
only minor pneumonic lesions; the
rapidity of the respiration is an
inaccurate guide to the degree of
pulmonary involvement
® Coughing is another important sign,
the type of cough varying with the
nature of the lesion.

Bacterial bronchopneumonia is usually
accompanied by a moist and painful
cough. In viral interstitial pneumonia the
coughing is frequent, dry and hacking,
often in paroxysms. Auscultation of the
thorax before and after coughing may
reveal coarse crackling sounds suggestive
of exudate in the airways. Cyanosis is not
a common sign and occurs only when
large areas of the lung are affected. A
nasal discharge may or may not be
present, depending upon the amount of
exudate present in the bronchioles and
whether or not there is accompanying
inflammation of the upper respiratory
tract. The odor of the breath may be
informative: it may have an odor of decay

2

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

when there is a large accumulation of
inspissated pus present in the air
passages; or it maybe putrid, especially in
horses affected with anaerobic bacterial
pleuropneumonia.

In acute bacterial bronchopneumonia,

toxemia, anorexia, depression, tachycardia
and a reluctance to lie down are common.
In the advanced stages, severe dyspnea
with an expiratory grunt are common.

In viral interstitial pneumonia,
affected animals are usually not toxemic
but they may have a fever and be
inappetent or anorexic. However, some
cases of viral interstitial pneumonia can
be diffuse and severe and cause severe
respiratory distress, failure to respond to
therapy and death within a few days. A
severe bronchointerstitial pneumonia of
foals aged 1-2 months of age has been
described. 14,32 The disease was charac-
terized clinically by sudden onset of fever
and increasingly severe dyspnea with
respiratory distress and no response to
treatment. In acute interstitial pneu-
monia of cattle, exemplified by the acute
disease seen in mature cattle moved on to a
lush pasture within the previous 10 days,
some animals may be found dead. Other
affected animals are severely dyspneic,
anxious, commonly mouth-breathing and
grunting with each expiration and, if forced
to walk, may collapse and die of asphyctic
respiratory failure.

Auscultation of the lungs is a

valuable aid to diagnosis. The stage of
development and the nature of the lesion
can be determined and the area of lung
tissue affected can be outlined. In the
early congestive stages of broncho-
pneumonia and interstitial pneumonia
the breath sounds are increased, especially
over the anteroventral aspects of the
lungs. Crackles develop in broncho-
pneumonia as bronchiolar exudation
increases, but in uncomplicated interstitial
pneumonia, clear, harsh breath sounds
are audible. In viral interstitial pneu-
monia, wheezes may be audible due to
the presence of bronchiolitis. When
complete consolidation occurs in either
form, loud breath sounds are the most
obvious sound audible over the affected
lung but crackles may be heard at the
periphery of the affected area in broncho-
pneumonia. Consolidation also causes
increased audibility of the heart sounds.
When pleurisy is also present a pleuritic
friction rub may be audible in the early
stages, and muffling of the breath sounds
over the ventral aspects of the lungs in the
late exudative stages. If a pleural effusion
is present, percussion of the thorax will
reveal dullness of the ventral aspects and
a fluid line can usually be outlined.
Consolidation can be detected also by
percussion of the thorax.

In chronic bronchopneumonia in
cattle there is chronic toxemia, rough hair
coat and a gaunt appearance. The respir-
atory and heart rates are above normal
and there is usually a moderate persistent
fever. However, the temperature may
have returned to within a normal range
even though the animal continues to have
chronic incurable pneumonia. The depth
of breathing is increased and both
inspiration and expiration are prolonged.
A grunt on expiration and open-mouth
breathing indicate advanced pulmonary
disease. A copious bilateral mucopurulent
nasal discharge and a chronic moist
productive cough are common. On
auscultation of the lungs, loud breath
sounds are usually audible over the
ventral half of the lungs, and crackles and
wheezes are commonly audible over the
entire lung fields but are most pronounced
over the ventral half.

With adequate treatment in the early
stages, bacterial pneumonia usually
responds favorably in 24 hours but viral
pneumonia may not respond at all or may
relapse after an apparent initial beneficial
response. The transient response may be
due to control of the secondary bacterial
invaders. In some bacterial pneumonias,
relapses also occur that are due either to
reinfection or to persistence of the infec-
tion in necrotic foci that are inaccessible
to antimicrobials. The final outcome
depends on the susceptibility of the
causative agent to the treatments avail-
able and the severity of the lesions when
treatment is undertaken. Pleurisy is a
common complication of pneumonia and
rarely occurs independently of it, and is
described later under that heading.

Pneumonia and pleuritis in horses
are described separately (see Equine
pleuropneumonia, below).

Congestive heart failure or cor
pulmonale may occur in some animals
which survive a chronic pneumonia for
several weeks or months.

Medical imaging

Thoracic radiography and ultrasonography
are now commonly performed in veterinary
teaching hospitals and specialty clinics.
They can provide considerable diagnostic
assistance in assessing the severity of the
lesion and explaining certain clinical
manifestations that may be difficult to
interpret. Ultrasonography is a useful
diagnostic aid in cattle and horses with
anaerobic bacterial pleuropneumonia and
pulmonary abscessation. 8,33,34 Gas echoes
within pleural or abscess fluid were found
to be a sensitive and specific indicator of
anaerobic infection as was a putrid breath
or pleural fluid.

In cattle with pleuropneumonia, ultra-
sonographic examination of both sides of

the thorax may reveal accumulations of
anechogenic and hypoechogenic fluid in
the pleural space in the ventral aspect of
the thorax. 33,35 In cattle, pleural effusion
associated with pleuritis is usually uni-
lateral because the pleural sacs do not
communicate. Bilateral pleural effusion
may indicate either bilateral pulmonary
disease or a noninflammatory cause such
as right-sided congestive heart failure or
hypoproteinemia.

CLINICAL PATHOLOGY
Respiratory secretions

The laboratory examination of the
exudates and secretions of the respiratory
tract is the most common diagnostic
procedure performed when presented
with cases of pneumonia. Nasal swabs,
tracheobronchial aspirates and broncho-
alveolar lavage samples can be submitted
for isolation of viruses, bacteria and fungi,
cytological examination and determination
of antimicrobial sensitivity. Tracheo-
bronchial aspirates are considered more
reliable for the cytological examination
of pulmonary secretions in horses
with suspected pneumonia or pleuro-
pneumonia. 36 Bronchoalveolar lavage
samples may be normal in horses affected
with pneumonia or pleuropneumonia. In
suspected cases of pleuropneumonia the
collection and culture of pleural fluid is a
valuable aid to diagnosis 10 and both
anaerobic and aerobic bacteria must be
considered. 10

Thoracocentesis

When pleural effusion is suspected,
thoracocentesis can be used to obtain
pleural fluid for analysis.

Hematology

Hematological examination can indicate
if the infection is bacterial or viral in
nature and its severity. The hematocrit will
be elevated in severely toxemic animals
that are not drinking water. Severe bacterial
bronchopneumonia and pleuritis is
characterized by marked changes in the
leukon. Serum fibrinogen concentrations
are markedly elevated in horses with
pleuropneumonia and pleuritis. 37 Some
limited studies indicate that the measure-
ment of acute-phase proteins in bovine
respiratory disease may be a valuable
diagnostic and prognostic aid. 38

Serology

When viral interstitial pneumonia is
suspected, acute and convalescent sera
are recommended for viral neutralization
titer evaluation. For specific diseases such
as porcine pleuropneumonia, serum can
be taken from a percentage of the herd
and submitted for serotyping to detennine
which serotype is most prevalent in the
herd.

Diseases of the lungs

513

Fecal samples

When lungworm pneumonia is suspected,
fecal samples can be submitted for detec-
tion of the larvae.

Necropsy

In outbreaks of respiratory disease where-
in the diagnosis is uncertain, necropsy of
selected early cases will often assist in
making a diagnosis.

NECROPSY FINDINGS

Gross lesions are usually observed in the
anterior and dependent parts of the lobes;
even in fatal cases where much of the
lung is destroyed, the dorsal parts of the
lobes may be unaffected. The gross
lesions vary a great deal depending upon
the type of pneumonia present. Broncho-
pneumonia is characterized by the
presence of serofibrinous or purulent
exudate in the bronchioles, and lobular
congestion or hepatization.

In the more severe, fibrinous forms
of pneumonia there is gelatinous exudation
in the interlobular septae and an acute
pleurisy, with shreds of fibrin present
between the lobes.

In interstitial pneumonia the

bronchioles are clean and the affected
lung is sunken, dark red in color and has
a granular appearance under the pleura
and on the cut surface. There is often an
apparent firm thickening of the inter-
lobular septae. These differences are readily
detected on histological examination.

In chronic bronchopneumonia of
cattle there is consolidation, fibrosis,
fibrinous pleuritis, interstitial and bullous
emphysema, bronchi filled with exu-
date, bronchiectasis and pulmonary
abscessation.

Lesions typical of the specific infec-
tions listed under etiology are described
under the headings of the specific
diseases.

TREATMENT

Antimicrobial therapy

In specific bacterial infections as listed
above, isolation of affected animals and
careful surveillance of the remainder of
the group to detect cases in the early
stages should accompany the adminis-
tration of specific antimicrobials to
affected animals. The choice of anti-
microbial will depend on the tentative
diagnosis, the experience with the drug in
previous cases and the results of drug
sensitivity tests. The common bacterial
pneumonias of all species will usually
recover quickly (24-72 h) if treated with
an adequate dose of the drug of choice
early in the course of the disease. Animals
with severe pneumonia will require daily
treatment for several days until recovery
occurs. Those with bacterial pneumonia
and toxemia must be treated early on an

DIFFERENTIAL DIAGNOSIS

There are two major difficulties in the
clinical diagnosis of pneumonia. The first is
to decide that the animal has pneumonia;
the second is to determine the nature of
the pneumonia and its cause. The
suspected cause will influence the
prognosis, the clinical' management and,
more particularly in infectious pneumonias,
the kind of antimicrobial therapy used.

There are two kinds of errors made in
the clinical diagnosis of pneumonia. One is
that the pneumonia is not detected
clinically because the abnormal lung
sounds are apparently not obvious. The
other is to make a diagnosis of pneumonia
because of the presence of dyspnea that is
due to disease in some other body system.

• In bacterial pneumonia the major
clinical findings are polypnea in the
early stages and dyspnea later,
abnormal lung sounds, and fever and
toxemia.

• In viral interstitial pneumonia

uncomplicated by secondary bacterial
pneumonia, there is no toxemia.
Pulmonary edema and congestion,
embolism of the pulmonary artery and
emphysema are often mistaken for
pneumonia but can usually be
differentiated by the absence of fever
and toxemia, on the basis of the history
and on auscultation findings.

• Diseases of other body systems may
cause polypnea and dyspnea.

Congestive heart failure, the terminal
stages of anemia, poisoning by
histotoxic agents such as hydrocyanic
acid, hyperthermia and acidosis are
accompanied by respiratory
embarrassment but not by the abnormal
sounds typical of pulmonary
involvement.

If pneumonia is present the next step
is to determine the nature and cause of
the pneumonia. All the practical laboratory
aids described earlier should be used when
necessary. This is of particular importance
when outbreaks of pneumonia are
encountered, in which case necropsy
examination of selected cases is indicated.
In single routine cases of pneumonia the
cause is usually not determined. However,
the age and class of the animal, the history
and epidemiological findings and the
clinical findings can usually be correlated
and a presumptive etiological diagnosis
made.

Pleuritis is characterized by shallow,
abdominal-type respiration, by pleuritic
friction sounds when effusion is minimal, a
muffling of lung sounds on auscultation,
the presence of dullness and a horizontal
fluid line on acoustic percussion when
there is sufficient pleural fluid present.
Thoracocentesis reveals the presence of
fluid.

In pneumothorax there is inspiratory
dyspnea and on the affected side the
abnormalities include:

• Absence of breath sounds over the
lobes but still audible sounds over the
base of the lung

• Increase in the absolute intensity of the

heart sounds

• Increased resonance on percussion.

Diseases of the upper respiratory
tract such as laryngitis and tracheitis are
accompanied by varying degrees of
inspiratory dyspnea, which is often loud
enough to be audible without a
stethoscope. In less severe cases,
auscultation of the mid-cervical trachea will
reveal moist wheezing sounds on
inspiration. These sounds are transmitted
down into the lungs and are audible on
auscultation of the thorax. These
transmitted sounds must not be
interpreted as due to pneumonia. In some
cases of severe laryngitis and tracheitis the
inspiratory sounds audible over the trachea
and lungs are markedly reduced because
of almost total obliteration of these
organs. In laryngitis and tracheitis there is
usually a more frequent cough than in
pneumonia and the cough can be readily
stimulated by squeezing the larynx or
trachea. In pneumonia the abnormal lung
sounds are audible on both inspiration and
expiration. Examination of the larynx
through the oral cavity in cattle and with
the aid of a rhinolaryngoscope in the horse
will usually reveal the lesions.

individual basis. Each case should be
identified and carefully monitored for
failure to recover, and an assessment
made. Clinical field trials to evaluate
different antimicrobials for the treatment
of acute bovine respiratory disease occur-
ring under natural conditions are becoming
more common and more meaningful,
particularly under commercial feedlot
conditions. 39

Antimicrobial agents in a long-acting
base may be used to provide therapy over
a 4-6- day period instead of the daily
administration of the shorter-acting prep-
arations. However, the blood levels from
the long-acting preparations are not as
high as the shorter- acting preparations
and treatment with these compounds
are not as effective in severely affected
animals.

Selection of antimicrobials is based
on the principles detailed in Chapter 4.
Briefly, antimicrobials for treatment of
bacterial respiratory disease should be
active against the causative agent, should
be able to achieve therapeutic concen-
trations in diseased lung and should be
convenient to administer. The anti-
microbials should be affordable and, if
used in animals intended as human food,
must be approved for use in such animals.

Antimicrobials for treatment of lung
disease are preferably those that achieve
therapeutic concentrations in diseased
lung tissue after administration of con-
ventional doses. This has been convincingly
demonstrated for the macrolide
(azithromycin, erythromycin), 40 triamilide

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

(tulathromycin) 41 and fluoroquinolone
(danofloxacin, enrofloxacin) 42,43 anti-
microbials and fluorfenicol 44 in a variety
of species. The beta-lactam antimicrobials
(penicillin, ceftiofur) are effective in
treatment of pneumonia in horses, pigs
and ruminants despite having chemical
properties that do not favor their accumu-
lation in lung tissue.

Routes of administration include oral
(either individually or in medicated feed
or water), parenteral (subcutaneous,
intramuscular, intravenous), or inhalational.
Intratracheal administration of anti-
microbials to animals with respiratory
disease is not an effective means of
achieving therapeutic drug concentrations
in diseased tissue. Aerosolization and
inhalation of antimicrobials has the
theoretic advantage of targeting therapy
to the lungs and minimizing systemic
exposure to the drug. However, while
administration by inhalation achieves
good concentrations of drug in bronchial
lining fluid, the drug does not penetrate
unventilated regions of the lungs, in
which case parenteral or oral adminis-
tration of antimicrobials is indicated.
Administration of gentamicin to horses
and ceftiofur sodium to calves with
pneumonia has been investigated.
Aerosol administration of gentamicin to
normal horses results in gentamicin
concentrations in bronchial lavage fluid
12 times that achieved after intravenous
administration. 45 Aerosolized ceftiofur
sodium (1 mg/kg) is superior to
intramuscular administration in treatment
of calves with M. haemolytica 46

Treatment of parasitic lung disease, such
as that caused by migrating larvae or lung
worms, is by administration of appropriate
anthelmintics such as ivermectin,
moxidectin or the benzimidazoles. Refer to
the sections in this book that deal with
these diseases for details of the specific
treatments. Treatment of P. jircveci pneu-
monia involves the administration of a
sulfonamide-trimethoprim combination
or dapsone (3 mg/kg orally every 24 h). 47

The antimicrobials and other drugs
recommended for the treatment of each
specific pneumonia listed under Etiology
are presented with each specific disease
elsewhere in the book. The common causes
for failure to respond favorably to
treatment for bacterial pneumonia include:

° Advanced disease when treatment
was undertaken
0 Presence of pleuritis and
pulmonary abscesses
° Drug-resistant bacteria
° Inadequate dosage of drug
° Presence of other lesions or

diseases which do not respond to
antimicrobials.

There is no specific treatment for the viral
pneumonias and while many of the
Mycoplasma spp. are sensitive to anti-
microbials in vitro, the pneumonias
associated with them do not respond
favorably to treatment. This may be due to
the intracellular location of the Mycoplasma
making them inaccessible to the drugs.
Because viral and mycoplasmal pneu-
monias are commonly complicated by
secondary bacterial infections, it is
common practice to treat acute viral and
mycoplasmal pneumonias with anti-
microbials until recovery is apparent.

Intensive and prolonged therapy
may be required for the treatment of
diseases such as equine pleuropneumonia.
It may include daily care and treatment in
a veterinary clinic consisting of daily
lavage of the pleural cavity including
thoracostomy to drain pulmonary
abscesses, and intensive antimicrobial
therapy and monitoring for several
weeks. 48

Mass medication

In outbreaks of pneumonia where many
animals are affected and new cases occur
each day for several days, the use of mass
medication of the feed and/or water
supplies should be considered. Outbreaks
of pneumonia in swine herds, lamb
feedlots, veal calf enterprises and beef
feedlots are usually ideal situations for
mass medication through the feed or
water. Mass medication may assist in the
early treatment of subclinical pneumonia
and is a labor-saving method of providing
convalescent therapy to animals that have
been treated individually. The major
limitation of mass medication is the
uncertainty that those animals that need
the drug will actually get it in the
amounts necessary to be effective. Total
daily water intake by animals is a function
of total dry matter intake and wellbeing,
and the water consumption is therefore
markedly reduced in toxemic animals.
The provision of a reliable concentration
of the drug in the water supply on a 24-
hour basis is also a problem. However,
with careful calculation and monitoring,
mass medication can be a valuable and
economical method of treating large
numbers of animals. The method of
calculating the amount of antimicrobials
to be added to feed or water supplies is
presented in Chapter 4 on antimicrobial
therapy.

When outbreaks of pneumonia occur
and new cases are being recognized at the
rate of 5-10% per day of the total in the
group, all the remaining in-contact animals
may be injected with an antimicrobial in a
long-acting base. This may help to treat
subclinical cases before they become
clinical and thus control the outbreak.

Other drugs

Nonsteroidal anti-inflammatory drugs

are useful in the treatment of infectious
respiratory disease of cattle and horses,
and likely other species. The drugs act by
inhibiting the inflammatory response
induced by the infecting organism and
tissue necrosis. Meloxicam (0.5 mg/kg
subcutaneously, once), when administered
with tetracycline, improves weight gain
and reduces the size of lesions in lungs of
cattle with bovine respiratory disease
complex over those of animals treated
with tetracycline alone. 49 NSAIDs also
improve the clinical signs of cattle with
respiratory disease. 50 Use of these drugs is
routine in horses with pneumonia or
pleuritis.

Corticosteroids have been used for
their anti-inflammatory effect in the
treatment of acute pneumonia. However,
there is no clinical evidence that they are
beneficial.

Bronchodilators have been investi-
gated in the treatment of pneumonia in
food animals. The beta-2 adrenergic
agonists are potent and effective
bronchodilators that can be administered
orally, intravenously or by inhalation.
These drugs also enhance mucociliary
clearance of material from the lungs. Most
administration is orally or by inhalation.
The use of beta-2 adrenergic agonist
bronchodilator drugs in food animals is
not permitted in most countries because
of the risk of contamination of foodstuffs
intended for consumption by people. This
is particularly the case with clenbuterol, a
drug approved in many countries for use
in horses that is administered to cattle
illicitly as a growth promoter. People can
be poisoned by clenbuterol in tissues of
treated cattle. Theophylline has been
evaluated as a bronchodilator to relieve
respiratory distress in cattle with
pneumonia. 51 When it was given orally at
a dose of 28 mg/kg BW daily for 3 days,
along with antimicrobial therapy, to
calves with naturally acquired respiratory
disease, the respiratory rate and rectal
temperature decreased. However, some
calves died, presumably from the
accumulation of lethal concentrations of
plasma theophylline. It is recommended
that the drug should not be used unless
plasma levels can be monitored.

Supportive therapy and housing

Affected animals should be housed in
warm, well-ventilated, draft- free accom-
modation and provided with ample fresh
water and light, nourishing food. During
convalescence premature return to work
or exposure to inclement weather should
be avoided. If the animal does not eat,
oral or parenteral force-feeding should be
instituted. If fluids are given intravenously

Diseases of the lungs

care should be exercised over the speed
with which they are administered. Injec-
tion at too rapid a rate may cause over-
loading of the right ventricle and death
due to acute heart failure.

Supportive treatment may include the
provision of oxygen, if it is available,
especially in the critical stages when
hypoxia is severe. In foals the oxygen can
be administered through an intranasal
tube passed back to the nasopharynx and
delivered at the rate of about 8 L/min for
several hours. Oxygen therapy is detailed
in the general section on treatment of
respiratory disease above.

REFERENCES

1. Hewicker-Trautwein M et al. Vet Rec 2002;
151:699.

2. Pearson EG et al. J Am Vet Med Assoc 1996;
209:1137.

3. NayarGPS et al. CanVetJ 1999; 40:277.

4. Gabor LJ. AustVet J 2003; 81:409.

5. Loeffen WLA et al.Vet Rec 1999; 145:123.

6. JankeBH et al. JVetDiagn Invest2001; 13:428.

7. Chaffin MK, Carter GK. Compend Contin Educ
PractVet 1993; 15:1642.

8. Chaffin MK et al. Compend Contin Educ Pract
Vet 16 1994; 362:1585.

9. Racklyeft DJ, Love DN AustVet J 2000; 78:549.

10. Sweeney CR et al. J Am Vet Med Assoc 1991;
198:839.

11. Prescott JF. Equine Vet J 1993; 25:88.

12. MairTS.Vet Rec 1996; 138:205.

13. Peek SF et al. J Vet Intern Med 2004; 18:132.

14. Prescott JF et al. CanVetJ 1991; 32:421.

15. Lakritz J et al. J Vet Intern Med 1993; 7:277.

16. NoutY et al. EquineVet J 2002; 34:542.

17. Kuhnert P et al. J Clin Microbiol 2004; 42:5542.

18. Garcia-Cantu MC et al. Equine Vet Educ 2000;
12:45.

19. McGorum BC et al. EquineVet J 1994; 26:249.

20. Gross DK et al. JVet Intern Med 2004; 18:718.

21. Foley JE et al. JVet Intern Med 2002; 16:238.

22. PusterlaN et al. EquineVet J 2002; 34:749.

23. Davis MS et al. EquineVet J Suppl 2002; 34:413.

24. Alley MR et al. N Z Vet J 1999; 47:155.

25. Li H et al. JVet Diagn Invest 2005; 17:171.

26. Yener Z et al. JVet Med A 2005; 52:268.

27. de al Concha-Bermejillo et al. JVet Diagn Invest
2003; 15:423.

28. Austin SM et al. J Am Vet Med Assoc 1995;
207:325.

29. Lonergan GH et al. J Am Vet Med Assoc 2001;
219:1122.

30. Willoughby RA et al. Can JVet Res 1991; 55:315.

31. Carr E et al. J Am Vet Med Assoc 1997; 210:1174.

32. Dunkel B et al. EquineVet J 2005; 37:435.

33. Flock M. Vet J 2004; 167:272.

34. Ramirez S et al. Vet Radiol Ultrasound 2004;
45:172.

35. Braun U et al.Vet Rec 1997; 141:12.

36. Rossier Y et al. J Am Vet Med Assoc 1991;
198:1001.

37. Collins MB et al. J Am Vet Med Assoc 1994;
205:1753.

38. Godson DL et al. Vet Immunol Immunopathol
1996; 51:277.

39. Jim GK et al. Can Vet J 1992; 33:245.

40. Davis JL et al. JVet Pharmacol Ther 2002; 25:99.

41. Benchaaoui HA et al. J Vet PharmacolTher 2004;
27:203.

42. Terhune TN et al. Am JVet Res 2005; 66:342.

43. ApleyMD,UpsonDW.AmJVetRes 1993; 54:937.

44. AslanVet al.Vet Q 2002; 24:35.

45. McKenzie HC, Murray MJ. Am J Vet Res 2000;
61:1185.

46. Sustronck B et al. ResVet Sci 1995; 59:267.

47. Clark-Price SC et al. J Am Vet Med Assoc 2004;
224:407.

48. Dechant J. CanVetJ 1997; 38:499.

49. Friton GM et al.Vet Rec 2005; 156:809.

50. Elitok B, Elitok OM. JVet Pharmacol Ther 2004;
27:317.

51. McKenna DJ et al. J Am Vet Med Assoc 1989;
195:603.

ASPIRATION PNEUMONIA

Aspiration or inhalation pneumonia is a
common and serious disease of farm
animals. Cases occur after careless
drenching or passage of a stomach tube
during treatment for other illness, for
example administration of mineral oil to
horses with colic. 1 Even when care is
taken these procedures are not without
risk. Other causes include the feeding of
calves and pigs on fluid feeds in inadequate
troughing, inhalation occurring in the
struggle for food. Dipping of sheep and
cattle when they are weak, or keeping
their heads under for too long, also results
in inhalation of fluid. Vomiting in rumi-
nants and horses may be followed by
aspiration, especially in cattle with
parturient paresis or during the passage
of a stomach tube if the head is held high.
Rupture of a pharyngeal abscess during
palpation of the pharynx or passage of a
nasal tube may cause sudden aspiration
of infective material. Animals suffering
from paralysis or obstruction of the larynx,
pharynx, or esophagus may aspirate food
or water when attempting to swallow.
Aspiration pneumonia is the consistent
lesion of crude oil poisoning in cattle
and probably results from vomiting or
regurgitation. 2

Lipid pneumonia

Lipid pneumonia usually results from
aspiration of mineral oil (liquid paraffin)
administered for gastrointestinal disease.
Pneumonia is sometimes the result of
inadvertent administration of the oil into
the trachea through a misplaced stomach
tube, or inhalation following oral adminis-
tration of oil. However, aspiration of oil
can occur even when it is delivered into
the stomach through a nasogastric tube, 3
presumably because of regurgitation of oil
either around the tube or after the tube
has been removed. Administration of oil
to sedated or severely depressed animals
may increase the risk of aspiration.

Clinical signs include cough, tachypnea,
tachycardia, pyrexia, respiratory distress
and abnormal lung sounds. Radiographs
can reveal an alveolar and interstitial
pattern. Examination of tracheal aspirates
reveals a neutrophilic inflammation and
the presence of lipid. Lipid can be readily
identified by Sudan or oil red O staining

of smears of the aspirate in acute cases.
Necropsy examination reveals consolidated
lungs. On cut section of these areas oil
can be visible. Chronic cases have tissue
necrosis and severe interstitial pneumonia.
Lipid droplets can be identified in
affected lung tissue after oil red O
staining of sections. 4 The presence and
nature of the lipid can be demonstrated
by thin-layer chromatography and gas
chromatography. 4 The prognosis for
recovery is poor. Treatment is supportive
and includes anti-inflammatory drugs,
antimicrobials, and oxygen. There is no
specific treatment. Prevention includes
careful insertion of nasogastric tubes,
verification of their placement in the
stomach and not administering mineral
oil to animals with a distended stomach
or ones that are heavily sedated or
severely depressed.

Esophageal obstruction

Esophageal obstruction is a common and
important cause of pneumonia in
horses. 2,5 Of 18 horses with esophageal
obstruction that had thoracic radiographs
performed, eight had evidence of aspir-
ation pneumonia. 5 Obstruction of the
esophagus in horses, and in other species,
leads to the accumulation of saliva and
feed material in the esophagus oral to the
obstruction. When the esophagus is full,
this material accumulates in the pharynx
with subsequent aspiration into the
trachea resulting in contamination of the
trachea and lower airways with feed
material and oropharyngeal bacteria.
Feed material is irritant and also causes
obstruction of the smaller airways. Pul-
monary defense mechanisms are weakened
or overwhelmed by the contamination
and infection and pneumonia result. The
duration of esophageal obstruction is a
good indicator of the risk of aspiration
pneumonia, although the extent of
contamination of the trachea with feed
material is not. 5 Affected horses are
pyrexic, tachycardic, and toxemic. Lung
sounds can include crackles and wheezes,
but the only auscultatory abnormality can
be decreased breath sounds in the ventral
thorax. Radiography reveals a charac-
teristic pattern of bronchopneumonia
restricted, at least initially, to the cranio-
ventral and caudoventral lung lobes in
adult horses. Ultrasonography reveals
comet tail lesions in the ventral lung fields
and variable consolidation. Pleuritis is a
not uncommon sequel to aspiration
pneumonia. Examination of tracheal
aspirates demonstrates neutrophilic
inflammation with presence of degenerate
neutrophils, bacteria that are both
intracellular and extracellular, and plant
material. Culture of tracheal aspirates
yields one or more of a wide variety of

6

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

bacteria including S. zooepidemicus,
Pasteurella sp., Actinobacillus sp, E. coli, and
anaerobes. Treatment involves prompt
relief of the esophageal obstruction and
administration of broad-spectrum anti-
microbials such as a combination of
penicillin, aminoglycoside, and metro-
nidazole. The prognosis for recovery from
aspiration pneumonia secondary to
esophageal obstruction is guarded to fair,
partly because the animal has to recover
from two diseases - the pneumonia and
the esophageal obstruction. Prevention of
aspiration pneumonia in horses with
esophageal obstruction includes prompt
relief of the obstruction and administration
of broad-spectrum antimicrobials.

Meconium aspiration syndrome

Aspiration of meconium during parturition
is associated with severe lung disease in
newborns. Fhssage of meconium in utero,
and subsequent aspiration by the fetus, is
a sign of fetal distress. It is suggested that
fetal distress results in expulsion of
meconium into the amniotic fluid. This is
followed by aspiration of contaminated
amniotic fluid. The passage of meconium-
contaminated amniotic fluid into the
lungs may occur prior to birth when the
fetus gasps for air in an attempt to correct
hypoxemia or when the calf takes its first
breath and aspirates meconium from the
oropharynx. Normally, fetal aspiration of
amniotic fluid does not occur because the
inspiratory forces are insufficient to allow
amniotic fluid to reach the lungs, and the
lung liquid, a locally produced viscous
material present in the trachea and lungs,
constantly flows up the major airways to
the oropharynx. The result is that the fetus
is doubly challenged in that it must deal
with both the cause of the fetal distress
and the pneumonia induced by aspiration
of meconium. Although meconium is
sterile, it induces a severe inflammatory
response in the lungs.

The meconium aspiration syndrome
is best described in newborn calves, 6
although there are numerous reports of its
experimental induction in piglets and lambs
as a model of the human disease. In a series
of calves under 2 weeks of age submitted to
a diagnostic laboratory, 42.5% had evidence
of meconium, squamous cells or keratin in
the lung. Diffuse alveolitis with exudation of
neutrophils, macrophages, multinucleated
cells and obstruction of small airways with
atelectasis were common.

Treatment of aspiration pneumonia in
farm animals is not well described.
Administration of antimicrobials is
prudent. Anti-inflammatory drugs are
indicated. Pentoxifylline is used in human
neonates with meconium aspiration, but
there are no reports of its use for this
purpose in farm animals.

Dusty feed

Although farm animals fed on dusty feeds
inhale many dust particles and bacteria,
which can be readily isolated from the
lung, this form of infection rarely results
in the development of pneumonia. Much
of the dust is filtered out in the bronchial
tree and does not reach the alveoli. How-
ever, this may be of importance in the
production of the primary bronchiolitis
that so often precedes alveolar emphy-
sema in horses. The inhalation of feed
particles in pigs in a very poorly ventilated
environment has been demonstrated to
cause foreign body pneumonia. Also, a
dry, dusty atmosphere can be created in a
piggery by overfrequent changing of
wood shavings used as bedding, and this
can lead to the production of foreign body
pneumonia. Liquids and droplets penetrate
to the depths of the alveoli and run freely
into the dependent portions, and aspir-
ation pneumonia often results.

REFERENCE

1. Scarratt WK et al. Equine Vet J 1998; 30:85.

2. Craig DR et al. Vet Surg 1989; 18:432.

3. Davis JL et al. Equine Vet Educ 2001: 13:230.

4. Bos M et al. Equine Vet J 2002; 34:744.

5. Feige K et al. Can \fet J 2000; 41:207.

6. Lopez A, Bildfell R. Vet Rathol 1992; 29:104.

CAUDAL VENA CAVAL
THROMBOSIS (POSTERIOR VENA
CAVAL THROMBOSIS) AND
EMBOLIC PNEUMONIA IN CATTLE

Embolic pneumonia as a sequel to
thrombosis of the posterior vena cava is a
relatively common disease of cattle in
Europe and the UK. The disease is rare in
cattle less than 1 year old although it can
occur at any age. A preponderance of
affected animals are in feedlots on heavy
grain diets and there are peaks of
incidence at those times of the year when
most cattle are on such diets. There is an
obvious relationship between the occur-
rence of this disease and that of hepatic
abscessation arising from lactic-acid-
induced rumenitis on heavy grain diets.

The etiology and pathogenesis of the
disease are based on the development of
a thrombus in the posterior vena cava and
the subsequent shedding of emboli,
which lodge in the pulmonary artery
causing embolism, endarteritis, multiple
pulmonary abscesses, and chronic sup-
purative pneumonia. Pulmonary hyper-
tension develops in the pulmonary artery,
leading to the development of aneurysms,
which may rupture causing massive
intrapulmonary or intrabronchial hemor-
rhage. In most cases the thrombi in the
vena cava originate from hepatic abscesses,
or postdiaphragmatic abscesses. Usually
there is an initial phlebitis and the sub-
sequent thrombus extends into the thoracic
part of the vessel. When the thrombus

occludes the openings of the hepatic
veins into the vena cava, there is con-
gestion of the liver and hepatomegaly,
ascites, and abdominal distension in
some of these cases. 1

The most common form of the
disease is characterized by manifestations
of respiratory tract disease. Commonly
there is a history of the disease for a few
weeks or longer but some animals are
'found dead' without prior recorded
illness. There is usually fever and an
increase in the rate and depth of respir-
ation, coughing, epistaxis and hemoptysis,
anemia with pallor, a hemic murmur, and
a low packed cell volume. Respirations
are painful and a mild expiratory grunt or
groan may be audible with each respir-
ation. Subcutaneous emphysema and
frothing at the mouth are evident in
some. Deep palpation in the intercostal
spaces and over the xiphoid sternum may
elicit a painful gnrnt. The lung sounds
may be normal in the early stages but,
with the development of pulmonary
arterial lesions, embolic pneumonia and
collapse of affected lung, widespread
rhonchi are audible on auscultation. There
can be ascites. 1 In one series of cases the
presence of anemia, hemoptysis, epistaxis,
and widespread abnormal lungs sounds
were characteristic features of the disease. 2
There are accompanying nonspecific signs
of inappetence, ruminal stasis and scant
feces.

About one-third of affected cattle
become progressively worse over a period
of 2-18 days with moderate to severe
dyspnea, and die of acute or chronic
anemia or are euthanized on humane
grounds. Almost half of the cases die
suddenly as a result of voluminous intra-
bronchial hemorrhage. It is probably the
only common cause in cattle of acute
hemorrhage from the respiratory tract
that causes the animal to literally drop
dead. The remainder have a brief, acute
illness of about 24 hours.

Some evidence of hepatic involvement
is often present, including enlargement of
the liver, ascites, and melena. Chronic cor
pulmonale develops in some with attend-
ant signs of congestive heart failure.

Radiography of the thorax of some
affected animals has found an increase in
lung density and markings. These are
irregular, focal or diffuse, and nonspecific.
More distinct opacities are present in
some and are referable to embolic infarcts
and larger pulmonary hemorrhages.
Radiographic abnormalities in the lungs
are detected in approximately one-third
of cows with caudal vena cava thrombosis. 2
Ultrasonography can be a useful
diagnostic aid in detecting changes in the
caudal vena cava. 2,3 The caudal vena cava
in affected cows is round to oval rather

Diseases of the lungs

5

than the triangular shape in normal
cattle, 2 and the hepatic, splenic, and portal
veins can be dilated.

There is typically anemia and leuko-
cytosis. Neutrophilia with a regenerative |
left shift and hypergammaglobulinemia I
due to chronic infection are common, j
Serum gamma-glutamyl transpeptidase i
activity is high in about one-third of cases. 2 j

The necropsy findings include a i
large, pale thrombus in the posterior vena ;
cava between the liver and the right
atrium. Occlusion of the posterior vena
cava results in hepatomegaly and ascites.
Hepatic abscesses of varying size and
number are common and often near the !
wall of the thrombosed posterior vena j
cava. 2 Pulmonary thromboembolism with
multiple pulmonary abscesses, suppurative
pneumonia and erosion of pulmonary
arterial walls with intrapulmonary hemor-
rhage are also common. The lungs reveal
emphysema, edema, and hemorrhage. A
variety of bacteria including streptococci,

E. coli, staphylococci and F. necrophorum
are found in the abscesses in the liver.

Animals that die suddenly are found
lying in a pool of blood and necropsy
reveals large quantities of clotted blood in
the bronchi and trachea.

The disease must be differentiated
from verminous pneumonia, chronic aspir-
ation pneumonia, pulmonary endarteritis
due to endocarditis, and chronic atypical
interstitial pneumonia. There is no
treatment that is likely to have any effect
on the disease and the principal task is to
recognize the disease early and slaughter
the animal for salvage if possible.

REFERENCE

1. Milne MH et al. Vet Rec 2001; 148:341.

2. Braun U et al. Vet Rec 2002; 150:209.

3. Braun U et al. Schweiz Arch Tierheilkd 1992;

134:235.

CRANIAL VENA CAVAL
THROMBOSIS

Thrombosis of the cranial vena cava
occurs in cows. 1 Cases in young animals
are also recorded and it is suggested that
they arise from navel infection. Clinical
signs include cough, tachypnea, muffled
heart sounds, exercise intolerance, and
excessive pleural fluid. As in caudal vena
caval thrombosis a number of pulmonary
abscesses develop. Pulmonary hyper-
tension is not a feature as it is in the
caudal lesion. However, increased jugular
vein pressure, dilatation of the jugular
vein and local edema may all occur. Ultra-
sound examination can reveal thrombosis
of the cranial vena cava extending into the
right atrium. 1

REFERENCE

1. Bueno AC et al. Vet Radiol Ultrasound 2000;

41:551.

PULMONARY ABSCESS

The development of single or multiple
abscesses in the lung causes a syndrome
of chronic toxemia, cough, and emaci- j
ation. Suppurative bronchopneumonia j
may follow. i

ETIOLOGY

Pulmonary abscesses may be part of a
primary disease or arise secondarily to
diseases in other parts of the body.

Primary diseases I

» R. equi pulmonary abscesses of foals 1 !
° S. zooepidemicus and Actinobacillus sp. j
in adult horses. 2 One-third of
infectious causes of abscesses in horses j
are polymicrobial, and anaerobic '

bacteria are isolated in 20% of cases 2 j
° Sequestration of an infected focus,
e.g. strangles in horses, caseous
lymphadenitis in sheep
° Tuberculosis

Actinomycosis rarely occurs as
granulomatous pulmonary lesions
0 Aerogenous infections with 'systemic'
mycoses, e.g. coccidioidomycosis,
aspergillosis, histoplasmosis,
cryptococcosis, and moniliasis
Helcococcus ovis in horses 3
° Mycoplasma bovis in cattle. 4

Secondary diseases

o Sequestration of an infected focus of
pneumonia, e.g. bovine
pleuropneumonia or
pleuropneumonia in horses
;l Pulmonary abscesses secondary to
ovine estrosis 5

° Emboli from endocarditis, caudal or
cranial vena caval thrombosis,
metritis, mastitis, omphalophlebitis
° Aspiration pneumonia from milk
fever in cows, drenching accident in
sheep - residual abscess
° Penetration by foreign body in
traumatic reticuloperitonitis.

PATHOGENESIS

Pulmonary abscesses may be present in
many cases of pneumonia and are not
recognizable clinically. In the absence of
pneumonia, pulmonary abscess is usually
a chronic disease, clinical signs being
produced by toxemia rather than by
interference with respiration. However,
when the spread is hematogenous and
large numbers of small abscesses develop
simultaneously, tachypnea occurs. In
these animals the respiratory embarrass-
ment cannot be explained by the reduc- |
tion in vital capacity of the lung. However,
in more chronic cases the abscesses may
reach a tremendous size and cause respir-
atory difficulty by obliteration of large
areas of lung tissue. In rare cases, erosion
of a pulmonary vessel may occur, resulting
in pulmonary hemorrhage and hemoptysis.

In many cases there is a period of
chronic illness of varying degree when the
necrotic focus is walled off by connective
tissue. Exposure to environmental stress
or other infection may result in a sudden
extension from the abscess to produce a
fatal, suppurative bronchopneumonia,
pleurisy, or empyema.

CLINICAL FINDINGS

In typical cases there is dullness, anorexia,
emaciation and a fall in milk yield in
cattle. The temperature is usually mod-
erately elevated and fluctuating. Cough-
ing is marked. The cough is short and
harsh and usually not accompanied by
signs of pain. Intermittent episodes of
bilateral epistaxis and hemoptysis may
occur, which may terminate in fatal
pulmonary hemorrhage following erosion
of an adjacent large pulmonary vessel.
Respiratory signs are variable depending
on the size of the lesions, and although
there is usually some increase in the rate
and depth this may be so slight as to
escape notice. When the abscesses are
large (2-4 cm in diameter) careful auscul-
tation and percussion will reveal the
presence of a circumscribed area of
dullness over which no breath sounds are
audible. Crackles are often audible at the
periphery of the lesion.

Multiple small abscesses may not be
detectable on physical examination but
the dyspnea is usually more pronounced.
There may be a purulent nasal discharge
and fetid breath but these are unusual
unless bronchopneumonia has developed
from extension of the abscess. Radiographic
examination can be used to detect the
presence of the abscess and give some
information on its size and location. 1

Most cases progress slowly and many
affected animals have to be euthanized
because of chronic ill-health; others die
from bronchopneumonia or emphysema.
Persistent fever, tachycardia, and polypnea
are common. A rare sequel is the
development of hypertrophic pulmonary
osteoarthropathy.

The clinical findings of R. equi pulmon-
ary abscessation in young foals are
presented under that disease.

Solitary lung abscesses are not un-
common in adult horses. Presenting signs
are usually low-grade fever and depression.
Most horses with lung abscesses cough.
There is excessive mucopurulent material
in the trachea and examination of a
tracheal aspirate reveals neutrophilic
inflammation. Radiographic examination
of the chest demonstrates the presence of
one or more abscesses. Abscesses are in
the caudal lung lobes in 60% of cases. 2
! Ultrasonography can be useful in detect-
j ing the abscess provided that it is
j confluent with the visceral pleura. The

8

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

prognosis for life and for return to racing
is excellent in horses that are treated
appropriately. 2

CLINICAL PATHOLOGY

Examination of nasal or tracheal mucus
may determine the causative bacteria but
the infection is usually mixed and
interpretation of the bacteriological find-
ings is difficult. Culture of tracheal
aspirates yields growth of pathogenic
bacteria in approximately 70% of samples
from horses with lung abscesses. 2
Hematological examination may give an
indication of the severity of the inflam-
matory process but the usual leukocytosis
and shift to the left may not be present
when the lesion is well-encapsulated. In
lung abscesses in foals and adult horses,
hyperfibrinogenemia and neutrophilic
leukocytosis are common. 1

NECROPSY FINDINGS

An accumulation of necrotic material in a
thick-walled fibrous capsule is usually
present in the ventral border of a lung,
surrounded by a zone of broncho-
pneumonia or pressure atelectasis. In
sheep there is often an associated
emphysema. In rare cases the abscess
may be sufficiently large to virtually
obliterate the lung. A well-encapsulated
lesion may show evidence of recent
rupture of the capsule and extension as an
acute bronchopneumonia. Multiple small
abscesses may be present when hemato-
genous spread has occurred.

DIFFERENTIAL DIAGNOSIS

The diagnosis might not be obvious when
respiratory distress is minimal and
especially when multiple, small abscesses
are present. These cases present a
syndrome of chronic toxemia which may
be mistaken for splenic or hepatic abscess.
Differentiation between tuberculous lesions
and nonspecific infections may require the
use of the tuberculin test. Focal parasitic
lesions, such as hydatid cysts, may cause a
similar syndrome, but are not usually
accompanied by toxemia or hematological
changes. Pulmonary neoplasms usually
cause chronic respiratory disease, a
progressive loss of weight and lack of
toxemia.

TREATMENT

Pulmonary abscesses secondary to
pneumonia in cattle and pigs are usually
not responsive to therapy. The daily
administration of large doses of anti-
microbials for several days may be
attempted but is usually not effective and
slaughter for salvage or euthanasia is
necessary. Treatment of pulmonary
abscesses in adult horses by adminis-
tration of broad-spectrum antimicrobials
is usually effective. 1,2 Most (> 80%)

racehorses with single abscesses return to
racing. 2

There is a report of diagnosis of
pulmonary abscess and bronchopleural
fistula in a filly by thoracoscopy and
partial pneumonectomy. 6 The unusual
feature of this case was the presence of a
bronchopleural fistula that necessitated
surgical correction. As noted above,
almost all horses with solitary pulmonary
abscesses recover with antimicrobial
therapy.

REVIEW LITERATURE

Roy MF, Lavoie JP. Diagnosis and management of

pulmonary abscesses in the horse. Equine Vet

Educ 2002; 14:322.

REFERENCES

1. Lavoie JP et al. Equine Vet J 1994; 26:348.

2. Ainsworth DM et al. J Am Vet Med Assoc 2000;

216:1283.

3. Rothschild CM et al. J Clin Microbiol 2004;

42:2224.

4. Adegboye DS et al. JVet Diagn Invest 1995; 7:333.

5. Dorchies P et al. Vet Rec 1993; 133:325.

6. Sanchez LC et al. Equine Vet Educ 2002; 14:290.

PULMONARY AND PLEURAL
NEOPLASMS

Primary neoplasms of the lungs, including
carcinomas and adenocarcinomas, are
rare in animals and metastatic tumors
also are relatively uncommon in large
animals. Primary tumors reported in
lungs or pleura of the farm animal species
include:

° Horses:

° Granular cell tumors are the most
common tumor arising in the
pulmonary tissue of horses

° Malignant melanomas in adult
gray horses

° Pulmonary adenocarcinoma (either
primary or as metastatic disease)

° Pulmonary leiomyosarcoma 1

° Bronchogenic carcinoma,
pulmonary carcinoma,
bronchogenic squamous cell
carcinoma, pulmonary
chondrosarcoma and bronchial
myxoma are all rare tumors in
lungs of horses

° Mesothelioma arise from the
visceral or parietal pleura
0 Cattle:

° Pulmonary adenocarcinoma is the
most commonly reported primary
lung tumor in cattle. 2 The
ultrastructure and origin of
some of these have been
characterized

° Lymphomatosis in young cattle
may be accompanied by
pulmonary localization
° Sheep:

° Ovine pulmonary adenocarcinoma
(jaagsiekte sheep retrovirus)

° Goats:

0 An asymptomatic, squamous-cell
type tumor, thought to be a benign
papilloma, has been observed in 10
of a series of 1600 adult Angora
goats. The lesions were mostly in
the diaphragmatic lobes, were
multiple in 50% of the cases and
showed no evidence of
malignancy, although some had
necrotic centers.

A wide variety of tumors metastasize to
the lungs and these tumors can originate
in almost any tissue or organ. A series of
thoracic neoplasms in 38 horses included
lymphosarcoma, metastatic renal cell
carcinoma, primary lung carcinomas,
secondary cell carcinoma from the stomach,
pleural mesothelioma, and malignant
melanoma. 3

The etiology of the tumors is unknown
in most cases, apart from those arising
from viral infections. Equine granular cell
tumors arise from the Swann cells of the
peripheral nervous system in the lungs. 4

Characteristically, primary pulmonary
or pleural tumors arise in middle-aged to
old animals. The prevalence of these
tumors is not well documented, although
they are rare in abattoir studies of horses. 5
The tumors occur sporadically, with the
exception of those associated with infec-
tious agents (bovine lymphomatosis,
ovine pulmonary adenocarcinoma).

The pathogenesis of pulmonary tumors
includes impairment of gas exchange,
either by displacement of normal lung
with tumor tissue and surrounding
atelectasis and necrosis, or obstruction of
the large airways (e.g. granular cell tumor
in horses).

CLINICAL FINDINGS

Clinical findings are those usually associ-
ated with the decrease in vital capacity of
the lungs and include dyspnea that
develops gradually, cough and evidence
of local consolidation on percussion and
auscultation. There is no fever or toxemia
and a neoplasm may be mistaken for a
chronic, encapsulated pulmonary abscess.
Major clinical findings included weight
loss, inappetence, and dyspnea and
coughing. An anaplastic small-cell
carcinoma of the lung of a 6-month-old
calf located in the anterior thorax caused
chronic bloat, anorexia, and loss of body
weight. 6 Some tumors, notably meso-
thelioma and adenocarcinoma, cause
accumulation of pleural fluid. 7,8 Hyper-
trophic pulmonary osteopathy occurs in
some animals with pulmonary tumors. 9

Granular cell tumors in horses
present as chronic coughing and exercise
intolerance in horses without signs of
infectious disease. 10 As the disease
progresses there is increased respiratory

Diseases of the pleura and diaphragm

519

rate and effort and weight loss, suggestive
of severe heaves. However, horses are
unresponsive to treatment for heaves. The
disease can progress to cor pulmonale
and right-sided heart failure. A bronchial
mass is evident on radiographic or endo-
scopic examination. There are no charac-
teristic hematologic or serum biochemical
changes.

Hemangiosarcomas of the thoracic
cavities of horses occur and are evident as
excess pleural fluid with a high red blood
cell count. 11-12

Thymoma, or lymphosarcoma as a

part of the disease bovine viral leukosis, is
not uncommon in cattle and may resemble
pulmonary neoplasm but there is usually
displacement and compression of the
heart, resulting in displacement of the
apex beat and congestive heart failure.
The presence of jugular engorgement,
ventral edema, tachycardia, chronic
tympany and hydropericardium may
cause a mistaken diagnosis of traumatic
pericarditis. Mediastinal tumor or abscess
may have a similar effect. Metastasis to
the bronchial lymph nodes may cause
obstruction of the esophagus with
dysphagia, and in cattle chronic ruminal
tympany. This tumor is also common in
goats, many of which show no clinical
illness.

Radiographic or ultrasonographic

examination is useful in demonstrating
the presence of a mass in the lungs or
thorax. 13 Endoscopic examination is
useful for detection of tumors that invade
the larger airways, such as granular cell
tumors of horses. Thoracoscopy and
pleural biopsy can be useful in the diag-
nosis of lesions at the pleural surfaces. 8

The nature of the tumor can some-
times be determined by examination of
pleural fluid, into which some tumors
shed cells, or of tumor tissue obtained by
biopsy. Examination of pleural fluid for
the presence of tumor cells is not very
sensitive as many tumors do not shed
sufficient numbers of cells to be detect-
able, but is quite specific in that detection
of abnormal cells is diagnostic.

TREATMENT

There is no effective treatment with the
exception of resection of localized tumors.
Granular cell tumors in horses have been
successfully treated by lung resection 14 or
transendoscopic electrosurgery. 15

REFERENCES

1. Rossdale PD et al. Equine Vet Educ 2004; 16:21.

2. Charan K et al. Vet Rec 1996; 138:163.

3. MairTS, Brown PJ. Equine Vet J 1993; 25:220.

4. KagawaY et al. J Comp Pathol 2001; 124:122.

5. Cotchin E et al. Vet Rec 1975; 97:339.

6. Piercy DWT et al.Vet Rec 1993; 132:386.

7. Foreman JH et al. J Am Vet Med Assoc 1990;
197:269.

8. Fry MM et al. Equine Vet J 2003; 35:723.

9. HeinolaT et al.Vet Rec 2001; 149:307.

10. Pusterla N et al.Vet Rec 2004; 153:530.

11. Freestone JF et al. AustVet J 1990; 67:269.

12. Rossier Y et al. J Am Vet Med Assoc 1990;
196:1639.

13. MairTS et al. Equine Vet Educ 2004; 16:30.

14. Facemire PR et al. J Am Vet Med Assoc 2000;
217:152.

15. Ohnesorge B et al. Vet Surg 2002; 31:375.

Diseases of the pleura and
diaphragm

HYDROTHORAX AND
HEMOTHORAX

The accumulation of edematous transudate
or whole blood in the pleural cavities is
manifested by respiratory embarrassment
caused by collapse of the ventral parts of
the lungs.

ETIOLOGY

Hydrothorax and hemothorax occur as
part of a number of diseases.

Hydrothorax

® As part of a general edema due to
congestive heart failure or
hypoproteinemia

• As part of African horse sickness or
bovine viral leukosis
° Chylous hydrothorax, very rarely due
to ruptured thoracic duct
° Secondary to thoracic neoplasia
° Yellow wood ( Temiinalia oblongata)
poisoning of sheep
® Dilated cardiomyopathy of
Holstein-Friesian cattle. 1

Hemothorax

0 Traumatic injury to thoracic wall, a
particular case of which is rib fractures
in newborn foals 2
° Hemangiosarcoma of pleura
0 Lung biopsy

° Strenuous exercise by horses. 3

PATHOGENESIS

Accumulation of fluid in the pleural
cavities causes compression atelectasis of
the ventral portions of the lungs and the
degree of atelectasis governs the severity
of the resulting dyspnea. Compression of
the atria by fluid may cause an increase in
venous pressure in the great veins,
decreased cardiac return and reduced
cardiac output. Extensive hemorrhage into
the pleural space can cause hemorrhagic
shock.

CLINICAL FINDINGS

In both diseases there is an absence of
systemic signs, although acute hemor-
rhagic anemia may be present when
extensive bleeding occurs in the pleural
cavity. There is dyspnea, which usually
develops gradually, and an absence of
breath sounds, accompanied by dullness
on percussion over the lower parts of the

chest. In thin animals the intercostal
spaces may be observed to bulge. If
sufficient fluid is present it may cause
compression of the atria and engorge-
ment of the jugular veins, and a jugular
pulse of increased amplitude may be
present. The cardiac embarrassment is not
usually sufficiently severe to cause con-
gestive heart failure, although this disease
may already be present.

The accumulation of pleural fluid or
blood is evident on radiographic or ultra-
sonographic examination of the thorax.
Large quantities of blood in the pleural
cavity have a characteristic swirling,
turbulent appearance.

CLINICAL PATHOLOGY

Thoracocentesis may yield a flow of clear
serous fluid in hydrothorax, or blood in
recent cases of hemothorax. The fluid is
bacteriologically negative and total
nucleated cell counts are low (< 5 x 10 9 /L,
< 5000 x 10 6 /dL).The pH, Pco^ and lactate
and glucose concentrations of pleural
fluid in animals with hydrothorax are
similar to those of blood.

NECROPSY FINDINGS

In animals that die of acute hemorrhagic
anemia resulting from hemothorax, the
pleural cavity is filled with blood, which
usually has not clotted, the clot having
been broken down by the constant
respiratory movement. Hydrothorax
is not usually fatal but is a common
accompaniment of other diseases, which
are evidenced by their specific necropsy
findings.

DIFFERENTIAL DIAGNOSIS

Hydrothorax and hemothorax can be
differentiated from pleurisy by the absence
of pain, toxemia and fever and by the
sterility of an aspirated fluid sample.

TREATMENT

Treatment of the primary condition is
necessary. If the dyspnea is severe,
aspiration of fluid from the pleural sac
causes a temporary improvement but
the fluid usually reaccumulates rapidly.
Parenteral coagulants and blood trans-
fusion are rational treatments in severe
hemothorax.

REFERENCES

1. Nart P et al.Vet Rec 2004; 18:355.

2. Schambourg MA et al. Equine Vet J 2003; 35:78.

3. Perkins G et al. J Vet Intern Med 1999; 13:375.

PNEUMOTH ORAX

Pneumothorax refers to the presence of
air (or other gas) in the pleural cavity.
Entry of air into the pleural cavity in
sufficient quantity causes collapse of the
lung and impaired respiratory gas

520

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

exchange with consequent respiratory
distress.

ETIOLOGY

Pneumothorax is defined as either spon-
taneous, traumatic, open, closed, or
tension. Spontaneous cases occur without
any identifiable inciting event. Open
pneumothorax describes the situation in
which gas enters the pleural space other
than from a ruptured or lacerated lung,
such as through an open wound in the
chest wall. Closed pneumothorax refers to
gas accumulation in the pleural space in
the absence of an open chest wound.
Tension pneumothorax occurs when a
wound acts as a one-way valve, with air
entering the pleural space during
inspiration but being prevented from
exiting during expiration by a valve -like
action of the wound margins. The result is
a rapid worsening of the pneumothorax.
The pneumothorax can be unilateral or
bilateral. The complete mediastinum of
most cattle and horses means that in
most instances the pneumothorax is
unilateral, provided that the leakage of air
into the pleural space occurs on only one
side of the chest.

Rupture of the lung is a common
cause of pneumothorax and can be either
secondary to thoracic trauma, for example
a penetrating wound that injures the lung,
or lung disease. Most cases of pneumo-
thorax in cattle are associated with
pulmonary disease, notably broncho-
pneumonia and interstitial pneumonia. 1
Pleuropneumonia is the most common
cause of pneumothorax in horses. 2
Pneumothorax in these instances results
from 'spontaneous' rupture of weakened
lung or development of bronchopleural
fistula.

Trauma to thoracic wall can lead to
pneumothorax when a wound penetrates
the thoracic wall, including the parietal
pleura. In cattle, the thoracic wall may be
punctured accidentally by farm machinery
being used around cattle, as for example
when bales of hay are being moved
among animals. Penetrating wounds of
the thoracic wall are common causes in
horses that impale themselves on fence
posts and other solid objects. 2,3 A special
case of perforating lung injury occurs in
newborns in which the rib is fractured
during birth and the lung lacerated by the
sharp edges of the fractured rib. 4 Bullet
and arrow wounds to the chest are not
uncommon causes of pneumothorax in
regions in which hunting is common.

Pneumothorax also occurs during
thoracotomy, thoracoscopy or drainage of
pleural or pericardial fluid. Pneumothorax
can result from injury or surgery to the
upper respiratory tract, presumably
because of migration of air around the

trachea into the mediastinum and sub-
sequent leakage into the pleural space. 1,2,5
Similarly, subcutaneous emphysema leads
to pneumothorax via the mediastinum. 5

PATHOGENESIS

Entry of air into the pleural cavity results
in collapse of the lung. There can be
partial or complete collapse of the lung.
Collapse of the lung results in alveolar
hypoventilation, hypoxemia, hypercapnia,
cyanosis, dyspnea, anxiety, and hyper-
resonance on percussion of the affected
thorax. Tension pneumothorax can also
lead to a direct decrease in venous return
to the heart by compression and collapse
of the vena cava.

The degree of lung collapse varies with
the amount of air that enters the cavity;
small amounts are absorbed very quickly
but large amounts may cause fatal anoxia.

CLINICAL FINDINGS

There is an acute onset of inspiratory
dyspnea, which may terminate fatally
within a few minutes if the pneumothorax
is bilateral and severe. If the collapse
occurs in only one pleural sac, the rib cage
on the affected side collapses and shows
decreased movement. There is a com-
pensatory increase in movement and
bulging of the chest wall on the unaffected
side. On auscultation of the thorax, the
breath sounds are markedly decreased in
intensity and commonly absent. The
mediastinum may bulge toward the
unaffected side and may cause moderate
displacement of the heart and the apex
beat, with accentuation of the heart
sounds and the apex beat. The heart
sounds on the affected side have a
metallic note and the apex beat may be
absent. On percussion of the thorax on
the affected side, a hyperresonance is
detectable over the dorsal aspects of the
thorax.

Affected animals are anxious, tachypneic
and in variable degrees of respiratory
distress. Because many cases of pneumo-
thorax in cattle and horses are secondary
to lung disease, particularly infectious
lung disease, 1,2 there are usually signs of
the inciting disease, including fever,
toxemia, purulent nasal discharge and
cough. Pneumothorax secondary to chest
wall trauma is usually readily apparent,
although fractured ribs that lacerate the
lung and cause pneumothorax or hemo-
thorax can be easily missed on physical
examination, especially in newborns.

Definitive diagnosis is based on demon-
stration of pneumothorax by radiographic
or ultrasonographic examination. Radi-
ography permits the detection of bilateral
and unilateral pneumothorax and permits
identification of other air leakage syn-
dromes, including pneumomediastinum,
pneumoperitoneum, and pneumo-

pericardium. 1,2 Many cattle with pneu-
monia and pneumothorax have radio-
graphic evidence of emphysematous
bullae. 1 Ultrasonography is also useful in
determining the extent of pneumothorax
and the presence of consolidated lung
and pleural fluid.

Complications of pneumothorax,
other than respiratory distress and death,
include septic pleuritis secondary to
contamination of the pleural space, either
secondary to trauma or from ruptured
infected lung.

The prognosis depends on the under-
lying disease and its severity. Of 30 cattle
with pneumothorax, mostly secondary to
pneumonia, 18 survived, eight were
euthanized and four died. 1 Of 40 horses
with pneumothorax, 23 survived, 12 were
euthanized and five died. 2 The prognosis
is better for animals with traumatic
pneumothorax or that secondary to
surgery than for animals with pneumo-
thorax due to pneumonia. 1,2

CLINICAL PATHOLOGY

Hematological and serum biochemical
values are indicative of the underlying or
concurrent disease - pneumothorax causes
no specific changes in these variables.
Arterial blood gas analysis reveals
hypoxemia and hypercapnia.

NECROPSY FINDINGS

The lung in the affected sac is collapsed.
In cases where spontaneous rupture
occurs there is discontinuity of the pleura,
usually over an emphysematous bulla.
Hemothorax may also be evident.

DIFFERENTIAL DIAGNOSIS

The clinical findings are usually diagnostic.
Diaphragmatic hernia may cause similar
clinical signs but is relatively rare in farm
animals. In cattle, herniation is usually
associated with traumatic reticulitis and is
not usually manifested by respiratory
distress. Large hernias with entry of liver,
stomach, and intestines cause respiratory
embarrassment, a tympanitic note on
percussion and audible peristaltic sounds
on auscultation.

TREATMENT

The treatment depends on the cause of
the pneumothorax and the severity of the
respiratory distress and hypoxemia.
Animals should receive treatment for the
underlying disease. Animals with closed
pneumothorax that are not in respiratory
distress or hypoxemic do not require
specific treatment for the pneumothorax
although the animal should be confined
and prevented from exercising until the
signs of pneumothorax have resolved. An
open pneumothorax, due to a thoracic
wound, should be surgically closed.

Diseases of the pleura and diaphragm

521

Emergency decompression of the pleural
cavity using a needle into the pleural cavity
connected to a tubing and submerged into
a flask of saline or water, creates a water-
seal drainage. Thoracostomy tubes attached
to Heimlich thoracic drainage valves are
effective in preventing aspiration of air. 3
Continuous suction, using thoracostomy
(e.g. 24 French, 40 cm (16 in) Argyle trocar
thoracic catheter) and a standard three-
bottle water seal drainage system or
commercial equivalent is preferable if there
are large continuing air leaks that may be
life-threatening. 3,7 Reinflation of the lung
can be monitored by repeated ultrasonic
examination. The animal should be kept as
quiet as possible and permitted no exercise.
Prophylactic antimicrobial treatment is
advisable to avoid the development of
pleurisy.

REFERENCES

1. Slack J A et al.J Am Vet Med Assoc 2004; 225:732.

2. Boy MG, Sweeney CR. J Am Vet Med Assoc 2000;
216:1955.

3. Laverty S et al. Equine Vet J 1996; 28:220.

4. Nart P et al. Vet Rec 2004; 18:355.

5. Kelly G et al. Irish Vet J 2003; 56:153.

6. Hance SR, Robertson JT. J Am Vet Med Assoc
1992; 200:1107.

7. Peek SF et al. JVet Intern Med 2003; 17:119.

DIAPHRAGMATIC HERNIA

Diaphragmatic hernia is uncommon in
farm animals. It occurs in cattle, especially
in association with traumatic reticulo-
peritonitis, 1,2 in which case the hernia is
small and causes no respiratory distress
and there may be no abnormal sounds in
the thorax. Diaphragmatic hernias in
horses are usually traumatic, in that there
is a tear in the diaphragm, although a
specific traumatic episode is not always
identified. Collision with a motor vehicle
can cause diaphragmatic hernia in horses.
The disease is reported in a gelding after
steeplechase racing and can occur in
mares during or after parturition. 3

CLINICAL FINDINGS

Clinical findings include chronic or
recurrent ruminal tympany caused by
herniation of reticulum preventing its
normal function in eructation. Muffled
heart sounds may be detectable on both
sides of the thorax.

Occasional cases of acquired hernia
not caused by foreign body perforation
also occur in cattle and horses.

Some of the acquired diaphragmatic
hernias in the horse are of long duration
with an additional factor, such as the
passage of a stomach tube or transpor-
tation, precipitating acute abdominal
pain. In a case of traumatic hernia in a
foal, a lack of exercise tolerance was the
only clinical sign. Colic and dyspnea may
occur as prominent clinical findings and

usually as acute episodes. 3,4 In some there
is a history of recent thoracic trauma,
although this can be severe months
previously. Affected horses may have one
or all of the following: tachypnea, painful or
forced respirations. Colic can be sudden
and severe but is usually preceded by
intermittent episodes in the preceding days
to months. The colic is a severe one, with
the herniated intestine likely to become
ischemic and necrotic. All the indications
for exploratory laparotomy may be
present except that the rectal findings are
negative. Although the intestine may be
incarcerated, abdominocentesis is likely to
be negative but blood-stained fluid is
present in the thoracic cavity. Clinical signs
suggesting that the blood supply to the
herniated intestine is compromised, but
which are not accompanied by abnormal
peritoneal fluid, suggest that the lesion is
in the thorax, scrotum, or omental bursa. 5

The presence of intestinal sounds in the
thorax can be misleading; they are often
present in the normal animal but their
presence, accompanied by dyspnea and
resonance on percussion, should arouse
suspicion. Radiography, ultrasonography,
thoracoscopy and exploratory laparotomy
are the most useful diagnostic procedures. 6
Radiography reveals the presence of gas-
and fluid-filled intestinal contents in the
thorax, apparent in cattle as oval rounded
masses over the heart. 7 Ultrasonography
demonstrates presence of bowel in the
thorax. There can be excessive pleural fluid.

Congenital hernias occur in all
species and the defects are usually large,
are in the dorsal tendinous part of the
diaphragm and have thin edges. Because
of the large size of the defect, much of the
abdominal viscera, including liver,
stomach and intestines, enters the thorax
and dyspnea is evident at birth. In some
cases the pericardial sac is incomplete and
the diaphragm is rudimentary and in the
form of a small fold projecting from the
chest wall. Affected animals usually sur-
vive for a few hours to several weeks. In
pigs a number of animals in each litter
may be affected. Surgical repair has been
performed in neonates, and successful
surgical intervention is recorded in one
horse, but the prognosis is usually poor.

The definitive treatment of acquired or
traumatic hernia is surgical replacement
of viscera in the abdomen and repair of
the defect in the diaphragm. Repair of a
diaphragmatic hernia through a standing
thoracotomy in a cow has been described. 7

REFERENCES

1. Newton -Clarke MJ, Rebhun WC. Cornell Vet

1993; 83:205.

2. Misk NA, Semieka MA. Vet Radiol Ultrasound

2001; 42:426.

3. Dabareiner RM, White NA. J Am \fct Med Assoc

1999; 214:1517.

4. Goehring LS et al. Equine Vet J 1999; 31:443.

5. Ethell MT et al. J AmVet Med Assoc 1999; 215:321.

6. Vachon AM, Fischer AT. Equine Vet J 1998; 30:467.

7. Singh SS et al. Vet Rec 1996; 139:240.

SYNCHRONOUS DIAPHRAGMATIC
FLUTTER IN HORSES (THUMPS)

Synchronous diaphragmatic flutter in
horses is caused by an abrupt and
powerful contraction of the diaphragm
synchronous with the heart beat. Con-
traction of the diaphragm occurs because
of stimulation of the phrenic nerve as it
passes over the atria of the heart. Thumps
is often associated with electrolyte
abnormalities in horses. The disease
occurs commonly in horses used for
strenuous exercise, and in particular
horses used for endurance racing. The
disease occurs in Standardbred and
Thoroughbred race horses, and individual
animals can be affected repeatedly. This
disease also occurs sporadically in adult
horses and ponies that have not exercised,
and peripartum mares (lactation tetany).

The syndrome is characterized by a
violent hiccough occurring synchronously
with every heart beat. The lateral aspect of
the thorax and cranial abdomen appear to
jump or 'thump' regularly in affected
horses. It is often unilateral, the contrac-
tion being felt very much more strongly
on one side than the other. The horse is
distressed because the hiccough interferes
with eating, and to an extent with respir-
ation. In some cases there are additional
signs suggestive of hypocalcemia. These
include muscular rigidity and fasciculation,
and a high-stepping gait. There is
often hypocalcemia, hemoconcentration,
alkalosis and hypokalemia, hypochloremia
and elevation of creatinine phosphokinase
levels in affected horses. Hypocalcemia
can be profound. The disease is reported
as a consequence of hypocalcemia
secondary to primary hypoparathyroidism
in two Thoroughbred horses. 1

The principles of treatment are cor-
rection of abnormalities in blood electro-
lyte concentration and hydration. Treatment
with calcium borogluconate slowly and
intravenously has been followed by rapid
recovery in many cases. Some horses
require administration of balanced
isotonic polyionic electrolyte solutions
intravenously (e.g. Ringer's solution or
0.9% sodium chloride).

The pathogenesis is thought to be
related to hyperirritability of the phrenic
nerve caused by metabolic disturbances,
including hypocalcemia, and the phrenic
nerve being stimulated by each atrial
depolarization to fire with each heart
beat. The stimulation occurs because of
the close physical proximity of the heart
to the nerve in the horse. Dietary
supplementation with calcium and other

522

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

electrolytes during a ride is recommended
but excessive calcium feeding beforehand
may reduce the activity of calcium
homeostatic mechanisms, and is to be
avoided.

Regular veterinary inspection of all
horses at the mandatory stops of endurance
rides will reveal those animals with
'thumps', which should not be allowed to
proceed in the event.

REFERENCE

1. Hudson NP et al. AustVet J 1999; 77:504.

PLEURITIS (PLEURISY)

Pleuritis refers to inflammation of the
parietal and visceral pleura. Inflammation
of the pleura almost always results in
accumulation of fluid in the pleural space.
Pleuritis is characterized by varying degrees
of toxemia, painful shallow breathing,
pleural friction sounds and dull areas on
acoustic percussion of the thorax because
of pleural effusion. Treatment is often dif-
ficult because of the diffuse nature of the
inflammation.

ETIOLOGY

Pleuritis is almost always associated with
diseases of the lungs. Pneumonia can
progress to pleuritis, and pleuritis can
cause consolidation and infection of the
lungs. Primary pleuritis is usually due to
perforation of the pleural space and
subsequent infection. Most commonly
this occurs as a result of trauma, 1 but it
can occur in cattle with traumatic reticulo-
peritonitis and in any species after
perforation of the thoracic esophagus. 2

Secondary pleuritis refers to that which
develops from infectious lung disease
subsequent to the following conditions.

Pigs

0 Glasser's disease
a Pleuropneumonia associated with
Actinobacillus ( Haemophilus )
pleuropneumoniae and Haemophilus
influenzae suis

- The prevalence of pneumonia and
pleurisy in pigs examined at slaughter
represents a significant loss in
production. 3

Cattle

Secondary to Mannheimia haemolytica
pneumonia in cattle, especially feedlot
cattle, which may be related to a high
percentage of fibrotic pleural lesions
found in adult cattle examined at the
abattoir
•> Tuberculosis

Sporadic bovine encephalomyelitis

- Contagious bovine pleuropneumonia
0 Histophilus somnus infection

'> Pleural lesions are common in veal
calves examined at slaughter.

Sheep and goats

® Pleuropneumonia associated with

Mycoplasma spp, including

Mycoplasma mycoides subsp. mycoides 4

and Haemophilus spp.

0 Streptococcus dysgalactiae in ewesP

Horses

The disease in horses is discussed
separately in the next section. Rare causes
of pleurisy and pleural effusion in horses
include lymphosarcoma and equine infec-
tious anemia. Mesothelioma of the pleura
causing persistent dyspnea, pleural effusion
and death is also recorded in the horse.
Thoracic hemangiosarcoma is recorded as a
cause of chylothorax in the horse. 6

Other causes

Sporadic and nonspecific diseases may

be accompanied by pleurisy. Examples
include septicemias due to Pseudomonas
aeruginosa; bacteremia with localization
causing a primary septic pleural effusion.
In horses, the infection is usually S. equi
and the original disease is strangles. In
goats, it is usually spread from a myco-
plasmal pneumonia.

Perforation of the diaphragm occurs
in traumatic reticuloperitonitis in cattle
and goats. Spread into the pleural cavity
can occur without actual penetration of
the diaphragm, as it enters via the
lymphatics. Abomasopleural fistula second-
ary to abomasal ulceration can cause
pleuritis in cattle. 7

Chronic pleuritis is an important
cause of loss in commercial piggeries. The
prevalence can be as low as 5.6% of pigs
at slaughter in specific-pathogen-free
piggeries and as high as 27% in con-
ventional piggeries. 8

PATHOGENESIS

Contact and movement between the
parietal and visceral pleura causes pain
due to stimulation of pain end organs in
the pleura. Respiratory movements are
restricted and the respiration is rapid and
shallow. There is production of sero-
fibrinous inflammatory exudate, which
collects in the pleural cavities and causes
collapse of the ventral parts of the lungs,
thus reducing vital capacity and interfer-
ing with gaseous exchange. If the
accumulation is sufficiently severe there
may be pressure on the atria and a
diminished return of blood to the heart.
Clinical signs may be restricted to one
side of the chest in all species with an
imperforate mediastinum. Fluid is resorbed
in animals that survive the acute disease
and adhesions develop, restricting move-
ment of the lungs and chest wall but
interference with respiratory exchange is
usually minor and disappears gradually as
the adhesions stretch with continuous
movement.

In all bacterial pleuritis, toxemia is
common and usually severe. The toxemia
may be severe when large amounts of pus
accumulate.

CLINICAL FINDINGS

The clinical findings of pleuritis vary from
mild to severe, depending on the species
and the nature and severity of the
inflammation. In peracute to acute stages
of pleuropneumonia there are fever,
toxemia, tachycardia, anorexia, de-
pression, nasal discharge, coughing,
exercise intolerance, breathing distress,
and flared nostrils. The nasal discharge
depends on the presence or absence of
pneumonia. It may be absent or copious
and its nature may vary from muco-
hemorrhagic to mucopurulent. The odor cf
the breath may be putrid, which is usually
associated with an anaerobic lesion.

Pleural pain

Pleural pain (pleurodynia) is common
and manifested as pawing, stiff forelimb
gait, abducted elbows and reluctance to
move or lie down. In the early stages of
pleuritis, breathing is rapid and shallow,
markedly abdominal and movement of
the thoracic wall is restricted. The breath-
ing movements may appear guarded,
along with a catch at end-inspiration. The
animal stands with its elbows abducted
and is disinclined to move. The appli-
cation of hand pressure on the thoracic
wall and deep digital palpation of inter-
costal spaces usually causes pain mani-
fested by a grunt, a spasm of the intercostal
muscles or an escape maneuver.

Pleuritic friction sounds
These may be audible over the thoracic
wall. They have a continuous to-and-fro
character, are dry and abrasive, and do not
abate with coughing. They may be diffi-
cult to identify if there is a coincident
pneumonia accompanied by loud breath
sounds and crackles. When the pleuritis
involves the pleural surface of the peri-
cardial sac a friction rub may be heard
with each cardiac cycle and be confused
with the friction sound of pericarditis.
However, there is usually in addition a
friction sound synchronous with respiratory
movements and the pericardial rub waxes
and wanes with expiration and inspir-
ation. Pleural friction rubs are audible only
during the initial stages of the disease -
they are not audible when fluid accumu-
lates in the pleural space.

Subcutaneous edema
Subcutaneous edema of the ventral body
wall extending from the pectorals to the
prepubic area is common in horses with
severe pleuritis but is less noticeable in
other species. Presumably this edema is
due to blockage of lymphatics normally
drained through the sternal lymph nodes.

Diseases of the pleura and diaphragm

Pleural effusion

In cattle, an inflammatory pleural effu-
sion is often limited to one side because
the pleural sacs do not communicate.
Bilateral pleural effusion may indicate
either a bilateral pulmonary disease
process or a noninflammatory abnormality
such as right-sided congestive heart
failure or hypoproteinemia.

Dullness on acoustic percussion
over the fluid-filled area of the thorax is
characteristic of pleuritis in which there is
a significant amount of pleural effusion.
The dull area has a horizontal level
topline, called a fluid line, which can be
demarcated by acoustic percussion. As
exudation causes separation of the
inflamed pleural surfaces and the pleural
effusion accumulates, the pain and fric-
tion sounds diminish but do not
completely disappear. On auscultation
there may still be pleuritic friction sounds
but they are less evident and usually
localized to small areas.

In the presence of a pleural effusion,
both normal and abnormal lung sounds
are diminished in intensity, depending on
the amount of the effusion. Dyspnea may
still be evident, particularly during inspir-
ation, and a pleuritic ridge develops at the
costal arch as a result of elevation of the
ribs and the abdominal-type respiration.
However, the degree of dyspnea is often
subtle and careful clinical examination
and counting of the breathing rate is
necessary to detect the changes in
breathing.

If the pleurisy is unilateral, movement
of the affected side of the thorax is
restricted as compared to the normal side.
In cattle, the pleural effusion is commonly
unilateral on the right side but both sides
may be affected, fhin is still evident on
percussion on deep palpation of the
intercostal spaces and the animal still
stands with its elbows abducted, is
disinclined to lie down or move but is not
as apprehensive as in the early stages.
Toxemia is often more severe during this
stage, the temperature and the heart rate
are usually above normal and the appetite
is poor. A cough will be present if there is
a concurrent pneumonia and it is painful,
short and shallow. Extension of the
inflammation to the pericardium may
occur. Death may occur at any time and is
due to a combination of toxemia and
anoxia caused by pressure atelectasis.

Recovery

Animals with pleuritis characteristically
recover slowly over a period of several
days or even weeks. The toxemia usually
resolves first but abnormalities in the
thorax remain for some time because of
the presence of adhesions and variable
amounts of pleural effusion in the loculi.

Rupture of the adhesions during severe
exertion may cause fatal hemothorax.
Some impairment of respiratory function
can be expected to persist and racing
animals do not usually regain complete
efficiency. Chronic pleurisy, as occurs in
tuberculosis in cattle and in pigs, is
usually subclinical, with no acute inflam-
mation or fluid exudation occurring.

Medical imaging

Radiographic examination may reveal the
presence of a fluid line and fluid dis-
placement of the mediastinum and heart
to the unaffected side and collapse of the
lung. However, in cattle, pleural effusion
cannot be located precisely by radiography
because only laterolateral radiographs of
the thorax can be taken. 9 Ultrasonography
is superior for the visualization of small
volumes of pleural fluid that cannot be
detected by auscultation and acoustic
percussion of the thorax.

Ultrasonography

Ultrasonography is more reliable for the
detection of pleural fluid in horses and
cattle than radiography. 10,11 Pleural fluid is
easily detected as hypoechoic to anechoic
fluid between the parietal pleural surface,
diaphragm and lung (Fig. 10.2).Transudative
pleural fluid appears homogeneously
anechoic to hypoechoic. Exudative fluid is
commonly present in horses and cattle
with pleuropneumonia and often contains
echogenic material. 12 Serosanguineous or

hemorrhagic fluid is also more echogenic
than transudates. Fibrin appears as filmy
and filamentous strands floating in the
effusion with loose attachments to
the pleural surfaces. Pockets of fluid
loculated by fibrin are commonly imaged
in horses with fibrinous pleuropneumonia.
Adhesions appear as echogenic attach-
ments between the parietal and visceral
pleural surfaces; the adhesions restrict
independent motion of the surfaces. The
presence of small, bright echoes (gas
echoes) swirling in pleural or abscess fluid
is associated with anaerobic infection of
the pleural cavity. Gas echoes are usually
most abundant in the dorsal aspects of
the pleural cavity. Other lung and pleural
abnormalities that may be visualized
include compression atelectasis, consoli-
dation, abscesses and displacement of the
lung as pleural effusion accumulates.

Pleuroscopy

Pleuroscopy using a rigid or flexible
fiberoptic endoscope allows direct inspec-
tion of the pleural cavity. The endoscope
is introduced into the pleural cavity in the
10th intercostal space just above the point
of the shoulder. The lung will collapse but
pneumothorax is minimized by the use of
a purse string suture placed around the
stab incision and blunt dissection of the
fascia and muscle layers for insertion of
the endoscope. Tire diaphragm, costo-
splenic angle, aorta, mediastinal structures
and thoracic wall are clearly visible. By

Fig. 10.2 Ultrasonogram and schematic of the thorax in a cow with
pleuropneumonia due to infection with Mannheimia haemolytica. There is an
accumulation of anechoic pleural effusion, which compresses the lung. The
ultrasonogram was obtained from the distal region of the sixth intercostal
space of the left thoracic wall with a 5.0 MHz linear scanner. 1 = Thoracic wall;
2 = Anechoic fluid; 3 = Lung. Ds, Dorsal; Vt, Ventral. (Reproduced with kind
permission of U. Braun.)

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PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

entering the thorax at different locations,
the ventral lung, the pericardium and
more of the diaphragm can be visualized.
Lung and pleural abscesses and pleural
adhesions may be visible.

Prognosis

The prognosis depends on the severity
and extent of the pleuritis and the
presence of pneumonia. The presence of
dull areas over the ventral two-thirds of
the thorax on both sides and more than
about 6 L of pleural fluid in the pleural
cavity of a mature horse suggests an
unfavorable prognosis. If the disease is in
an advanced stage when first recognized
and there is extensive fibrinous inflam-
mation, the response to treatment can be
protracted and extensive long-term daily
care will be necessary. Also, the common
failure to culture the primary causative
agent, particularly in horses, makes j
specific therapy difficult.

CLINICAL PATHOLOGY
Thoracocentesis (pleurocentesis)

Thoracocentesis to obtain a sample of the
fluid for laboratory examination is necess-
ary for a definitive diagnosis. The fluid is
examined for its odor, color and viscosity,
protein concentration and presence of
blood or tumor cells, and is cultured for
bacteria. It is important to determine
whether the fluid is an exudate or a
transudate. Pleural fluid from horses
affected with anaerobic bacterial pleuro-
pneumonia may be foul-smelling.
Examination of the pleural fluid usually
reveals an increase in leukocytes up to
40 000-100 000 /j.lL and protein concen-
trations of up to 50g/L (5.0g/dL). The
fluid should be cultured for both aerobic
and anaerobic bacteria and Mycoplasma
spp.

Hematology

In peracute bacterial pleuropneumonia in
horses and cattle, leukopenia and
neutropenia with toxic neutrophils are
common. In acute pleuritis with severe
toxemia, hemoconcentration, neutropenia
with a left shift and toxic neutrophils are
common. In subacute and chronic stages
normal to high leukocyte counts are often
present. Hyperfibrinogenemia, decreased
albumin-globulin ratio and anemia are
common in chronic pleuropneumonia.

NECROPSY FINDINGS

In early acute pleurisy there is marked
edema, thickening and hyperemia of the
pleura, with engorgement of small vessels
and the presence of tags and shreds of
fibrin. These can most readily be seen
between the lobes of the lung. In the
exudative stage the pleural cavity contains
an excessive quantity of turbid fluid
containing flakes and clots of fibrin. The
pleura is thickened and the central parts

of the lung are collapsed and dark red in
color. A concurrent pneumonia is usually
present and there may be an associated
pericarditis. In the later healing stages,
adhesions connect the parietal and
visceral pleurae. Type I fibrinous adhesions
appear to be associated with pneumonia
while type II fibrinous proliferative
adhesions are idiopathic.

DIFFERENTIAL DIAGNOSIS

The diagnosis of pleuritis is confirmed by:

• The presence of inflammatory fluid in
the pleural cavity

• Pleural friction sounds, common in the
early stages of pleuritis and loud and
abrasive; they sound very close to the
surface, do not fluctuate with coughing
common in the early stages and may
continue to be detectable throughout
the effusion stage

• The presence of dull areas and a
horizontal fluid line on acoustic
percussion of the lower aspects of the
thorax, characteristic of pleuritis and the
presence of pleural fluid

• Thoracic pain, fever and toxemia are
common.

Pneumonia occurs commonly in
conjunction with pleuritis and
differentiation is difficult and often
unnecessary. The increased intensity of
breath sounds associated with
consolidation and the presence of crackles
and wheezes are characteristic of
pneumonia.

Pulmonary emphysema is

characterized by loud crackles, expiratory
dyspnea, hyperresonance of the thorax and
lack of toxemia unless associated with
bacterial pneumonia.

Hydrothorax and hemothorax are not
usually accompanied by fever or toxemia
and pain and pleuritic friction sounds are
not present. Aspiration of fluid by needle
puncture can be attempted if doubt exists.
A pleural effusion consisting of a
transudate may occur in cor pulmonale
due to chronic interstitial pneumonia in
cattle.

Pulmonary congestion and edema

are manifested by increased vesicular
murmur and ventral consolidation without
hydrothorax or pleural inflammation.

! TREATMENT

j The principles of treatment of pleuritis are
pain control, elimination of infection and
prevention of complications.

Antimicrobial therapy

The primary aim of treatment is to control
the infection in the pleural cavities using
the systemic administration of anti-
microbials, which should be selected on
the basis of culture and sensitivity of
pathogens from the pleural fluid. Before
the antimicrobial sensitivity results are
available it is recommended that broad-
spectrum antimicrobials be used. Long-

term therapy daily for several weeks may
be necessary.

Drainage and lavage of pleural
cavity

Drainage of pleural fluid removes exudate
from the pleural cavity and allows the
lungs to re-expand. Criteria for drainage
include:

° An initial poor response to treatment
° Large quantities of fluid causing

respiratory distress
° Putrid pleural fluid
• Bacteria in cells of the pleural fluid.

Clinical experience suggests that drainage
improves the outcome.

Pleural fluid can be drained using inter-
mittent thoracocentesis or indwelling chest
tubes. 3 Intermittent drainage is satisfactory
in an animal with a small amount of fluid.
Small (12-20' French) chest tubes are
temporarily inserted at 2-3-day intervals to
remove the fluid. Aspiration may not be
easy in some cases as the drainage tube
may become blocked with fibrin and
respiratory movements may result in
laceration of the lung. Drainage may be
difficult or almost impossible in cases in
which adhesion of visceral and parietal
pleura are extensive and fluid is loculated.

Indwelling chest tubes may be required
unilaterally or bilaterally depending on the
patency of mediastinal fenestration and
the degree of fluid loculation. A large bore
(24-32 French) chest tube is inserted and
secured to prevent it from sliding out.
Unidirectional drainage through the tube
is facilitated by a Heimlich valve and
monitored regularly. Pleural fluid is
allowed to drain or drip passively, since
suction often results in obstruction of the
tube with fibrin or peripheral lung tissue.
Loculation of fluid may interfere with
proper drainage and necessitate replace-
ment of tubes. Complications include
subcutaneous cellulitis or pneumothorax.

Pleural lavage may assist in removal
of fibrin, inflammatory debris, and necrotic
tissue; it can prevent loculation, dilute
thick pleural fluid and facilitate drainage.
One chest tube is placed dorsally and one
ventrally; 5-10 L of sterile, warm isotonic
saline is infused into each hemithorax by
gravity flow. After infusion, the chest tube
is reconnected to a unidirectional valve
and the lavage fluid is allowed to drain.

Thoracotomy has been used success-
fully for the treatment of pericarditis and
pleuritis and lung abscesses in cattle. 13
Claims are made for the use of dexa-
methasone at 0.1 mg/kg BW to reduce the
degree of pleural effusion. In acute cases
of pleurisy in the horse analgesics such as
phenylbutazone are valuable to relieve
pain and anxiety, allowing the horse to
eat and drink more normally.

Diseases of the pleura and diaphragm

525

Fibrinolytic therapy

Pleural adhesions are unavoidable and
may become thick and extensive with the
formation of loculation which traps
pleural fluid, all of which prevents full
recovery. However, some animals will
stabilize at a certain level of chronicity,
will survive for long periods and may be
useful for light work or as breeding
animals. Fibrinolytic agents such as
streptokinase have been used in human
medicine to promote the thinning of
pleural fluid, provide enzymatic debride-
ment of the pleurae, lyse adhesions and
promote drainage of loculi. However,
these have not been evaluated in farm
animals with pleuritis.

REFERENCES

1. Collins MB et al. J Am Vet Med Assoc 1994;
205:1753.

2. Dechant JE et al. Equine Vet J 1998; 30:170.

3. Enoe C et al. PrevVet Med 2002; 54:337.

4. Bajmocy E et al. ActaVet Hung 2000; 48:277.

5. Scott PR. Vet Rec 2000; 146:347.

6. Brink P et al. EquineVet J 1996; 28:241.

7. Costa LR et al. Can Vet J 2002; 43:217.

8. Cleveland-Nielsen A et al. Prev Vet Med 2002;
55:121.

9. Braun U et al. Vet Rec 1997; 141:12.

10. ReefVB et al. J AmVet Med Assoc 1991; 198:2112.

11. Flock M. Vet J 2004; 167:272.

12. Braun U et al. Vet Rec 1997; 141:723.

13. Ducharme NG et al. J Am Vet Med Assoc 1992;
200 : 86 .

EQUINE PLEUROPNEUMONIA
(PLEU RITIS. PLEURISY)

ETIOLOGY

Pleuropneumonia of horses is almost
always associated with bacterial infection
of the lungs, pleura, and pleural fluid. The
most common bacterial isolates from
tracheal aspirates or pleural fluid of
horses with pleuropneumonia are:

° Aerobes or facultative anaerobes

including: S. equi var. zooepidemicus,
Pasteurella spp., Actinobacillus spp.,
Enterobacteriaceae (particularly E. coli,
Klebsiella spp., and Enterobacter spp.).
Pseudomonas spp., Staphylococcus spp.
and Bordetella spp. 1-3 S. zooepidemicus
is isolated from over 60%,
Enterobacteriaceae from
approximately 40% of cases, and
Pasteurellal Actinobacillus spp. from
approximately one-third of cases. 2,3
Corynebacterium pseudotuberculosis can
cause septic pericarditis and pleuritis,
although this is an uncommon
disease. 4 Mycoplasma felis is an
unusual cause of pleuritis in horses. 5,6
R. equi, usually a cause of pneumonia
in foals, rarely causes
pleuropneumonia in
immunocompetent adult horses 7
° Obligate anaerobes, including
Bacteroides spp. (including B. fragilis

Synopsis : .

Etiology Most infections are
polymicrobial combinations of 5. equi var.
zooepidemicus, Actinobacillus sp.,
Pasteurella sp., Enterobacteriaceae and
anaerobic bacteria, including Bacillus
fragilis. Disease due to infection by a single
bacterial species occurs. Other causes are
Mycoplasma felis, penetrating chest
wounds and esophageal perforation
Epidemiology Recent prolonged
transport, racing, viral respiratory disease
and anesthesia increase the likelihood of a
horse developing pleuropneumonia.
Aspiration of feed material secondary to
esophageal obstruction or dysphagia also
causes the disease

Pathogenesis Overwhelming challenge
of oropharyngeal bacteria or reduced
pulmonary defense mechanisms allow
proliferation of bacteria in small airways,
alveoli, and lung parenchyma. Subsequent
inflammation and further spread of
infection involve the visceral pleura
Impaired drainage of pleural fluid and
increased permeability of pleural capillaries
cause the accumulation of excessive pleural
fluid, which then becomes infected. Fibrin
deposition and necrosis of lung causes
formation of intrathoracic abscesses. Death
is due to sepsis and respiratory failure
Clinical signs Fever, depression,
anorexia, respiratory distress, cough, nasal
discharge, exercise intolerance, reduced
breath sounds on thoracic auscultation and
presence of pleural fluid and pneumonia
on thoracic radiology and ultrasonography.
Chronic disease is characterized by weight
loss, increased respiratory rate, nasal
discharge, and exercise intolerance
Clinical pathology Leukocytosis,
hyperfibrinogenemia, hypoalbuminemia,
hyperglobulinemia. Pleural fluid
leukocytosis, hyperproteinemia and
presence of intra- and extracellular
bacteria. Similar findings in tracheal
aspirate

Diagnostic confirmation Clinical
signs, examination of pleural fluid
Treatment Systemic administration of
broad-spectrum antimicrobials for weeks to
months, chronic effective drainage of the
pleural space, and nursing care
Prevention Reduce exposure of horses to
risk factors including prolonged
transportation and viral respiratory
disease

and B. tectum), Prevotella spp.,
Clostridium spp., Eubacterium and
Fusobacterium spp. 1-3,8 Bacteroides sp.
are isolated from approximately 20%,
Clostridium sp. from 10%, and
Eubacterium sp. from 6% of horses
with pleuropneumonia. 2 Obligate
anaerobes are cultured from
approximately 70% of horses with
severe pneumonia. 8

Equine pleuropneumonia is associated

with polymicrobial infections of the

lungs and pleura in 50-80% of cases,
although disease associated with infec-
tion with a single bacterial species occurs. 1,2
Infections with a single bacterial species
are usually by S. zooepidemicus, Pasteurellal
Actinobacillus sp. or one of the Entero-
bacteriaceae, whereas almost all infec-
tions by anaerobes are polymicrobial. 2
Infection by obligate anaerobic bacteria is
associated with disease of more than
5-7 days' duration. 9

Pleuritis is also caused by penetrating
chest wounds, 3 perforated esophagus, 10
and thoracic neoplasia. 11 Other diseases,
such as congestive heart failure, may cause
pleural effusion without inflammation.

EPIDEMIOLOGY

Pleuropneumonia occurs worldwide in
horses of all ages and both sexes, although
most cases occur in horses more than
1 and less than 5 years of age. 2 Estimates
of the incidence or prevalence of the
disease are not available. The case
fatality ratevaries between 5% and 65%,
with the higher rate reported in earlier
studies. 12,13

Risk factors

The risk of a horse developing pleuro-
pneumonia is increased by a factor of:

o 4 if the horse is a Thoroughbred
racehorse

o 14 if the horse was transported more
than 500 miles in the previous week
o 10 if the horse has a recent (< 2 week)
history of viral respiratory tract
disease or exposure to a horse with
such disease

° 4 if the horse has raced within the
previous 48 hours 14

Other suggested risk factors include
general anesthesia, surgery, disorders of
the upper airway, exercise -induced pul-
monary hemorrhage, esophageal obstruc-
tion, and dysphagia.

PATHOGENESIS

Bacterial pleuropneumonia develops
following bacterial colonization of the
lungs with subsequent extension of
infection to the visceral pleura and pleural
space. 9 Organisms initially colonizing the
pulmonary parenchyma and pleural space
are those normally present in the upper
airway, oral cavity, and pharynx, with
subsequent infection by Enterobacteriaceae
and obligate anaerobic bacteria. 9

Bacterial colonization and infection
of the lower airway is attributable to
either massive challenge or a reduction in
the efficacy of normal pulmonary defense
mechanisms or a combination of these
factors. 9 Confinement with the head
elevated for 12-24 hours, such as occurs
during transport of horses, decreases
mucociliary transport and increases the

526

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

number of bacteria and inflammatory
cells in the lower respiratory tract and
probably contributes to the development
of lower respiratory tract disease. 14,15
Transport alters the composition of
pulmonary surfactant, which can impair
the activity of pulmonary defense mech-
anisms, allowing otherwise innocuous
bacterial contamination to cause
disease. 16,17

Overwhelming bacterial challenge
may occur in dysphagic horses, horses
with esophageal obstruction and race
horses that inhale large quantities of track
debris while racing. A single bout of
exercise on a treadmill markedly increases
bacterial contamination of the lower
airways. 18 Viral respiratory disease may
decrease the efficacy of normal lung
defense mechanisms.

Bacterial multiplication in pulmon-
ary parenchyma is associated with the
influx of inflammatory cells, principally
neutrophils, tissue destruction and
accumulation of cell debris in alveoli and
airways. Infection spreads both through
tissue and via airways. Extension of
inflammation, and later infection, to the
visceral pleura and subsequently pleural
space causes accumulation of excess fluid
within the pleural space. Pleural fluid
accumulates because of a combination of
excessive production of fluid by damaged
pleural capillaries (exudation) and impaired
reabsorption of pleural fluid by thoracic
lymphatics.

Accumulation of parapneumonic
pleural effusions has been arbitrarily
divided into three stages: exudative,
fibrinopurulent and organizational: N

1. The exudative stage is characterized
by the accumulation of sterile,
protein-rich fluid in the pleural space
as a result of increased pleural
capillary permeability

2. Bacterial invasion and proliferation,
further accumulation of fluid, and
deposition of fibrin in pleural fluid and
on pleural surfaces occurs if the disease
does not resolve rapidly and is referred
to as the fibrinopurulent stage

3. The organizational stage is
associated with continued fibrin
deposition, restriction of lung
expansion, and persistence of
bacteria. The pleural fluid contains
much cellular debris and
bronchopleural fistulas may develop.

These categorizations are useful diagnos-
tically and therapeutically.

CLINICAL SIGNS OF ACUTE DISEASE

The acute disease is characterized by the
sudden onset of a combination of fever,

depression, inappetence, cough, exercise
intolerance, respiratory distress, and nasal
discharge. The respiratory rate is usually
elevated as is the heart rate.

Nasal discharge ranges from sero-
sanguineous to mucopurulent, is usually
present in both nares and is exacerbated
when the horse lowers its head. The
breath may be malodorous, although
this is a more common finding in horses
with subacute to chronic disease. Horses
with pleuritis are often reluctant to cough
and if they do, the cough is usually soft
and gentle. Ventral edema occurs in
approximately 50% of horses with
pleuropneumonia. 3

The horse may appear reluctant to
move or may exhibit signs of chest pain,
including reluctance to move, pawing and
anxious expression, which may be mistaken
for colic, laminitis, or rhabdomyolysis.
Affected horses often stand with the elbows
abducted.

Auscultation of the thorax reveals
attenuation of normal breath sounds in
the ventral thorax in horses with signifi-
cant accumulation of pleural fluid. How-
ever, the attenuation of normal breath
sounds may be mild and difficult to
detect, especially in large or fat horses or
in horses in which there is only slight
accumulation of pleural fluid. Auscultation
of the thorax with the horse's respiratory
rate and tidal volume increased by having
it breathe with a large airtight bag over its
nostrils may reveal crackles and wheezes
in the dorsal lung fields and attenuation
of the breathe sounds ventrally. There is
often fluid in the trachea detectable as a
tracheal rattle.

Percussion of the chest wall may
reveal a clear line of demarcation below
which the normal resonant sounds are
muffled. This line of demarcation repre-
sents the dorsal limit of the pleural fluid.
Both lung fields should be examined to
identify localized areas of consolidation.
Careful percussion of the thorax is a
cheap and effective way of identifying the
presence and extent of pleural fluid
accumulation.

Ultrasonographic examination of

the thorax is a very sensitive technique
with which to detect accumulation of
pleural fluid, determine the character of
the fluid, identify localized areas of fluid
accumulation or pulmonary consolidation,
identify sites for thoracocentesis and
monitor response to treatment. 20,21 The
examination is best performed using a
3.5-5. 0 sector scanner. Linear probes,
such as those used for routine repro-
ductive examination, are adequate to
identify fluid but do not allow good
examination of all areas of the chest
accessible with sector scanners. The entire
thorax should be examined in a

systematic fashion. The presence of and
characteristics of fluid within the pleural
space, presence and location of pulmon-
ary consolidation or abscessation and
potential sites for diagnostic and therapeutic
thoracocentesis should be identified. For
horses with long-standing disease, the
area cranial to the heart should be
examined for the presence of cranial
thoracic masses (abscesses). This examin-
ation requires that the horse's ipsilateral
forelimb be placed well forward, usually
with the aid of an assistant, to allow
adequate visualization of the cranial
thorax.

o Excessive pleural fluid can be

detected by thorough
ultrasonographic examination of both
hemithoraces. Pleural fluid initially
accumulates ventrally in acute cases,
but may become localized dorsally in
chronic cases with septation of the
pleural space and trapping of fluid
° The pleural fluid may contain small
gas echoes, an indication of infection
with anaerobic bacteria and a poor
prognosis, 20 strands of fibrin or
echogenic material consistent with
cellular debris. Sterile pleural effusion,
such as may be present during the
earliest stages of the disease, is clear
and homogeneous without fibrin
strands. With increasing chronicity the
amount of fibrin increases, the
parietal and visceral pleura become
thickened, and the pleural fluid
becomes echogenic consistent with
the presence of cellular debris
° Regions of consolidated or atelectatic
lung adjacent to the visceral pleura
may be evident on ultrasonographic
examination, but lung consolidation
deeper in the lung is not evident
° Ultrasonography is more sensitive
than radiographic examination in
detection of small quantities of pleural
fluid. 21

Radiographic examination of horses
with excessive pleural fluid reveals ventral
opacity that obscures the ventral diaphrag-
matic and cardiac silhouettes. It is not
possible on radiographic examination to
differentiate accumulation of pleural fluid
from consolidation of the ventral lung
lobes. 21 Radiographic examination may
be useful in demonstrating lesions, such
as pulmonary abscesses or consolidation,
that are not confluent with the visceral
pleura and therefore not able to be
detected by ultrasonographic examination. 21

Collection of pleural fluid by
thoracocentesis of both hemithoraces
and of a tracheal aspirate is necessary to
characterize the nature of the pleural fluid
and determine the bacterial species
present (see clinical pathology). Both

Diseases of the pleura and diaphragm

tracheal aspirates and pleural fluid should
be examined in any horse with pleuro-
pneumonia as bacteria may be recovered
from one sample but not the other. 2
Examination of bronchiolar lavage fluid is
not useful in diagnosing pleuropneumonia
in horses. 22

The clinical course of the acute form
of the disease may be less than 10 days if
effective therapy is instituted before the
pleural effusion becomes infected or there
is substantial deposition of fibrin in the
pleural space. The prognosis for a return
to previous function is good in horses that
respond. However, most cases, even if
appropriate therapy is instituted, progress
to at least stage 2 of the disease process
and the disease becomes chronic.

CLINICAL SIGNS IN CHRONIC DISEASE

The chronic disease is characterized by
intermittent fever, weight loss, cough,
increased respiratory rate, nasal discharge,
malodorous breath, exercise intolerance,
and depression. Severely affected horses
may display signs of respiratory distress.
Signs of thoracic pain are less than in the
acute disease.

Findings on auscultation of the chest
are similar to those of the acute disease in
as much as there is attenuation of normal
breath sounds ventrally and the presence
of crackles and wheezes dorsally, There is
frequently ventral edema of the thorax.

Ultrasonographic examination reveals
the presence of excessive pleural fluid that
is very echogenic, consistent with it
containing cellular debris, and containing
large amounts of fibrin. The visceral and
parietal pleura are thickened and there
may be evidence of lung atelectasis,
consolidation, or abscessation. Septation
of the pleural space by fibrin and fibrous
tissue results in localized accumulation of
purulent pleural fluid. Air in the pleural
space may indicate the presence of one or
more bronchopleural fistulae.

Radiographic examination reveals a
combination of ventral opacity, pulmon-
ary consolidation, pneumothorax, and
abscessation.

Complications

Complications of pleuropneumonia
include:

Development of jugular
thrombophlebitis (25 % of cases)
Pulmonary, mediastinal, or pleural
abscesses (10-20% of cases)

Cranial thoracic mass (5-10% of
cases)

Bronchopleural fistula (5%)

Pericarditis (2%)

Laminitis (1-14 %). 3,17 ' 19

Development of intrathoracic abscesses

is evident as chronic disease, weight loss,
cough and fever, readily detected by a

combination of ultrasonographic and radio-
graphic examination.

Cranial thoracic masses are evident
as an elevation in heart rate, prominent
jugular pulse, spontaneous jugular
thrombosis, and forelimb pointing. The
signs are referable to a mass in the cranial
thorax displacing the heart caudally and
to the left and impairing venous return to
the heart in the cranial vena cava. 23
Ultrasonographic and radiographic examin-
ation reveals the presence of the mass.

Bronchopleural fistulae develop when
a section of pulmonary parenchyma
sloughs, leaving an open bronchiole that
communicates with the pleural, space. Mild
pneumothorax develops. The broncho-
pleural fistula can be diagnosed by infusion
of fluorescein dye into the pleural space and
detecting its presence at the nares, or by
pleuroscopic examination. 24,26

Prognosis

The prognosis for life for horses able to
be treated aggressively is very good
(60-95 %) 3,13 and the prognosis for return
to previous function if the horse survives
is reasonable (60%). 13 The prognosis for
return to previous function for horses that
develop chronic disease and complications
is poor (31%). 13

CLINICAL PATHOLOGY

Acute pleuropneumonia is characterized
by leukocytosis with a mature neutro-
philia, mild to moderate anemia, hyper-
fibrinogenemia, and hypoalbuminemia. 24
There are similar findings in horses with
chronic disease and hyperglobulinemia is
also usually present. Severely affected
horses with acute disease often have
hemoconcentration and azotemia.

Pleural fluid in acute cases is usually
cloudy and red to yellow. It has an increased
leukocyte number (> 10 000 cells/pL,
10 x 10 9 cells/L) comprised principally of
degenerative neutrophils, an increased
protein concentration (> 2.5 g/dL, 25 g/L)
and may contain intracellular and extra-
• cellular bacteria. 27 A Gram stain of the

I

I fluid should be examined. The pleural
i fluid should be cultured for aerobic and
! anaerobic bacteria. A putrid odor suggests
; infection by anaerobic bacteria. Sterile
pleural fluid has a pH, Po 2 and Pco 2 and
| lactate, glucose and bicarbonate concen-

■ tration similar to that of venous blood. 28
, Infected pleural fluid is acidic, hypercarbic

■ and has an increased concentration of
lactate and decreased concentrations of

; bicarbonate and glucose compared to
! venous blood. 28

Tracheal aspirates have a leukocytosis
; comprised of degenerate neutrophils with
I intra- and extracellular bacteria. Cultures
j of tracheal aspirates more frequently yield
j growth than do cultures of pleural fluid
I (90% v 66%) 2

DIAGNOSTIC CONFIRMATION

The presence of excessive pleural fluid
containing bacteria and degenerate
neutrophils in combination with clinical
signs of respiratory disease provides
confirmation of the disease.

DIFFERENTIAL DIAGNOSIS

Diseases that may cause respiratory distress

and pleural effusion in horses include:

• Intrathoracic neoplasia,
including mesothelioma,
lymphoma, and extension of
gastric squamous cell carcinoma

• Penetrating chest wounds

• Esophageal perforation

• Diaphragmatic hernia

• Congestive heart failure

• Hemangiosarcoma (causing
hemothorax)

• African horse sickness

• Pulmonary hydatidosis 29

• Pulmonary infarction and
pneumonia 30

NECROPSY FINDINGS

The pneumonia involves all areas of the
lungs but is most severe in the cranial and
ventral regions. The pleura are thickened
and have adherent fibrin tags and there is
excessive pleural fluid. The pleural fluid
contains strands of fibrin and is usually
cloudy and serosanguineous to yellow.
Histologically, there is a purulent, fibrino-
necrotic pneumonia and pleuritis.

TREATMENT

Given early recognition of the disease and
prompt institution of appropriate therapy
the prognosis for horses with pleuro-
pneumonia is favorable. However, the long
course of the disease and the associated
expense often limit therapeutic options and
make the outcome a decision based on
economic rather than medical grounds.

The principles of treatment are
prompt, broad-spectrum antimicrobial
therapy, removal of infected pleural fluid
and cellular debris, including necrotic
lung, relief of pain, correction of fluid and
j electrolyte abnormalities, relief of respir-
: atory distress, treatment of complications,
and prevention of laminitis.

Antimicrobial treatment

The prompt institution of systemic,
t broad-spectrum antimicrobial therapy

j is the single most important component
of treatment of horses with pleuro-
I pneumonia. Antimicrobial therapy is
; almost always started before the results of
j bacterial culture of pleural fluid or tracheal
i aspirate are received and the antimicrobial
j sensitivity of isolated bacteria are deter-
\ mined. Use of antibiotics or combinations
; of antibiotics with a broad spectrum of
1 antimicrobial activity is important

528

RART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

because of the polymicrobial nature of
most infections and because the wide
range of Gram-positive and Gram-
negative bacteria that may be associated
with the disease makes prediction of the
susceptibility of the causative organisms
difficult. Furthermore, superinfection with
bacteria, especially Enterobacteriaceae
and obligate anaerobes, commonly occurs
in horses with disease initially associated
with a single bacterial species. Adminis-
tration of drugs that are effective in the
treatment of penicillin-resistant obligate
anaerobes is also important.

Recommended doses for anti-
microbials used in the treatment of
pleuropneumonia are provided in Table
10.6. Antimicrobial therapy should be
broad-spectrum to include coverage of
the likely bacteria involved in the disease.
It should therefore provide coverage
against Streptococcus spp., Actinobacillus/
Pasteurella spp., Enterobacteriaceae and
anaerobes, including Bacteroides spp. A
combination of penicillin G, an amino-
glycoside and metronidazole provides
broad -spectrum coverage and is a
frequently used empirical therapy until
the results of bacterial culture are known.
Results of bacterial culture and sub-

sequent antimicrobial susceptibility
testing may aid selection of further
antimicrobials. However, superinfection
with Gram-negative and anaerobic
bacteria is common and there is a sound
rationale for continued use of a combi-
nation of antimicrobials providing broad-
spectrum coverage throughout treatment
of the disease.

Antimicrobial therapy will be pro-
longed in most cases, usually being
required for at least 1 month and often
several months. As the disease resolves it
may be possible to change from parenteral
antibiotics to orally administered anti-
biotics such as a combination of
trimethoprim-sulfonamide, although the
clinical response to this combination is
sometimes disappointing, doxycycline or
enrofloxacin.

The decision to discontinue anti-
microbial therapy should be based on
lack of fever, nasal discharge, respiratory
distress or cough, lack of evidence of
intrathoracic abscesses on ultrasonographic
and radiographic examination of the
thorax, and resolution of neutrophilia and
hyperfibrinogenemia. There should be
no appreciable pleural fluid on ultra-
sonographic examination.

Thoracic drainage

Chronic, effective drainage of the pleural
cavity and intrathoracic abscesses is
critical for successful treatment of horses
with pleuropneumonia. 31 Horses with
sterile pleural fluid may require only a
single drainage of pleural fluid. More
severely affected horses may require
intermittent drainage on each of several
days, and most cases will require insertion
of a tube into the pleural space to provide
continuous drainage for several days to
several weeks. Horses with chronic
disease may benefit from a thoracotomy
that provides continuous drainage and
the ability to lavage the chest. Ultra-
sonographic examination of the chest is
very useful in identifying the presence of
pleural fluid, the optimal sites for drainage
and the efficacy of drainage.

Intermittent thoracic drainage can
be achieved by inserting a bovine teat
cannula or similar blunt cannula into the
pleural space. This should be done
aseptically and under local anesthesia. If
ultrasonographic examination is not
available, the cannula should be placed in
the sixth to eighth intercostal space on
the right side or the seventh to ninth on
the left side just above the level of the

"lisIsUr 1 R r l-Vc 1/1.9 ? b -; ..f Vlc/ilfri

Drug

Dose, route and interval

(9# j 6) j’fi Wl " :i ^ i’BTTi • • - - :

Comments

Procaine penicillin G

22-44 OOOlU/kg IM q 12 h

Effective against Streptococcus sp. and most anaerobes with the exception of
Bacteroides fragilis. Achieves low plasma concentrations but has prolonged
duration of action. Cheap. Synergistic with aminoglycosides. Should not be
used as sole treatment

Sodium or potassium penicillin G

22-44 000 lU/kg IV q 6h

Effective against Gram-positive organisms (except penicillinase-producing
bacteria such as Staphybcoccus spp.) and most anaerobes. Achieves high
plasma concentrations. Synergistic with aminoglycosides. Expensive

Ampicillin sodium

11-22 mg/kg IV or IM q 6 h

Wider spectrum than penicillin G. Achieves high plasma concentrations.
Synergistic with aminoglycosides

Ceftiofur sodium

2.2 mg/kg IM or IV q 12 h

Wide spectrum of action against Gram-positive and Gram-negative organisms
and most anaerobes. Can be used as sole treatment, though not recommended.
Clinical results sometimes disappointing

Chloramphenicol

50 mg/kg, PO q 6 h

Good spectrum of action, including anaerobic bacteria. Poor oral bioavailability
and disappointing clinical efficacy. Use prohibited in some countries. Potential
human health hazard. Risk of diarrhea

Gentamicin sulfate

7 mg/kg, IV or IM q 24 h

Active against Staphybcoccus spp. and many Gram-negative organisms. Inactive
against anaerobes. Poor activity against Streptococcus spp. Synergistic with
penicillin

Enrofloxacin

7 mg/kg IV or PO q 24 h

Active against some Gram-positive and Gram-negative bacteria. Not good or
reliable activity against streptococci. Contraindicated in young animals because
of risk of cartilage damage

Amikacin sulfate

21 mg/kg IV or IM q 24 h

Wider spectrum of Gram-negative activity than gentamicin. Expensive

T rimethoprim-sulf onamides

15-30 mg/kg PO q 12 h

Theoretical wide spectrum of action. Disappointing clinical efficacy

Rifampin

5-1 0 mg/kg PO q 1 2 h

Penetrates abscesses well. Active against Gram-positive and some Gram-negative
bacteria. Must be used in conjunction with another antibiotic (not an
aminoglycoside)

Doxycycline

10 mg/kg PO q 12 h

Broad spectrum of activity, but resistance unpredictable. Only moderate blood
concentrations. Suitable for prolonged therapy but not treatment of the acute
disease. Risk of diarrhea

Ticarcillin— clavulanic acid

50 mg/kg IV q 6 h

Broader spectrum of Gram-negative activity than penicillin G. Expensive

Metronidazole

15-25 mg/kg PO q 6-8 h

Active against anaerobes only. Used in conjunction with other antimicrobials
(especially penicillin and aminoglycosides). Neurotoxicity rare

IV, intravenously; PO, orally; IM = intramuscularly; q, dose administered every

'h' hours.

Diseases of the pleura and diaphragm

olecranon. Pleural fluid that does not
contain large fibrin clots (which clog the
cannula) can be drained and the cannula
removed. However, the process is slow if
large quantities of fluid must be removed.
Intermittent drainage is indicated when
the quantities of pleural fluid are small
(< 5L), relatively cell free or localized.
This situation is most likely to occur in
horses with acute disease.

Insertion of large plastic chest tubes
(20-30 French, 6-10 mm outside diameter)
facilitates rapid fluid removal, allows
drainage of viscid fluid and provides
continuous drainage. The chest tube
should be inserted in an aseptic fashion
under local anesthesia at sites indicated
by ultrasonographic examination or as
described above. A one-way valve should
be attached to the external end of the tube
to prevent aspiration of air and develop-
ment of a pneumothorax. A balloon or
condom with the end removed is an
effective one-way valve. The chest tube is
secured to the chest wall with a purse-
string suture. The tube may be retained
for several days to a week, but should be
monitored frequently (every few hours)
and cleared of fibrin clots as needed.

Complications of drainage of pleural
fluid include: collapse of the animal if the
fluid is removed too rapidly; pneumothorax;
sudden death due to cardiac puncture or
laceration of a coronary vessel; and
perforation of abdominal viscera. Collapse
can be prevented by administering fluids !
intravenously during pleural fluid
drainage and by removing the fluid
gradually (over a period of 30 min). Some
horses develop a cellulitis around the
chest tube that requires that the tube be
removed.

Thoracotomy may be required in
chronic cases to provide drainage of
intrathoracic abscesses or chronic pleural
effusion that is refractory to treatment
with antimicrobials. 31 Thoracotomy is an
effective intervention in many horses with
advanced pleuropneumonia and should
not be considered an emergency or heroic
procedure.

Pleural lavage

Infusion and subsequent removal of
5-10 L of warm saline or balance polyionic
electrolyte solution into the affected
pleural space may be beneficial in the
treatment of cases with viscid fluid or
fluid containing large amounts of fibrin
and cell debris. The fluid can be infused
through the chest tube that is used to
drain the pleural space. Care should be
taken not to introduce bacteria with the
infusion.

Supportive therapy

Acutely or severely ill horses may be
dehydrated, azotemic, and have acid-base

disturbance. These horses should be
treated with appropriate fluids adminis-
tered intravenously.

Pleuropneumonia is a painful disease
and every attempt should be made to
relieve the horse's chest pain. NSAIDs,
including flunixin meglumine (1 mg/kg,
orally, intramuscularly or intravenously,
every 8h) or phenylbutazone (2.2 mg/kg,
orally or intravenously, every 12 h) often
provide effective analgesia and presumably
reduce inflammation in the pleural space.

Horses should be provided with good
nursing care, including a comfortable
stall, free access to palatable water, and a
good diet. Affected horses will often not
eat adequately and should be tempted
with fresh and nutritious fodder.

Attention should be paid to the horse's
feet to detect early signs of laminitis
and allow appropriate measures to be
taken.

CONTROL

Prevention of pleuropneumonia involves
reduction of risk factors associated with
the disease. The main risk factors are
other infectious respiratory disease and
transportation. Every effort should be
made to prevent and treat respiratory
disease in athletic horses, including
institution of effective vaccination pro-
grams. Horses with infectious respiratory
disease should not be vigorously exercised
until signs of disease have resolved.

Transportation of athletic horses is
common and essential for their partici-
] pation in competitive events. It cannot,
i therefore, be eliminated. Every effort
should be made to minimize the adverse
j effects of transportation on airway health.
; Recommendations for transport of horses
first made in 1917 are still relevant. 32,33
j Updated, these recommendations include:

Not transporting a horse unless it is
healthy. Horses with fever should not
be transported

Knowledgeable staff familiar with the
horse should accompany it
Suitable periods of rest and
acclimation should be provided before
recently transported or raced horses
are transported

The time during which horses are
confined for transportation should be
kept to a minimum. Horses should be
loaded last and unloaded first in
flights with mixed cargo
The route taken should be the most
direct and briefest available
Horses should be permitted adequate
time to rest at scheduled breaks. If
possible, on long journeys horses
should be unloaded and allowed
exercise (walking) and access to hay
and water

0 Horses should have frequent,

preferably continuous, access to feed
and water during transportation
° Horses should not be exercised after
arrival until they are free of fever,
cough, or nasal discharge
° Horses should not be restrained
during transportation such that they
are unable or unwilling to lower their
heads

° Air quality should be optimal in the
vehicle used to transport the horse.

REVIEW LITERATURE

Chaffin MK, Carter GK. Equine bacterial pleuro-
pneumonia. Part I. Epidemiology, patho-
physiology, and bacterial isolates. Compend
Contin Educ PractVet 1993; 15:1642-1650.

Chaffin MK et al. Equine bacterial pleuropneumonia:
Part II. Clinical signs and diagnostic evaluation.
Compend Contin Educ Pract Vet 1994;

16:362-378.

Chaffin MK et al. Equine bacterial pleuropneumonia:
Part III. Treatment sequelae and prognosis.
Compend Contin Educ Pract Vet 1994;

16:1585-1595.

Raidal SL. Equine pleuropneumonia. Br Vet J 1995;
151:233-262.

Racklyeft DJ et al. Towards an understanding of
equine pleuropneumonia: factors relevant for
control. AustVet J 2000; 78:334-338.

REFERENCES

1. Sweeney CR et al. J Am Vet Med Assoc 1985;
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j 2. Sweeney CR et al. J Am Vet Med Assoc 1991;

| 198:839.

| 3. Collins MB et al. J Am Vet Med Assoc 1994;

205:1753.

4. Perkins SL et al. J Am Vet Med Assoc 2004;
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5. Hoffman AM et al. Cornell Vet 1992; 82:155.

i 6. Morley PS et al. Equine Vet J 1996; 28:237. ■>

7. Vengust M et al. Can Vet J 2002; 43:706.

8. Racklyeft DJ, Love DN AustVet J 2000; 78:549.

9. Raidal SL. BrVet J 151:1995; 233-262.

10. Dechant JE et al. Equine Vet J 1998; 30:170.

11. MairTS, Brown PJ. Equine Vet J 1993; 25:220.

12. Raphel CF, Beech J. J Am Vet Med Assoc 1982;
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13. Seltzer KL, Byars TD. J Am Vet Med Assoc 1996;
20:1300.

14. Raidal SL et al. AustVet J 1995; 72:45.

15. Raidal SL et al. AustVet J 1996; 73:45.

16. Hobo S et al. Am JVetRes 1997; 58:531.

17. Hobo S et al. Vet Rec 2001; 148:74.

18. Raidal SL et al. AustVet J 1997; 75:293.

19. Chaffin MK, Carter GK. Compend Contin Educ
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20. Reimer JM et al. J Am Vet Med Assoc 1989;
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21. ReefVB et al. J Am Vet Med Assoc 1991; 198:2112.

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23. Byars TD et al. Equine \fet J 1991; 23:22.

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PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

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Diseases of the upper
respiratory tract

RHINITIS

Rhinitis (inflammation of the nasal mucosa)
is characterized clinically by sneezing,
wheezing, and stertor during inspiration
and a nasal discharge that may be serous,
mucoid, or purulent in consistency depend-
ing on the cause.

ETIOLOGY

Rhinitis usually occurs in conjunction
with inflammation of other parts of the
respiratory tract. It is present as a minor
lesion in most bacterial and viral pneu-
monias but the diseases listed are those in
which it occurs as an obvious and import-
ant part of the syndrome.

Cattle

° Catarrhal rhinitis in infectious bovine
rhinotracheitis, adenoviruses 1, 2 and
3 and respiratory syncytial virus
infections

° Ulcerative/erosive rhinitis in bovine
malignant catarrh, mucosal disease,
rinderpest

° Rhinosporidiosis caused by fungi, the
blood fluke Schistosoma nasalis and
the supposedly allergic 'summer
snuffles' also known as atopic rhinitis 1
° Familial allergic rhinitis in cattle in
which the progeny of affected cows
are susceptible to allergic rhinitis 2
' Bovine nasal eosinophilic granuloma
due to Nocardia sp. 3

Horses

Glanders, strangles, and epizootic
lymphangitis

Infections with the viruses of equine
viral rhinopneumonitis (herpesvirus-
1), equine viral arteritis, influenza
H3N8 equine rhinovirus,
parainfluenza virus, reovirus,
adenovirus

Chronic rhinitis claimed to be caused
by dust in dusty stables, and acute
rhinitis occurring after inhalation of
smoke and fumes
Nasal granulomas due to chronic
infections with Pseudoallescheria
boijdii 1 and Aspergillus , Conidiobolus
and Mucomceous fungi 5
Equine grass sickness (dysautonomia,
pp 1988-1990) in the chronic form
causes rhinitis sicca.

Sheep and goats

Melioidosis, bluetongue, rarely
contagious ecthyma and sheep pox

° Oestrus ovis and Elaeophora schneideri
infestations
0 Allergic rhinitis

0 Purulent rhinitis and otitis associated
with P. aeruginosa in sheep showered
with contaminated wash. 6

Pigs

° Atrophic rhinitis, inclusion body
rhinitis, swine influenza, some
outbreaks of Aujeszky's disease.

PATHOGENESIS

Rhinitis is of minor importance as a
disease process except in severe cases
when it causes obstruction of the passage
of air through the nasal cavities. Its major
importance is as an indication of the pre-
sence of some specific diseases. The type
of lesion produced is important. The erosive
and ulcerative lesions of rinderpest,
bovine malignant catarrh and mucosal
disease, the ulcerative lesions of glanders,
melioidosis, and epizootic lymphangitis
and the granular rhinitis of the anterior
nares in allergic rhinitis all have diag-
nostic significance.

In atrophic rhinitis of pigs the destruc-
tion of the turbinate bones and distortion
of the face appear to be a form of
devitalization and atrophy of bone caused
by a primary, inflammatory rhinitis.
Secondary bacterial invasion of facial
tissue of swine appears to be the basis of
necrotic rhinitis.

CLINICAL FINDINGS

The primary clinical finding in rhinitis is a
nasal discharge, which is usually serous
initially but soon becomes mucoid and, in
bacterial infections, purulent. Erythema,
erosion, or ulceration may be visible on
inspection. The inflammation may be
unilateral or bilateral. Sneezing is charac-
teristic in the early acute stages and this is
followed in the later stages by snorting
and the expulsion of large amounts of
mucopurulent discharge. A chronic
unilateral purulent nasal discharge lasting
several weeks or months in horses
suggests nasal granulomas associated
with mycotic infections. 4,5

'Summer snuffles'

'Summer snuffles' of cattle presents a
characteristic syndrome involving several
animals in a herd. Cases occur in the
spring and autumn when the pasture is in
flower and warm moist environmental
conditions prevail. The disease may be
most common in Channel Island breeds.
There is a sudden onset of dyspnea with a j
profuse nasal discharge of thick, orange to !
yellow material that varies from a j
mucopurulent to caseous consistency. !
Sneezing, irritation, and obstruction are i
severe. The irritation may cause the ;
animal to shake its head, rub its nose j
along the ground or poke its muzzle ’

repeatedly into hedges and bushes. Sticks
and twigs may be pushed up into the
nostrils as a result and cause laceration and
bleeding. Stertorous, difficult respiration
accompanied by mouth breathing may be
evident when both nostrils are obstructed.
In the most severe cases a distinct
pseudomembrane is formed that is later
snorted out as a complete nasal cast. In the
chronic stages multiple proliferative non-
erosive nodules 2-8 mm in diameter and
4 mm high with marked mucosal edema
are visible in the anterior nares. 7

Familial allergic rhinitis
In familial allergic rhinitis in cattle, the
clinical signs begin in the spring and last
until late fall. 2 Affected animals exhibit
episodes of violent sneezing and extreme
pruritus manifested by rubbing their
nostrils on the ground, trees, and other
inanimate objects and frequently scratch-
ing the nares with their hind feet.
Dyspnea and loud snoring sounds are
common and affected animals frequently
clean their nostrils with their tongues. The
external nares contain a thick mucoid
discharge and the nasal mucosa is
edematous and hyperemic. The clinical
abnormalities resolve during the winter
months. All affected animals are positive
to intradermal skin testing for a wide
variety of allergens.

Mycotic rhinitis

Mycotic rhinitis in the horse is charac-
terized by noisy respirations, circumferential
narrowing of both nasal passages and
thickening of the nasal septum. The nasal
conchae and turbinates may be roughened
and edematous, and the ventral meati
decreased in size bilaterally. The nasal
discharge may be unilateral or bilateral.
Endoscopically, granulomas may be found
in almost any location in the nasal cavities
and extending on to the soft palate and
into the maxillary sinus. 5 The disease is
I discussed in detail in Chapter 24.

Endoscopic examination

i Endoscopic examination using a flexible
. fiberoptic endoscope or a rigid endoscope
I is very useful for the visual inspection of
lesions affecting the nasal mucosae of
horses and cattle that are not visible
externally. Radiographic or computed
tomographic imaging can be used to
detect atrophic rhinitis, although use of
these techniques on a wide scale is clearly
not practical. 8

CLINICAL PATHOLOGY

Examination of nasal swabs of scrapings for
bacteria, inclusion bodies or fungi may aid
in diagnosis. Discharges in allergic rhinitis
usually contain many more eosinophils
than normal. Nasal mucosal biopsy speci-
mens are useful for microbiological and
histopathological examination. 3

Diseases of the upper respiratory tract

NECROPSY FINDINGS

Rhinitis is not a fatal condition, although
animals may die of specific diseases in
which rhinitis is a prominent lesion.

DIFFERENTIAL DIAGNOSIS

Rhinitis is readily recognizable clinically.
Differentiation of the specific diseases
listed under Etiology, above, is discussed
under their respective headings.

Allergic rhinitis in cattle must be
differentiated from maduromycosis,
rhinosporidiosis, and infection with the
pasture mite ( Tyrophagus palmarum). The
differential diagnosis may be difficult if
allergic rhinitis occurs secondary to some
of these infections.

Rhinitis in the horse must be
differentiated from inflammation of the
facial sinuses or guttural pouches in which
the nasal discharge is usually purulent and
persistent and often unilateral, and there is
an absence of signs of nasal irritation. A
malodorous nasal discharge, frontal bone
distortion, draining tracts at the poll, and
neurological abnormalities are common in
cattle with chronic frontal sinusitis as a
complication of dehorning . 9

TREATMENT

Specific treatment aimed at control of
individual causative agents is described
under each disease. Thick tenacious
exudate that is causing nasal obstruction
may be removed gently and the nasal
cavities irrigated with saline. A nasal
decongestant sprayed up into the nostrils
may provide some relief. Newborn piglets
with inclusion body rhinitis may be
affected with severe inspiratory dyspnea
and mouth-breathing that interferes with
sucking. The removal of the exudate from
each nostril followed by irrigation with a
mixture of saline and antimicrobials will
provide relief and minimize the develop-
ment of a secondary bacterial rhinitis.
Animals affected with allergic rhinitis
should be taken off the pasture for about
a week and treated with antihistamine
preparations.

OBSTRUCTION OF THE NASAL
CAVITIES

Nasal obstruction occurs commonly in
cattle and sheep. The disease is usually
chronic and due to:

In sheep, infestation with Oestrus ovis
rj In cattle, most often enzootic nasal
granuloma, acute obstruction or the
allergic condition 'summer snuffles'.
Cystic enlargement of the ventral nasal
conchae in cattle can cause unilateral 10
or bilateral nasal obstruction."

Minor occurrences include the following:

° Large mucus-filled polyps developing
in the posterior nares of cattle and

sheep and causing unilateral or
bilateral obstruction
° Granulomatous lesions caused by a
fungus, Rhinosporidium sp. and by the
blood fluke, Schistosoma nasalis
° A chronic pyogranuloma due to
Coccidioides immitis infection has
occurred in the horse 12
» Foreign bodies may enter the cavities
when cattle rub their muzzles in
bushes in an attempt to relieve the
irritation of acute allergic rhinitis
° Nasal amyloidosis occurs rarely in
mature horses and is characterized
clinically by stertorous breathing and
raised, firm, nonpainful, nodular
swellings on the rostral nasal septum
and floor of the nasal cavity. 13
Affected horses do not have any other
illness and surgical removal of the
lesions is recommended
° Infestation of the nasopharynx of
horses by Gasterophilus pecorum
causes obstruction of the upper
airway. 14

Neoplasms

Neoplasms of the olfactory mucosa are
not common but do occur, particularly in
sheep, goats, and cattle, where the
incidence in individual flocks and herds
may be sufficiently high to suggest an
infectious cause. 15 The lesions are usually
situated just in front of the ethmoid bone,
are usually unilateral but may be bilateral
and have the appearance of adeno-
carcinomas of moderate malignancy. In
cattle, the disease is commonest in
6-9-year- olds and may be sufficiently
extensive to cause bulging of the facial
bones. The tumors are adenocarcinomas
arising from the ethmoidal mucosa, and
they metastasize in lungs and lymph
nodes. Clinical signs include nasal
discharge, often bloody, mouth-breathing
and assumption of a stretched- neck
posture. There is evidence to suggest that
a virus may be associated. A similar
syndrome is observed in cattle with other
nasal tumors such as osteoma.

Neoplasia that obstructs the nasal
cavity occurs in horses with squamous
cell carcinoma or adenocarcinoma of the
sinus or nasal cavity, angiosarcoma and a
variety of other rare tumors. 16 Epidermal
inclusions cysts of the nasal diverticulum
of horses can cause obstruction of the
nasal cavity, but are not neoplasms. 1 '
Cysts of the paranasal sinuses can cause
marked facial deformity and obstruction
to air passages. 18

Enzootic nasal adenocarcinoma
Enzootic nasal adenocarcinoma occurs in
sheep and goats. 15 The disease is sporadic
but has occurred in related flocks, which
suggests that it may be an enzootic
problem. The clinical findings include a

persistent serous, mucous, or mucopurulent
nasal discharge and stridor. Affected
sheep progressively develop anorexia,
dyspnea, and mouth-breathing and most
die within 90 days after the onset of signs.
The tumors originate unilaterally or
occasionally bilaterally in the olfactory
mucosa of the ethmoid turbinates. They
are locally invasive but not metastatic.
Histologically the tumors are classified as
adenomas or, more frequently, adeno-
carcinomas. The etiology is unknown, but
a retrovirus may be involved. Budding
and extracellular retrovirus-like particles
have been observed ultrastructurally in
enzootic nasal tumors of goats. 15

Ethmoidal hematomas
Ethmoidal hematomas are encapsulated,
usually expanding, insidious, potentially
distorting and obstructing lesions of the
nasal cavities that occur in horses. 19
Chronic unilateral nasal discharge is
common and lesions are usually advanced
at the time of diagnosis. There is stertorous
breathing and upper airway obstruction
in later stages of the disease. The nasal
discharge is serous or mucoid and
intermittently sanguineous, sanguino-
purulent and usually unrelated to
exercise. Diagnosis is made by endoscopy
and radiography. Surgical removal is
possible and successful in some cases.
Multiple intralesional injection of
formalin (1-100 mL of 10% neutral
buffered formalin injected at 10 day
intervals) through an endoscope can cure
the tumor but there is the risk of serious
adverse effects if the ethmoidal hematoma
penetrates the cribriform plate. 5,20 The
procedure involves the injection of a
sufficient volume of 10% neutral buffered
formalin to distend the lesion. The
formalin is injected via an endoscope
once every 10 days until the lesion
resolves by sloughing. Between one and
20 injections are required. However, the
prognosis for long-term resolution of the
tumor is poor because of high rates of
recurrence.

CLINICAL FINDINGS

In cattle, sheep, and pigs there is severe
inspiratory dyspnea when both cavities
are blocked. The animals may show great
distress and anxiety and breathe in gasps
through the mouth. Obstruction is usually
not complete and a loud, wheezing sound
occurs with each inspiration. A nasal
discharge is usually present but varies
from a small amount of blood-stained
serous discharge when there is a foreign
body present to large quantities of
purulent exudate in allergic rhinitis.
Shaking of the head and snorting are also
common signs. If the obstruction is
unilateral the distress is not so marked
and the difference in breath streams

kmki i titNCKAL ivi tuiciisit ■ <_napter io: uiseases ot tne respiratory system

between the two nostrils can be detected
by holding the hands in front of the nose.
The magnitude of the air currents from
each nostril on expiration can be assessed
with the aid of a piece of cotton thread
(watching the degree of deflection). The
passage of a stomach tube through each
nasal cavity may reveal evidence of a space-
occupying lesion. The diameter of the tube
to be used should be one size smaller than
would normally be used on that animal to
insure that the tube passes easily. The signs
may be intermittent when the obstruction
is caused by a pedunculated polyp in the
posterior nares.

TREATMENT

Treatment must be directed at the primary
cause of the obstruction. Removal of
foreign bodies can usually be effected
with the aid of long forceps, although
strong traction is often necessary when
the obstructions have been in position for
a few days. As an empirical treatment in
cattle oral or parenteral administration of
iodine preparations is in general use in
chronic nasal obstruction.

REFERENCES

1. Wiseman A et al. Vet Rec 1982; 110:420.

2. Krahwinkel DJ et al. J Am Vet Med Assoc 1988;
192:1593.

3. ShibaharaT et al. AustVet J 2001; 79:363.

4. Davis PR et al. J Am Vet Med Assoc 2000; 217:707.

5. Marriott MR et al. AustVet J 1999; 77:371.

6. Watson PJ et al. Vet Rec 2003; 153:704.

7. Olchowy TWJ et al. J Am Vet Med Assoc 1995;
207:1211.

8. Frame EM et al.Vet Rec 2000; 146:558.

9. Ward JL, Rebhun WC. J Am Vet Med Assoc 1992;
201 :326.

10. Jean GS, Robertson JT. Can Vet J 1987; 28:251.

11. Ross MW et al. J Am Vet Med Assoc 1986;
188:857.

12. Hodgin EC et al. J Am Vet Med Assoc 1984;
184:339.

13. Shaw J, Sautet JY. Vet Pathol 1987; 24:183.

14. Smith MA et al.Vet Rec 2005; 156:283.

15. De Las Heras M et al. \fet Fhthol 1991; 28:474.

16. Dixon PM, Head KW. Vet J 1999; 157:279.

17. Frankeny RL. J Am Vet Med Assoc 2003; 223:221.

18. Lane J et al. EquineVetJ 1987; 19:537.

19. Stich KL et al. Compend Contin Educ Pract Vet
2001; 23:1094.

20. Frees KE et al. J Am Vet Med Assoc 2001; 219:950.

EPISTAXIS AND HEMOPTYSIS

Epistaxis is bleeding from the nostrils
regardless of the origin of the hemor-
rhage, and hemoptysis is the coughing up
of blood, with the hemorrhage usually
originating in the lungs. Both epistaxis
and hemoptysis are important clinical
signs in cattle and horses. The bleeding
may be in the form of a small volume of
blood-stained serous discharge coming
from the nose only, or it can be a large
volume of whole blood coming pre-
cipitously from both nostrils and some-
times the mouth. The first and most
important decision is to determine the
exact location of the bleeding point.

ETIOLOGY

Epistaxis occurs commonly in the horse
and may be due to lesions in the nasal
cavity, nasopharynx, auditory tube
diverticulum (guttural pouch) or lungs
(see Table 10.5). Exercise-induced pul-
monary hemorrhage is described under
that heading earlier in this chapter.

Hemorrhagic lesions of the nasal
cavity, nasopharynx, and guttural pouch
in the horse usually cause unilateral
epistaxis of varying degree depending on
the severity of the lesions. Pulmonary
lesions in the horse resulting in hemor-
rhage into the lumen of the bronchi also
result in epistaxis. Blood originating from
the lungs of the horse is discharged most
commonly from the nostrils and not the
mouth because of the horse's long soft
palate. Also, blood from the lungs of the
horse is not foamy when seen at the nose
because the horizontal position of the
major bronchi allows blood to flow out
freely without being coughed up and
made foamy. It was previously thought
that upper respiratory tract hemorrhage
could be distinguished from lower
respiratory tract hemorrhage by the blood
in the latter case being foamy. This does
not apply in the horse. Froth is usually the
result of pulmonary edema, in which case
it is a very fine, pink, stable froth.

Bleeding from lesions of the upper
respiratory tract of horses usually occur
spontaneously while the horse is at rest.
One of the commonest causes of
unilateral epistaxis in the horse is mycotic
ulceration of the blood vessels in the wall
of the guttural pouch (guttural pouch
mycosis).

Other less common causes of nasal
bleeding include hemorrhagic polyps of
the mucosa of the nasal cavity or
paranasal sinuses, and encapsulated
hematomas, which look like hemorrhagic
polyps, commencing near the ethmoidal
labyrinth and expanding into the nasal
cavity and the pharynx. There is respir-
atory obstruction, coughing, choking, and
persistent unilateral epistaxis. The capsule
of the hematoma is respiratory epithelium.
Surgical correction has been achieved.
Another cause, most uncommonly, is a
parasitic arteritis of the internal carotid
artery as it courses around the guttural
pouch. 1

Mild epistaxis is a common finding
in horses and cattle with severe
thrombocytopenia. 2

Erosions of the nasal mucosa in
glanders, granulomatous and neoplastic
diseases and trauma due to passage of a
nasal tube or endoscope, or from physical
trauma externally, are other obvious
causes.

A case of fibrous dysplasia in the
ventral meatus of a horse with epistaxis is

recorded. 3 Similarly, in congestive heart
failure and purpura hemorrhagica there
may be a mild epistaxis.

Neoplasia, and notably hemangio-
sarcoma, of the upper or lower respiratory
tract can cause epistaxis. 4

Envenomation of horses by rattle-
snakes in the western USA caused a
clinical syndrome that includes swelling
of the head, dyspnea, and epistaxis. 5

Poisoning by bracken fern or moldy
sweet clover is a common cause of spon-
taneous epistaxis in cattle. The epistaxis
may be bilateral, and hemorrhages of
other visible and subcutaneous mucous
membranes are common. An enzootic
ethmoidal tumor has been described in
cattle in Brazil and was at one time a
disease of some importance in Sweden. 6
The lesion occupies the nasal cavities,
causes epistaxis and may invade
paranasal sinuses.

In hemoptysis in horses the blood
flows along the horizontal trachea and
pools in the larynx until the swallowing
reflex is stimulated and swallowing
occurs; or coughing is stimulated and
blood is expelled through the mouth
and nostrils. In some horses repeated
swallowing, without eating or drinking,
can be a good indicator that bleeding is
occurring. The origin of the hemorrhage is
usually in the lungs and in cattle the usual
cause is a pulmonary arterial aneurysm
and thromboembolism from a posterior
vena caval thrombosis, usually originating
from a hepatic abscess. 7 Recurrent attacks
of hemoptysis with anemia and abnormal
lung sounds usually culminate in an acute
intrapulmonary hemorrhage and rapid
death.

The origin of the hemorrhage in
epistaxis and hemoptysis maybe obvious,
as in traumatic injury to the turbinates
during passage of a stomach tube
intranasally or if a systemic disease with
bleeding defects is present. In many other
cases, however, the origin of the hemor-
rhage is not obvious and special exam-
ination procedures may be required.
Careful auscultation of the lungs for
evidence of abnormal lung sounds
associated with pulmonary diseases is
necessary.

CLINICAL EXAMINATION

The nasal cavities should be examined
visually with the aid of a strong, pointed
source of light through the external nares.
Only the first part of the nasal cavities can
be examined directly but an assessment
of the integrity of the nasal mucosa can
usually be made. In epistaxis due to
systemic disease or clotting defects the
blood on the nasal mucosa will usually
not be clotted. When there has been
recent traumatic injury to the nasal

Diseases of the upper respiratory tract

533

mucosa or erosion of a blood vessel by a
space-occupying lesion such as tumor or
nasal polyp, the blood will usually be
found in clots in the external nares.

The nasal cavities should then be
examined for any evidence of obstruction
as set out in the previous section. When
the blood originates from a pharyngeal
lesion there are frequent swallowing
movements and a short explosive cough,
which may be accompanied by the
expulsion of blood from the mouth.
Hematological examinations are indicated
to assist in the diagnosis of systemic
disease or clotting defects. Radiological
examinations of the head are indicated
when space-occupying lesions are
suspected.

In the horse, the use of the flexible
fiberoptic endoscope will permit a thorough
examination of the nasal cavities,
nasopharynx, guttural pouch and larynx,
trachea and major bronchi.

TREATMENT

Specific treatment of epistaxis and
hemoptysis depends on the cause.
Hemorrhage from traumatic injuries to
the nasal mucosa does not usually require
any treatment. Space- occupying lesions
of the nasal mucosa may warrant surgical
therapy. Epistaxis associated with guttural
pouch mycosis may require ligation of the
affected artery. The ineffectiveness of
therapy for exercise-induced pulmonary
hemorrhage has been discussed above.
There is no successful treatment for the
hemoptysis due to pulmonary aneurysm
and posterior vena caval thrombosis in
cattle. General supportive therapy is as for
any spontaneous hemorrhage and
includes rest, blood transfusions, and
hematinics.

REFERENCES

1. Owen RR. EquineVet J 1974; 6:143.

2. Hoyt PG et al. J Am Vet Med Assoc 2000; 217:717.

3. Livcscy 1VJ A et al. EquineVet J 1984; 16:144.

4. Southwood LL et al. J Vet Intern Med 2000;
14:105.

5. Dickinson C.E et al. J Am Vet Med Assoc 1996;
208:1866.

6. Tokarnia CH et al. Pesqui AgroBras SerVet 1972;
7:41.

7. Braun U et al.Vct Rec 2002; 150:209.

LARYNGITIS, TRACHEITIS,
BRONCHI TIS

Inflammation of the air passages usually
involves all levels and no attempt is made
here to differentiate between inflam-
mations of various parts of the tract. They
are all characterized by cough, noisy
inspiration and some degree of inspir-
atory embarrassment.

ETIOLOGY

All infections of the upper respiratory
tract cause inflammation, either acutely or

as chronic diseases. In most diseases the
laryngitis, tracheitis, and bronchitis form
only a part of the syndrome and the
causes listed below are those diseases in
which upper respiratory infection is a
prominent feature.

Cattle

° Infectious bovine rhinotracheitis
(bovine herpesvirus-1), calf diphtheria
(necrotic laryngitis), Histophilus
somnus

° Tracheal stenosis in feedlot cattle,
'honker cattle', etiology unknown 1
° Congenital cavitation of the arytenoid
may contribute to laryngeal abscess
development

° Syngamus laryngeus infests the larynx
of cattle in the tropics.

Sheep

° Chronic infection with Actinomyces
pyogenes.

Horses

° Equine herpesvirus (EVR), equine
viral arteritis (EVA), equine viral
influenza (EVI), strangles (S. equi)
c Idiopathic ulceration of the mucosa
covering the arytenoid cartilages 2

Pigs

° Swine influenza.

PATHOGENESIS

Irritation of the mucosa causes frequent
coughing, and swelling causes partial
obstruction of the air passages, with
resulting inspiratory dyspnea. Necrotic
laryngitis in calves is associated with
marked changes in pulmonary function,
modifies tracheal dynamics and disturbs
the growth process by increasing the
energetic cost of breathing; this can result
in impaired feed intake and predisposition
to secondary pulmonary infection and
subsequent respiratory failure from pro-
gressive exhaustion. 3

CLINICAL FINDINGS

Coughing and inspiratory dyspnea with
laryngeal roaring or stridor are the
common clinical signs. In the early stages
of acute infections the cough is usually
dry and nonproductive and is easily
induced by grasping the trachea or larynx,
or by exposure to cold air or dusty
atmospheres. In acute laryngitis, the soft
tissues around the larynx are usually
enlarged and painful on palpation. In
chronic affections, the cough may be less
frequent and distressing and is usually dry
and harsh. If the lesions cause much
exudation or ulceration of the mucosa, as
in bacterial tracheobronchitis secondary
to infectious bovine rhinotracheitis in
cattle, the cough is moist, and thick
mucus, flecks of blood and fibrin may be
coughed up. Thecough is very painful and
the animal makes attempts to suppress it.

Fever and toxemia are common and
affected animals cannot eat or drink
normally.

Inspiratory dyspnea varies with the
degree of obstruction and is usually
accompanied by a loud stridor and harsh
breath sounds on each inspiration. These
are best heard over the trachea although
they are quite audible over the base of the
lung, being most distinct on inspiration.
The respiratory movements are usually
deeper than normal and the inspiratory
phase more prolonged and forceful.
Additional signs, indicative of the
presence of a primary specific disease,
may also be present.

Examination of the larynx is usually
possible through the oral cavity using a
cylindrical speculum of appropriate size
and a bright, pointed source of light. This
is done relatively easily in cattle, sheep,
and pigs but is difficult in the horse.
Lesions of the mucosae of the arytenoid
cartilages and the vault of the larynx are
usually visible if care and time are taken.
In laryngitis, there is usually an excessive
quantity of mucus, which may contain
flecks of blood or pus in the pharynx.
Palpation of the pharyngeal and laryngeal
areas may reveal lesions not readily
visible through a speculum. During open-
ing of the larynx, lesions in the upper part
of the trachea are sometimes visible. The
use of a fiberoptic endoscope allows a
detailed examination of the upper respir-
atory tract.

Inflammation or lesions of the larynx
may be severe enough to cause marked
inspiratory dyspnea and death from
asphyxia. In calves and young cattle with
diphtheria the lesion may be large
enough (or have a pedicle and act like a
valve) to cause severe inspiratory dyspnea,
cyanosis, anxiety and rapid death. The
excitement associated with loading for
transportation to a clinic or of a clinical
examination, particularly the oral exam-
ination of the larynx, can exaggerate the
dyspnea and necessitate an emergency
tracheotomy.

Most cases of bacterial laryngitis will
heal without obvious residual sign after
several days of antimicrobial therapy.
Some cases in cattle become chronic in
spite of therapy due to the inflammation
extending down into the arytenoid
cartilages resulting in a chronic chondritis
due to a sequestrum similar to osteomyelitis.
Abscess formation is another common
cause of chronicity. Secondary bacterial
infection of primary viral diseases, or
extension of bacterial infections to the
lungs commonly results in pneumonia.

Tracheal stenosis in cattle is charac-
terized by extensive edema and hemor-
rhage of the dorsal wall of the trachea,
resulting in coughing (honking), dyspnea

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

and respiratory stertor. 1 Complete
occlusion of the trachea may occur.
Affected animals may be found dead
without any premonitory signs.

CLINICAL PATHOLOGY

Laboratory examinations may be of value
in determining the presence of specific
diseases.

NECROPSY FINDINGS

Upper respiratory infections are not
usually fatal but lesions vary from
acute catarrhal inflammation to chronic
granulomatous lesions depending upon
the duration and severity of the infection.
When secondary bacterial invasion occurs
a diphtheritic pseudomembrane may be
present and be accompanied by an
accumulation of exudate and necrotic
material at the tracheal bifurcation and in
the dependent bronchi.

DIFFERENTIAL DIAGNOSIS

Inflammation of the larynx usually results in
coughing, and inspiratory dyspnea with a
stertor and loud abnormal laryngeal
sounds on auscultation over the trachea
and over the base of the lungs on
inspiration. Lesions of the larynx are usually
visible by laryngoscopic examination, those
of the trachea and major bronchi are not
so obvious unless special endoscopic
procedures are used. Every reasonable
effort should be used to inspect the larynx
and trachea. Obstruction of the nasal
cavities and other parts of the upper
respiratory tract may also be difficult to
distinguish unless other signs are present.

TREATMENT

Most of the common viral infections of
larynx, trachea, and major bronchi will
resolve spontaneously if the affected
animals are rested, not worked and not
exposed to inclement weather and dusty
feeds. Secondary bacterial complications
must be recognized and treated with the
appropriate antimicrobial.

The bacterial infections can result in
severe inflammation with necrosis and
granulomatous lesions and must be
treated with antimicrobials. Calves with
calf diphtheria should be treated with a
broad-spectrum antimicrobial daily for
3-5 days. Several days are usually required
for the animal to return to normal. A
broad-spectrum antimicrobial daily or
more often for up to 3 weeks or more
may be necessary for treatment of the
chondritis.

NSAIDs such as flunixin meglumide
may be used in an attempt to reduce the
laryngeal edema associated with some
severe cases of bacterial laryngitis in
cattle.

Animals with severe lesions and marked
inspiratory dyspnea may require a

tracheotomy and insertion of a
tracheotomy tube for several days until
the lesion heals. The tube must be
removed, cleaned out and replaced at
least once daily because of the accumu-
lation of dried mucus plugs which inter-
fere with respiration. The techniques of
tracheotomy and permanent tracheostomy
in the horse have been described. 4,5
Surgical excision of chronic granulo-
matous lesions and abscesses of the
larynx may be indicated following failure
of long-term antimicrobial therapy but
postoperative complications of laryngeal
and pharyngeal paralysis may occur.
Laryngotomy as a treatment for chronic
laryngeal obstruction in cattle with long-
term survival of 58% has been described. 6

Tracheolaryngostomy of calves with
chronic laryngeal obstruction due to
necrobacillosis has been used with a high
degree of success. 7 Under general
anesthesia and dorsal recumbency, an
incision is made over the lower third of
the thyroid and cricoid cartilages and the
first two tracheal rings. 7 The larynx is
easily visualized and necrotic tissue
removed using a curette. The edges of the
cartilages are sutured closed. A wedge-
shaped piece of the first two tracheal
rings is removed to create a tracheostomy,
which is allowed to close after about
1 week when the postoperative swelling
has subsided with the aid of daily care of
the surgical site and the possible use of
flunixin meglumide. 7 No tracheotomy
tube is required.

REFERENCES

1 . Erickson ED, Doster A]?. J Vet Diagn Invest 1993;
5:449.

2. Kelly G et al. Equine Vet 2003; J 35:276

3. Leukeux P, ArtT.VetRec 1987; 121:353.

4. Shappel KK et al. J Am Vet Med Assoc 1988;
192:939.

5. Dixon P. In Pract 1988; 10:249.

6. Gasthuys F et al. Vet Rec 1992; 130:220.

7. West HJ.Vet J 1997; 153:81.

TRAUMATIC

LARYNGOTRACHEITIS, TRACHEAL
COMPRESSION AND TRACHEAL
COLLAPSE

Traumatic laryngotracheal injury can
occur following endotracheal intubation
used for general anesthesia. 1 Naso-
tracheal intubation can result in mucosal
injury to the nasal meatus, the arytenoid
cartilages, the trachea, the dorsal
pharyngeal recess, the vocal cords and the
entrance to the guttural pouches. 1 The
laryngeal injury is attributed to the tube
pressure on the arytenoid cartilages and
vocal folds and the tracheal damage is
due to the pressure exerted by the inflated
cuff on the tracheal mucosa.

Tracheal collapse occurs in calves, 2,3
in mature cattle, 4 in goats and in horses,

including miniature horses and foals. 3
Dynamic collapse is a cause of exercise
intolerance in race horses that is evident
only by endoscopic examination of the
trachea during strenuous exercise. 6
Restriction of the tracheal lumen and
laxity of the dorsal tracheal membrane
results in varying degrees of inspiratory
dyspnea with stridor, coughing, and
reduced exercise tolerance. A 'honking 1
respiratory noise is common in affected
calves when coughing spontaneously or
when the trachea is palpated. Tracheal
collapse in calves is associated with
injuries associated with dystocia and
clinical signs usually occur within a few
weeks after birth. In some cases the
trachea is compressed at the level of the
thoracic inlet in association with callus
formation of healing fractured ribs
attributed to dystocia. In some cases in
cattle, there is no history of dystocia or
pre-existing disease or previous mani-
pulation of the trachea and the overall
lumen size may be reduced to less than
25% of normal. 7 Auscultation of the
thorax may reveal loud referred upper
airway sounds. Tracheal prostheses have
been used for the treatment of tracheal
collapse in calves and Miniature horses. 8

Tracheal obstruction and collapse
can result from tracheitis associated with
pneumonia in the horse, tracheal
neoplasia, tracheal stricture, presence of
foreign bodies in the trachea and
compression by masses external to the
trachea. 5,9 It is suggested that increased
respiratory effort associated with pneu-
monia causes collapse of the soft tissue
structures of the trachea, rather than
collapse of the tracheal rings. Tracheal
nipture due to blunt trauma in the horse
may result in severe subcutaneous emphy-
sema and pneumomediastinum. 4 Con-
servative therapy is usually successful.
Tracheal compression secondary to
enlargement of the cranial mediastinal
lymph nodes can also cause inspiratory
dyspnea 10 and conservative treatment
with antimicrobials is successful.

REFERENCES

1. Holland M et al. J Am Vet Med Assoc 1986;

189:1447.

2. Jelinski M,Vinderkop M. Can Vet J 1990; 31:783.

3. Fingland RB et al.Vct Surg 1990; 19:371.

4. Fubini SL et al. J Am Vet Med Assoc 1985; 187:69.

5. Fenger CK, Kohn CW. J Am Vet Med Assoc 1992;

200:1698.

6. Tetens J et al. J Am Vet Med Assoc 2000; 216:722.

7. Ashworth CD et al. Can Vet J 1992; 33:50.

8. Couetil LL et al J Am Vet Med Assoc 2004;

225:1727.

9. MairTS, LancjG. Equine Vet Educ 2005; 17:146.

10. RiggDLetal.J Am Vet Med Assoc 1985; 186:283.

PHARYNGITIS

Pharyngitis in all species is associated
with infectious diseases of the upper

Diseases of the upper respiratory tract

535

airway. It is most studied in horses,
probably because of the frequency of
examination of the upper airway in this
species. Pharyngitis in horses has many
similarities to tonsillitis in children. 1 The
disorder in horses involves follicular
lymphoid hyperplasia of the pharynx and
involves both the pharyngeal tonsil and
the extensive and diffuse lymphoid tissue
in the walls and dorsal aspect of the
pharynx. These tissues form the mucosal
associated lymphoid tissues and are an
important component of the normal
immunological response of horses. 2 The
condition occurs in approximately 34% of
Thoroughbred race horses 3 and is
probably as common in other breeds of
horse. The condition is first detectable in
2-3-month-old foals and reaches its
highest prevalence and greatest severity
in yearlings and 2-year-old horses in race
training. 4 It is evident on endoscopic
examination as diffuse, multiple, small,
white nodules in the roof and walls of the
pharynx. The nodules can be confluent
and there is often excessive mucus
present in severely affected horses. The
clinical significance of the condition is
debated. Affected race horses do not have
impaired race performance. 4 Affected
horses recover spontaneously as they age,
or after treatment with topical anti-
inflammatory drugs. The condition is
probably a normal aging process and
necessary for development of a competent
immune system in young horses. 1

Infestation of the nasopharynx of
horses by larvae of the bot fly
Gasterophilus pecorum causes obstruction
of the upper airway and a parasitic
pharyngitis. 5 Diagnosis is by visualization
of the parasite during endoscopic
examination.

REFERENCES

1. Lunn DP. Equine Vet J 2001; 33:218.

2. Kumar P et al. EquineVet J 2001; 33:224.

3. Sweeney CR et al. J Am Vet Med Assoc 1991;

198:1037.

4. Auer DE et al. Aust Vet J 1985; 62:124.

5. Smith MA et al. Vet Rec 2005; 156:283.

UPPER AIRWAY OBSTRUCTION IN
HORSES: LARYNGEAL
HEMIPLEGIA ('ROA RERS ')

Obstruction of the upper airway is a
common cause of exercise intolerance in
horses and is characterized in most cases
by unusual respiratory noise during heavy
exercise.

ETIOLOGY

The cause of laryngeal hemiplegia is
degeneration of the recurrent laryngeal
nerve with subsequent neurogenic atrophy
of the cricoarytenoid dorsalis and other
intrinsic muscles of the larynx. 1 The
etiology of neuronal degeneration is

unknown but the pathological changes
are typical of a distal axonopathy. 1 The
disease is usually idiopathic but occasional
cases are caused by guttural pouch
mycosis or inadvertent perivascular injec-
tion of irritant material, such as phenyl-
butazone, around the jugular vein and
vagosympathetic trunk. Bilateral laryngeal
paralysis is usually associated with
intoxication (organophosphate, haloxon)
or trauma from endotracheal intubation
during general anesthesia.

EPIDEMIOLOGY

Prevalence

The disease affects large horses more
commonly than ponies, and it is com-
monly recognized in draft horses,
Thoroughbreds, Standardbreds, Warm-
bloods and other breeds of large horse.
The prevalence of laryngeal hemiplegia
in Thoroughbred horses in training is
between 1.8 and 13% 2-4 depending,
among other factors, on the criteria used
to diagnose the condition. Among
apparently normal Thoroughbred horses
examined after racing, grade 4 laryngeal
hemiplegia was detected in 0.3% of
744 horses, grade 3 in 0.1%, and grade
2 in 1.1%. 5 Male horses over 160 cm tall
are at most risk of developing the
disease. 6 There is evidence of a Familial
distribution of the disease with offspring
of affected parents being more frequently
affected (61%) than adult offspring of
unaffected parents (40%). 7

PATHOGENESIS

Axonal degeneration causes preferential
atrophy of the adductor muscles of the
larynx, although both adductor (dorsal
cricoarytenoid muscle) and adductor
(lateral cricoarytenoid muscle) are
involved. 8 Fiber-type grouping of laryngeal
muscles, evidence of recurrent laryngeal
neuropathy, is present in draft foals as
young as 2 weeks of age, indicating an
early onset of the disease. 9 The disease is
progressive in some horses. 10

Compromised function of the adductor
muscles results in partial occlusion of the
larynx by the arytenoid cartilage and vocal
fold during inspiration. The obstruction is
most severe when airflow rates through the
larynx are large, such as during strenuous
exercise. Laryngeal obstruction increases
the work of breathing, decreases the
maximal rate of oxygen consumption and
exacerbates the hypoxemia and hyper-
carbia normally associated with strenuous
exercise by horses. 11-12 These effects result
in a severe limitation to athletic capacity
and performance.

CLINICAL FINDINGS

Clinical findings include exercise intoler-
ance and production of a whistling or
roaring noise during strenuous exercise.

The disease can be detected by analysis of
respiratory noise. 13

Endoscopic examination of the upper
airway provides the definitive diagnosis in
most cases. Examination of the larynx is
performed with the horse at rest and the
position and movement of the arytenoid
cartilages assessed. Laryngeal function
can also be observed during swallowing,
brief (30-60 s) bilateral nasal occlusion,
and during and after exercise. Endoscopic
examination during strenuous exercise
on a treadmill of horses with grade III
disease may be beneficial in determining
the severity of the disease. 14-15 Horses
with early or mild degeneration of the
recurrent laryngeal nerve and associated
laryngeal musculature can have normal
laryngeal function at rest. However, the
loss of muscle function becomes apparent
during exercise, when the laryngeal
muscles of affected animals fatigue more
rapidly than do those of normal animals,
with the result that laryngeal dysfunction
can become apparent during or imme-
diately after exercise. Endoscopic examin-
ation during exercise is useful in differ-
entiating the disease from axial deviation
of the aryepiglottic folds . 16

The severity of the disease is graded I
through IV:

0 Grade I is normal, there being
synchronous, full abduction and
adduction of both arytenoid cartilages
0 Grade II presents as weakness of the
adductors evident as asynchronous
movement and fluttering of the
arytenoid cartilage during inspiration
and expiration, but with full abduction
during swallowing or nasal occlusion
° Grade III has asynchronous

movement of the arytenoid cartilage
during inspiration or expiration; full
abduction is not achieved during
swallowing or nasal occlusion
° Grade IV implies marked asymmetry
of the larynx at rest and no substantial
movement of the arytenoid cartilage
during respiration swallowing or nasal
occlusion. 17

There are no characteristic changes in the
hemogram or in serum biochemical vari-
ables in resting horses. During exercise
there is a marked exacerbation of the
normal exercise-induced hypoxemia and
the development of hypercapnia in
affected horses. 11-12

NECROPSY FINDINGS

Lesions are confined to an axonopathy
of the recurrent laryngeal nerves and
neurogenic muscle atrophy of the intrinsic
muscles of the larynx.

DIAGNOSTIC CONFIRMATION

Diagnostic confirmation is achieved by
endoscopic examination of the larynx.

536

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

DIFFERENTIAL DIAGNOSIS

Differential diagnoses of exercise
intolerance and exercise-induced
respiratory noise include:

• Dorsal displacement of the soft palate

• Subepiglottic cysts

• Arytenoid chondritis

• Aryepiglottic fold entrapment

• Axial deviation of the aryepiglottic
folds 16

TREATMENT

Treatment requires a prosthetic laiyngo-
plasty with or without ventriculectomy.
The disease is not life-threatening and
horses that are not required to work
strenuously or in which respiratory noise
associated with mild exercise is not
bothersome to the rider may not require
surgery.

REVIEW LITERATURE

Cahill JI, Goulden BE. The pathogenesis of equine
laryngeal hemiplegia - a review. N Z Vet J 1987;
35:82-87.

REFERENCES

1. Cahill JI, Goulden BE.N ZVet J 1986; 34:161.

2. Lane JG et al. Equine Vet J 1987; 19:531.

3. Sweeney CR et al. J Am Vet Med Assoc 1991;
198:1037.

4. Hillidge CJ.Vet Rec 1986; 118:535.

5. Brown JA et al. Equine Vet J 2005; 37:397.

6. Cahill JI, Goulden N ZVet J 1987; 35:82.

7. Ohnesorge B et al. Zentralbl Vet A 1993; 40:134.

8. Duncan ID et al. Equine Vet J 1991; 23:94.

9. Harrison GD et al. Acta Neuropathol 1992;
84:307.

10. Dixon PM et al. Equine Vet J 2002; 34:29.

11. Christley RM et al. Equine Vet J 1997; 29:6.

12. King CM et al. Equine Vet J 1994; 26:220.

13. Cable CS et al. Am J Vet Res 2002; 63:1707.

14. Hammer EJ et al. J Am Vet Med Assoc 1998;
212:399.

15. Dart AJ et al. Aust Vet J 2001; 79:109.

16. King DS et al. Vet Surg 2001; 30:151.

17. Ducharme NG et al.Vet Surg 1991; 20:174.

DORSAL DISPLACEMENT OF THE
SOFT PALATE (SOFT PALATE
PARESIS)

The soft palate of equids is unique in that
it provides an airtight seal between the
oropharynx and nasopharynx during
respiration. The horse is an obligate nasal
breather except during very unusual
circumstances. During swallowing the
soft palate is transiently displaced
dorsally as part of the normal act of
deglutition to permit passage of the feed
bolus. Displacement of the soft palate
other than during deglutition is abnormal
and can be intermittent, which is usually
associated with exercise, or persistent,
which is usually associated with
disruption of the nerve supply to the
pharynx.

Intermittent dorsal displacement of
the soft palate

Intermittent dorsal displacement of the soft
palate occurs during exercise in some
horses and causes an expiratory obstruction
to air flow through the larynx and pharynx.
Estimates of the prevalence of the disease
are unreliable because of the transient
nature of the displacement and the fact that
it only occurs during exercise. It is estimated
to occur in 0.5-1. 3% of Thoroughbred race
horses. 1 The cause of intermittent displace-
ment of the soft palate during exercise is
unknown, although a number of mechan-
isms, including palatal myositis, 2 ulcers of
the caudal border of the soft palate, caudal
retraction of the larynx and lower respir-
atory disease, are suggested. Retro-
pharyngeal lymphadenopathy can cause
neurogenic paresis of the pharyngeal and
palatal muscles, with dorsal displacement
of the soft palate the most obvious sign of
pharyngeal collapse during exercise. 3
The immediate cause of the displacement
is the negative intrapharyngeal pressure
generated during exercise.

Displacement of the soft palate during
strenuous exercise places the soft palate
dorsal to the epiglottis, a position in
which it impedes flow of air during
expiration. 4 Ffeak expiratory airflow, minute
ventilation, tidal volume and rate of
oxygen consumption are all decreased in
horses with dorsal displacement of the
soft palate, whereas inspiratory flow and
breathing rate are not affected. 4

Clinical signs

The clinical signs include exercise intoler-
ance and intermittent production of a
gurgling noise during strenuous exercise.
Endoscopic examination of resting horses
usually demonstrates a normal pharynx and
larynx. Brief nasal occlusion (30-60 s) that
induces displacement of the soft palate, in
combination with a history of respiratory
noise during exercise, increases the
likelihood of the disorder. Endoscopic
examination of affected horses during or
immediately after exercise may reveal dorsal
! displacement of the soft palate. Radio-
graphic examination of the pharynx may
reveal a shortened epiglottis (< 7 cm) in
some affected horses.

DIFFERENTIAL DIAGNOSIS

Differential diagnoses for exercise
intolerance and respiratory noise include

laryngeal hemiplegia, subepiglottic
cysts, arytenoid chondritis pnd
aryepiglottic fold entrapment. The

important differentiating factor is that the
noise occurs predominantly during
expiration, and has a more gurgling sound
to it than does the noise produced by
horses with laryngeal hemiplegia.

Treatment

There is no definitive treatment. Usual
methods of surgical intervention include
augmentation of the epiglottis by injec-
tion of polytetrafluoroethylene (Teflon)
paste, resection of the caudal edge of
the soft palate or sternothyrohyoideus
myectomy, 5 although some of these
interventions may have deleterious effects
on upper airway airflow. 6 A newer
surgical technique involves the 'laryngeal
tie-forward' procedure. 7 Reports of success
of surgical treatment of the disease are
not definitive, in part because horses with
the disorder that went untreated are not
examined. It is plausible that the response
to surgical treatment could be the result of
enforced rest rather than the manipulation.
Treatment of retropharyngeal lymph-
adenopathy may be beneficial. Nonsurgical
treatment includes the use of anti-
inflammatory drugs, tongue-ties, a variety
of bits and a laryngohyoid support
apparatus. 8

Persistent dorsal displacement of the
soft palate

Persistent dorsal displacement of the soft
palate is usually the result of damage to
the innervation of the pharyngeal and
palatal muscles as a result of:

° Guttural pouch mycosis
0 Guttural pouch empyema
° Retropharyngeal lymph node
abscessation

c Equine protozoal myeloencephalitis
° Otitis media

° Myositis or muscle disease, such as
white muscle disease
° Botulism.

Blockade of the pharyngeal branch of the
vagus nerve by injection of local anes-
thetic causes persistent dorsal displacement
of the soft palate whereas blockade of the
hypoglossal and glossopharyngeal nerves
does not. 9,10

Clinical signs

Persistent dorsal displacement of the soft
palate causes dysphagia and stertorous
respiration. Food material discharges
from the nares and there is frequent
coughing, probably secondary to the
aspiration of feed material. Affected
horses may develop aspiration pneumonia.
If the condition persists, there is dehy-
dration and weight loss. Endoscopic
examination of the upper airways reveals
dorsal displacement of the soft palate and
may reveal other abnormalities, such as
guttural pouch mycosis, that may provide
a cause for the disease.

Treatment

Treatment should be directed toward
resolution of the underlying disease, and
provision of food and water. It is often

Diseases of the upper respiratory tract

537

necessary to feed affected horses through
a nasogastric tube.

REFERENCES

1. Brown J A et al. Equine Vet J 2005; 37:397.

2. Blythe LL et al. J Am Vet Med Assoc 1983;
183:781.

3. Derksen FJ et al. In: Proceedings of the Dubai
International Equine Symposium 1997:23.

4. Franklin SH et al. Equine Vet J Suppl 2002; 34:379.

5. Smith JJ, Emberstson RM.Vet Surg 2005; 34:5.

6. Holcombe SJ et al. J Appl Physiol 1994; 77:2812.

7. Woodie JB et al. Equine Vet J 2005; 37:418.

8. Woodie JB et al. EquineVet J 2005; 37:425.

9. Holcombe SJ et al. J Am Vet Med Assoc 1998;
59:504.

10. Holcombe SJ et al. Am JVet Res 1997; 58:1022.

OTHER CONDITIONS OF THE
UPPER AIRWAY OF HORSES

Aryepiglottic fold entrapment
(epiglottic entrapment)

Entrapment of the epiglottis in the fold of
tissue that extends from the arytenoid
cartilage to the ventrolateral aspect of the
epiglottis causes exercise intolerance and
respiratory noise during exercise in
racehorses. 1 The disorder occurs in both
young and mature race horses, and is
found in approximately 1 % of Thorough-
bred race horses. 2,3 The entrapment is
often detected during rhinolaryngoscopic
examination of racehorses, although it
might not be the cause of poor per-
formance. 3 The presence of aryepiglottic
fold entrapment causes a predominantly
expiratory obstruction to air flow across
the larynx during exercise. The inter-
ference with airflow, if any, does not
appreciably impair performance in all
horses. 3

Clinical signs

Clinical signs are of exercise intolerance
and respiratory noise during exercise.
Acute cases can be associated with epi-
glottitis, whereas chronic cases are usually
an incidental finding during endoscopic
examination of the upper airway.

Endoscopic examination of the upper
airway reveals the border of the epiglottis
to be obscured by the aryepiglottic folds.
Normally, the serrated margin of the
epiglottis and dorsal blood vessels extend-
ing to the lateral margins of the epiglottis
are readily apparent, but when the
epiglottis is entrapped these features are
no longer visible. Because of the fre-
quently intermittent nature of the entrap-
ment, the horse should be examined on
several occasions and preferably imme-
diately after strenuous exercise. Radio-
graphy of the pharynx reveals the
entrapped epiglottis.

Treatment

Treatment consists of surgical revision of
the aryepiglottic fold. However, given that
the chronic condition has not been

demonstrated to adversely affect per-
formance, and that the complication rate
for surgical correction of the disorder is
60%, careful consideration should be
given to not attempting surgical repair,
especially in animals performing to
expectation. 3 Entrapment associated
with acute epiglottitis should include
administration of antimicrobials and anti- j
inflammatory agents to resolve the
epiglottitis.

Epiglottitis

This is usually a disease of racehorses,
although animals of any age can be
affected. The clinical signs are exercise
intolerance, respiratory noise and cough-
ing. The disease can readily be mistaken
for epiglottic entrapment. The epiglottis is
thickened and ulcerated, and these changes
are apparent on endoscopic examination.
Treatment includes topical application of
a mixture of nitrofurazone, dimethyl
sulfoxide, glycerin and prednisolone,
and systemic administration of anti-
inflammatory drugs. The prognosis for
recovery is excellent. 4

Subepiglottic cysts

Fluid- filled cysts in the subepiglottic,
dorsal pharyngeal or soft palate tissues
cause exercise intolerance and abnormal
respiratory noise in exercising adult
horses and mild dysphagia, chronic cough
and nasal discharge in foals. 5,6 The cysts
are usually embryonic remnants, although
cysts may be acquired in adult horses by
obstruction or inflammation of mucous
glands. 6 Endoscopic examination of the
upper airway reveals the presence of
smooth-walled cysts. Subepiglottic cysts
may only be apparent on careful
examination of the epiglottis, although
most will cause the epiglottis to assume a
more upright posture than is normal.
Treatment is surgical removal.

Arytenoid chondritis

This is a progressive disease of the
arytenoid cartilages in which there is
distortion of the cartilage with consequent
partial occlusion of the lumen of the
larynx. The cause of the disease is not
known but it is most common in race-
horses in heavy work. 7 Distortion and
swelling of the cartilage, combined with
restricted abduction, increase resistance
to airflow through the larynx and cause
respiratory noise during exercise and
exercise intolerance. In severe cases
respiratory noise and increased respiratory
effort may be apparent at rest. The disease
can occur as a progression of idiopathic
mucosal ulceration of the axial aspect of
the arytenoid cartilages. 8

Endoscopic examination reveals the
cartilage to be enlarged and distorted and
there may be luminal projections of

cartilage and granulation tissue. In less
severe cases there is mild swelling of the
cartilage and ulceration of the mucosa
covering the cartilage. Bilateral disease is
uncommon. The cartilage contains areas
of necrosis, dystrophic mineralization and
granulation tissue.

Treatment

Treatment requires surgical removal of the
affected cartilage, although progression of
the disease can be achieved in horses
with mild lesions by administration of
antimicrobials and anti-inflammatory
drugs.

Mucosal lesions of the arytenoid
cartilages

Lesions of the mucosa of the axial aspect
of the arytenoid cartilages are observed in
Thoroughbred race horses. 3,8 The con-
dition occurs in approximately 2.5% of
Thoroughbred race horses and 0.6% of
Thoroughbred yearlings. 3,8 The patho-
genesis is unknown. The disorder is
recognized during endoscopic examination
of the horses for other reasons (before
sale, examination for exercise-induced
pulmonary hemorrhage). Endoscopic
appearance of the lesion is that of a
roughly circular lesion of the mucosa of
the axial surface of the arytenoid cartilage,
with or without visual evidence of inflam-
mation, and without deformity of the
underlying cartilage. 8 The lesions can
progress to arytenoid chondritis, although
most do not. 8 Because of the risk of
progression, medical therapy including
systemic or local administration of anti-
microbial and anti-inflammatory drugs is
indicated. 8 The prognosis for full recovery
is excellent.

Axial deviation of the aryepiglottic
folds

This is one of the most common abnor-
malities detected during laryngoscopic
examination of horses running on a
treadmill. 9 The disorder can only be
detected in horses by endoscopic exam-
ination of the larynx while the horse is
performing strenuous exercise. Collapse
of the axial portion of the aryepiglottic
folds causes obstruction of the laryngeal
airway during inspiration. Treatment is by
transendoscopic laser ablation of the
portion of the fold that collapses during
exercise. 10

Epiglottic retroversion

This uncommon cause of exercise
intolerance and respiratory noise during
strenuous exercise is detected during
endoscopic examination of exercising
horses. 11 During exercise, the epiglottis of
affected horses flips into the larynx during
inspiration and back to its normal posi-
tion during expiration. The cause is
unknown but the condition can be

!8

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

induced by injection of local anesthetic
around the hypoglossal and glosso-
pharyngeal nerves. 12 Treatment is rest.

Retropharyngeal lymphadenopathy

Lymphadenopathy of the retropharyngeal
lymph nodes is usually associated with
S. equi var. equi infection and is often a
sequel to strangles (see Strangles). 13,14
Shedding of S. equi from clinically
inapparent retropharyngeal lymph node
abscesses is an important source of new
infections in horse barns. Retro-
pharyngeal lymphadenopathy is also
caused by trauma to the pharynx and
neoplasia (predominantly lympho-
sarcoma). Enlargement of the retro-
pharyngeal lymph nodes compresses the
nasopharynx, increases resistance to air
flow and may impair swallowing.

Clinical signs

Clinical signs are swelling of the parotid
region, although this may be slight even
in horses with marked respiratory
distress, pain on palpation of the parotid
region, stertorous respiratory noise,
respiratory distress and dysphagia evident
as food material discharging from the
nostrils. Affected horses are frequently
depressed, inappetent and pyrexic.

Endoscopic examination of the
upper airway will reveal ventral displace-
ment of the dorsal wall to the pharynx
and narrowing of the nasopharynx. There
may be deviation of the larynx to the side
away from the mass. Guttural pouch
empyema often coexists with retro-
pharyngeal lymph node infection and the
guttural pouches should be examined.
Radiography will reveal the presence of a
soft tissue density in the retropharyngeal
region with compression of the guttural
pouches and pharynx. Hematological
examination often demonstrates a mature
neutrophilia and hyperfibrinogenemia.
The serum antibody titer to the M protein
of S. equi is usually elevated.

Treatment

Treatment consists of administration of
penicillin (procaine penicillin 20 000 IU/kg,
intramuscularly every 12 h) until signs of
the disease resolve, followed by adminis-
tration of a combination of sulfonamide
and trimethoprim (15-30 mg/kg orally
every 12 h for 7-14 d). Administration of
anti-inflammatory drugs such as phenyl-
butazone (2.2 mg/kg intravenously or
orally every 12 h) is important in reducing
inflammation and swelling and thereby
allowing the horse to eat and drink.
Horses that have severe respiratory
distress may require a tracheotomy.
Dysphagic horses may require fluid and
nutritional support. Surgical drainage of
the abscess is difficult and should be

reserved for cases with large, cavitating
lesions evident on radiographic or ultra-
sonographic examination.

Control consists of preventing infection
of horses by S. equi var. equi and adequate
treatment of horses with strangles.

REFERENCES

1. Boles C et al. J Am Vet Med Assoc 1978; 172:883.

2. Sweeney CR et al. J Am Vet Med Assoc 1991;
198:1037.

3. Brown JA. Equine Vet J 2005; 37:397.

4. Hawkins J,Tulleners ER J Am Vet Med Assoc 1994;
205:1577.

5. Stick JA, Boles CL. J Am Vet Med Assoc 1980;
77:62.

6. Haynes PF et al. Equine Vet J 1990; 22:369.

7. Haynes PF et al. J Am Vet Med Assoc 1980;
177:1135.

8. Kelly G et al. Equine Vet J 2003; 35:276.

9. Tan RH et al. Vet J 2004; 170:243.

10. King DS et al. Vet Surg 2001; 30:151.

11. Rarente EJ et al. Equine Vet J 1998; 30:270.

12. Holcombe SJ et al. Equine Vet J Suppl 1999; 30:45.

13. Todhunter RJ et al. J Am Vet Med Assoc 1985;
187:600.

14. Golland LC et al. AustVet J 1993; 72:161.

DISEASES OF THE GUTTURAL
POUCHES (AUDITORY TUBE
DIVERTICULUM, EUSTACHIAN
TUBE DIVERTICULUM)

The guttural pouches are diverticula of
the auditory (or eustachian) tubes found
in equids and a limited number of other
species. 1,2 The function of the guttural
pouch is unclear, although it may have a
role in regulation of cerebral blood pres-
sure, swallowing, and hearing. 1 It is
unlikely to have a role in brain cooling. 2
Each guttural pouch of an adult horse has
a volume of approximately 300 mL and is
divided by the stylohyoid bone into lateral
and medial compartments.

The medial compartment of the
guttural pouch contains a number of
important structures including the internal
carotid artery and glossopharyngeal,
hypoglossal, and spinal accessory nerves in
addition to branches of the vagus nerve and
the cervical sympathetic trunk. Retro-
pharyngeal lymph nodes lie beneath the
mucosa of the ventral aspect of the medial
compartment, an important factor in the
development of guttural pouch empyema.

In the lateral compartment the
external carotid artery passes along the
ventral aspect as do the glossopharyngeal
and hypoglossal nerves. Involvement of
any of the above-mentioned structures is
important in the pathogenesis and
clinical signs of guttural 'pouch disease,
and may result in abnormalities, such as
Homer's syndrome, that are not readily
recognized as being caused by guttural
pouch disease.

The common diseases of the guttural
pouch are described below.

GUTTURAL POUCH EMPYEMA

ETIOLOGY

Empyema is the accumulation of purulent
material in one or both guttural pouches.
Initially, the purulent material is liquid,
although it is usually viscid, but over time
becomes inspissated and is kneaded
into ovoid masses called chondroids.
Chondroids occur in approximately 20%
of horses with guttural pouch empyema. 3
The condition is most commonly associ-
ated with S. equi var. equi infection and is
a recognized sequel to strangles. 3-5 There-
fore, any horse with guttural pouch
empyema should be isolated and treated
as if it were infected with S. equi var. equi
until proven otherwise. The empyema
may be associated with other conditions
of the guttural pouches, especially if there
is impaired drainage of the pouch
through the pharyngeal opening of the
eustachian tube.

EPIDEMIOLOGY

The epidemiology, apart from its associ-
ation with strangles, has not been
defined. The disease occurs in all ages of
horses, including foals, and all equids,
including asses and donkeys. 3 The case
fatality rate is approximately 10%, with
one-third of horses having complete
resolution of the disease. 3 Guttural pouch
empyema occurs in approximately 7% of
horses with strangles. 4 The recovery rate
for horses with uncomplicated empyema
treated appropriately is generally
considered to be good, although the
presence of chondroids worsens the
prognosis.

PATHOGENESIS

The pathogenesis of guttural pouch
empyema is unclear although when
secondary to strangles it is usually due to
the rupture of abscessed retropharyngeal
lymph nodes into the medial compart-
ment. Continued drainage of the abscesses
presumably overwhelms the normal
drainage and protective mechanisms of
the guttural pouch, allowing bacterial
colonization, influx of neutrophils and
accumulation of purulent material.
Swelling of the mucosa, especially around
the opening to the pharynx, impairs
drainage and facilitates fluid accumulation
in the pouch. The accumulation of
material in the pouch causes distension
and mechanical interference with swallow-
ing and breathing. Inflammation of the
guttural pouch mucosa may involve the
nerves that lie beneath it and result in
neuritis with subsequent pharyngeal and
laryngeal dysfunction and dysphagia.

CLINICAL FINDINGS

These include: 3

ri Purulent nasal discharge

Diseases of the upper respiratory tract

o Swelling of the area caudal to the
ramus of the mandible and ventral to
the ear

«• Lymphadenopathy
o Carriage of the head with the nose
elevated above its usual position
o Dysphagia and other cranial nerve
dysfunction
° Respiratory stertor.

The nasal discharge is usually unilateral,
as is the disease, intermittent and white to
yellow. Guttural pouch empyema is not
usually associated with hemorrhage,
although the discharge may be blood
tinged. Bilateral disease, and the resultant
neuritis and mechanical interference
with swallowing and breathing, may
cause discharge of feed material from
the nostrils, dysphagia and respiratory
stertor.

Endoscopic examination of the

pharynx reveals drainage of purulent
material from the pharyngeal opening of
the eustachian tube of the affected side.
The guttural pouch contains a variable
quantity of purulent material, although in
severe cases the quantity of fluid may be
sufficient to prevent adequate examin-
ation of the pouch with an endoscope.

Radiographic examinations demon-
strate the presence of radiodense material
in the guttural pouch, sometimes the
presence of an air-gas interface (fluid
line) within the pouch and distension of
the pouch with impingement into the
nasopharynx. 5 Chondroids are evident as
multiple circular radiodensities. Passage
of a catheter into the guttural pouch via
the pharyngeal opening pennits aspiration
of fluid for cytology and bacterial culture.

CLINICAL PATHOLOGY

Hematological examination may reveal
evidence of chronic infection, including a
mild leukocytosis, hyperproteinemia, and
hyperfibrinogenemia. Fluid from the
affected guttural pouch contains large
numbers of degenerate neutrophils and
occasional intracellular and extracellular
bacteria. Bacterial culture yields S. equi
in approximately 30% of cases and
S. zooepidemicus in approximately 40% of
cases. 3

NECROPSY FINDINGS

Lesions of guttural pouch empyema
include the presence of purulent material
in the guttural pouch and inflammation
of the mucosa of the affected guttural
pouch.

DIAGNOSTIC CONFIRMATION

Diagnostic confirmation in a horse with
clinical signs of guttural pouch disease is
achieved by demonstration of purulent
material in the guttural pouch by
endoscopic or radiographic examination
and examination of the fluid.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis of guttural pouch
empyema includes:

• Abscessation of retropharyngeal
lymph nodes

• Guttural pouch tympany

• Guttural pouch mycosis.

Guttural pouch empyema should also be
differentiated from other causes of nasal
discharge in horses including:

• Sinusitis

• Recurrent airway obstruction
(heaves)

• Pneumonia

• Esophageal obstruction

• Dysphagia of other cause.

Infection by Mycobacterium avium
complex organisms causes nasal discharge
and granulomatous lesions in the guttural
pouch . 6

TREATMENT

The principles of treatment are removal of
the purulent material, eradication of
infection, reduction of inflammation,
relief of respiratory distress and provision
of nutritional support in severely affected
horses.

Removal of purulent material may

be difficult but can be achieved by
repeated flushing of the affected guttural
pouch. The guttural pouch can be flushed
through a catheter (10-20 French,
3.3-7 mm male dog urinary catheter)
inserted as needed via the nares, or a
catheter (polyethylene 240 tubing) with a
coiled end inserted via the nares and
retained in the pouch for several days. 7
The pouch can also be flushed through
the biopsy port of an endoscope inserted
into the guttural pouch.

The choice of fluid with which to flush
the guttural pouch is arbitrary but
frequently used fluids include normal
(isotonic) saline, lactated Ringer's solu-
tion or 1% (v/v) povidone-iodine solu-
tion. It is important that the fluid infused
into the guttural pouch be nonirritating as
introduction of fluids such as hydrogen
peroxide or strong solutions of iodine (e.g.
10% v/v povidone iodine) will exacerbate
the inflammation of the mucosa and
underlying nerves and can actually
prolong the course of the disease. 8 The
frequency of flushing is initially daily, with
reduced frequency as the empyema
resolves.

Infusion of antibiotics into the
guttural pouches -is probably without
merit. Because of the viscid nature of the
empyema fluid, it is necessary to infuse
large volumes of lavage solution (1-2 L)
on consecutive days. It may be necessary
to treat for 7-10 days. The infusion of
acetylcysteine (60 mL of a 20% solution)

into the pouch after lavage with 1-2 L of
saline has been reported to be effective in
aiding the removal of purulent material. 9
Removal of chondroids usually requires
surgery, although dissection and removal
of chondroids through the pharyngeal
opening has been described. 10 A stone
remover inserted through the biopsy
channel of the endoscope can be use-
ful for removal of small numbers of
chondroids, but is tedious if there are
large numbers of them. A rule of thumb is
that if the chondroids occupy more than
one-third of the volume of the guttural
pouch, then removal should be carried
out surgically.

Systemic antimicrobial adminis-
tration is recommended for all cases of
guttural pouch empyema because of the
frequent association of the disease with
bacterial infection and especially S. equi
and S. zooepidemicus infection of the
retropharyngeal lymph nodes. 3 The
antibiotic of choice is penicillin G
(procaine penicillin G, 20 000 IU/kg
intramuscularly every 12 h for 5-7 d),
although a combination of sulfonamide
and trimethoprim (15-30 mg/kg orally
every 12 h for 5-7 d) is often used.
Topical application of antimicrobials
into the guttural pouch is probably
ineffective because they do not penetrate
the infected soft tissues of the pouch and
retropharyngeal area.

NSAIDs such as flunixin meglumine
(1 mg/kg intravenously or orally every
12 h) or phenylbutazone (2.2 mg/kg intra-
venously or orally every 12 h) are used to
reduce inflammation and pain. Severely
affected horses may require relief of
respiratory distress by tracheotomy.
Dysphagic horses may need nutritional
support, including administration of
fluids.

Chronic cases refractory to treatment
might require fistulation of the guttural
pouch into the pharynx. 11

CONTROL

Prevention of guttural pouch empyema is
based on a reduction in the frequency and
severity of S. equi infection in horses (see
Strangles) .

REVIEW LITERATURE

Freeman DE. Diagnosis and treatment of diseases of
the guttural pouch (Part 1). Compend Contin
Educ PractVet 1980; 2:S3-S11.

Freeman DE. Diagnosis and treatment of diseases of
the guttural pouch (Part II). Compend Contin
Educ PractVet 1980; 2:S25-S31.

REFERENCES

1. Baptiste KE.Vet J 1998; 155:139.

2. Maloney SK et al. S Afr J Sci 2002; 98:189.

3. Judy CE et al. J Am Vet Med Assoc 1999; 215:1666.

4. Sweeney CR et al. J Am Vet Med Assoc 1987;
191:1446.

5. Newton JR et al. Vet Recl997; 140:84.

6. Sills RC et al.Vet Fhthol 1990; 27:133.

540

PART 1 GENERAL MEDICINE ■ Chapter 10: Diseases of the respiratory system

7. White SL, Williamson L.Vet Med 1987; 82:76.

8. Wilson J. Equine Vet J 1985; 17:242.

9. Bentz BG et al. Equine Pract 1996; 18:33.

10. Seahorn TL, Schumacher J. J Am Vet Med Assoc

1991; 199:368.

11. Hawkins JF et al. J Am Vet Med Assoc 2001;

218:405.

GUTTURAL POUCH M YCOSIS
ETIOLOGY

Mycosis of the guttural pouch is caused
by infection of the dorsal wall of the
medial compartment of the pouch, caudal
and medial to the articulation of the
stylohyoid bone and the petrous temporal
bone. 1 The most common fungi isolated
from the lesions are Aspergillus ( Emericella )
nidulans, Aspergillus fumigatus and, rarely,
Penicillium spp. and Mucor spp., although
spores of these fungi are present in the
guttural pouches of normal horses. 2

EPIDEMIOLOGY

The disease occurs in horses of both
genders and all breeds. Horses are affected
at all ages, with the youngest recorded case
being a 6-month-old foal. 3 The overall
prevalence is low, although precise figures
are lacking. The case fatality rate is
approximately 33%.

PATHOGENESIS

The pathogenesis of the disease is unclear,
although it is likely that fungal spores gain
access to the guttural pouch through the
pharyngeal opening. The spores then
germinate and proliferate in the mucosa of
the dorsal, medial aspect of the medial
compartment of the guttural pouch. The
location of the lesion is consistent but the
reason for the disease occurring in this
particular position is unclear. Factors that
predispose to the development of mycotic
lesions have not been determined,
although it appears unlikely that fungal
infection is the initial insult to the mucosa.
Invasion of guttural pouch mucosa is
followed by invasion of the nerves, arteries,
and soft tissues adjacent to it. Invasion of
the nerves causes glossopharyngeal,
hypoglossal, facial, sympathetic or vagal
dysfunction. Invasion of the internal carotid
artery, and occasionally the maxillary or
external carotid, causes weakening of the
arterial wall and aneurysmal dilatation of
the artery, with subsequent rupture and
hemorrhage. Death is caused by hemor-
rhagic shock or, in horses with dysphagia,
aspiration pneumonia or starvation.

Guttural pouch mycosis is usually
unilateral, although in approximately 8%
of cases there is erosion of the medial
septum and spread of infection into the
other pouch. 4 There is no predisposition
for either the left or right pouch. 4 Guttural
pouch mycosis presents as either epistaxis
that is not associated with exercise or as
cranial nerve disease.

CLINICAL FINDINGS

Epistaxis is usually severe and frequently
life-threatening. There is profuse bleeding
of bright red blood from both nostrils
during an episode, and between episodes
there may be a slight, serosanguineous
nasal discharge. There are usually several
episodes of epistaxis over a period of
weeks before the horse dies. Most horses
that die of guttural pouch mycosis do so
because of hemorrhagic shock. 3,4

Signs of cranial nerve dysfunction
are common in horses with guttural
pouch mycosis and may precede or
accompany epistaxis.

° Dysphagia is the most common sign
of cranial nerve disease and is
attributable to lesions of the
glossopharyngeal and cranial
laryngeal (vagus) nerves. Dysphagic
horses may attempt to eat or drink
but are unable to move the food bolus
from the oral cavity to the esophagus
° Affected horses frequently have nasal
discharge that contains feed material
and often develop aspiration
pneumonia

° Lesions of the recurrent laryngeal
nerve cause laryngeal hemiplegia
° Horner's syndrome (ptosis of the
upper eyelid, miosis, enophthalmos
and prolapse of the nictitating
membrane) is seen when the lesion
involves the cranial cervical ganglion
or sympathetic nerve trunk
° Facial nerve dysfunction, evident as
drooping of the ear on the affected
side, lack of facial expression, inability
to close the eyelids, corneal ulceration
and deviation of the muzzle away
from the affected side, also occurs.

Signs of cranial nerve and sympathetic
trunk dysfunction may resolve with eradi-
cation of the infection, but are frequently
permanent. 4

Guttural pouch mycosis is also associ-
ated with pain on palpation of the parotid
region, head shyness and abnormal
head position. The infection may spread
to the atlanto-occipital joint, causing pain
on movement of the head, 5 or to the
brain, causing encephalitis. 6

Endoscopic examination of the
guttural pouch reveals a plaque of dark
yellow to black necrotic material in the
dorsal aspect of the medial compartment.
A sample of the material can be collected
through a biopsy port of the endoscope
and submitted for culture. The mycotic
plaque cannot be easily -dislodged by
manipulation with biopsy instruments or
the end of the endoscope. In cases with
ongoing or recent hemorrhage, the
presence of large quantities of blood may
prevent identification of the mycotic
plaque. Both pouches should always be

examined because of the occasional
occurrence of bilateral disease or exten-
sion of the disease through the medial
septum.

Radiographic examination of the

guttural pouches may reveal the presence
of a lesion in the appropriate position, but
is frequently unrewarding.

CLINICAL PATHOLOGY

There are no characteristic findings on the
hemogram, nor are there serum bio-
chemical abnormalities. Horses with
repeated hemorrhage may be anemic.
Immunoblot may identify the presence of
serum antibodies specific for A fumigatus
in infected horses, 7 although the diag-
nostic usefulness has not been determined.
Culture of a sample of the necrotic tissue
will frequently yield one of the causative
fungi.

NECROPSY FINDINGS

Lesions of guttural pouch mycosis include
the presence of a clearly demarcated,
yellow-brown to black, dry plaque of
necrotic tissue in the dorsal aspect of the
medial compartment of the guttural
pouch. The plaque of tissue is firmly
adherent to underlying tissues and may
perforate the medial septum and invade
the other pouch. The infection may
involve the adjacent nerves and blood
vessels and spread to soft tissues and
bone. Histological examination reveals
the presence of inflammatory cells in
nerves and tissues surrounding the gross
lesion. There is chromatolysis and degener-
ation of neurones in affected nerves. The
internal carotid artery may have an
aneurysmal dilatation or there may be
rupture of the arterial wall without dila-
tation. There is usually partial thrombosis
of the arterial wall.

DIFFERENTIAL DIAGNOSIS

Differential diagnoses for epistaxis not
associated with exercise include ethmoidal
hematoma or guttural pouch
empyema, neoplasia, rupture of the
longus capitis muscle 8 or penetration by
a foreign body . 9

TREATMENT

Treatment of guttural pouch mycosis
involves prevention of death from hemor-
rhage and administration of antifungal
agents.

Prevention of hemorrhage from the
internal carotid or maxillary artery is
achieved by surgical ligation, transarterial
coil embolization or occlusion with intra-
arterial balloons of one or more of the
external carotid, internal carotid or
maxillary artery. 10,11 Because of the high
rate of death from hemorrhage in horses
with guttural pouch mycosis, some

Diseases of the upper respiratory tract

authorities recommend that all horses with
the disease have the internal artery ligated
or occluded. 4,10 Medical treatment of horses
with hemorrhage secondary to guttural
pouch mycosis is rarely successful. 10

Administration of antifungal agents
by instillation into the guttural pouch
through a catheter or endoscope has been
reported, although there is disagreement
about the need for such treatment in horses
that have had the problematic arteries
ligated or occluded. 12 Oral administration of
antifungal agents is generally ineffective
or prohibitively expensive, although
itraconazole (5 mg/kg orally once daily)
may be useful. 13 Agents reported to be
usefully given by topical administration
include enilconazole (60 mL of 33 mg/mL
solution once daily for 3 weeks),
miconazole (60 mL of 1 mg/mL solution),
natamycin and nystatin. 4,10,13 Topical
therapy is laborious because it must be
continued for weeks and involves place-
ment and maintenance of a catheter in the
guttural pouch, or instillation of medication
by daily endoscopy.

Horses with signs of cranial nerve or
sympathetic trunk damage may not
recover completely even if cured of the
fungal infection because of irreparable
damage to the affected nerves. Provision
of supportive care, including fluid and
nutrient administration to dysphagic
horses and administration of antibiotics
to prevent or treat aspiration pneumonia,
may be indicated.

CONTROL

There are no recognized effective measures
to control or prevent the disease.

REVIEW LITERATURE

Freeman DE. Diagnosis and treatment of diseases of
the guttural pouch (Part 11). Compcnd Contin
Educ PractVet 1980; 2:S25-S31.

LcFctge OM et al. The mystery of fungal infection in
the guttural pouches. Vet J 2003; 168:60.

REFERENCES

1. Cook WR ct al.Vct Rec 1968; 83:422.

2. Blomme E et al. Equine Vet Educ 1998; 10:86.

3. Cook WR Vet Rec 1968; 78:396.

4. Greet TRC. Equine Vet J 1987; 19:483.

5. Walmsley JP. Equine Vet J 1988; 20:219.

6. Wagner PC et al. Can Vet J 1978; 27:109.

7. Guillot J et al. Am JVet Res 1997; 58:1364.

8. Sweeney CR et al. J Am Vet Med Assoc 1993;
202:1129.

9. Bayly WM, Robertson JT. J Am Vet Med Assoc
1982; 180:1232.

10. Lane JG. Equine Vet J 1989; 21:321.

11. Leveille R et al. Vet Surg 2000; 29:389.

12. Spiers VC et al. Equine Vet J 1995; 27:151.

13. Davis EW, Legendre AM. J Vet Intern Med 1994;
8:304.

G UTTURAL POUCH TYMPANY

ETIOLOGY AND EPIDEMIOLOGY

Guttural pouch tympany refers to the
gaseous distension of one, rarely both,
guttural pouches of young horses.
Tympany develops in foals up to 1 year of
age butis usually apparent within the first
several months of life. Fillies are more
commonly affected than are colts by a
ratio of 2-4:1. 1 The cause is not known
although a polygenic cause has been
proposed for Arabians. 2

CLINICAL FINDINGS

Clinical findings include marked swelling
of the parotid region of the affected side
with lesser swelling of the contralateral
side. The swelling of the affected side is
not painful on palpation and is elastic and
compressible. 3 There are stertorous breath
sounds in most affected foals due to
impingement of the distended pouch on
the nasopharynx. Respiratory distress
may develop. Severely affected foals may
be dysphagic and develop aspiration
pneumonia.

Endoscopic examination of the

pharynx reveals narrowing of the naso-
pharynx by the distended guttural pouch.
The guttural pouch openings are usually
normal. There are usually no detectable
abnormalities of the guttural pouches
apart from distension. Radiographic
examination demonstrates air-filled
pouches, and dorsoventral images permit
documentation of which side is affected.
There are no characteristic changes in the
hemogram or serum biochemical profile.

There are no characteristic lesions and
necropsy examination usually does not
demonstrate a cause for the disease.

TREATMENT

Treatment consists of surgical fenestration
of the medial septum allowing drainage
of air from the affected pouch into the
unaffected side. The prognosis for long-
term resolution of the problem after
surgery is approximately 60 %}

REFERENCES

1. McCue PM ct al. J Am Vet Med Assoc 1989;
194:1761.

2. Blazyczek I et al. J Hered 2004; 95:195.

3. Freeman DE. Compend Contin Educ Pract Vet
1980; 2:S25-S31.

OTHER GUTTURAL POUCH
DISEASES

j Rupture of the longus capitis muscle

or avulsion of its insertion on the
basisphenoid bone causes epistaxis and is

usually associated with trauma to the
head, such as is caused by rearing and
falling over backwards. 1 Endoscopic
examination reveals:

0 Compression of the nasopharynx that
is asymmetric

° Blood in the guttural pouch
° Submucosal hemorrhage and swelling
of the medial aspect of the medial
compartment of the guttural pouch. 1

Radiographic examination reveals ventral
deviation of the dorsal pharynx and loss
of the usual radiolucency associated with
the guttural pouch. Treatment is con-
servative and consists of supportive care,
monitoring the hematocrit, and adminis-
tration of broad-spectrum antibiotics if
there is concern of the development of
secondary infection. The prognosis for
complete recovery is guarded.

Various neoplasms have been recorded
as involving the guttural pouches. The
presenting signs are: swelling of the
parotid region, epistaxis, dysphagia or
signs of cranial nerve disease. Neoplasms
include melanoma, lymphosarcoma,
hemangiosarcoma, squamous cell carci-
noma and sarcoma. 2 Diagnosis is made
by physical, endoscopic and radiographic
examination and biopsy. The prognosis is
very poor to hopeless.

REFERENCES

1. Sweeney CR et al. J Am Vet Med Assoc 1993;
202:1129.

2. McConnico RS et al. Equine Vet Educ 2001;
13:175.

CONGENITAL DEFECTS

Primary congenital defects are rare in the
respiratory tracts of animals. Hypoplasia
of the epiglottis is detected occasionally in
horses. Tracheal hypoplasia is recognized
in calves and Miniature horses. Secondary
defects, which are associated with major
defects in other systems, are more com-
mon. Most of the defects in lambs are
associated with defects of the oral cavity,
face, and cranial vault. 1 Accessory lungs
are recorded occasionally 2,3 and if their
bronchi are vestigial the lungs can present
themselves as tumor-like masses occupy-
ing most of the chest. Pulmonary hypo-
plasia is associated with congenital
diaphragmatic hernia.

REFERENCES

1. Dennis SM.AustVet J 1975; 51:347.

2. Smith RE, McEntee C. Cornell Vet 1974; 64:335.

3. Osborne JC, Troutt HF. Cornell Vet 1977; 67:222.

rHM I I GENERAL MEDICINE

Diseases of the urinary system

INTRODUCTION 543

PRINCIPLES OF RENAL
INSUFFICIENCY 543

Renal insufficiency and renal
failure 544

CLINICAL FEATURES OF URINARY
TRACT DISEASE 545

Abnormal constituents of the
urine 545

Variations in daily urine flow 547

Abdominal pain, painful and difficult
urination (dysuria and
stranguria) 547

Morphological abnormalities of kidneys
and ureters 548

Palpable abnormalities of the bladder
and urethra 548

Acute and chronic renal failure 548

Uremia 548

SPECIAL EXAMINATION OF THE
URINARY SYSTEM 548

Urinalysis 548

Introduction

Diseases of the bladder and urethra are
more common and more important than
diseases of the kidneys in farm animals.
Occasionally, renal insufficiency develops
as a sequel to diseases such as pyelo-
nephritis, embolic nephritis, amyloidosis
and nephrosis. A knowledge of the
physiology of urinary secretion and
excretion is required to properly under-
stand disease processes in the urinary
tract. The principles of renal insufficiency
presented here are primarily extrapolated
from research in other species, parti-
cularly human medicine. Although, in
general, these principles probably apply
to farm animals, the details of renal
function and renal failure in farm animals
have received only limited study.

Diseases of the reproductive tract are
not presented in this book and the reader
is referred to textbooks on the subject.
Inevitably, some of the reproductive
diseases are mentioned in the differential
diagnosis of the medical conditions
presented here and in circumstances in
which the reproductive tract is affected
coincidentally. Reference to these entries
in the text can be made through the
index.

Collection of urine samples 548
Tests of renal function and detection of
renal injury 549

Diagnostic examination techniques 552

PRINCIPLES OF TREATMENT OF
URINARY TRACT DISEASE 553

DISEASES OF THE KIDNEY 555

Glomerulonephritis 555
Hemolytic-uremic-like syndrome 556
Nephrosis 556
Renal ischemia 556
Toxic nephrosis 557
Renal tubular acidosis 558
Interstitial nephritis 558
Embolic nephritis 558
Pyelonephritis 559
Hydronephrosis 560
Renal neoplasms 560

DISEASES OF THE BLADDER,
URETERS AND URETHRA 561

Cystitis 561

Paralysis of the bladder 561

Principles of renal
insufficiency

The kidneys excrete the end-products of
tissue metabolism (except for carbon
dioxide), and maintain fluid, electrolyte
and acid-base balance, by varying the
volume of water and the concentration of
solutes in the urine. It is convenient to
think of the kidney as composed of many
similar nephrons, the basic functional
units of the kidney. Each nephron is
composed of blood vessels, the glomerulus
and a tubular system that consists of the
proximal tubule, the loop of Henle, the
distal tubule and the collecting duct.

The glomerulus is a semipermeable filter
that allows easy passage of water and low-
molecular-weight solutes but restricts
passage of high- mol ecular-weight sub-
stances such as plasma proteins.
Glomerular filtrate is derived from plasma
by simple passive filtration driven by arterial
blood pressure. Glomerular filtrate is
identical to plasma except that it contains
little protein or lipids. The volume of filtrate,
and therefore its content of metabolic end-
products, depends upon the hydrostatic
pressure and the plasma oncotic pressure
in the glomerular capillaries and on the
proportion of glomeruli which are func-

11

Rupture of the bladder
(uroperitoneum) 562
Uroperitoneum in foals
(uroabdomen) 562
Urolithiasis in ruminants 565
Urolithiasis in horses 570
Urethral tears in stallions and
geldings 571

Urinary bladder neoplasms 571

CONGENITAL DEFECTS OF THE
URINARY TRACT 571

Renal hypoplasia 571
Renal dysplasia 572
Polycystic kidneys 572
Ectopic ureter 572
Ureteral defect 572
Patent urachus 573
Eversion of the bladder 573
Rupture of the bladder 573
Urethral defect 573
Urethral atresia 573
Hypospadias 573

tional. Because these factors are only
partially controlled by the kidney, in the
absence of disease, the rate of filtration
through the glomeruli is relatively constant.

The epithelium of the tubules actively
and selectively reabsorbs substances from
the glomerular filtrate while permitting
the excretion of waste products. Glucose
is reabsorbed entirely, within the normal
range of plasma concentration; phosphate
is reabsorbed in varying amounts depend-
ing upon the needs of the body to
conserve it; other substances such as
inorganic sulfates and creatinine are not
reabsorbed in appreciable amounts. The
tubules also actively secrete substances,
particularly electrolytes as they function
to regulate acid-base balance. As a result
of the balance between resorption and
secretion, the concentration of solutes in
the urine varies widely when the kidneys
are functioning normally.

The principal mechanism that regulates
water reabsorption by the renal tubules
is antidiuretic hormone (ADH). Tissue
dehydration and an increase in serum
osmolality stimulates secretion of ADH
from the posterior pituitary gland. The
renal tubules respond to ADH by con-
serving water and returning serum
osmolality to normal, thereby producing a
concentrated urine.

544

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases ot the urinary system

Diseases of the kidneys, and in some
instances of the ureters, bladder, and
urethra, reduce the efficiency of the kidney's
functions, resulting in: disturbances in
protein, acid-base, solute and water
homeostasis and in the excretion of
metabolic end-products. A partial loss of
function is described as renal insuf-
ficiency. When the kidneys can no longer
regulate body fluid and solute composition,
renal failure occurs.

RENAL INSUFFICIENCY AND
RENAL FAILURE

Renal function depends upon the number
and functionality of the individual
nephrons. Insufficiency can occur from
abnormalities in:

° The rate of renal blood flow
0 The glomerular filtration rate
® The efficiency of tubular reabsorption.

Of these three abnormalities, the latter
two are intrinsic functions of the kidney,
whereas the first depends largely on
vasomotor control which is markedly
affected by circulatory emergencies such
as shock, dehydration, and hemorrhage.
Circulatory emergencies may lead to a
marked reduction in glomerular filtration
but they are extrarenal in origin and
cannot be considered as true causes of
renal insufficiency. However, prolonged
circulatory disruption can cause renal
ischemia and ultimately renal insufficiency.

Glomerular filtration and tubular
reabsorption can be affected independently
in disease states and every attempt
should be made to clinically differentiate
glomerular disease from tubular disease.
This is because the clinical and clinico-
pathological signs of renal dysfunction
depend on the anatomical location of the
lesion and the imbalance in function
between glomeruli and tubules. Renal
dysfunction tends to be a dynamic pro-
cess so the degree of dysfunction varies
with time. If renal dysfunction is so severe
that the animal's continued existence is
not possible it is said to be in a state of
renal failure and the clinical syndrome of
uremia will be present.

CAUSES OF RENAL INSUFFICIENCY
AND UREMIA

The causes of renal insufficiency, and
therefore of renal failure and uremia, can
be divided into prerenal, renal, and
postrenal groups.

Prerenal causes include congestive
heart failure and acute circulatory failure,
either cardiac or peripheral, in which
acute renal ischemia occurs in response to
a decrease in renal blood flow. Proximal
tubular function is affected by renal
ischemia to a much greater extent than
the glomerulus or distal tubules; this is

because of the high metabolic demands
of the proximal tubules. However, those
parts of the tubules within the medulla
are particularly susceptible to hypoxic
damage because of the low oxygen ten-
sion in this tissue, the dependency of
blood flow on glomerular blood flow and
the high metabolic rate of this tissue.
Renal medullary necrosis is a direct
consequence of these factors. In rumi-
nants, severe bloat can interfere with
cardiac output and lead to renal ischemia.

Renal causes include glomerulo-
nephritis, interstitial nephritis, pyelo-
nephritis, embolic nephritis and
amyloidosis. Acute renal failure can be
produced in any of the farm animal
species by administration of a variety of
toxins (see Toxic nephrosis, below). The
disease can also occur secondary to sepsis
and hemorrhagic shock. Experimental
uremia has also been induced by surgical
removal of both kidneys but the results,
especially in ruminants, are quite different
from those in naturally occurring renal
failure. The clinical pathology is similar
but there is a prolonged period of nor-
mality after the surgery.

Postrenal uremia may also occur,
specifically complete obstruction of the
urinary tract by vesical or urethral calculus,
or more rarely by bilateral urethral
obstruction. Internal rupture of any part
of the urinary tract, such as the bladder,
ureters, or urethra, wall also cause postrenal
uremia.

PATHOGENESIS OF RENAL
INSUFFICIENCY AND RENAL FAILURE

Damage to the glomerular epithelium
destroys its selective permeability and
permits the passage of plasma proteins into
the glomerular filtrate. The predominant
protein is initially albumin, because of
its negative charge and a lower molecular
weight than globulins; however, with
advanced glomerulonephritis (such as
renal amyloidosis) all plasma proteins are
lost. Glomerular filtration may cease
completely when there is extensive
damage to glomeruli, particularly if there
is acute swelling of the kidney, but it is
believed that anuria in the terminal stages
of acute renal disease is caused by back
diffusion of all glomerular filtrate through
the damaged tubular epithelium rather
than failure of filtration. When renal
damage is less severe, the remaining
nephrons compensate to maintain total
glomerular filtration by increasing their
filtration rates. When this occurs, the
volume of glomerular filtrate may exceed
the capacity of the tubular epithelium to
reabsorb fluid and solutes. The tubules
may be unable to achieve normal urine
concentration. As a result, an increased

volume of urine with a constant specific
gravity is produced and solute diuresis
occurs. This is exacerbated if the tubular
function of the compensating nephrons is
also impaired. The inability to concentrate
urine is clinically evident as polyuria
and is characteristic of developing renal
insufficiency.

Decreased glomerular filtration also
results in retention of metabolic waste
products such as urea and creatinine.
Although marked increases in serum urea
concentration are probably not responsible
for the production of clinical signs, because
urea readily crosses cell membranes and
is an effective osmole, the serum urea
nitrogen concentration can be used to
monitor glomerular filtration rate. How-
ever, the utility of serum urea nitrogen
concentration as a measure of glomerular
filtration rate is reduced because serum
urea concentrations are influenced by the
amount of protein in the diet, by
hydration and by gastrointestinal metab-
olism of urea. Serum urea concentrations
are higher in animals on high-protein
diets and dehydration increases serum
urea concentration by increasing resorp-
tion of urea in the loop of Henle,
independent of effects of hydration of
glomerular filtration rate. Urea is excreted
into saliva of ruminants and metabolized
by ruminal bacteria. In contrast, creatinine
is excreted almost entirely by the kidney,
creatine originates from breakdown of
creatine phosphate in muscle, and serum
concentrations of creatinine are a useful
marker of glomerular filtration rate. The
relationship between serum creatinine
concentration and glomerular filtration
rate is hyperbolic - a reduction in
glomerular filtration rate by half results in
a doubling of the serum creatinine con-
centration. Phosphate and sulfate retention
also occurs when total glomerular filtra-
tion is reduced and sulfate retention
contributes to metabolic acidosis in renal
insufficiency. Phosphate retention also
causes a secondary hypocalcemia, due in
part to an increase in calcium excretion in
the urine. In horses, the kidneys are an
important route of excretion of calcium so
the decreased glomerular filtration rate
present in horses with chronic renal
failure can result in hypercalcemia. Vari-
ations in serum potassium levels also
occur and appear to depend on potassium
intake. Hyperkalemia can be a serious
complication in renal insufficiency in
humans, where it is one of the principal
causes of the myocardial asthenia and
fatal heart failure that occur in uremia in
this species.

Loss of tubular resorptive function is
evidenced by a continued loss of sodium
and chloride; hyponatremia and hypo-
chloremia eventually occur in all cases of

renal failure. The continuous loss of large
quantities of fluid due to solute diuresis
can cause clinical dehydration. More
often it makes the animal particularly
susceptible to dehydration when there is
an interruption in water availability or
when there is a sudden increase in body
water loss by another route - as in
diarrhea.

The terminal stage of renal insuffi-
ciency - renal failure - is the result of the
cumulative effects of impaired renal
excretory and homeostatic functions.
Continued loss of large volumes of dilute
urine causes dehydration. If other circu-
latory emergencies arise, acute renal
ischemia might result, leading to acute
renal failure. Prolonged hypoproteinemia
results in rapid loss of body condition and
muscle weakness. Metabolic acidosis is
also a contributing factor to muscle weak-
ness and mental attitude. Hyponatremia
and hyperkalemia cause skeletal muscle
weakness and myocardial asthenia. Hypo-
calcemia may be sufficient to contribute
to circulatory failure and to nervous signs.
All these factors play some part in the
production of clinical signs of renal
failure, which are typically manifest as
weakness, lethargy, inappetence and,
with extensive glomerular lesions, depen-
dent edema due to hypoproteinemia. In
some cases one or other of them might be
of major importance so the clinical
syndrome is variable and is rarely diag-
nostic for renal failure. Bleeding diathesis
can also be present in severely uremic
animals and has been associated with a
lack of antithrombin (a small protein
readily lost through the damaged
glomerulus), platelet factor 3, platelet
dysfunction or disseminated intravascular
coagulation.

Renal failure is seen as the clinical
state of uremia. It is characterized bio-
chemically by an increase in blood levels
of urea and creatinine (azotemia) and by
retention of other solutes as described
above. Uremia can also occur in urinary
tract obstruction.

Clinical features of urinary
tract disease

The major clinical manifestations of
urinary tract disease are:

° Abnormal constituents of urine
9 Variations in daily urine flow
° Abdominal pain, painful urination
(dysuria) and difficult urination
(dysuria and stranguria)

° Abnormal size of kidneys
0 Abnormalities of the bladder and
urethra

° Acute and chronic renal failure.

Clinical features of urinary tract disease

545

ABNORMAL CONSTITUENTS OF
THE URINE

Proteinuria

Proteinuria can be prerenal, renal, or post
renal in origin. Prerenal proteinuria is
due to an abnormal plasma content of
proteins that traverse glomerular capillary
walls, with the proteins having normal
permselectivity properties (such as hemo-
globin, myoglobin, immunoglobulin light
chains). Renal proteinuria is due to
abnormal renal handling of normal
plasma proteins, and is functional or
pathological. Functional renal proteinuria
is mild and transient as a result of altered
renal physiology during or in response to
a transient phenomenon, such as high-
intensity exercise or fever. Pathological
renal proteinuria is due to structural or
functional lesions within the kidney,
regardless of their magnitude or duration.
There are three subcategories of patho-
logical renal proteinuria: glomerular,
which is due to lesions altering the
permselectivity properties of the glomerular
capillary wall; tubular, which is due to
lesions that impair tubular recovery of
plasma proteins that ordinarily traverse
glomerular capillary walls having normal
permselectivity properties (typically low-
molecular-weight proteins); and interstitial,
which is due to inflammatory lesions or
disease processes (such as acute inter-
stitial nephritis) that result in exudation of
proteins from the peritubular capillaries
into the urine. Postrenal proteinuria is
due to entry of protein into the urine after
it enters the renal pelvis, and is urinary
or extraurinary. Urinary postrenal
proteinuria is due to the entry of proteins
derived from hemorrhagic or exudative
processes affecting the renal pelvis, ureter,
urinary bladder, and urethra. Extraurinary
postrenal proteinuria is due to entry of
proteins derived from the genital tract or
external genitalia during voiding or in the
process of collecting urine for analysis.

Normal urine contains only small
amounts of protein that are insufficient to
be detected using standard tests. It should
be noted that the highly alkaline urine
produced by herbivores produces a false-
positive reaction (trace or 1+) for protein
on urine dipstick tests. Prerenal proteinuria
may be present in hemoglobinuria and
myoglobinuria. Functional renal proteinuria
is observed in normal foals, calves, kids,
and lambs in the first 40 hours after they
receive colostrum. Pathological renal or
postrenal proteinuria and hematuria may
be present when urinary tract infections
are present. Postparturient cows usually
have protein present in a free- catch urine
sample as a result of washout of uterine
fluids; this is a classic example of extra-
urinary postrenal proteinuria. Demon-

stration that proteinuria originates in
the kidney is easier if elements that form
in the kidney, such as tubular casts, are
also present in the urine, or morpho-
logical abnormalities of the kidneys
are palpable per rectum or identified
ultrasonographically.

Proteinuria is most accurately quanti-
fied by determining the amount of protein
passed in a 24-hour period, which is
impractical in clinical cases. Proteinuria is
more easily quantified by indexing the
protein concentration to creatinine con-
centration in single urine sample; this has
been shown to provide an accurate
representation of 24-hour protein loss in
the urine.

Chronic pathological renal proteinuria
may cause hypoproteinemia as in chronic
glomerulonephritis and acute tubular
nephrosis in horses and in amyloidosis of
cattle. When proteinuria originates from
pyelonephritis or cystitis other clinical
and clinicopathological evidence of these
diseases is usually present.

Casts and cells

Casts are organized, tubular structures
that vary in appearance depending on
their composition. They occur only when
the kidney is involved in the disease
process. Casts are present as an indication
of inflammatory or degenerative changes
in the kidney, where they form by
agglomeration of desquamated cells and
Tamm-Horsfall protein. Casts may not
form in all cases of renal disease. In
addition, casts readily dissolve in alkaline
urine and are best detected in fresh urine
samples.

Erythrocytes, leukocytes, and epithelial
cells in urine may originate in any part of
the urinary tract.

Hematuria

Hematuria can result from prerenal
causes when vascular damage occurs,
such as trauma to the kidney, septicemia
and purpura hemorrhagica. Renal causes
include acute glomerulonephritis, renal
infarction, embolism of the renal artery,
tubular damage as caused by toxic insult,
and pyelonephritis. Postrenal hematuria
occurs particularly in urolithiasis and
cystitis. A special instance of hematuria
is enzootic hematuria of cattle when
hemorrhage originates from tumors of
the urinary bladder. Hematomas of the
bladder wall (cystic hematoma) cause
hematuria in neonatal foals. 1 Typically,
lesions of the kidney, bladder, and
proximal urethra cause hemorrhage
throughout or towards the end of uri-
nation, whereas lesions of the middle and
distal urethra are responsible for bleeding
at the beginning of urination. 2

In severe cases of hematuria blood
may be voided as grossly visible clots but

6

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

more commonly it causes a deep red to
brown coloration of the urine. Less severe
cases may show only cloudiness that
settles to form a red deposit on standing.
The hematuria may be so slight that it is
detectable only on microscopic examin-
ation of a centrifuged sediment. In females,
free-flow urine samples may be contami-
nated by blood from the reproductive
tract; it may therefore be necessary to
collect a sample by catheterization to
avoid the chance of contamination of the
urine occurring in the vagina.

Blood in urine gives positive results on
biochemical tests for hemoglobin and
myoglobin. Because red blood cells can be
lysed in dilute urine, red-colored urine
should be examined microscopically for
the presence of erythrocytes. The presence
of a heavy brown deposit is not sufficient
basis for a diagnosis of hematuria as this
may also occur in hemoglobinuria. If the
bladder or urethra are involved in the
process that causes hematuria, abnor-
malities may be detectable on physical
examination. Gross hematuria persisting
for long periods may result in severe
blood loss anemia. Severe urinary tract
hemorrhage of undetermined origin in
aged mares has been recorded. 3 The
syndrome is widely recognized, though
not well documented, in Arabian mares.
Endoscopic examination reveals hemor-
rhage in one ureter but ultrasonographic
examination of the kidneys does not
reveal any significant abnormalities.
Surgical removal of the affected kidney is
not recommended, as the hemorrhage
sometimes recurs in the remaining
kidney. Treatment is nonspecific. Severe
hematuria can also occur in horses with
pyelonephritis. 4

Hemoglobinuria

False hemoglobinuria can occur in
hematuria when erythrocytes are lysed
and release their hemoglobin. In this case,
erythrocytes can be detected only by
microscopically examining urine sedi-
ment for cellular debris.

True hemoglobinuria causes a deep
red to brown coloration of urine and gives
a positive reaction to biochemical tests for
hemoglobin. There is no erythrocyte
debris in sediment. Dipstick tests for
proteinuria may not be positive unless the
concentration of hemoglobin is very
high. 3 There are many causes of intra-
vascular hemolysis, the source of hemo-
globinuria. The specific causes are listed
under Hemolytic anemia.

Normally, hemoglobin liberated from
circulating erythrocytes is converted to
bile pigments in the cells of the reticulo-
endothelial system. If hemolysis exceeds
the capacity of this system to remove the
hemoglobin, it accumulates in the blood

until it exceeds a certain renal threshold
and then passes into the urine. Some
hemoglobin is reabsorbed from the
glomerular filtrate by the tubular epi-
thelium, but probably not in sufficient
amounts to appreciably affect the hemo-
globin content of the urine. Hemo-
globinuria will only be present when the
plasma concentration exceeds the renal
threshold. Consequently hemoglobin is
grossly visible in plasma by the time
hemoglobinuria is visible. Hemoglobin
precipitates to form casts in the tubules,
especially if the urine is acidic, and as a
result some plugging of tubules occurs,
but the chief cause of uremia in hemolytic
anemia is ischemic tubular nephrosis.

Myoglobinuria

The presence of myoglobin (myo-
hemoglobin) in the urine is evidence of
severe muscle damage. The only notable
occurrence in animals is azoturia of
horses. Myoglobinuria does not occur
commonly in enzootic muscular dystrophy,
possibly because there is insufficient
myoglobin in the muscles of young
animals. The myoglobin molecule (mol-
ecular weight 16 500) is much smaller
than hemoglobin (molecular weight
64 000) and passes the glomerulus much
more readily, so a detectable dark brown
staining of the urine occurs without very
high plasma levels of myoglobin. Detect-
able discoloration of the serum does not
occur as in hemoglobinemia. Inherited
congenital porphyria is the other disease
that causes a red-brown discoloration of
urine. In porphyria, the plasma is also
normal in color, but urine porphyria is
differentiated from myoglobinuria on the
basis of a negative reaction to the guaiac
test and the characteristic spectrograph.
The porphyrins in inherited congenital
porphyria are the only pigments that
fluoresce under ultraviolet light.

The presence and type of pigment in
the urine can be determined accurately by
spectrographic examination, but this is
rarely clinically available. Myoglobinuria
is usually accompanied by clinical signs
and clinical biochemistry abnormalities of
acute myopathy, and clinical differentiation
of myoglobinuria from hemoglobinuria is
usually made on the basis of the clinical
signs and serum biochemical findings,
including measurement of muscle-
derived enzymes such as creatine kinase.
As with hemoglobin, myoglobin can
precipitate in tubules and may contribute
to uremia.

Pyuria

Leukocytes or pus in urine indicates
inflammatory exudation at some point in
the urinary tract, usually the renal pelvis
or bladder. Pyuria may occur as grossly
visible clots or shreds, but is often

detectable only by microscopic exam-
ination of urine sediment. Individual cells
and leukocytic casts may be present.
Pyuria is usually accompanied by the
presence of bacteria in urine.

Bacteriuria

Diagnosis of urinary tract infection is
based on finding a clinically relevant
bacteriuria in urine collected by free
catch (midstream collection into a sterile
container), catheterization or cysto-
centesis. 6 In horses and adult cattle,
collection of urine is limited to free catch
and catheterization, because the size of
the animal and intrapelvic position of the
bladder prevent cystocentesis. In contrast,
cystocentesis can be performed under
ultrasonographic guidance in calves,
small ruminants, and pigs. When culturing
a urine sample obtained by catheter-
ization, the first 20 mL or so should be
discarded because of the potential for
contamination from vaginal or distal
urethral flora.

Reference values for urine bacterial
concentrations are available for the horse;
marked bacteriuria suggestive of bacterial
infection may be defined as more than
40 000 colony forming units (cfu)/mL
from free-catch specimens, and more than
1000 cfu/mL from catheterized specimens. 6

Crystalluria

Crystalluria should not be overinterpreted
in fann animals. Crystals in the urine of
herbivorous animals have no special
significance unless they occur in very large
numbers and are associated with clinical
signs of irritation of the urinary tract.
Calcium carbonate and tuple phosphate
crystals are commonly present in nonnal
urine. If they occur in large numbers, it may
suggest that the urine is concentrated and
indicate the possible future development of
urolithiasis. The presence of calcium
carbonate crystals in the peritoneal fluid of
a neonatal foal has been used to confirm a
diagnosis of ruptured bladder. 7

Glucosuria

Glucosuria in combination with ketonuria
occurs only in diabetes mellitus, an
extremely rare disease in ruminants.
Glucosuria might occur in association
with enterotoxemia due to Clostridium
perfringens type D and can occur after
parenteral treatment with dextrose solu-
tions, adrenocorticotropic hormones or
glucocorticoid analogs. Horses with
tumor of the pars intermedia of the
pituitary gland often have glucosuria.
Glucosuria occurs also in acute tubular
nephrosis as a result of failure of tubular
resorption.

Ketonuria

Ketonuria is a more common finding
in ruminants, occurring in starvation,

Clinical features of urinary tract disease

547

acetonemia of cattle and pregnancy
toxemia of ewes and does. A small
amount of ketonuria is normally present
in dairy cows in early lactation. As a
result, it is important that the assay
method used to demonstrate ketonuria is
appropriate for urine, since there may be
a risk for false-positive reactions on
some tests. The standard test is sodium
nitroprusside, which turns an intense
purple color in the presence of aceto-
acetate, one of the three ketoacids.

VARIATIONS IN DAILY URINE
FLOW

An increase or decrease in urine flow is
often described in animals, but accuracy
demands physical measurement of the
amount of urine voided over a 24-hour
period. This is not usually practicable in
large-animal practice and it is often
necessary to guess whether the flow is
increased or decreased. Accurate measure-
ment of the amount of water consumed is
often easier. Care should be taken to
differentiate between increased daily flow
and increased frequency without increased
flow. The latter is much more common.
Decreased urine output rarely if ever
presents as a clinical problem in agri-
cultural animals.

Normal urine production is highly
variable in large animals and is depen-
dent to a large extent on diet, watering
systems and the pala tability of the water.
Pregnant mares housed in tie stalls
consume approximately 53 ± 6.2 (SD) mL
of water per kilogram body weight (BW)
per day, of which 50 ± 8 mL/kg is from
drinking water with the remainder being
water in feed. 8 However, most of this
water is excreted in the feces with fecal
and urinary water excretion being 33.5 ±

8 (mL/kg)/d and 7.6 ± 2 (mL/kg)/d,
respectively. 8 Neonatal foals produce
urine at an average rate of 150 (mL/kg)/d.“

Polyuria

Polyuria occurs when there is an increase
in the volume of urine produced. Fblyuria
can result from extrarenal causes as
when horses habitually drink excessive
quantities of water (psychogenic poly- !
dipsia) and, much less commonly, in j
central diabetes insipidus, when there |
is inappropriate secretion of antidiuretic j
hormone (ADH) from the pituitary, j
Polyuria occurs in horses with tumors of j
the pars intermedia of the pituitary gland, j
Although the cause of the polyuria is not j
known it might be secondary to osmotic j
diuresis associated with the glucosuria, or j
to central diabetes insipidus. Central
diabetes insipidus is reported in sibling
colts. 10 It is extremely rare in other species
but has been reported in a ram 11 and
a cow. Another extrarenal cause is

administration of diuretic drugs including
corticosteroids.

Kidney disease results in polyuria
when the resorptive capacity of the
remaining tubules is exceeded. Polyuria
can also occur when the osmotic gradient
in the renal medulla is not adequate to
produce concentrated urine. Nephrogenic
diabetes insipidus causes polyuria because
the tubules fail to respond to ADH.

When polyuria is suspected, a urine
sample should be collected to determine
specific gravity or osmolality. If urine is
isosthenuric with a constant specific
gravity of 1.008-1.012 (the specific gravity
of plasma), then the presence of renal
disease should be considered. Serum urea
and creatinine concentrations should be
determined to evaluate glomerular filtra-
tion. If serum urea and creatinine concen-
trations are within normal limits, a water
deprivation test can be performed to
assess the animal's ability to produce
concentrated urine. 12

Persistent urachus (also called
pervious or patent urachus). Failure of the
urachus to obliterate at birth causes urine
to dribble from the urachus continuously.
Urine may also pass from the urethra.
Retrograde infection from omphalitis is
common, resulting in cystitis.

Abnormalities of micturition are
classified as neurogenic or non- neurogenic.
Micturition is mediated principally by the
pelvic and pudendal nerves through
lumbosacral spinal cord segments under
the involuntary control of centers in the
brain stem and voluntary control of
the cerebrum and cerebellum. Reported
neurogenic causes of urinary incontinence
in horses include cauda equine neuritis,
herpesvirus 1 myelitis, Sudan grass
toxicosis, sorghum poisoning, trauma, and
neoplasia. Non-neurogenic causes of
urinary incontinence in horses include
ectopic ureter, cystitis, urolithiasis, hypo-
estrogenism, and abnormal vaginal
conformation. 13

Oliguria and anuria

Reduction in the daily output (oliguria)
and complete absence of urine (anuria)
occur under the same conditions and vary
only in degree. In dehydrated animals,
urine flow naturally decreases in an effort
to conserve water as plasma osmolality
pressure increases. Congestive heart
failure and peripheral circulatory failure
may cause such a reduction in renal blood
flow that oliguria follows. Complete anuria
occurs most commonly in urethral
obstruction, although it can also result
from acute tubular nephrosis. Oliguria
occurs in the terminal stages of all forms
of nephritis. Anuria and polyuria lead to
retention of solutes and disturbances of
acid-base balance that contribute to the
pathogenesis of uremia.

Pollakiuria

This is an abnormally frequent passage of
urine. Pollakiuria may occur with or with-
out an increase in the volume of urine
excreted and is commonly associated with
disease of the lower urinary tract such as
cystitis, the presence of calculi in the
bladder, urethritis and partial obstruction
of the urethra. Other causes of pollakiuria
include equine herpesvirus infection,
sorghum cystitis and neuritis of the cauda
equina in horses, neoplasia, obstructive
lesions and trauma to the urethra, abnor-
mal vaginal conformation and urachal
infection.

Dribbling is a steady, intermittent
passage of small volumes of urine, some-
times precipitated by a change in posture
or increase in intra-abdominal pressure,
reflecting inadequate or lack of sphincter
control. Dribbling occurs in large animals
with incomplete obstructive urolithiasis
and from persistent urachus.

ABDOMINAL PAIN, PAINFUL AND
DIFFICULT URINATION (DYSURIA
AND STRANGURIA)

Abdominal pain and painful urination
(dysuria) and difficult and slow urination
(stranguria) are manifestations of dis-
comfort caused by disease of the urinary
tract. Acute abdominal pain from urinary
tract disease occurs only rarely and is
usually associated with sudden distension
of the renal pelvis or ureter, or infarction
of the kidney. None of these conditions is
common in animals, but occasionally
cattle affected with pyelonephritis may
have short episodes of acute abdominal
pain due to either renal infarction or
obstruction of the pelvis by necrotic
debris. During these acute attacks of pain,
the cow may exhibit downward arching of
the back, paddling with the hind feet,
rolling and bellowing. Abdominal pain
from urethral obstruction and distension
of the bladder is manifested by tail-
switching, kicking at the belly and
repeated straining efforts at urination
accompanied by grunting. Horses with
acute tubular nephrosis following vitamin
K 3 administration might show renal colic
with arching of the back, backing into
corners and rubbing of the perineum and
tail head. 14

Dysuria or painful/difficult urination

occurs in cystitis, vesical calculus, and
urethritis and is manifested by the
frequent passage of small amounts of
urine. Grunting may occur with painful
urination and the animal may remain in
the typical posture after urination is
completed. Differentiating pain caused by
urinary disease from pain due to other
causes depends largely upon the presence

548

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

of other signs indicating urinary tract
involvement.

Stranguria is slow and painful
urination associated with disease of the
lower urinary tract including cystitis,
vesical calculus, urethral obstruction, and
urethritis. The animal strains to pass each
drop of urine. Groaning and straining
may precede and accompany urination
when there is urethral obstruction. In
urethritis, groaning and straining occur
immediately after urination has ceased
and gradually disappear and do not recur
until urination has been repeated.

Urine scalding of the perineum
or urinary burn is caused by frequent
wetting of the skin with urine. It may be
the result of urinary incontinence or the
animal's inability to assume normal
posture when urinating.

MORPHOLOGICAL
ABNORMALITIES OF KIDNEYS
AND URETERS

Enlargement or decreased size of kidneys
may be palpable on rectal examination or
detected by ultrasonography. In cattle,
gross enlargement of the posterior aspect
of the left kidney may be palpable in the
right upper flank. Abnormalities of the
kidneys such as hydronephrosis in cattle
may also be palpable on rectal exam-
ination. Increases in the size of the ureter
may be palpable on rectal examination
and indicate ureteritis or hydroureter.

PALPABLE ABNORMALITIES OF
THE BLADDER AND URETHRA

Abnormalities of the bladder that may be
palpable by rectal examination include:
gross enlargement of the bladder, rupture
of the bladder, a shrunken bladder
following rupture, and palpable abnor-
malities in the bladder such as cystic
calculi. Abnormalities of the urethra
include: enlargement and pain of the
pelvic urethra and its external aspects in
male cattle with obstructive urolithiasis,
and obstruction of the urethral process of
male sheep with obstructive urolithiasis.

ACUTE AND CHRONIC RENAL
FAILURE

The clinical findings of urinary tract
disease vary with the rate of development
and stage of the disease. In most cases,
the clinical signs are those of the initiating
cause. In horses, mental depression, colic,
and diarrhea are common with oliguria or
polyuria. Cattle with uremia are similar
and in addition are frequently recumbent
and in severe and terminal cases may
have a bleeding diathesis. In chronic renal
disease of all species, there is a severe loss
of body weight, weakness, anorexia,
polyuria, polydipsia, and ventral edema.

UREMIA

Uremia is the systemic state that occurs in
the terminal stages of renal insufficiency.

Anuria or oliguria may occur with
uremia. Oliguria is more common unless
there is complete obstruction of the
urinary tract. Chronic renal disease is
usually manifested by polyuria, but
oliguria appears in the terminal stages
when clinical uremia develops. The
uremic animal is depressed and anorexic
with muscular weakness and tremor. In
chronic uremia, the body condition is
poor, probably as a result of continued
loss of protein in the urine, dehydration
and anorexia. The respiration is usually
increased in rate and depth but is not
dyspneic; in the terminal stages it may
become periodic in character. The heart
rate is markedly increased because of
terminal dehydration and myocardial
asthenia but the temperature remains
normal except in infectious processes and
some cases of acute tubular nephrosis. An
ammoniacal or uriniferous smell on the
breath is often described but is usually
undetectable. Uremic encephalopathy
occurs in a small proportion of cattle and
horses with chronic renal failure. 15

The animal becomes recumbent and
comatose in the terminal stages. The
temperature falls to below normal and
death occurs quietly, the whole course of
the disease having been one of gradual
intoxication. Necropsy findings, apart
from those of the primary disease, are
nonspecific and include degeneration
of parenchymatous organs, sometimes
accompanied by emaciation and moderate
gastroenteritis. There are rare reports
of encephalopathy caused by renal
insufficiency. 15

Uremia has been produced experi-
mentally in cattle by bilateral nephrectomy
and urethral ligation. 17,18 There is a pro-
gressive increase in serum urea concen-
tration (mean daily increase of 53 mg/dL),
serum creatinine concentration (mean
daily increase of approximately 3.5 mg/dL),

, and serum uric acid concentration,
i Similar findings are reported in prerenal
j uremia in cattle. Interestingly, serum
! phosphate and potassium concentrations
j were for the most part unchanged
i because of increased salivary secretion,
i and metabolic acidosis was not evident.

! Serum potassium concentrations were
i mildly increased after 5-7 days of bilateral
| nephrectomy.

I

Special examination of the
urinary system

Lack of accessibility limits the value of
physical examination of the urinary tract

in farm animals. Rectal examination can
be carried out on horses and cattle and is
described in Chapter 1. In small ruminants
and calves, the urinary system is largely
inaccessible to physical examination
although the kidneys may be palpated
transabdominally.

Urinalysis and determination of blood
urea and creatinine should be components
of any examination of the urinary system.

URINALYSIS

Urinalysis is an essential component of
the examination of the urinary system.
The reader is referred to a textbook of
veterinary clinical pathology for details of
the biochemical and microscopic exam-
ination of the urine. The common abnor-
malities of urine are discussed under
manifestations of diseases of the urinary
system.

COLLECTION OF URINE SAMPLES

Collection of urine samples can be dif-
ficult. Free flow and catheterized samples
are equally useful for routine urinalysis.
Horses will often urinate a short time
after they are walked into a freshly
bedded box stall. Cows urinate if they are
relaxed and have their perineum and
vulval tip massaged upwards very gently,
without touching the tail. Steers and bulls
may urinate if the preputial orifice is
massaged and splashed with warm water.
Ewes often urinate immediately after
rising if they have been recumbent for
some time. Occluding their nostrils and
threatening asphyxia may also induce
urination just as they are released and
allowed to breathe again; however, this is
a stressful procedure and should not be
performed in sick or debilitated sheep. An
intravenous injection of furosemide
(0.5-1.0 mg/kg BW) produces urination in
most animals in about 20 minutes. The
sample is useful for microbiological
examination but its composition has been
drastically altered by the diuretic.
Diuretics should be used with extreme
caution in dehydrated animals.

CATHETERIZATION OF THE BLADDER

Urine samples obtained by catheterization
are preferred for microbiological examin-
ation. Rams, boars, and young calves
usually cannot be catheterized because of
the presence of a suburethral diverticulum 5
and the small diameter of the urethra.
A precurved catheter and fluoroscopic
guidance can be used to facilitate
catheterization of rams and bucks. 19 Ewes
and sows have vulvas that are too small to
allow access to the urethra. Cows can be
catheterized relatively simply provided
that a fairly rigid, small-diameter (0.5 cm)
catheter is used. A finger can be inserted

Special examination of the urinary system

into the suburethral diverticulum to direct
the tip of the catheter over the diverticulum
and into the external urethral orifice.
Mares can be catheterized easily, either by
blindly passing a rigid catheter into the
external urethral orifice or by using a
finger as a guide for a flexible catheter.
Male horses can also be catheterized
easily if the penis is relaxed. When
urethral obstruction is present the penis is
usually relaxed, but administration of an
ataractic drug (acepromazine is often
used) makes manipulation of the penis
easier and often results in its complete
relaxation. Because of the long urethra,
the catheter must be well lubricated. The
catheter should be rigid enough to pass
through the long urethra but flexible
enough to pass around the ischial arch. In
all species, catheterization overcomes the
natural defense mechanisms that prevent
infectious organisms from ascending the
urinary tract. As a result, attention to
hygiene during catheterization is essential.

TESTS OF RENAL FUNCTION AND
DETECTION^ RENAL INJURY

The simplest and most important test of
urinary function is the determination of
whether or not urine is being voided. This
can be accomplished in large animals by
restraining them on a clean, dry floor
which is examined periodically. Placing
an absorbent cloth under recumbent foals
and calves will also help determine if
urine is being passed.

Renal function tests evaluate the func-
tional capability of the kidney and, in
general, assess blood flow to the kidneys,
glomerular filtration and tubular function.
These tests depend on whether they are
based on the examination of serum,
urine or both, and assess either function
or the presence of injury. The most
practical screening tests for the presence of
decreased renal function are determination
of serum creatinine concentration and
urine specific gravity. Determination of
both assists differentiation of renal
azotemia from prerenal azotemia. In
prerenal azotemia, tubular function
remains intact and renal conservation of
water is optimized, resulting in the
production of a concentrated urine.
Animals with prerenal azotemia therefore
have increased serum concentrations of
creatinine and urea, and increased urine
specific gravity. For comparison, animals
with some degree of renal azotemia have
increased serum concentrations of
creatinine and urea and a lower than
expected value for urine specific gravity.
Determination of urine specific gravity
should therefore be routinely performed
in all dehydrated animals before the
initiation of treatment, because oral or

intravenous fluid therapy will directly
change urine specific gravity.

Tests of urine

Urine samples for analysis should be
collected by midstream voiding, or
cystocentesis in small male ruminants.
Bethanechol (0.075 mg/kg subcutaneously)
has occasionally been used to produce
urine in reluctant individuals, but a
spontaneously voided sample is preferred
for initial screening. The sample should be
centrifuged and the supernatant should
be used for laboratory analysis and the
sediment and remaining supernatant for
routine urine analysis.

Specific gravity

Specific gravity of urine is the simplest
test to measure the capacity of renal
tubules to conserve fluid and excrete
solute. For most species, the normal
specific gravity range is 1.015-1.035, and
in azotemic animals, specific gravity
should be greater than 1.020 if the
azotemia is prerenal in origin. In chronic
renal disease the urine specific gravity
decreases to 1.008-1.012 and is not
appreciably altered by either deprivation
of water for 24 hours or the adminis-
tration of large quantities of water by
stomach tube. It is important to recognize
that a specific gravity of less than 1.008
indicates that the kidney can produce a
dilute urine and, if sustained, indicates
better renal function than a fixed urine
specific gravity of 1.008-1.012.

Specific gravity can be inaccurate
when other refractive particles are present
in urine, such as glucose or protein. Urine
specific gravity should therefore be used
with caution in animals with proteinuria
! or glucosuria. As an alternative to specific
; gravity, osmolality of a fluid directly
measures the concentration of solute in
; the fluid. Urine osmolality therefore
: provides a more accurate assessment of
; the tubule's ability to conserve or excrete
I solute than does specific gravity, and is
the preferred test of urine concentrating
ability for research studies. However,
urine specific gravity is sufficiently accurate
for clinical use in animals without
proteinuria or glucosuria, 20 in that there is
a linear relationship between urine specific
gravity and osmolality, and that urine
specific gravity explains 52% of the vari-
ation in urine osmolality, the 95%
confidence interval for predicting osmolality
from the specific gravity measurement
being ± 157 mosmol/kg. 21

! Enzymuria

; A clinically useful index of tubular
: injury is determining the gamma-
i glutamyltransferase (GGT) activity in
urine. Most enzymes present in serum
; have a molecular weight greater than that

of albumin and are normally not detect-
able in the glomerular filtrate; the presence
of high-molecular-weight enzymes
in urine is called parenchymatous
enzymuria. For comparison, the presence
of low-molecular-weight enzymes (such
as lysozyme) in urine is called tubular
enzymuria because damage to the
proximal tubule impairs its ability to
reabsorb enzymes from the glomerular
filtrate. 22

Most of the GGT activity in urine
originates from the luminal brush border
of the proximal tubular epithelial cells of
the kidney. High levels of GGT activity in
the urine result from an increase in the
rate of proximal tubular epithelial cell
destruction, with GGT being released into
the urine during the active phase of tissue
destruction; an increase in urine GGT
activity therefore reflects parenchymatous
enzymuria. The activity of GGT (or
other high-molecular-weight enzymes
such as p-N-acetylglucosaminidase,
p-glucuronidase, N-acetyl-fS-

glucosaminidase) in urine can therefore
be used to detect the presence of proximal
renal tubular epithelial cell damage
before the onset of renal dysfunction. 22-24
GGT is the preferred enzyme to identify
the presence of parenchymatous enzymuria
because the assay is inexpensive and
widely available, and the kidney has the
highest content of GGT of any organ in
the body, thereby increasing the sensi-
tivity of the test.

Urine GGT activity is frequently
indexed to an indicator of urine concen-
tration, such as urine creatinine concen-
! tration, 22-24 in order to correct for
I denominator effects induced by changes
I in urine volume, and a GGT:creatinine
! higher than 25 IU/g creatinine is con-
: sidered abnormal in the horse. However,
i it may be more appropriate to calculate
I the fractional clearance of GGT (which
i compares the extent of tubular damage to
the amount of functioning kidney mass)

; instead of the urinary GGT to creatinine
| ratio (which compares the amount of
tubular damage to muscle mass). 22,23
: Indexing GGT to creatinine is not
physiologically valid because enzymes
present in urine are not filtered through
the glomerulus; using the urine GGT
; activity alone therefore appears to be
more appropriate. Interestingly, urine GGT
activity appears more sensitive as an index
of tubular injury than the urine GGT to
creatinine ratio in horses and sheep, 25-27
; and appears to be the most sensitive
indicator of tubular injury in animals being
i treated with aminoglycosides.

Glucosuria

Glucose is freely filtered by the glomerulus
and reabsorbed from the filtrate in the

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

proximal tubules. Glucosuria in the face
of a normal serum glucose concentration
therefore indicates the presence of
abnormal proximal tubular function.
Glucosuria occurs early in the develop-
ment of aminoglycoside-induced proximal
tubule nephropathy, and may provide a
useful inexpensive and practical screening
test for nephrotoxicity in animals without
hyperglycemia. 26

Proteinuria

Urine protein concentrations in animals
without lower urinary tract disease or
hematuria are normally much lower than
serum protein concentrations and similar
to cerebrospinal fluid protein concen-
tration. Glomerular filtrate normally
contains low concentrations of low-
molecular-weight proteins such as fb-
microglobulin (molecular weight 11 800)
and lysozyme (molecular weight 14 400).
This is because the healthy glomerulus
excludes high-molecular-weight proteins
such as albumin (molecular weight
65 000) and globulins from the glomerular
filtrate; normally functioning proximal
tubules reabsorb these low-molecular-
weight proteins, leading to very low urine
protein concentrations. Alterations in
tubular function can therefore lead to
proteinuria, but typically glomerular
injury produces much larger increases in
urine protein concentration than those
produced by altered proximal tubule
function.

Determination of urine protein con-
centrations requires a sensitive analytical
test, such as the Coomassie brilliant blue
method. Urinary protein concentrations
may be indexed to the urine creatinine
concentration in order to account for
denominator effects of changes in urine
volume. Dividing the urinary protein
concentration (mg/dL) by the creatinine
concentration (mg/dL) produces a unit-
less ratio, which provides a sensitive and
reliable diagnostic method for the detec-
tion and quantification of proteinuria. 28 In
general, increased urinary concentrations
of albumin and fb-microglobulin indicate
glomerular proteinuria and tubular
proteinuria, respectively. Proteinuria is
massive and sustained in cattle and sheep
with advanced renal amyloidosis and
animals with advanced glomerulonephritis
(glomerular proteinuria) but is mild in
animals without glomerular disease but
with proximal tubular injury (tubular
proteinuria). A urine protein concentration
to creatinine concentration ratio of less
than 13 is considered to be more
indicative of tubular than glomerular
proteinuria. 29 Microalbuminuria does not
appear to have been evaluated as an early
and sensitive test of glomerular disease in
large animals but increases in urine

albumin concentration would be expected
in animals with glomerular disease.

Tests of serum

These tests depend on either the accumu-
lation, in cases of renal insufficiency, of
metabolites normally excreted by the
kidney or the excretion of endogenous
substances by the kidney. Determination
of serum urea and creatinine concen-
tration are essential components of an
evaluation of the urinary system. These
serum indices of function are simple
estimates of glomerular filtration because
urea and creatinine are freely filtered by
the glomerulus. Serum concentrations
of urea and creatinine do not rise
appreciably above the normal range until
60-75% of nephrons are destroyed.

Serum urea and creatinine concen-
trations are influenced by blood flow to
the kidneys and may be increased in
prerenal uremia. They also suffer from the
disadvantage that their serum concen-
trations can vary with the rate of protein
catabolism and are not dependent only
on renal function. In cattle, for example,
serum urea concentrations caused by
prerenal lesions may be higher than those
resulting from renal disease, because
salivary secretion of urea, rumen metab-
olism of urea and decreased feed intake
(and therefore decreased protein intake)
may lower serum urea concentration in
chronic disease.

Creatinine in herbivores is essentially
totally derived from endogenous creatine.
Creatine is produced by the liver from
amino acids and circulates in the plasma
before being taken up by skeletal muscle,
where it stores energy in the form of
phosphocreatine. Creatine is converted to
creatinine by a non-enzymatic irreversible
process and is distributed throughout the
body water. Creatinine is therefore released
from skeletal muscle at a constant rate in
\ animals without myonecrosis and is
: therefore an indirect index of muscle
i mass; this is the reason why serum
creatinine concentrations are highest in
intact males, intennediate in adult females
and lowest in neonates and cachetic
animals. Serum creatinine concentrations
: are constant within an animal because
they reflect muscle mass, which does not
change rapidly; an increase in serum
creatinine concentration of more than
0.3 g/dL should be considered to be
clinically significant. 30

i Serum creatinine concentration is
: routinely measured using the Jaffe
reaction, in which a colored product is
: formed from creatinine and picrate in an
, alkaline solution. However, the alkaline
■ picrate reaction has poor specificity, as it
i also detects a number of non- creatinine
\ chromogens in serum, which do not

appear to be present in urine. In other
words, the creatinine concentration may
be overestimated in serum but is accurately
measured in urine. The former induces
some error in the calculation of fractional
clearance of electrolytes. The progression
of renal failure may be monitored by
plotting the reciprocal of serum creatinine
concentration against time. Extrapolation
of the resultant linear relationship to the x
axis intercept provided some clinically
useful prognostic information in a horse
with advanced renal failure. 31

Glomerular filtration rate
The accepted gold standard measurement
for renal function is measurement of the
glomerular filtration rate using inulin
clearance. Inulin, a metabolically inert
carbohydrate, crosses freely across the
glomerulus and is neither absorbed nor
secreted by renal tubules. Endogenous
creatinine clearance has also been used to
estimate glomerular filtration rate; how-
ever, this test suffers from inaccuracies
related to the presence of noncreatinine
chromogens in plasma and the tubular
secretion of creatinine in some species.
Although the renal clearances of inulin or
creatinine are the preferred research
methods for measuring renal excretory
function, these techniques are impractical
in clinical patients and male ruminants
because they require urethral catheter-
ization, rinsing of the bladder contents
and timed urine collections.

Renal excretory function is more
practically assessed in clinical patients by
measuring the plasma clearance of
compounds of exogenous origin (such as
phenolsulfonphthalein or sodium
sulfanilate), as these techniques do not
require urine collection. Plasma clearance
of technetium-diethyleneaminopentaacetic
acid (Tc-DTPA) or technetium-
mercaptoacetyltriglycine (Tc-MAG 3 ) have
also been evaluated in horses 32,33 but the
technique requires measurement by a
gamma camera and is therefore not
! suitable for use in the field. Plasma
i clearance tests have been evaluated in

■ cattle, goats, sheep, and horses and
provide a useful clinical test to monitor

\ renal function in an individual animal
; over time. 30,34-36 However, the accuracy of
: plasma clearance techniques may not be

■ adequate for research studies.

Tests of urine and serum

! Urine osmolality to serum osmolality
; ratio

; A urine:plasma osmolality ratio of 1
; indicates isosmotic clearance of materials
by the kidney. A ratio less than 1 indicates
j that the kidneys are diluting the urine,
j and a ratio more than 1 indicates that the
: urine is being concentrated. Because the
; plasma osmolality is much more constant

Special examination of the urinary system

55

than urine osmolality, the important
clinical factor is whether urine osmolality
is less than, equal to, or greater than 300
mosmol/kg, Measurement of urine
osmolality requires a dedicated laboratory
unit and is rarely indicated in the clinical
management of renal disease because of
the widespread availability of hand-held
refractometers. In fact, measurement
of urine osmolality is needed only in
research studies.

Water deprivation test
This can be used to assess renal concen-
trating ability in animals that have
isosthenuria with urine specific gravity of
1.008-1.012 but do not have azotemia. 12
Water deprivation tests should not be
performed on animals that are already
azotemic and should be undertaken with
extreme caution and frequent (hourly to
2-hourly) monitoring in animals that are
polyuric but not azotemic. Animals that
are unable to conserve water because of
renal disease can rapidly become dehy-
drated and develop prerenal uremia as a
result.

In brief, the water deprivation test
monitors the animal's ability to detect an
increase in serum osmolality, release
antidiuretic hormone and produce a
concentrated urine as a result of the
action of antidiuretic hormone on the
kidney. The test usually requires docu-
mentation that the animal has polyuria
and polydipsia, with water consumption
greater than cohorts of the same age,
lactation stage and diet, when housed
under the same conditions. Before
conducting the water deprivation test, the
animal is weighed and a Foley catheter is
placed in the bladder (females), or the
animal is housed in a dry stall (males).
Access to water is prevented and the urine
and serum are tested every 1-2 hours or
when voided in males. The test should be
stopped when the urine specific gravity
increases to more than 1.015-1.020, when
there is an increase in serum creatinine
concentration of 0.3 g/dL or greater, or
when there has been a decrease in body
weight of 5% or more.

Animals that concentrate their urine
after water deprivation are diagnosed
with psychogenic polydipsia and their
water availability is gradually decreased.
Animals that fail to concentrate their
urine after water deprivation are diag-
nosed with diabetes insipidus; nephro-
genic diabetes insipidus can be ruled
out if the animal produces a concentrated
urine within a few hours of an intra-
muscular injection of exogenous vaso-
pressin (0.15-0.30 U/kg BW). In the latter
case, the diagnosis is neurogenic
diabetes insipidus as a result of in-
adequate release of antidiuretic honnone.

Such cases are extremely rare in large
animals and have been attributed to
pituitary neoplasia (particularly pituitary
adenoma in horses) or encephalitis. 10
Determination of plasma vasopressin
concentrations using a radioimmunoassay
may assist in differentiation of nephro-
genic from neurogenic diabetes insipidus;
in the former the plasma vasopressin
concentration increases during the water
deprivation test. However, because the
assay for plasma vasopressin concen-
tration is not widely available and has not
been validated for all large animals, 10 the
response to exogenous vasopressin is the
preferred clinical test for differentiating
nephrogenic from neurogenic diabetes
insipidus. Two related horses have been
diagnosed with nephrogenic diabetes
insipidus, 10 suggesting that this may be
inherited as an X-linked disorder.

Water deprivation tests are not needed
if urine specific gravity is below 1.008,
because the presence of hyposthenuria
indicates that tubular function is acting to
conserve solute and produce dilute urine.
In other words, a specific gravity below
1.008 is a better clinical sign than a
constant specific gravity of 1.008-1.012,
because a low specific gravity indicates
the presence of some tubular function.
Low specific gravity may occur in diabetes
insipidus, following excessive water intake
or fluid administration, or following
diuretic administration. Neonatal animals
on fluid diets and lactating dairy cows
often produce dilute urine.

Renal clearance studies
In animals with renal disease, serum
creatinine and urea nitrogen concen-
trations are insensitive indicators of renal
dysfunction and exceed the upper limit of
the reference range only after extensive
loss of nephron function. Increases in
serum concentrations of creatinine or urea
nitrogen cannot be used to distinguish
between prerenal, renal, and postrenal
azotemia. Urine specific gravity can be
used to differentiate prerenal from renal
azotemia. However, results of urinalysis
do not reflect the magnitude of the
disease and they are not specific for
specific renal disease.

Calculation of renal clearance of
creatinine, urea nitrogen, and electrolytes,
along with measurement of specific
enzyme activity in the urine, is a more
sensitive indicator of damage to the tubules
than serum biochemical analysis. 37,38
Urinary diagnostic indices have been
used to evaluate renal function and to
detect and estimate the extent of renal
damage in adult cattle, calves, horses, and
foals. For example, it can be clinically
useful to determine the urine to serum
concentration, the ratio of urinary

creatinine to urea nitrogen, the renal
clearance of creatinine and urea nitrogen,
the urine to serum osmolality ratio, the
urine protein concentration or urine
protein to creatinine ratio, the fractional
clearances of electrolytes, and urine
enzyme activity. Early diagnosis of reiial
injury facilitates initiation of appropriate
treatment and reduces the incidence of
irreversible renal failure. Sequential
measurement of these indices can aid in
the determination of prognosis and
allows monitoring and evaluation of the
extent of recovery of renal function.

The tests require simultaneous sam-
pling of blood and urine. 37 Samples can
also be collected daily for several days and
weekly to determine any age-related
changes, and these are available for calves
from birth to 90 days of age. 24

Fractional clearance

The fractional clearance from plasma of a
given substance is calculated by comparing
the amount of the substance excreted in
the urine with the amount filtered
through the glomerulus. The fonnula used
to calculate fractional clearance of sub-
stance X (FC X ) is:

FC X (%) = ([U X ]/[S X ]) x

1 00/ ( 1 0I cm itiniuJ / IScrealiniiid )

where [Lf x ] and [S x ] are the urine and
serum concentrations of X, respectively,
and [U creatinjnc ] and [S crMtinin J are the urine
and serum concentrations of creatinine,
respectively. Fractional clearance has been
erroneously called fractional excretion; the
latter term is confusing, inappropriate
and has no scientific basis. 39 The frac-
tional clearance provides information
regarding the action of tubular transport
mechanisms on the filtered substances;
a value below 100% indicates net
reabsorption, whereas a ratio above 100%
indicates net secretion.

Sodium and inorganic phosphate are
reabsorbed from the glomerular filtrate by
the renal tubules; therefore, the fractional
clearance of sodium and phosphate
provide clinically useful indices of tubular
function. Sodium retention is an import-
ant proximal tubular function and the
fractional clearance of Na is usually less
than 1% for animals (and often < 0.2%)
unless they have a high oral or intra-
venous sodium intake, when fractional
clearance values can be increased to 4%.
Renal phosphorus excretion is affected by
acid-base status and body calcium and
phosphate status and is therefore a less
specific indicator of tubular function than
fractional clearance of sodium. Values for
the fractional clearance of phosphorus
normally vary from 0. 1-0.4%, although
higher values may be seen in ruminants
with high phosphate intakes. Typically,

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

tubular function can be adequately
characterized by determining the frac-
tional clearance of sodium alone, or
sodium and phosphorus; the fractional
clearance of chloride rarely adds useful
information in clinical cases because it is
highly correlated to the fractional clear-
ance of sodium, 40 and determination of
the fractional clearance of potassium is
hampered by methodological limitations
associated with zwitterion formation in
urine. Determination of the fractional
clearance of calcium can be useful when
dietary intake and metabolism of calcium
are being evaluated. Substantial variations
in fractional clearance values are present
in horses over a 24-hour period as a result
of the electrolyte load ingested with
feed. 41 Some standardization of the time
of urine collection in relationship to
feeding is therefore needed in research
studies, but is clearly impractical in
clinical cases.

Fractional clearance values for a num-
ber of electrolytes have been determined
for horses, 42,43 foals, 37 cattle, 40-44 ' 46 and
sheep. 47 Renal clearance, urinary excre-
tion of endogenous substances and
urinary diagnostic indices have been
measured in healthy neonatal foals. 37 The
urine volume of neonatal foals is pro-
portionately greater than that of calves
and the normal neonatal foal produces a
dilute urine. 37 When compared with
normal values in adult horses, fractional
clearance of electrolytes was similar for
sodium but higher for potassium, phos-
phorus, and calcium. Renal function in
newborn calves is similar to adult cattle
within 2-3 days of birth and calves can
excrete large load volumes in response to
water overload and conserve water in
response to water deprivation as efficiently
as adult cattle.

Animals with acute renal azotemia
have low urinary creatinine:serum
creatinine and urine nitrogen:serum
nitrogen; animals with acute prerenal
azotemia have normal to high urinary
creatinine:serum creatinine and urinary
nitrogen:serum nitrogen. However,
animals with acute renal azotemia also
have a low urine specific gravity relative
to the serum creatinine concentration,
and it remains to be determined whether
measurement of urinary creatinine and
urea concentrations and serum urea con-
centrations provide any more information
in clinical cases than that provided by
urine specific gravity and serum creatinine
concentration.

Summary of renal function tests

In summary, the serum creatinine or urea
concentration provides a useful screening
test for the presence of urinary tract
disease, with an increase in serum

creatinine concentration of more than
0.3 mg/dL over baseline providing a
useful clinical test for the presence of
nephrotoxicosis in normally hydrated
animals being treated with potentially
nephrotoxic agents. Azotemia can be
prerenal, renal, or post renal in origin; the
cause is most practically differentiated in
azotemic animals by measuring the
specific gravity of urine before any treat-
ment has been administered. In animals
suspected of having urinary tract disease,
the urinary protein concentration and
protein to creatinine ratio provide clinically
useful indices of glomerular and tubular
function and injury, the urine specific
gravity and fractional clearance of sodium
and phosphorus provide clinically useful
indices of tubular function in animals not
on intravenous or oral fluids and
consuming a normal diet, and deter-
mination of urine GGT activity and analysis
of urine for the presence of casts provide
clinically useful and sensitive indices of
tubular injury. The results of most other
laboratory tests rarely provide additional
information in an animal suspected to have
urinary tract disease, and are not currently
recommended for routine clinical use.

DIAGNOSTIC EXAMINATION
TEC HNIQUE S

Ultrasonography

Transcutaneous and transrectal ultra-
sonography is commonly used to detect
and characterize anatomical abnor-
malities of the kidneys, ureters, bladder,
and urethra in horses, cattle, and small
ruminants. Ultrasonography is an effec-
tive screening test for diagnosing obstruc-
tive conditions of the urinary tract,
including hydronephrosis, hydroureter,
and bladder distension, and can be used
to visualize the kidney and guide the
biopsy needle during renal biopsy. 48
Removal of the haircoat and the use of an
ultrasonographic coupling gel assist in
obtaining acceptable acoustic coupling,
whereas saturation of a foal's haircoat
with alcohol or coupling gel may be
adequate when clipping is not desirable.

Techniques for ultrasonographic 49
evaluation of the urinary system of the
horse have been described, and extensive
information is available that documents
age-related changes in renal dimen-
sions. 50,51 Ureteral tears have been iden-
tified using transrectal ultrasonography. 52
Uroperitoneum is readily diagnosed in
foals by ultrasonographic examination, as is
the underlying lesion in the bladder or
urachus. Ultrasonography has been used to
visualize the renal changes in foals follow-
ing administration of phenylbutazone. 53

In cattle, the right kidney is easily
accessible to ultrasonography from the

body surface. 38 Images of the right kidney
are visualized best with the transducer
placed in the lumbar or paralumbar
region, whereas images of the left kidney
are best obtained using a transrectal
approach. Ultrasonographic changes in
the cow with pyelonephritis include: a
dilated renal collecting system, renal or
ureteral calculi, echogenic material within
the renal collecting system, and subjective
enlargement of the kidney with acute
disease or a small irregular kidney with
chronic disease. 54 Cattle with enzootic
bovine hematuria due to chronic bracken
fern ingestion have a thickened bladder
wall (normally < 2 mm) on transrectal
ultrasonography and irregular sessile
masses (transitional cell papilloma) extend-
ing into the bladder lumen. 55

Techniques for ultrasonographic evalu-
ation of the urinary system of the sheep
have been described. 56

Renal biopsy

Percutaneous renal biopsy can be carried
out in sedated and adequately restrained
cows and horses. A coagulation profile
should be run before renal biopsy is
attempted in animals with severe and
chronic renal disease or those animals
suspected to have a coagulopathy. Renal
biopsy is contraindicated in animals with
documented pyelonephritis because of
the risk of perirenal abscessation after the
biopsy procedure.

The left kidney is usually biopsied
because it is more accessible. In cows, the
left kidney is moved to the right para-
lumbar fossa and fixed in position by
rectal manipulation. In horses, the left
kidney is identified using transabdominal
ultrasonography and fixed in position by
palpation per rectum. 57 The skin over the
biopsy site is aseptically prepared and
5-10 mL of local anesthetic is infiltrated
along the proposed track for the biopsy
needle. A small stab incision is made in
the skin with a scalpel and a renal biopsy
sample is collected by introducing a
biopsy needle through the abdominal
wall and manipulating it into the caudal
pole of the kidney. The renal biopsy is
fixed in 10% formalin and submitted for
examination and histological diagnosis.
Biopsy of the caudal pole minimizes the
risk of trauma to the renal pelvis, renal
artery, and renal vein.

Possible complications of renal biopsy
are hemorrhage or abscessation in animals
with pyelonephritis. Hemorrhage after
renal biopsy can be extensive, and is
usually perirenal but rarely life threaten-
ing. Occasionally, severe hematuria is
present for hours after the biopsy pro-
cedure, but usually resolves within a few
days. Because of the potential for life-
threatening sequelae, renal biopsy should

Principles of treatment of urinary tract disease

only be performed when the etiology is
uncertain and histologic examination will
direct treatment, or when an early and
accurate prognosis is desired. In animals
with acute tubular injury, electron micro-
scopic examination of the basement
membrane is required to accurately prog-
nose return to normal function.

Endoscopy

Transurethral endoscopy can be easily
performed in mares, stallions, geldings,
and cows in order to examine the urethra
and bladder, and flow of urine from both
ureters. Horses and cows are sedated and
adequately restrained for the procedure.
Biopsy of diseased tissue or mechanical
disruption of calculi can be attempted
under endoscopic guidance. Identification
of an ectopic ureter may be assisted by
intramuscular administration of azo-
sulfamide (1.9 mg/kg BW) or intravenous
administration of sodium fluorescein
(11 mg/kg BW), phenolsulfonphthalein
(0.01 mg/kg BW) or indigo carmine
(0.25 mg/kg BW) to color the urine being
produced, 5-20 minutes before endo-
scopy; this assists visualization of the
urine stream. 58

Cystometry and urethral pressure
profile

Urodynamic tests have been evaluated in
the mare that allow comparison of the
normal micturition reflex with that of the
incontinent patient. Cystometry involves
measurement of luminal pressure during
inflation of the bladder with measured
volumes of 0.9% NaCl or carbon dioxide.
The pressure-volume relationship during
filling with fluid or gas provides infor-
mation on bladder capacity, maximal
luminal pressure during the detrusor
reflex, and stiffness of the bladder wall.
The urethral pressure profile involves
measurement of pressure along the
urethra while withdrawing a fluid- or gas-
filled catheter at constant rate. The
catheter tip pressure is graphed against
distance, and the maximum urethral
closure pressure is determined as the
maximum urethral pressure minus bladder
luminal pressure. The functional urethral
length is defined as the length of the
urethra in which urethral pressure
exceeds bladder luminal pressure.

The test can be performed in restrained
mares with or without xylazine sedation
(1.1 mg/kg BW, intravenously), but sedation
is recommended. Values for cystometry
and urethral pressure profiles in female
horses and pony mares are available. 59

Test of uroperitoneum and bladder
rupture

Ultrasonographic examination of the
abdomen is most useful in detecting the
presence of excessive fluid, and this

examination frequently allows visualization
of the lesion in the bladder or urachus.
Further testing is sometimes needed to
confirm that the fluid is urine. Generally,
in uroperitoneum, substantial quantities
of fluid can be easily obtained by
abdominocentesis. Warming the fluid
may facilitate detection of the urine odor,
although this is a subjective and poorly
sensitive diagnostic test. If there is doubt
that the fluid is urine, its creatinine con-
centration can be compared to the serum
creatinine. If creatinine in the fluid is at
least twice the serum value, the fluid is
confirmed as urine, although ruptured
bladder should be suspected whenever
the abdominal fluid creatinine concen-
tration exceeds that of serum. In animals
with uroabdomen or suspected to have
uroabdomen, the administration of 30 mL
of sterile 1% methylene blue into the
bladder via a urethral catheter or cysto-
centesis has been used to confirm that the
bladder is the site of urine leakage.
Abdominal paracentesis is performed
some minutes after administration and
the fluid examined visually forthe presence
of a blue tinge. Absence of a blue color
suggests the presence of ureteral or renal
rupture.

Radiography

Radiographic examination has limited
value for the diagnosis of urinary tract
disease in farm animals but contrast
studies may be used to examine the lower
urinary tract in neonatal animals. With the
widespread availability of ultrasonography
and endoscopy, the indications for radi-
ography have become limited. A positive-
contrast urethrogram was of value in
diagnosing urethral recess dilatation in a
bull calf, 60 and intravenous urography was
successful in diagnosing a dilated ureter
in a 4-month-old heifer calf. 61 Historically,
excretory urography, positive contrast
cystography and urethrography have
been used, particularly in foals, but these
tests are expensive, not widely available
and time-consuming. Radiography is
currently being performed on animals
with equivocal results using other cheaper,
faster and more widely available tests.

Principles of treatment of
urinary tract disease

Fluid and electrolytes

Treatment of acute renal failure in all
species is aimed at removing the primary
cause and restoring normal fluid balance
by correcting dehydration, acid-base
disorders, and electrolyte abnormalities.
The prognosis for acute renal failure will
depend on the initiating cause and
severity of the lesion. If the acute disease

process can be stopped the animal may be
able to survive on its remaining functional
renal tissue. When toxic nephrosis is
suspected, an attempt should be made to
identify and remove the initiating cause
or to move the animal from the suspect
environment.

Ruminants with chronic renal failure
typically have mild to marked hypo-
natremia and hypochloremia; the
serum calcium and potassium concen-
trations may be decreased because of
inappetence, serum magnesium concen-
tration may be normal or increased, and
serum phosphate concentration may be
normal or increased, because urine pro-
vides a route of excretion of magnesium
and phosphorus. The acid-base status is
characterized by metabolic acidosis in
severely affected cases to metabolic
alkalosis in mildly affected cases. Rumi-
nants with acute renal failure have similar
clinicopathological changes, although
the scrum phosphorus concentration is
usually markedly elevated in acute renal
failure because many cases are initiated
by decreased renal blood flow.

Horses with acute or chronic renal
failure have similar electrolyte changes to
those in ruminants, with the marked
difference being the presence of hyper-
calcemia and hypophosphatemia in
some horses. Hypercalcemia in horses
with renal disease is suspected to be due
to the relatively greater efficiency of
intestinal calcium absorption in the horse,
with urine being the predominant route
of excretion. Decreases in the function of
nephrons in the horse will therefore
decrease the urinary loss of calcium and
result in hypercalcemia. The hyper-
calcemia is marked and is thought to
result directly in hypophosphatemia in
horses with renal failure.

Balanced electrolyte solutions or normal
saline supplemented with potassium and
calcium can be used to correct fluid and
electrolyte deficits. The required volume
of replacement fluid can be determined
on the basis of clinical signs as outlined in
Chapter 2. As the fluid deficit is corrected,
the patient should be observed for
urination. If anuria or oliguria is present,
the rate of fluid administration should be
monitored to prevent overhydration. If
the patient has anuria or oliguria after the
fluid volume deficit is corrected, a diuretic
should be administered to help restore
urine flow. Furosemide (1-2 mg/kg BW
every 2 h) or mannitol (0.25-2.0 g/kg BW
in a 20% solution) may be used, but
furosemide is preferred because of its
much lower cost and ease of adminis-
tration. Diuretics should not be used until
dehydration has been corrected. After
urine flow is restored, the resulting
diuresis will increase the maintenance

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

fluid requirement. B vitamins should be
frequently administered because their
rate of loss in the urine is anticipated to be
higher than normal in animals with renal
failure. Animals nonresponsive to fluid
loading and diuretics could be admin-
istered low-dose ('renal dose') dopamine
as a continuous intravenous infusion
(2-5 pg/kg BW/min) with dopamine
being diluted in 0.9% NaCl, 5% dextrose
or lactated Ringer's solution. Dopamine is
an oq, f^, [) 2 , DA t and DA 2 agonist and
therefore has a complex pharmacodynamic
profile that is dependent upon species,
organ, and cardiovascular status. Dopamine
is theoretically the preferred pharma-
cological agent to selectively increase
renal blood flow and therefore glomerular
filtration rate in animals with renal failure,
although low-dose dopamine infusion
does not alter creatinine clearance (an
index of glomerular filtration rate) in
healthy adult horses and has not been
shown to be of benefit in treating renal
failure in humans. 62 At low doses
(<5pg/kg BW/min) dopamine acts
primarily as an inotropic agent and at
higher doses primarily as a vasopressor.
The mean arterial blood pressure and
electrocardiogram should therefore be
monitored during dopamine adminis-
tration to insure that dopamine infusion
does not lead to hypertension or clinically
significant cardiac arrhythmias. Although
there are good theoretical grounds for use
of dopamine in animals with renal failure,
this is no longer the practice in human
medicine because of the lack of efficacy of
the drug in preventing or treating acute
renal failure. Animals that remain anuric
after intravenous fluid administration of
furosemide/mannitol and dopamine have
a grave prognosis and can only be
managed with peritoneal dialysis or
hemodialysis.

Intermittent-flow peritoneal dialysis

has been used successfully in a foal with a
ruptured urinary bladder. 63 A urinary
catheter was placed in the bladder and
secured to the perineal region. An area of
the ventral midline was clipped and
prepared for aseptic surgery. Local anes-
thetic was infused, and a stab incision was
made in the skin with a scalpel blade. An
11 French peritoneal dialysis catheter was
placed in the stab incision then forced
into the abdomen. The rigid stylet was
removed, the catheter was secured to the
skin and the stab incision site was
bandaged. Fteritoneal fluid was allowed to
drain; dialysis was then accomplished by
infusing 2 L of a hypertonic dialysis
solution, clamping the catheter for 1 hour,
then opening the catheter and allowing
drainage to occur for 2-3 hours. Dialysis
was repeated nine times over a 36-hour
period. 63 Intermittent-flow peritoneal

dialysis has also been used in an adult
horse using a similar catheterization
technique (24 French de Pezzer catheter)
and infusion of 10-15 L of warmed,
sterile, acetated Ringer's solution. 64 How-
ever, only 26-65% of the infused solution
was recovered from the abdomen.

Continuous-flow peritoneal dialysis
has been used successfully in an adult
horse with azotemia refractory to intra-
venous fluids, furosemide, dopamine
infusion and intermittent- flow peritoneal
dialysis. 64 A 28 French indwelling thoracic
tube was placed in the ventral abdomen
and a 2.2 mm diameter, 15 cm long spiral
fenestrated catheter was placed in the left
flank via peritoneoscopy to allow for
inflow of dialysate. Acetated Ringer's with
1.5% glucose was continuously infused
through the catheter in the left flank at
approximately 3 L/h, with abdominal
fluid being collected into a sterile closed
collection system from the catheter in the
ventral midline of the abdomen.

Hemodialysis was used successfully
to treat a foal with presumed oxytetracycline
nephrotoxicosis. 65 Hemodialysis was per-
formed under isoflurane anesthesia after
surgical placement of a Teflon/Silastic
arteriovenous shunt in the median artery
and vein using a dialysis delivery system,
a hollow- fiber artificial kidney, and
acetate-base dialysate. Anticoagulation
during dialysis was accomplished with a
loading dose of heparin (100 U/kg BW)
and then hourly boluses of 20 U/kg BW to
prolong the activated clotting time. Three
dialysis treatments, lasting 4-6 hours,
were administered over a 4-day period,
resulting in a marked reduction in
azotemia. Hemodialysis is more efficient
than peritoneal dialysis and requires
shorter treatment intervals, but does
require vascular access and anticoagulation
treatment, which may predispose to
hypotension. 65

The treatment of chronic renal failure
will depend on the stage of disease and
the value of the animal. In chronic failure,
therapy is aimed at prolonging life. In
food-producing animals, emergency
slaughter is not recommended because
the carcass is usually unsuitable for human
consumption. Animals in chronic failure
should have free access to water and salt,
unless edema is present. Stresses such as
sudden environmental and dietary changes
should be avoided. The ration should be
high in energy-giving food and properly
balanced for protein. Acute renal failure
may occur in patients in chronic failure
and can be treated like other cases of
acute renal failure.

Antimicrobial agents

Selection of antimicrobial agents for the
treatment of urinary tract infections

should be based on quantitative urine
culture of a catheterized urine sample. A
clinically relevant bacterial concentration
indicative of cystitis or pyelonephritis is
1000 or 40 000 cfu/mL of urine from a
catheterized or midstream free-catch
sample, respectively. 66

The ideal antimicrobial for treatment
of urinary tract infections should meet
several criteria. It should:

° Be active against the causal bacteria
° Be excreted and concentrated in the
kidney and urine
° Be active at the pH of urine
° Have low toxicity, particularly
nephrotoxicity
° Be easily administered
° Be low in cost

° Have no harmful interactions with
other concurrently administered
drugs.

Appropriate first-line antimicrobials
include penicillin, ampicillin, amoxicillin,
ceftiofur, and cefquinome in ruminants
and trimethoprim-sulfa and ceftiofur in
horses. Antimicrobial therapy for lower
urinary tract infections should continue
for at least 7 days; for upper urinary tract
infections 2-4 weeks of treatment is often
necessary. Success of therapy can be
evaluated by repeating the urine culture
7-10 days after the last treatment.

Manipulation of urine pH should be
considered as part of the treatment of
bacterial urinary tract infections. In general,
Escherichia coli attach best to urinary
epithelial cells at pH 6.0, whereas
Corynebacterium renale attaches best in
alkaline urine. In other words, when
treating an E. coli pyelonephritis or
cystitis, the diet should be altered to
ensure an alkaline urine pH. Likewise,
urine pH should be acidic when treating
urinary tract infections due to C. renale.

REVIEW LITERATURE

Osbaldiston GW, Moore WE. Renal function tests in
cattle. J Am Vet Med Assoc 1971; 159:292-301.
Koterba AM, Coffman JR. Acute and chronic renal
disease in the horse. Compend Contin Educ Pract
Vet 1981; 3:S461-S469.

Fetcher A. Renal disease in cattle. Part 1. Compend
Contin Educ Pract Vet 1985; 7:S701-S707; Part 2.
Compend Contin Educ Pract Vet 1986;
8.-S338-S345.

Kohn CW, Chew DJ. Laboratory diagnosis and
characterization of renal disease in horses. Vet
Clin North Am Equine Pract 1987; 3:585-615.
Lees GE, Brown SA, Elliott J et al. Assessment and
management of proteinuria in dogs and cats: 2004
ACVIM forum consensus statement (small
animal). JVet Intern Med 2005; 19:377-385.

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Diseases of the kidney

GLOMERULONEPHRITIS

Glomerulonephritis can occur as a
primary disease or as a component of
diseases affecting several body systems,
such as equine infectious anemia and
chronic swine fever. In primary glomerulo-
nephritis, the disease involves only the
kidney, predominantly affecting the
glomeruli although the inflammatory
process extends to affect the surrounding
interstitial tissue and blood vessels. Pri-
mary and secondary glomerulonephritis
are rare causes of clinical disease in farm
animals. The disease is sometimes
associated with other chronic, systemic
illness such as in cows with Johne's
disease, bovine virus diarrhea, or lepto-
spirosis; pigs with hog cholera or African
swine fever; and horses with equine
infectious anemia. Proliferative glomerulo-
nephritis is reported as an incidental
finding in normal sheep, cattle, goats, and
pigs. Clinical disease from glomerulo-
nephritis is rare in these species but has
been reported in cattle 1 and as a con-
genital condition in sheep, described
below. Proliferative glomerulonephritis
can cause chronic renal failure in horses. 2
Glomerulonephritis is present is animals
with amyloidosis, which is a generalized
deposition of antibody-antigen complexes.
Amyloidosis is discussed in detail in
Chapter 9.

The immune system plays a major role
in the pathogenesis of glomerular lesions.
Glomerular injury can be initiated by an
immune response whereby antibodies are
directed against intrinsic glomerular
antigens or by foreign antigens planted in
the glomerulus. Alternatively, and more
commonly, circulating antigen-antibody
complexes may be deposited in the
glomerulus. As the complexes accumulate,
they stimulate an inflammatory response
that damages the glomerular filtration
system. Inflammatory damage to the
glomerulus alters the selective permeability
of the filtration system allowing plasma
protein, particularly albumin, to pass into
the glomerular filtrate. In horses, the
glomerular lesion is thought to be caused
by the deposition of circulating antigen-
antibody complexes but the origin of these
complexes is unknown. Infections with
streptococci and equine infectious anemia
virus may be involved but are not likely to
be involved in all cases.

Dermatitis-nephropathy syndrome
is a systemic necrotizing vasculitis and

glomerulonephritis syndrome of growing
pigs in the UK and Canada. 3 The cause is
unknown but an immune-mediated
pathogenesis is suspected. Growing pigs
are affected with a morbidity ranging
from 1-3%. The skin is affected with a
papular dermatopathy with a characteristic
distribution of bluish red spots at least
1 cm in diameter beginning first in the
perineal region and then extending to the
pelvic limbs and along the ventral body
wall to the neck and ears. In the glomeruli,
there are extensive granular complement
deposits with scattered immunoglobulins.

Porcine dense deposit disease, porcine
membranoproliferative glomerulonephritis
type II is a common cause of early loss of
piglets in the Norwegian Yorkshire breed. 4,5
The disease is associated with extensive
complement activation due to a deficiency
of factor H, a plasma protein that
regulates complement. Affected piglets
are clinically normal at birth and for the
first few weeks of life. 1 Thereafter they
become unthrifty and die from renal
failure within 72 days of birth. In the
kidneys there is extensive glomerular
proliferation and marked thickening of
the glomerular capillary wall. Large
amounts of dense deposits are con-
sistently found within the glomerular
basement membrane. This disease is
inherited with a simple autosomal recessive
pattern and complete penetrance. A
pathogenetic mechanism of a defective or
missing complement regulation protein is
hypothesized. A spontaneous glomerulo-
nephritis of unknown etiology and
unrelated to any breed has been recorded
in pigs. 6 A necrotizing glomerulonephritis
is listed as occurring in pigs fed a waste
product from an industrial plant pro-
ducing a proteolytic enzyme. Glomerulo-
nephritis has also been recorded in pigs in
the absence of clinical illness, although an
association with the 'thin sow 7 syndrome
is suggested.

In Finnish Landrace Iambs less than
4 months of age there is an apparently
inherited disease that is remarkably
similar to forms of human glomerulo-
nephritis. Affected lambs appear to absorb
an agent from colostrum that induces an
immunological response, followed by
the granular deposition of immune
complexes and complement within the
glomerular capillary walls; this initiates a
fatal mesangiocapillary glomerulitis.
Many affected lambs are asymptomatic
until found dead. Some have signs of
tachycardia, edema of the conjunctiva,
nystagmus, walking in circles and con-
vulsions. The kidneys are enlarged and
tender. There is severe proteinuria and
low plasma albumin. Serum urea concen-
tration is increased (> 35 mmol/L) with
hyperphosphatemia and hypocalcemia.

6

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

At necropsy the kidneys are large and
pale and have multifocal pinpoint yellow
and red spots throughout the cortex. On
histopathological examination there are
severe vascular lesions in the choroid
plexuses and the lateral ventricles of the
brain. The disease is thought to be con-
ditioned in its occurrence by inheritance
and to be limited to the Finnish Landrace
breed. However, cases have also occurred
in crossbred lambs. 7

Glomerulopathy and peripheral
neuropathy in Gelbvieh calves is a
familial, and probably heritable, disease
causing illness in calves of this breed of
less than 13 months of age. The initial
physical abnormality is posterior ataxia
that progresses to generalized paresis and
recumbency.® The neurological deficits
include loss of conscious proprioception,
diminished or absent peripheral reflexes
but maintained consciousness. Affected
animals continue to eat and drink normally.
Serum creatinine and urea concentrations
are markedly elevated. Necropsy exam-
ination reveals neuropathy, myelopathy,
and glomerulopathy. The disease is
terminal.

Glomerulonephritis is a common
cause of chronic renal failure in horses.
Several forms of glomerulonephritis are
recognized in horses: membranous

glomerulonephritis, post-streptococcal
glomerulonephritis, membranoproljferative
glomerulonephritis and focal glomerulo-
sclerosis. 9 As discussed above, most
are probably immune-mediated and
associated with circulating antibody-
antigen complexes. Over 80% of horses
with equine infectious anemia have
glomerular lesions, and viral antigen-
antibody complexes are present in the
glomerular basement membrane. Purpura
hemorrhagica is associated with glomerulo-
nephritis.

REFERENCES

1. Hogasen K et al. J Clin Invest 1995; 95:1054.

2. Divers TJ. Compend Contin Educ PractVet 1983;
5:S310.

3. Helie P et al. Can\fet J 1995; 36:150.

4. Jansen JH et al.Vet Rec 1995; 137:240.

5. Jansen JH et al. Am J Pathol 1993; 143:1356.

6. Bourgall A, Drolet R. J Vet Diagn Invest 1995;
7:122.

7. Dore M et al. Can Vet J 1987; 28:40.

8. Panciera RJ et al.Vet Pathol 2003; 40:63.

9. Biervliet JV et al. Compend Contin Educ PractVet
2002; 24:892.

HEMOLYTIC-UREMIC-LIKE

SYNDROME

Glomerular and tubulointerstitial disease,
consistent with profound microangiopathy
and glomerular degeneration in humans
with hemolytic-uremic syndrome, has
been diagnosed in two horses. Both
horses were in oliguric renal failure and

had clinicopathological evidence of intra-
vascular hemolysis and morphological
evidence of arteriolar microangiopathy
and intravascular coagulation. The mortality
rate is expected to be extremely high.
The pathogenesis in horses is unclear,
although hemolytic-uremic syndrome in
humans is due to toxins produced by
E coli 0157IH7. 1

REFERENCE

1. Morris CF et al. J Am Vet Med Assoc 1987;
191:1453.

NEP HRO SIS

Nephrosis includes degenerative and
inflammatory lesions primarily affecting
the renal tubules, particularly the proximal
convoluted tubules. It can occur as a
sequel to renal ischemia and following
toxic insult to the kidney. Nephrosis is the
most common cause of acute kidney
failure. Uremia from nephrosis may
develop acutely or may occur in the ter-
minal stages of chronic renal disease.

RENAL ISCHE MIA

Reduced blood flow through the kidneys
usually results from general circulatory
failure. 1 There is transitory oliguria
followed by anuria and uremia if the
circulatory failure is not corrected.

ETIOLOGY

Any condition which predisposes the
animal to marked hypotension and release
of endogenous pressor agents potentially
can initiate hemodynamically mediated
acute renal ischemia and renal failure.
Ischemia may be acute or chronic.

Acute renal ischemia

° General circulatory emergencies such
as shock, dehydration, acute
hemorrhagic anemia, acute heart
failure. Renal failure secondary to calf
diarrhea has been described 2
° Embolism of renal artery, recorded in
horses

° Extreme ruminal distension in cattle.

Chronic renal ischemia

° Chronic circulatory insufficiency such
as congestive heart failure.

PATHOGENESIS

Acute ischemia of the kidneys occurs
when compensatory vasoconstriction
affects the renal blood vessels in response
to a sudden reduction in cardiac output.
As blood pressure falls, glomerular filtra-
tion decreases and metabolites that are
normally excreted accumulate in the
bloodstream. The concentration of urea in
the blood increases, giving rise to the
name prerenal uremia. As glomerular
filtration falls, tubular resorption increases,
causing reduced urine flow. Up to a
certain stage, the degenerative changes

are reversible by restoration of renal blood
flow, but if ischemia is severe enough and
of sufficient duration, the renal damage is
permanent. Acute circulatory disturb-
ances are more likely to be followed by
degenerative lesions than chronic con-
gestive heart failure.

The parenchymatous lesions vary from
tubular necrosis to diffuse cortical necrosis
in which both tubules and glomeruli are
affected. The nephrosis of hemoglobinuria
appears to be caused by the vaso-
constriction of renal vessels rather than a
direct toxic effect of hemoglobin on renal
tubules. Uremia in acute hemolytic anemia
and in acute muscular dystrophy with
myoglobinuria may be exacerbated by
plugging of the tubules with casts of
coagulated protein, but ischemia is also
an important factor.

CLINICAL FINDINGS

Renal ischemia does not appear as a
distinct disease and its signs are masked
by the clinical signs of the primary
disease. Oliguria and azotemia will go
unnoticed in most cases if the circulatory
defect is corrected in the early stages.
However, renal insufficiency may cause a
poor response to treatment with trans-
fusion or the infusion of other fluids in
hemorrhagic or hemolytic anemia, in
shock or dehydration. In these cases,
unexplained depression or a poor response
to therapy indicates that renal involve-
ment should be investigated. The general
clinical picture is one of acute renal failure
and is described under uremia.

CLINICAL PATHOLOGY

Laboratory tests can be used to evaluate
renal function once the circulatory con-
dition has been corrected. Urinalysis as
well as serum urea nitrogen and creatinine
concentrations are most commonly used
as indices. Serum biochemistry on serially
collected samples may also be used to
monitor the response to therapy. On
urinalysis, proteinuria is an early indi-
cation of damage to the renal parenchyma.
The passage of large volumes of urine of
low specific gravity after a period of oliguria
is usually a good indication of a return of
normal glomerular and tubular function.

NECROPSY FINDINGS

Lesions of renal ischemia are present
primarily in the cortex, which is pale and
swollen. There may be a distinct line of
necrosis visible at the corticomedullary
junction. Histologically there is necrosis
of tubular epithelium and, in severe cases,
of the glomeruli. In hemoglobinuria and
myoglobinuria hyaline casts are present in
the tubules.

TREATMENT

Treatment must be directed at correcting
fluid, electrolyte and acid-base disturb-

Diseases of the kidney

DIFFERENTIAL DIAGNOSIS

Evidence of oliguria and azotemia in the
presence of circulatory failure suggests
renal ischemia and the possibility of
permanent renal damage. It is important to
attempt to differentiate the early reversible
prerenal stage from the stage when
degeneration of renal parenchyma has
occurred. When ischemic renal lesions are
present, urinalysis may be helpful in
diagnosis, particularly if urine is not
appropriately concentrated in a dehydrated
patient. After irreversible ischemic changes
have occurred it is impossible to
differentiate clinically between ischemia
and other primary renal diseases such as
glomerulonephritis and toxic nephrosis.
History and clinical signs of chronic disease
will help determine if the acute syndrome
is superimposed on chronic renal disease.

ance as soon as possible. If renal damage
has occurred, supportive treatment as
suggested for the treatment of acute renal
failure should be instituted.

TOXIC NEPHROSIS

The kidneys are particularly vulnerable
to endogenous and exogenous toxins
because they receive a large proportion of
the total cardiac output and because sub-
stances are concentrated in the kidney for
excretion.

ETIOLOGY

Most cases of nephrosis are caused by
the direct action of toxins but hemo-
dynamic changes may contribute to the
pathogenesis.

Toxins

° Metals - mercury, arsenic, cadmium,
selenium, organic copper compounds;
nephrosis can be reproduced
experimentally in horses by the oral
administration of potassium
dichromate and mercuric chloride, 3,4
including topical blistering agents
containing mercuric chloride
0 Antimicrobials such as

aminoglycosides, and overdosing with
neomycin and gentamicin in
treatment of calves. Treatment with
tetracycline preparations accidentally
contaminated by tetracycline
degradation compounds and repeated
daily dosing with long-acting
oxytetracycline preparations may
induce toxicity. Treatment with
sulfonamides

° Horses treated with vitamin K 3
(menadione sodium bisulfite)
administered by intramuscular or
intravenous injection
° Horses treated with vitamin D 2
(ergocalciferol) and cholecalciferol

(Pa)

° Treatment of horses with nonsteroidal
anti-inflammatory drugs (NSAIDs),
including phenylbutazone and
flunixin meglumine. Dose rates of
more than 8.8 mg/kg BW of
phenylbutazone per day for 4 days are
likely to cause nephrosis. Doses of 4.4
mg/kg BW are considered to be safe
but the toxicity is enhanced by water
deprivation. More commonly, NSAID
toxicity occurs as interstitial nephritis
and renal crest necrosis. The usual
presentation of NSAID toxicosis in
horses is gastrointestinal ulceration,
including right dorsal colitis
0 Benzimidazole compounds used as
anthelmintics; only some of them but
including thiabendazole
° Monensin in ruminants
° Low-level aldrin poisoning in goats
° Highly chlorinated naphthalenes
° Oxalate in plants, listed under the
heading of oxalate poisoning
° Oxalate in fungi, e.g. Penicillium spp.
and mushrooms

° Oxalate in ethylene glycol or ascorbic
acid, which is a metabolic precursor to
oxalate

° Primary hyperoxaluria due to
inherited metabolic defect in beef
master calves 5

° Tannins in the foliage of oak trees and
acorns 6

° Unidentified toxin in Amaranthus
retroflexus in pigs and cattle in
Narthecium asiaticum fed to cattle and
Isotropis forrestii in ruminants
° Mycotoxins: ochratoxins and citrinins,
fumonisins in ruminants
° Ingestion of Lophyrotoma interrupt a
(sawfly) larvae by cattle
° Cantharidin in horses following
ingestion of dead blister beetles in
alfalfa hay and hay products
° Most nonspecific endogenous or
exogenous toxemias cause some
degree of temporary nephrosis.

PATHOGENESIS

In acute nephrosis there is obstruction to
the flow of glomerular filtrate through the
tubules as a result of interstitial edema
and intraluminal casts. If there is suffi-
cient tubular damage, there may be back
leakage of glomerular filtrate into the
interstitium. There may also be a direct
toxic effect on glomeruli, which decreases
glomerular filtration. The combined effect
is oliguria and uremia. In subacute cases,
impaired tubular resorption of solutes
and fluids may lead to polyuria.

CLINICAL FINDINGS

Clinical signs may not be referable to the
urinary system. In peracute cases, such as
those caused by vitamin K 3 administered
by injection, there may be colic and
stranguria. In acute nephrosis there is

oliguria and proteinuria with clinical signs
of uremia in the terminal stages. These
signs include depression, dehydration,
anorexia, hypothermia, a slow or an elev-
ated heart rate, and weak pulse. Diarrhea
may be present that is sufficiently intense
to cause severe clinical dehydration. In
cattle there is a continuous mild hypo-
calcemia with signs reminiscent of that
disease, which responds, in a limited way,
to treatment with calcium. Cattle with
advanced and severe nephrosis may exhibit
a bleeding diathesis. Polyuria is present in
chronic cases.

Many systemic diseases such as septi-
cemia cause temporary tubular nephrosis.
The degree of renal epithelial loss is not
sufficient to cause complete renal failure
and, provided the degree of renal damage
is small, complete function is regained.

CLINICAL PATHOLOGY

In acute tubular nephrosis, urinalysis
abnormalities are usually present before
serum urea and creatinine concentration
are increased. Proteinuria, glucosuria,
enzymuria, and hematuria are initial
changes on urinalysis in experimental
toxic nephrosis. The earliest indication of
tubular epithelial damage in experi-
mentally induced nephrosis is the detec-
tion of the proximal tubule enzyme GGT
in urine. 4 Hypoproteinemia may be pre-
sent. In acute renal disease of horses,
hypercalcemia and hypophosphatemia
can be present, 7 although this is not the
usual finding. In the chronic stages the
urine is isosthenuric and may or may not
contain protein. Azotemia occurs when
uremia is present. Ultrasonographically,
renal changes are seen in foals receiving
high daily doses of phenylbutazone. 8

NECROPSY FINDINGS

In acute cases the kidney is swollen and
wet on the cut surface and edema,
especially of perirenal tissues, may be
apparent. Histologically there is necrosis
and desquamation of tubular epithelium,
and hyaline casts are present in the
dilated tubules. In phenylbutazone poison-
ing the renal lesion is specifically a renal
medullary necrosis. There may also be
ulcers in all or any part of the alimentary
tract from the mouth to the colon if
phenylbutazone was administered orally.

TREATMENT

Treatment should be directed at general
supportive care for acute renal disease as
outlined above. If the toxin can be iden-
tified, it should be removed. Treatment
for specific toxins may be available, as
described elsewhere in the text. Hemo-
dialysis was used successfully to treat
a foal with presumed oxytetracycline
nephrotoxicosis. 9

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

DIFFERENTIAL DIAGNOSIS

Clinical differentiation from acute
glomerulonephritis is difficult but clinical
signs of involvement of other organs in the
toxic process may be present.

• A combination of polyuria and glycosuria
is an uncommon finding in large animals
and is usually caused by nephrosis

• Diabetes mellitus is rare in horses and
extremely rare in ruminants

• Cushing's syndrome (chronic
hyperadrenocorticism pituitary pars
intermedia dysfunction) is more
common in horses but this includes
characteristic signs of polyuria,
glycosuria, debilitation, hirsutism,
polyphagia, and hyperglycemia

• Diarrhea in terminal stages of uremia in
a horse can be confused with the other
causes of acute diarrhea. It requires a
blood urea and creatinine estimation
and a urinalysis for differentiation

REVIEW LITERATURE

Fetcher A. Renal disease in cattle. Part 1. Compend
Contin Educ PractVet 1985; 7:S701-S707; Part 2
Compend Contin Educ Pract Vet 1986;
8:S338-S345.

Schmitz DG. Toxic nephropathy in horses. Compend
Contin Educ PractVet 1988; 10:104-111.

Angus KW. Nephropathy in young lambs. Vet Rec
1990; 126:525-528.

REFERENCES

1. DiversTJ et al. Equine Vet J 1987; 19:178.

2. Mechor GD et al. Cornell Vet 1993; 83:325.

3. Bayly WM et al. Cornell Vet 1986; 76:287.

4. Bayly WM et al. Cornell Vet 1986; 76:306.

5. Rhyan JC et al. J Am Vet Med Assoc 1992;
201:1907.

6. Ostrowski SR et al. J Am Vet Med Assoc 1989;
195:481.

7. Elfers RS et al. Cornel! Vet 1986; 76:317.

8. Lcveille R et al. Can Vet J 1996; 37:235.

9. Vivrette S et al. J Am Vet Med Assoc 1993; 203:105.

RENAL TUBULA R ACIDOSIS

Renal tubular acidosis (RTA) is a rare
disease of large animals that is charac-
terized by normal glomerular function but
abnormal tubular function. RTA should
be suspected whenever there is a hyper
chloremic strong ion (metabolic) acidosis
with no discernible extrarenal cause; a
common extrarenal cause of hyper-
chloremic strong ion acidosis is aggressive
intravenous administration of 0.9% NaCl.

Four major types of tubular functional
defect exist: 1) renal diabetes insipidus,
where the tubules do not respond to
antidiuretic hormone; 2) Fanconi's
syndrome, which is a genetic defect in
humans related to the tubular resorption
of glucose, various amino acids, urate, and
phosphate; 3) distal RTA (type I), which
is a defect in the ability to secrete
hydrogen ions in the distal convoluted
tubules against a concentration gradient; 1
and 4) proximal RTA (type II), which is

characterized by decreased bicarbonate
reabsorption in the proximal convoluted
tubules. 2 Reabsorption of bicarbonate
requires energy, therefore disease pro-
cesses that lead to proximal tubular
damage have the potential to result in
proximal RTA. 3 Other causes of RTA have
been described in humans but have not
been documented in large animals. The
urine of animals with proximal RTA (type
II) is acidic, whereas the urine of animals
with distal RTA (type I) is very alkaline,
regardless of the serum bicarbonate
concentration.

Only a few cases of RTA have been
documented in horses, and these have
been predominantly of the distal type.
Horses with distal RTA (type I) have a
profound strong ion acidosis due to
hyperchloremia (normal anion gap meta-
bolic acidosis), accompanied by an
alkaline urine pH (typically > 8.0) and
increased fractional clearance of sodium. 1
A practical diagnostic test for distal RTA
involves examining the ability of the distal
convoluted tubules to excrete hydrogen
ions by the oral administration of ammo-
nium chloride (O.lg/kg BW in 6L of
water via nasogastric tube). Inability to
achieve an acidic urine (pH < 6.5) after
oral ammonium chloride administration
is consistent with a diagnosis of distal
RTA (type I). A practical diagnostic test for
proximal RTA (type II) is measuring the
change in urine Pco 2 during oral or
intravenous sodium bicarbonate adminis-
tration. 2 Normally, urine and plasma Pco 2
are similar but, during bicarbonate
diuresis, urine Pco 2 becomes greater than
plasma Pco 2 . The Pco 2 gradient during
intravenous sodium bicarbonate adminis-
tration is therefore measured; one horse
with proximal RTA developed a urine to
plasma Pco 2 gradient of 29 mmHg during
bicarbonate loading. 2

Treatment of horses with distal RTA
(type I) has been symptomatic and focuses
on oral or intravenous administration
of sodium bicarbonate. 1 Spontaneous
recovery has been reported in horses.
Treatment of horses with proximal RTA
(type H) is uncertain. 2

REFERENCES

1. Ziemer EL et al. J Am Vet Med Assoc 1987;

190:289.

2. Trotter GW et al. J Am Vet Med Assoc 1986;

188:1050.

3. Macleay JM, Wilson JH. J Am Vet Med Assoc 1998;

212:1597.

IN TERS TITIAL N EPH RITIS

Interstitial nephritis is rarely recognized
as a cause of clinical disease in farm
animals although it is a frequent post-
mortem finding in some species. Inter-
stitial nephritis may be diffuse or have a
focal distribution. In calves, focal interstitial

nephritis (white-spotted kidney) is a
common incidental finding at necropsy
but does not present as a clinical urinary
tract disease. 1 Focal interstitial nephritis
of cattle is not associated with lepto-
spirosis or active bacterial infection. 2 In
pigs, diffuse interstitial nephritis is
observed following infection by Leptospira
sp. and is important clinically because of
the resultant destruction of nephrons that
occurs. The kidney is an important
reservoir for Leptospira spp. in other
species, particularly cattle, but renal
disease is not a common clinical problem
in carrier animals. 3

Chronic interstitial fibrosis is a com-
mon postmortem finding in horses
suffering from chronic renal failure. 4 This
is believed to represent an end-stage
condition rather than primary interstitial
disease. The initiating cause of the renal
disease is usually not evident but most
cases are believed to begin with acute
tubular nephrosis. Horses with chronic
interstitial nephritis have the clinical
syndrome of chronic renal failure with
uremia.

REFERENCES

1. Monaghan M. IrVet J 1985; 39:15.

2. Uzal FA et al.Vet Microbiol 2002; 86:369.

3. Ellis WA.Vet Rec 1985; 117:101.

4. Divers T|. Compend Contin Educ Pract Vet 1983;
5:S310.

EMBOLIC NEPHRITIS

Embolic lesions in the kidney do not
cause clinical signs unless they are very
extensive, in which case septicemia may
be followed by uremia. Even though
embolic nephritis may not be clinically
evident, transient proteinuria and pyuria
may be observed if urine samples are
examined at frequent intervals.

ETIOLOGY

Embolic suppurative nephritis or renal
abscess may occur after any septicemia or
bacteremia when bacteria lodge in renal
tissue.

Emboli may originate from localized
septic processes such as:

° Valvular endocarditis, in all species
° Suppurative lesions in uterus, udder,
navel, peritoneal cavity in cattle

or be associated with systemic infections
such as:

° Septicemia in neonatal animals,
including Actinobacillus equidi
infection in foals and E. coli
septicemia in calves
° Erysipelas in pigs, Corynebacterium
pseudotuberculosis in sheep and goats
° Septicemic or bacteremic Streptococcus
equi infection in horses.

Diseases of the kidney

PATHOGENESIS

Bacterial emboli localize in renal tissue
and cause the development of focal sup-
purative lesions. Emboli can block larger
vessels and cause infarction of portions of
kidney, the size varying with the caliber of
the occluded vessel. Infarcts are not
usually so large that the residual renal
tissue cannot compensate fully and they
usually cause no clinical signs. If the urine
is checked repeatedly, the sudden appear-
ance of proteinuria, casts, and microscopic
hematuria, without other signs of renal
disease, suggests the occurrence of a renal
infarct. The gradual enlargement of focal
embolic lesions leads to the development
of toxemia and gradual loss of renal
function. Clinical signs usually develop
only when multiple emboli destroy much
of the renal parenchyma, or when there is
one or more large infected infarcts.

CLINICAL FINDINGS

Usually there is insufficient renal damage
to cause signs of renal disease. Signs of
toxemia and the primary disease are
usually present. The kidney may be
enlarged on rectal examination. Repeated
showers of emboli or gradual spread from
several large, suppurative infarcts may
cause fatal uremia. Spread to the renal
pelvis may cause signs similar to pyelo-
nephritis. Large infarcts may cause bouts
of transient abdominal pain.

CLINICAL PATHOLOGY

Hematuria and pyuria are present but
microscopic examination may be neces-
sary to detect these abnormalities when
the lesions are minor. Proteinuria is
present but is also normally present in
neonatal animals in the first 30-40 hours
of life. Culture of urine at the time when
proteinuria occurs may reveal the identity
of the bacteria infecting the embolus.
Hematology usually reveals evidence of
an acute or chronic inflammatory process.

NECROPSY FINDINGS

In animals that die of intercurrent disease
the early lesions are seen as small gray
spots in the cortex. In later stages these
lesions may have developed into large
abscesses, which may be confluent and in
some cases extend into the pelvis. Fibrous
tissue may surround long-standing lesions
and healed lesions consist of areas of scar
tissue in the cortex. These areas have
depressed surfaces and indicate that
destruction of cortical tissue has occurred.
Extensive scarring may cause an obvious
irregular reduction in the size of the
kidney.

TREATMENT

General information on treatment of
urinary tract infections is presented in the
section on treatment of urinary tract
diseases. Antimicrobials should be selected

DIFFERENTIAL DIAGNOSIS

Differentiation from pyelonephritis is
difficult unless the latter is accompanied by
signs of lower urinary tract infection such
as cystitis or urethritis. The kidney is
enlarged in both conditions and the
findings on urinalysis are the same when
embolic nephritis invades the renal pelvis.
Many cases of embolic nephritis go
unrecognized clinically because of the
absence of overt signs of renal
involvement.

Severely dehydrated neonatal animals
may experience prerenal uremia and are
susceptible to ischemic tubular nephrosis.
The presence of other signs of sepsis
should increase suspicion of the presence
of embolic nephritis.

The sudden occurrence of bouts of acute
abdominal pain in some cases of renal
infarction may suggest acute intestinal
obstruction, but defecation is usually
unaffected and rectal examination of the
intestines is negative.

on the basis of quantitative urine culture
and susceptibility testing. In treating
septicemic neonatal animals, particular
care must be taken to avoid the use of
potentially nephrotoxic drugs. Antibiotic
treatment should be continued for a fairly
lengthy period (7-14 d). In embolic
nephritis, the primary disease must be
controlled as well as the renal disease to
prevent recurrence of the embolic lesions.
In neonatal animals this may involve
treatment for septic shock. The urine
culture should be repeated at intervals
after treatment is completed to insure
that the infection has been completely
controlled.

PYELONEPHRITIS

Pyelonephritis usually develops by
ascending infection from the lower
urinary tract. Clinically it is characterized
by pyuria, hematuria, cystitis, ureteritis,
and suppurative nephritis.

ETIOLOGY

Pyelonephritis may develop in a number
of ways:

° Secondary to bacterial infections of
the lower urinary tract
° Spread from embolic nephritis of
hematological origin such as
septicemia in cattle associated with
Pseudomonas aeruginosa
° Specific pyelonephritides associated
with C. renale, Corynebacterium pilosum
(formerly C. renale type 2) and
Corynebacterium cystitidus (formerly
C. renale type 3) in cattle and
Corynebacterium suis in pigs
o Secondary to anatomical

abnormalities of the kidneys or distal

structures permitted ascending
infection of the kidney
° In association with nephroliths,
although whether the nephrolith or
the pyelonephritis occurred first is
uncertain.

PATHOGENESIS

Pyelonephritis develops when bacteria
from the lower urinary tract ascend the
ureters and become established in the renal
pelvis and medulla. Bacteria are assisted
in ascending the ureters by urine stasis
and reflux of urine from the bladder. Urine
stasis can occur as a result of blocking of
the ureters by inflammatory swelling or
debris, by pressure from the uterus in
pregnant females and by obstructive
urolithiasis. Initially the renal pelvis and
medulla are affected because they are
relatively more hypoxic and localized
tissue hypertonicity depresses the phago-
cytic function of leukocytes. Infection in
advanced cases may extend to the cortex.
Pyelonephritis causes systemic signs of
toxemia and fever and, if renal involve-
ment is bilateral and sufficiently exten-
sive, uremia develops. 1 Pyelonephritis
is always accompanied by pyuria and
hematuria because of the inflammatory
lesions of the ureters and bladder. 1

Pyelonephritis in cattle due to C. renale
used to be very common but clinical
disease has decreased markedly, with the
majority of pyelonephritis cases in cattle
now being due to E. coli. The reason for
the decrease in C. renale isolation from
clinical cases is unclear but is probably
related to a change in diet towards
concentrates with an associated decrease
in urine pH; other potential reasons could
be the widespread use of beta-lactam
antibiotics and the marked decrease in
urethral catheterization in order to obtain
a urine sample in cows suspected to be
ketotic. C. renale attaches most efficiently
to well-differentiated epithelial cells
(transitional epithelium cells), with poor
attachment at pH less than 6.8, a rapid
increase in adhesion from 6.8 to 7.6, and a
high rate of attachment at pH above 7.6. 2
C. renale used to be typed as 1, 2, and 3,
but the latter two have been renamed
C. pilosum (formerly C. renale type 2) and
C. cystitidus (formerly C. renale type 3),
with apparent type differences in their
preferred colonization site in the vagina
and urethra. 2,3 Uropathogenic strains of
E. coli also attach to epithelial cells by a
type 1 pili, with the optimal pH for
attachment of 6.0. Attachment of bacterial
to urinary epithelium appears to be an
important virulence attribute.

Transmission of C. suis in pigs may
occur after mating with infected boars,
because many boars carry C. suis in their
preputial sac fluid. Field observations

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

suggest that slight trauma at breeding,
especially in small gilts, may be an
important factor in transmission . 4

CLINICAL FINDINGS

The clinical findings in pyelonephritis
vary between species. In sows there may
be an initial period during which a vaginal
discharge is noted but most affected
animals die without premonitory illness.
Characteristically, affected pigs will lose
weight and eventually become emaciated . 5
The disease in cattle is described in detail
in the section on bovine pyelonephritis.

The disease in horses is often chronic,
although acute disease occurs. Gross
hematuria is recognized in some horses
with pyelonephritis, although this is not
a common finding . 5 Ultrasonographic
examination of the kidneys can confirm
the diagnosis, based on the presence of
abnormally shaped kidneys with loss
of the corticomedullary gradient, hypo- or
hyperechoic abnormalities in the renal
cortex, and increased echogenicity. These
findings should prompt examination of
the urine for leukocytes, casts, protein,
and bacteria.

CLINICAL PATHOLOGY

Erythrocytes, leukocytes, and cell debris
are present in the urine on microscopic
examination and may be grossly evident
in severe cases, particularly in horses . 3
Quantitative urine culture is necessary to
determine the causative bacteria.

NECROPSY FINDINGS

The kidney is usually enlarged and lesions
in the parenchyma are in varying stages of
development. Characteristic lesions are
necrosis and ulceration of the pelvis and
papillae. The pelvis is usually dilated and
contains clots of pus and turbid urine.
Streaks of gray, necrotic material radiate
out through the medulla and may extend
to the cortex. Affected areas of parenchyma
are necrotic and may be separated by
apparently normal tissue. Healed lesions
appear as contracted scar tissue. Infarction
of lobules may also be present, especially
in cattle. Histologically the lesions are
similar to those of embolic nephritis
except that there is extensive necrosis
of the apices of the papillae. Necrotic,
suppurative lesions are usually present in
the bladder and ureters.

TREATMENT

General principles of treatment of urinary
tract infections are presented above in the
section on treatment of urinary tract
disease. A specific treatment for severe
asymmetric pyelonephritis is unilateral
nephrectomy, but this should only be
done in nonazotemic animals. Ait over-
looked component of treatment is alter-
ation in urinary pH, which will affect the
ability of the bacteria to attach to epi-

DIFFERENTIAL DIAGNOSIS

The presence of pus and blood in the urine
may suggest cystitis or embolic nephritis as
well as pyelonephritis. It may be difficult to
distinguish between these diseases but
renal enlargement or pain on rectal
palpation of the kidney indicates renal
involvement. Ultrasonographic changes
associated with pyelonephritis include a
dilated renal collecting system, renal or
ureteral calculi, increased echogenicity, loss
of corticomedullary echogenicity and
subjective enlargement of the kidney with
acute disease or a small irregular kidney
with chronic disease . 5,6 Parenchymal
hyperechogenicity can be caused by
tubular degeneration and replacement
fibrosis.

thelial cells. As a generalization, C. renale
attaches best in alkaline urine and E. coli
attaches best in acidic urine. Refer also to
the section on bovine and porcine cystitis
pyelonephritis.

REFERENCES

1. Rebhun WC et al. J Am Vet Med Assoc 1989;
194:953.

2. Takai S et al. Infect Immunity 1980; 28:669.

3. Sato H et al. Infect Immunity 1982; 36:1242.

4. Pijoan C et al. J Am Vet Med Assoc 1983; 183:428.

5. Kistardt KK et al. Can Vet J 1999; 40:571.

6. Hayashi H et al. J Am Vet Med Assoc 1994;
205:736.

HYDRONEPHROSIS

Hydronephrosis is a dilatation of the renal
pelvis with progressive atrophy of the
renal parenchyma. It occurs as a con-
genital or an acquired condition following
obstruction of the urinary tract. Any
urinary tract obstruction can lead to
hydronephrosis but the extent and
duration of the obstruction are important
in determining the severity of the renal
lesion. Urinary tract obstructions that are
chronic, unilateral, and incomplete are
more likely to lead to hydronephrosis.
Acute obstructions of bladder or urethra
that are corrected promptly are not
usually associated with significant kidney
damage. As a result, recurrence of the
obstruction rather than renal failure is the
major sequel to urolithiasis in ruminants.
In cases of acute complete obstruction the
clinical picture is dominated by signs of
anuria, dysuria, or stranguria.

Chronic or partial obstructions cause
progressive distension of the renal pelvis
and pressure atrophy of the renal paren-
chyma. If the obstruction is unilateral, the
unaffected kidney can compensate fully
for the loss of function and the obstruc-
tion may not cause kidney failure.
Unilateral obstruction may be detectable
on palpation per rectum of a grossly dis-
tended kidney. Chronic bilateral obstruc-

tions, although they are rare in large
animals, can cause chronic kidney failure.
Hydronephrosis and chronic renal failure
have been recorded in a steer suffering
from chronic partial obstruction of the
penile urethra by a urolith . 1 Partial
obstruction of the ureters by papillomas
of the urinary bladder has been recorded
in a series of cows . 2 Compression by
neoplastic tissue in cases of enzootic
bovine leukosis may also cause hydro-
nephrosis. Ultrasonography can be used
as an aid to diagnosis . 2

REFERENCES

1. Aldridge BM, Garry FB. Cornell Vet 1992; 82:311.

2. Skye DV. J Am Vet Med Assoc 1975; 166:596.

R ENAL NEOPLAS MS

Primary tumors of the kidney are
uncommon. Carcinomas occur in cattle
and horses and nephroblastomas occur in
pigs. Enlargement of the kidney is the
characteristic sign; in cattle and horses
neoplasms should be considered in the
differential diagnosis of renal enlarge-
ment. In pigs, nephroblastomas may
reach such a tremendous size that they
cause visible abdominal enlargement.
Renal adenocarcinomas are very slow-
growing but are not usually diagnosed
until the disease is well advanced. The
gross and histological descriptions of a
series of primary renal cell tumors in
slaughter cattle has been recorded . 1 In
horses, the most common signs are
weight loss, reduced appetite and inter-
mittent bouts of abdominal pain . 2,3
Some affected horses have massive
ascites, hemoperitoneum, or hematuria . 2,3
Metastasis of the tumor to the axial
skeleton can result in lameness, which
can be the clinical abnormality that is
recognized first . 4,5 The tumor can also
metastasize to the lungs and mouth . 3,6
Masses on the left kidney of horses are
usually readily palpable on rectal exam-
ination . 3 Horses with renal carcinoma can
have clinically apparent periods of hypo-
glycemia . 7 Hypoglycemia is confirmed by
measurement of serum glucose concen-
tration and is attributable to production of
insulin-like growth factor by the neoplastic
tissue . 8 Ultrasonographic examination of
the kidney, and renal biopsy, confirm the
diagnosis.

Metastatic neoplasms occur fairly
commonly in the kidney, particularly in
enzootic bovine leukosis, but they do not
cause clinical renal disease. Tumor masses
may be palpable as discrete enlargements
in the kidneys of cattle or may involve the
kidney diffusely, causing generalized
enlargement of the kidney.

REFERENCES

1. Kelley LCet al. Vet Pathol 1996; 33:133.

2. Man Mol KAC, Fransen JA.MA Rec 1986; 119:238.

Diseases of the bladder, ureters and urethra

561

3. West HJ et al. EquineVet J 1987; 19:548.

4. Rhind SM, Sturgeon B. EquineVet Educ 1999;
11:171.

5. Rumbaugh ML et al. EquineVet J 2003; 35:107.

6. Rhind SM et al. J Comp Pathol 1999; 120:97.

7. Baker JL et al. J Am Vet Med Assoc 2001; 218:235.

8. Swaim JM et al. J Vet Intern Med 2005; 19:613.

Diseases of the bladder,
ureters and urethra

CY STITIS

Inflammation of the bladder is usually
associated with bacterial infection and is
characterized clinically by frequent, pain-
ful urination (pollakiuria and dysuria)
and the presence of blood (hematuria),
inflammatory cells and bacteria in the
urine.

ETIOLOGY

Cystitis occurs sporadically as a result of
the introduction of infection into the
bladder when trauma to the bladder has
occurred or when there is stagnation of
the urine. In farm animals the common
associations are:

° Cystic calculus
0 Difficult parturition
° Contaminated catheterization
0 Late pregnancy
0 As a sequel to paralysis of the
bladder. A special case of bladder
paralysis occurs in horses grazing
sudax or Sudan grass and in horses
with equine herpesvirus
myoencephalopathy.

In the above cases, the bacterial popu-
lation is usually mixed but predominantly
E. coli. There is also the accompaniment of
specific pyelonephritides in cattle and pigs,
associated with C. renale and Eubacterium
s uis, respectively. Many sporadic cases
also occur in pigs, especially after farrow-
ing. Common isolates from these are
£. coli, Streptococcus, and Pseudomonas spp.
Corynebacterium matruchotii causes
encrusted cystitis in horses. 1

Enzootic hematuria of cattle resembles
but is not a cystitis.

PATHOGENESIS

Bacteria frequently gain entrance to the
bladder but are usually removed by the
flushing action of voided urine before
they invade the mucosa. Mucosal injury
facilitates invasion but stagnation of urine
is the most important predisposing cause.
Bacteria usually enter the bladder by
ascending the urethra but descending
infection from embolic nephritis may also
occur.

CLINICAL FINDINGS

The urethritis that usually accompanies
cystitis causes painful sensations and

the desire to urinate. Urination occurs
frequently and is accompanied by pain
and sometimes grunting; the animal
remains i n the urination posture for some
minutes after the flow has ceased, often
manifesting additional expulsive efforts.
The volume of urine passed on each
occasion is usually small. In very acute
cases there may be moderate abdominal
pain, as evidenced by treading with the
hindfeet, kicking at the belly and
swishing with the tail, and a moderate
febrile reaction. Acute retention may
develop if the urethra becomes blocked
with pus or blood, but this is unusual.

Chronic cases show a similar syndrome
but the signs are less marked. Frequent
urination and small volume are the
characteristic signs. In chronic cases, the
bladder wall may feel thickened on rectal
examination and, in horses, a calculus
may be present. In acute cases no
palpable abnormality may be detected but
pain may be evidenced. Endoscopic
examination of the bladder of affected
horses reveals widespread inflammation
of the cystic mucosa and occasionally the
presence of a cystic calculus.

CLINICAL PATHOLOGY

Blood and pus in the urine is typical of
acute cases and the urine may have a
strong ammonia odor. In less severe cases
the urine may be only turbid and in
chronic cases there may be no abnor-
mality on gross inspection. Microscopic
examination of urine sediment will reveal
erythrocytes, leukocytes, and desquamated
epithelial cells. Quantitative bacterial
culture is necessary to confirm the diag-
nosis and to guide treatment selection.

NECROPSY FINDINGS

Acute cystitis is manifested by hyperemia,
hemorrhage and edema of the mucosa.
The urine is cloudy and contains mucus.
In subacute and chronic cases the wall is
grossly thickened and the mucosal
surface is rough and coarsely granular.
Highly vascular papillary projections may
have eroded, causing the urine to be
bloodstained or contain large clots of
blood. In the cystitis associated with Sudan
grass, soft masses of calcium carbonate
may accumulate in the bladder and the
vaginal wall may be inflamed and coated
with the same material.

TREATMENT

Antimicrobial agents are indicated to
control the infection and determination of
the antimicrobial susceptibility of the
causative bacteria is essential. Relapses
are common unless treatment is continued
for a minimum of 7 and preferably 14 days.
Repeated bacterial culture of urine at least
once during and again within 7-10 days
after completion of treatment should be

DIFFERENTIAL DIAGNOSIS

The clinical and laboratory findings of
cystitis resemble those of pyelonephritis
and cystic urolithiasis.

• Pyelonephritis is commonly
accompanied by bladder involvement '
and differentiation depends on whether
there are lesions in the kidney. This may
be determined by rectal examination
but in many cases it is not possible to
make a firm decision. Provided the
causative bacteria can be identified this
is probably not of major importance as
the treatment will be the same in either
case. However, the prognosis in
pyelonephritis is less favorable than in
cystitis. Thickening of the bladder wall,
which may suggest a diagnosis of
cystitis, occurs also in enzootic
hematuria and in poisoning by the
yellow-wood tree ( Terminalia
oblongata ) in cattle and by sorghum in
horses

• The presence of calculi in the bladder
can usually be detected by rectal
examination, by ultrasonographic
examination, by endoscopic
examination in female ruminants and in
both sexes of horses, or by radiographic
examination in smaller animals

• Urethral obstruction may also cause
frequent attempts at urination but the
urine flow is greatly restricted, usually
only drops are voided and the
distended bladder can be felt on rectal
examination

used to assess the success of therapy.
Recurrence of the infection is usually due
to failure to eliminate foci of infection in
the accessory glands and in the bladder
wall.

The prognosis in chronic cases is poor
because of the difficulty of completely
eradicating the infection and the common
secondary involvement of the kidney.
Free access to water should be permitted
at all times to insure a free flow of urine.

PARALYSIS OF THE BLADDER

Paralysis of the bladder is uncommon in
large animals. Paralysis usually occurs as a
result of neurological diseases affecting
the lumbosacral spinal cord such as equine
herpes myelopathy and cauda equina
syndrome, and particularly ascending
spinal meningitis in lambs after tail
docking, hi all species, compression of the
lumbar spinal cord by neoplasia (lympho-
sarcoma, melanoma) or infected tissue
(vertebral osteomyelitis) can cause para-
lysis of the bladder. Excessive tension on
the tail, such as with tail ropes or use of
the tail for restraint in cattle, can injure
the cauda equina and cause bladder
paralysis. In horses, spinal cord degener-
ation following consumption of sorghum
can lead to bladder paralysis and posterior

562

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

ataxia. Iatrogenic bladder paralysis occurs
in horses in which there has been
epidural injection of an excessive quantity
of alcohol. Equine protozoal myelo-
encephalitis can cause signs of cauda
equina dysfunction in horses, as does
equine polyneuritis. In some horses,
idiopathic bladder paralysis and overflow
incontinence may occur sporadically in
the absence of other neurological or
systemic signs. 2 When the bladder is
markedly distended from a urinary tract
obstruction, it may take several days after
removal of the obstruction before normal
bladder tone returns.

When bladder paralysis arises from
spinal cord disease, other upper or lower
motor neuron signs are usually present.
Bladder involvement is indicated by
incontinence with constant or inter-
mittent dribbling of urine. Urine flow is
often increased during exercise. The
bladder is enlarged on examination per
rectum and urine can be easily expressed
by manual compression. In horses,
chronic distension of the bladder leads to
accumulation of a sludge of calcium
carbonate crystals. Urine stasis produces
ideal conditions for bacterial growth and
cystitis is a common sequel. Treatment is
supportive and aimed at relieving bladder
distension by regular catheterization and
lavage. During catheterization, care must
be taken to avoid introducing infection.
Manual or pharmacologically induced
emptying of the bladder is incomplete so
there is a constant risk of cystitis.
Pharmacological enhancement of bladder
emptying can sometimes be achieved by
administration of parasympathomimetic
agents such as bethanechol (para-
sympathetic stimulation via the pelvic
nerve stimulates detrusor contraction)
and sympatholytics such as prazosin and
phenoxybenzamine (sympathetic stimu-
lation via the hypogastric nerve causes
detrusor relaxation and internal sphincter
contraction). The administration of anti-
microbial agents as a prophylaxis against
the development of cystitis is advisable.
The prognosis for paralysis associated
with spinal cord disease depends on the
prognosis for the primary disease. Paralysis
in the absence of spinal cord disease has a
poor prognosis.

Cattle ingesting Cistus salvifolius, a
shrub found in the Mediterranean region,
had urinary retention as the primary
clinical sign. 3 Cattle had decreased
appetites and rumen motility, weight loss,
and persistent elevation of the tail head
and difficulty in urination. A greatly
distended urinary bladder was always
detected on palpation per rectum. The
mortality rate in advanced cases was high,
and affected animals have severe cystitis,
pyelonephritis and a marked increase in

bladder wall thickness. No evidence of
neurological injury was present, and it is
likely that urine retention was secondary
to severe cystitis and swelling of the
bladder wall that prevented normal
urination.

REFERENCES

1. Saulez MN et al. J Am Vet Med Assoc 2005;
226:246.

2. Holt PE, Mair TS. Vet Rec 1990; 127:108.

3. Yeruham I et al. Rev Med Vet 2002; 153:627.

RUPTURE OF THE BLADDER
(UROPERITONEUM)

This occurs most commonly in castrated
male ruminants as a sequel to obstruction
of the urethra by calculi. Rare cases are
recorded in cows as a sequel to a difficult
parturition 1 ^ 3 and in mares after normal
parturition, 4 possibly because of com-
pression of a full bladder during foaling. In
cattle, abnormal fetal position during
prolonged dystocia is suspected to obstruct
the urethra and distend the bladder. Sub-
sequent manipulation within the pelvic
canal during correction of the dystocia is
suspected to lead to rupture of a distended
bladder. 3 Uroperitoneum in foals is dis-
cussed in the next section.

After the bladder ruptures, uro-
peritoneum results in a series of abnor-
malities that arise from failure of the
excretory process combined with solute
and fluid redistribution between the
peritoneal fluid and extracellular fluid.
The peritoneal membrane serves as a
semipenneable membrane through which
low-molecular-weight solutes readily
pass. High-molecular-weight compounds
also diffuse across the peritoneal mem-
brane but at a much slower rate. Urine is
usually hypertonic especially in animals
whose water intake is decreased by uremia.
Osmotic pressure from hypertonic urine
promotes movement of extracellular
water into the peritoneal cavity. This move-
ment, combined with reduced intake,
results in clinical dehydration. Urine
usually has a lower concentration of
sodium and chloride and higher concen-
trations of urea, creatinine, potassium, and
phosphate than plasma. Diffusion along
these concentration gradients across the
peritoneal membrane results in a general
pattern of azotemia with hyponatremia,
hypochioremia, hyperkalemia, and hyper-
phosphatemia. 5 There are minor differ-
ences between species in these general
biochemical changes. In particular, the
blood concentration of urea rises much
more slowly in ruminants than in horses,
and hyperkalemia is not as common in
ruminants as in horses because excessive
potassium can be excreted in the saliva
and therefore eliminated in the feces.

Bladder rupture leads to gradual
development of ascites from uro-
peritoneum, ruminal stasis, constipation,
and depression. In cattle, uremia may take
1-2 weeks to develop to the point where
euthanasia is necessary. The degree of
uremia between individual patients can
be highly variable. With therapy, the
survival rate of steers in one study was
49%. The best predictor of survival among
clinical pathology tests was the serum
phosphate concentration: all animals with
levels greater than 9.0 mg/dL (2.9 mmol/L)
died. 6 In mature horses, clinical signs of
depression, anorexia, colic, abdominal
distension, and uremia develop within
1-2 days following rupture.

In cases of ascites or when urinary tract
obstruction is evident, it is important in
considering treatment and prognosis
to determine whether the bladder has
ruptured. The urea and creatinine concen-
trations in plasma can be compared to the
values in the peritoneal fluid. The ratio of
urea in peritoneal fluid to that in serum is
a good guide in the early stages, but after
40 hours the ratio of the peritoneal to
serum creatinine greater than 2:1 is diag-
nostic of uroperitoneum. 7 Treatment is
surgical with a goal of bladder repair. To
avoid the costs of laparotomy in feedlot
animals, a urethrostomy is created or an
indwelling catheter is placed and the
rupture is allowed to repair itself.

REFERENCES

1. Smith JAet al. CornellVet 1983; 73:3.

2. LaxT, Drew RA. Vet Rec 1974; 94:615.

3. Carr EA et al. J Am Vet Med Assoc 1993; 202:631.

4. Nyrop KA et al. Compend Contin Educ Pract\fet
1984; 6:S510.

5. Sockett DC et al. CornellVet 1986; 76:198.

6. DoneckerJM, Bellamy JEC. Can Vet J 1982; 23:355.

7. Genetzky RM, Hagemoser WA. Can Vet J 1985;
26:391.

UROPERITONEUM IN FOALS
(URO ABDOMEN)

ETIOLOGY

Uroperitoneum, the accumulation of
urine in the peritoneal cavity, occurs in
foals as a result of a variety of situations:
n Congenital (i.e. present at birth)
rupture of the bladder
° Bladder rupture associated with sepsis
° Rupture of the urachus, often
secondary to sepsis
0 Avulsion of the bladder from its
urachal attachment, presumably as a
result of trauma or strenuous exercise 1
° Rarely, as embryological failure of the
halves of the bladder to unite
(schistocystitis) 1
° Ureteral defects.

The etiology of congenital rupture is
unclear, but its association with birth,
markedly greater prevalence in colts, and

Diseases of the bladder, ureters and urethra

5l

the traumatic nature of the lesion suggests
that it occurs during birth as a result of
compression of a distended bladder.
Intra-abdominal pressures of the mare
during parturition are large, and these
compressive forces are experienced by
the foal during phase 2 of parturition.
Compression of a distended bladder can
cause rupture. The greater prevalence in
colts is speculated to be a result of the
greater resistance to bladder emptying
conferred by the longer urethra of male
foals.

Rupture of the bladder occurs as a
distinct entity in septic foals. The under-
lying reason for bladder rupture is unclear
but is usually related to infection, inflam-
mation and necrosis of the lower urinary
tract. 2,3 This cause of uroperitoneum in
foals is increasingly recognized as the most
common, especially amongst hospitalized
foals.

Rupture of the urachus occurs in septic
foals. It is probably of similar etiology to
rupture of the bladder in septic foals. The
urachus of affected foals almost always
has infection, inflammation and necrosis
evident on histological examination.

Avulsion of the bladder from its urachal
attachments is presumed to occur as a
result of trauma, such as might occur with
vigorous exercise. The possibility also
exists that there is an underlying defect
in affected foals, such as urachitis or
omphalitis.

Embryological failure of the halves of
the bladder to unite during organogenesis
has been reported anecdotally and in case
reports, although adequate documentation
of its occurrence is lacking. 1,2 This defect
would be a true congenital anomaly,
arising during gestation.

Ureteral defects are an uncommon
cause of uroperitoneum in foals. The
defects appear to be congenital and more
common in fillies. Both ureters can be
affected. 4

The relative frequency of these diseases
is that approximately 20% of foals with
uroperitoneum do so because of urachal
rupture, approximately 30% because of
rupture of the dorsal bladder wall, 18%
because of rupture of the ventral bladder
wall and the remainder because of mul-
tiple defects involving combinations of
the urachus, dorsal and ventral bladder. 3,5

Uroperitoneum also occurs in calves
as a consequence of umbilical infection. 6

EPIDEMIOLOGY

The epidemiology of uroperitoneum is
not well documented. The incidence in
foals appears to be approximately 0.2%,
although this estimate is based on a study
conducted 50 years ago. 7 The prevalence
in hospitalized foals is 2. 5%. 3 Male foals
are at greater risk than are females for

congenital rupture, more than 80% of
foals with this disease being colts. 5,8 In
contrast, there is no sex predilection for
development of uroperitoneum in foals
with sepsis. 2,3 The age at diagnosis ranges
from 2 to more than 60 days, with most
cases recognized within the first 2 weeks
of life. The average age at diagnosis is
approximately 4-5 days, although the age
at presentation depends on the under-
lying cause. Foals with congenital rupture
of the bladder or ureteral defects are
usually recognized at about 3-5 days of
age, while foals with uroperitoneum
secondary to sepsis are usually older
(5-9 days of age, but up to 60 days). 2,3,5
The prognosis for survival for foals with
uroperitoneum depends on the under-
lying cause and availability of appropriate
treatment. Foals with congenital rupture
of the bladder that are recognized and
treated in a timely fashion have an
excellent prognosis (> 80%) for survival,
whereas those with uroperitoneum
secondary to sepsis have a more guarded
prognosis (50-60%) because of the

• 2 3 5

sepsis. '

PATHOPHYSIOLOGY

The pathophysiology of uroperitoneum is
that of postrenal azotemia. Regardless of
the underlying cause of the uroperitoneum,
accumulation of urine within the peritoneal
cavity results in substantial electrolyte,
acid-base and cardiovascular effects in
affected foals. The basic principle is that
affected foals are unable to excrete meta-
bolic waste products that are normally
excreted in the urine, and are unable to
maintain water and electrolyte balance.
Young foals derive almost all of their
nutritional needs, including water, from
mare's milk. Mare's milk has a low sodium
concentration (approximately 12mEq/L)
and a high potassium concentration
(25 mEq/L) compared to serum, and a dry
matter content of 11%. 9 Therefore, foals
ingest a diet that contains a large quantity
of water and potassium but little sodium.
Consequently, the urine of foals contains
little sodium (7 mmol/L) and has a low
osmolality (100 mosmol/kg). 10,11 Leakage
of urine into the peritoneum, a semi-
permeable membrane, results in con-
siderable fluid and electrolyte shifts.
Partial equilibration of water and electro-
lytes across the peritoneal membrane
results from diffusion of water from the
peritoneum with resultant dilution of
serum and reductions in serum sodium
and chloride concentrations. The low
concentration of sodium in uriniferous
peritoneal fluid favors diffusion of sodium
from the blood into the peritoneal fluid,
with the result that there is a reduction in
intravascular sodium content and a con-
sequent reduction in effective circulating

volume. Excretion of relatively large
quantities of potassium in urine and
accumulation of potassium-rich fluid
in the peritoneum allows diffusion of
potassium into the blood and an increase
in plasma potassium concentration.

The peritoneal membrane is per-
meable to creatinine and urea, as evidenced
by the efficacy of peritoneal lavage in
treatment of renal failure in a variety of
species, including horses. Consequently,
serum creatinine and urea concentrations
are higher in foals with uroperitoneum
than in unaffected foals. However,
equilibration of concentrations of these
compounds is not complete and peritoneal
fluid concentrations of urea, creatinine,
and potassium are higher than those in
serum.

Foals with uroperitoneum have compro-
mised circulatory function because of
reduced effective circulating plasma
(blood) volume, despite having an
increased total body water content.
Circulatory function is further impaired
by a combination of the hyperkalemia,
abdominal distension and accumulation
of fluid in the pleural space, with the
result that foals with uroperitoneum can
have signs of mild to moderate circulatory
compromise.

Hyperkalemia and acidosis associated
with uroperitoneum predispose affected
foals to development of malignant cardiac
rhythm, including ventricular tachycardia
and fibrillation. This abnormal cardiac
rhythm is a common cause of death of
affected foals.

CLINICAL SIGNS

Clinical signs in foals with uroperitoneum
depend in part on the underlying disease.
Foals with congenital rupture or mild
sepsis have progressive signs of lethargy,
decreased appetite, mild abdominal dis-
comfort, and abdominal distension. These
signs usually first become apparent at
2-4 days of age.Thesefoals do not typically
have a fever. As the disease progresses
and the amount of urine accumulated in
the peritoneum increases, foals have
progressive distension of the abdomen
and make frequent attempts to urinate.
Foals attempting to urinate ventroflex the
back (mild lordosis) and have a wide-
based stance, in contrast with foals with
tenesmus, which characteristically have a
narrow-based stance (all four limbs being
under the body) and arch their back.
Affected foals sometimes produce small
quantities of urine, but usually there is
lack of urination. Abdominal distension is
most apparent when the foal is standing.
In moderate to severe cases there is a
readily appreciable fluid wave on ballot-
ment of the abdomen. As abdominal
distension increases the foal's tidal

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

volume is impaired and breathing becomes
rapid and shallow. The extremities become
cool as cardiovascular function is impaired.

Ventral edema and preputial swelling
occur in some foals. Foals with a urachal
rupture close to or within the abdominal
wall or in the subcutaneous tissues will
have subcutaneous accumulation of urine
(which can be mistaken for ventral
edema).

Foals with uroperitoneum secondary
to sepsis usually have signs of sepsis as
the initial and predominant sign of
disease. These signs can range from mild
fever and enlargement of the umbilical
structures to septic shock and its attend-
ant abnormalities. Initial signs of uro-
peritoneum in these foals are easily
overlooked. As the disease develops these
foals have progressive abdominal dis-
tension. Signs of cardiovascular dysfunction
can be incorrectly attributed to worsening
of sepsis. It is important when treating
septic foals to maintain a high index of
suspicion and constant vigilance for
development of uroperitoneum.

Infusion of contrast agents, such as
methylene blue or fluorescein, into the
bladder with subsequent detection of
these compounds in the peritoneal fluid
has been used to diagnose uroperitoneum.
However, use of this method of diagnosis
is now obsolete except in those instances
in which ultrasonographic examination of
the foal is not possible.

Imaging

Ultrasonographic examination of the
abdomen of foals has simplified detection
of uroperitoneum in foals and is the
preferred imaging modality for detec-
tion of excessive peritoneal fluid in
foals. The ultrasound examination is best
performed with a 5 MHz sector scanner,
with more detailed examination of the
umbilical structures performed using a
7 MHz linear or sector scanner. However,
diagnosis of the presence of excessive
peritoneal fluid can be achieved using a
7 MHz linear scanner, such as is routinely
used for examination of the mare repro-
ductive tract. The examination is performed
transcutaneously.

Ultrasonography reveals the presence
of an excessive quantity of fluid that is
minimally echogenic. Intestine, mesentery,
and omentum are readily visualized
floating in this fluid. The presence of a
large quantity of minimally echogenic
fluid in the peritoneum of foals is
very specific (effectively 100%) for uro-
peritoneum. The procedure is also sensi-
tive, especially if performed repeatedly to
detect changes in the amount of fluid,
especially when the initial examination is
equivocal. The umbilical structures should
be examined closely and the urachus

tracked to the bladder. Frequently a defect
in the urachus or umbilicus is identified. 3
The thorax of affected foals should also be
examined, as foals with large quantities of
urine in the peritoneum often have a
substantial accumulation of pleural fluid.
This can be important when considering
anesthesia in these foals.

Radiographic examination of foals
with suspected uroperitoneum is rarely
performed because of the utility of ultra-
sonographic examination in this disease.
Plain abdominal radiography is of limited
usefulness in the detection of uro-
peritoneum or localizing the source of
urine. Positive contrast cystography using a
10% solution of iohexol or similar water-
soluble contrast agent administered into
the bladder through a Foley catheter can be
useful in detection of leaks, especially small
leaks that cannot be visualized on
ultrasonographic examination. Care should
be taken to insure that the bladder is
sufficiently distended to insure that any
leak is visualized. Use of barium contrast
medium or negative-contrast cystography
(infusion of air into the bladder) are
contraindicated. Intravenous pyelography
is of very limited usefulness in the detec-
tion of ureteral defects because of the
difficulty in localizing the site of the leak.

Electrocardiographic examination
can reveal cardiac arrest, atrioventricular
block, presumed intraventricular block,
ventricular premature complexes, ven-
tricular tachycardia and ventricular
fibrillation. 5,8 These abnormalities are
most likely to occur in foals that are
hyperkalemic at the time of induction of
anesthesia.

CLINICAL PATHOLOGY

Foals with uncomplicated uroperitoneum
have hyponatremia, hypochloremia,
hypobicarbonatemia (metabolic acidosis),
acidemia, hyperkalemia, and azotemia.
Severely affected foals can be profoundly
hyponatremic (< 110 mEq/L) and hyper-
kalemic (> 7 mEq/L). 2-5 Serum creatinine
and urea nitrogen concentrations are
elevated. When interpreting serum urea
nitrogen concentrations in foals it should
be borne in mind that the urea concen-
tration in normal foals is much lower than
in adults (see Table 3.6).

Diagnosis based on serum electrolyte
abnormalities is confounded in hospitalized
foals that are being treated with intravenous
fluids. 2-3 Administration of fluids prevents
the development of hyponatremia and
hypochloremia in septic foals that develop
uroperitoneum during the course of their
disease. However, fluid administration
does not prevent the increases in serum
creatinine or urea nitrogen concentration. 2

Hematological abnormalities reflect
any underlying sepsis.

Analysis of peritoneal fluid reveals that
it has a low specific gravity (< 1.010), low
total protein concentration (« 2.5 g/dL,
25 g/L) and low white cell count
(<1000 cells/pL, 1 x 10 9 cells/L). It can
have a uriniferous odor, but this is not a
reliable diagnostic sign. Peritoneal fluid
from foals with uroperitoneum has elev-
ated concentrations of creatinine (usually
twice that in a contemporaneous serum
sample), urea nitrogen (twice that of
serum) and potassium. 5 Microscopic
examination of the fluid can reveal
calcium carbonate crystals, the presence
of which is diagnostic for urine.

NECROPSY FINDINGS

Necropsy examination confirms the pre-
sence of uroperitoneum and the struc-
tural defect allowing leakage of urine into
the abdomen. The defect can have signs
of healing, which can make it readily
confused with a malformation, because
affected foals can survive for days after
the rupture occurs - sufficient time for
partial healing of the defect.

DIFFERENTIAL DIAGNOSIS

Demonstration of an excessive quantity of
poorly echogenic fluid in the abdomen of a
foal that is passing little if any urine and
that has hyponatremia and hyperkalemia is
diagnostic of uroabdomen. Confirmation
of the diagnosis can be achieved by
measurement of creatinine concentration
in the peritoneal fluid. Ultrasonographic
examination greatly facilitates the
diagnosis.

The principal differential diagnoses for
azotemia in foals are uroperitoneum and
renal disease. Primary renal disease in
foals can cause hyponatremia,
hyperkalemia, and azotemia, but there is
no accumulation of fluid in the
peritoneum. Additionally, in primary renal
disease there are abnormalities in urine
composition (presence of blood, protein,
leukocytes, and casts). Hyponatremia and
hyperkalemia can occur in foals with
enterocolitis, but the other clinical signs
are diagnostic of this disease. Addison's
disease (mineralocorticoid deficiency) does
occur in foals but is rare, and there is no
accumulation of fluid in the abdomen .' 2

TREATMENT

Definitive treatment of uroperitoneum in
foals is surgical repair of the defect.
However, there is no need for surgery on
an emergency basis. Rather, care should
be taken to correct life-threatening
electrolyte and fluid abnormalities before
the foal is subjected to anesthesia. Prin-
ciples of medical treatment are prevention
of potentially lethal cardiac arrhythmia,
correction of electrolyte, fluid and acid-
base abnormalities and relief of abdominal
distension.

Diseases of the bladder, ureters and urethra

565

Potentially life-threatening electro-
lyte abnormalities, especially hyper-
kalemia, should be corrected urgently
and before any attempted surgical
correction of the anatomical defect.

Correction of fluid and electrolyte
abnormalities is best achieved by draining
the abdomen and insuring continued
voiding of urine while administering
isotonic fluids intravenously. Because the
foal has normal kidney function, draining
urine from the abdomen allows the foal to
restore normal serum electrolyte concen-
trations and fluid balance provided that
the foal is allowed to nurse and/or is
administered parenteral fluids.

Peritoneal drainage is achieved by
placement of a catheter into the abdo-
men. The catheter should be placed with
a view to it remaining in place until the
electrolyte abnormalities have been
corrected and the foal is a suitable can-
didate for surgical repair of the anatomical
defect. An ideal catheter is a Foley
balloon-tipped catheter placed into the
abdomen through a small (5 mm) incision
in the skin and external abdominal wall.
The catheter should be placed in the
inguinal region and to one side of the
linear alba, so as to avoid injury and
contamination of a future surgical site and
to minimize the chances of the catheter
being plugged by omentum. The catheter
is inserted under local anesthesia and the
balloon is inflated to secure the catheter
in the abdomen. The catheter can be
further secured by a suture. Sedation or
tranquilization should be avoided in foals
at risk of cardiac or respiratory distress
because of the electrolyte abnormalities.
Urine should be allowed to drain from the
catheter into a closed collection system
that minimizes the chances of ascending
infection of the peritoneum.

Hyperkalemia is usually readily
corrected by peritoneal drainage and
administration of potassium -free fluid,
such as 0.9% sodium chloride. Serum
potassium concentration declines quickly
when effective peritoneal drainage is
obtained and serum potassium concen-
trations can normalize in 8-12 hours. If
emergency management of hyperkalemia
is required administration of 5% dextrose
either alone or, if hyponatremia is also
present, in 0.9% sodium chloride, is
effective in reducing serum potassium
concentration. Sodium bicarbonate
(1-3 mEq/kg BW, intravenously) will also
decrease serum potassium concentration.
Calcium gluconate antagonizes the effect
of hyperkalemia on cardiac function and
is useful in the treatment of hyperkalemic
arrhythmias. The serum potassium con-
centration should be less than 5.5 mEq/L
before the foal is anesthetized. Mare's
milk, which is rich in potassium, should

be withheld until the serum potassium
concentration is below the required level.

Hyponatremia is resolved by drainage
of the peritoneum and administration of
0.9-1. 8% sodium chloride intravenously.
Serum sodium concentration, especially if
markedly low, should be corrected slowly
to prevent the development of hypo-
natremic encephalopathy. Serum sodium
concentrations should be increased by
approximately 1 (mEq/L)/h.

Affected foals should be administered
broad-spectrum antibiotics because of the
risk of peritonitis and because many foals
with uroperitoneum have sepsis. The
immune status of young foals should be
examined by measurement of serum IgG
concentration and, if it is less than
800 mg/dL (8 g/L), the foal should receive
20-40 mL/kg of plasma.

Correction of the defect in the bladder
or urachus is surgical. Nonsurgical
management has been described in a foal
in which a Foley catheter was inserted in
the bladder and left in place for 5 days.
The bladder was constantly drained of
urine and this allowed the tear to heal. 13
This technique offers an alternative to
surgical repair of bladder rupture. How-
ever, surgical repair is definitive and is the
recommended method of treatment.

Subcutaneous rupture of the urachus
can similarly be treated by placement of a
Foley catheter through the patent urachus
and into the bladder. The defect in the
urachus is then allowed to heal and the
catheter is removed in 3-6 days.

PREVENTION AND CONTROL

There are no recognized means of pre-
venting or controlling this disease. Mini-
mizing the risk of foals developing septic
disease is expected to reduce the incidence
of uroperitoneum secondary to sepsis.

REFERENCES

1. Hardy J. Equine Vet Educ 1998; 10:21.

2. Dunkel B et al. J Vet Intern Med 2005; 19:889.

3. Kablack KA et al. Equine Vet J 2000; 32:505.

4. Divers TJ et al. J Am Vet Med Assoc 1988; 192:384.

5. Richardson DW, Kohn CW. J Am Vet Med Assoc
1983; 182:267.

6. Bell GJ et al.Vet Rec 2004; 154:508.

7. Bain AM. AustVet J 1954; 30:9.

8. Hackett RP. Compend Contin Educ Pract Vet
1984; 6:S488.

9. UllreyDE et al. J Anim Sci 1966; 25:217.

10. Pipkin FB et al. J Reprod Fertil Suppl 1991; 44:736.

11. Brewer BD ct al. J Vet Intern Med 1991; 5.28.

12. Couetill LL, Hoffman AM. J Am Vet Med Assoc
1998; 212:1594.

13. Lavoie JP, Harnagel SH. 1988; J Am Vet Med
Assoc 192:1577.

UROLITHIASIS IN RUMINANTS

Urolithiasis is common as a subclinical
disorder among ruminants raised in
management systems where the ration is
composed primarily of grain or where
animals graze certain types of pasture. In

these situations, 40-60% of animals
may form calculi in their urinary tract.
Urolithiasis becomes an important clinical
disease of castrated male ruminants when
calculi cause urinary tract obstruction,
usually obstruction of the urethra.
Urethral obstruction is characterized,
clinically by complete retention of urine,
frequent unsuccessful attempts to urinate
and distension of the bladder. Urethral
perforation and rupture of the bladder
can be sequelae. Mortality is high in cases
of urethral obstruction and treatment is
surgical. As a result, prevention is import-
ant to limit losses from urolithiasis.

ETIOLOGY

Urinary calculi, or uroliths, form when
inorganic and organic urinary solutes are
precipitated out of solution. The pre-
cipitates occur as crystals or as amorphous
'deposits'. Calculi form over a long period
by a gradual accumulation of precipitate
around a nidus. An organic matrix is an
integral part of most types of calculus.
Several factors affect the rate of urolith
formation, including conditions that
affect the concentration of specific solutes
in urine, the ease with which solutes are
precipitated out of solution, the provision
of a nidus and the tendency to concretion
of precipitates. These are presented under
Epidemiology. Factors that contribute to
the clinical syndrome of obstructive
urolithiasis are dealt with separately.

EPIDEMIOLOGY
Species affected

Urolithiasis occurs in all ruminant species
but is of greatest economic importance in
feeder steers and wethers (castrated
lambs) being fed heavy concentrate
rations, and animals on range pasture in
particular problem areas. These range
areas are associated with the presence of
pasture plants containing large quantities
of oxalate, estrogens, or silica. When cattle
graze pasture containing plants with high
levels of silica, uroliths occur in animals of
all ages and sexes. 1 The prevalence of
uroliths is about the same in cows,
heifers, bulls, and steers grazing on the
same pasture and they may even occur in
newborn calves. Females and bulls usually
pass the calculi and obstructive urolithiasis
is primarily a problem in castrated male
animals.

Obstructive urolithiasis is the most
common urinary tract disease in breeding
rams and goats. 2

There are three main groups of factors
that contribute to urolithiasis:

® Those that favor the development of

a nidus about which precipitation

and concretion can occur
° Those that facilitate precipitation of

solutes on to the nidus

566

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

® Those that favor concretion by

cementing precipitated salts to the

developing calculus.

Nidus formation

A nidus favors the deposition of crystals
about itself. A nidus may be a group of
desquamated epithelial cells or necrotic
tissue that may be formed as a result in
occasional cases from local infection in
the urinary tract. When large numbers of
animals are affected it is probable that
some other factor, such as a deficiency
of vitamin A or the administration of
estrogens, is the cause of excessive
epithelial desquamation. When stilbestrol
was used as a growth promoter, mortality
rates of 20% due to obstructive urolithiasis
were recorded in wethers receiving
stilbestrol implants compared with no
mortalities in a control group. Diets low in
vitamin A have been suspected as a cause
of urolithiasis but vitamin A deficiency
does not appear to be a major causative
factor.

Precipitation of solutes

Urine is a highly saturated solution
containing a large number of solutes,
many of them in higher concentrations
than their individual solubilities permit in
a simple solution. Several factors may
explain why solutes remain in solution.
Probably the most important factor in
preventing precipitation is the presence of
protective colloids that convert urine
into a gel. These colloids are efficient up
to a point, but their capacity to maintain
the solution may be overcome by abnor-
malities in one or more of a number of
other factors. Even in normal animals,
crystals of a number of solutes may be
present in the urine intermittently and
urine must be considered to be an
unstable solution. The physical character-
istics of urine, the amount of solute
presented to the kidney for excretion and
the balance between water and solute in
urine all influence the ease of calculus
formation. In most cases these factors can
also be influenced by management
practices.

The pH of urine affects the solubility
of some solutes, mixed phosphate and
carbonate calculi being more readily
formed in an alkaline than an acid
medium.

Ammonium chloride or phosphoric
acid added to the rations of steers
increases the acidity of the urine and
reduces the incidence of calculi. The
mechanism is uncertain but is probably
related to the effect of pH on the stability
of the urinary colloids or the effect of
diuresis. In contrast, variations in pH
between 1 and 8 have little influence on
the solubility of silicic acid, the form of
silica excreted in the urine of ruminants.

As a result, dietary supplementation with
ammonium chloride does not consistently
prevent the formation of siliceous calculi. 3

The amount of solute presented to
the kidney for excretion is influenced
by the diet. Some pasture plants can
contain up to 6% silica. Although rumi-
nants grazing on these plants absorb only
a small portion of the ingested silica, the
kidney is the major route of excretion of
absorbed silicic acid. The urine of these
animals often becomes supersaturated
with silicic acid, which promotes the
polymerization or precipitation of the
silicic acid and calculus formation.

Feeding sodium chloride prevents
the formation of silica calculi by
reducing the concentration of silicic acid
in the urine and maintaining it below the
saturation concentration. An excessive
intake of minerals may occur from highly
mineralized artesian water, or from diets
containing high concentrations, parti-
cularly of phosphates in heavy-concentrate
diets. Sheep with a high dietary intake of
phosphorus have an increased concen-
tration of phosphorus in their urine and
an increased development of calculi. In
cattle, sediment begins to appear in urine
when concentrates reach 1.5% of the
body weight, and urolithiasis formation
begins when concentrates have been fed
for 2 months at the rate of 2.5% of the
animal's body weight.

Diets high in magnesium such as
some calf milk replacers have also been
associated with an increasing incidence of
obstructive urolithiasis. 4 Supplemental
calcium in the diet helps prevent calculus
fonnation when phosphate or magnesium 4
intake is high.

Ingestion of plants with a high
oxalic acid content can be a risk factor for
formation of calcium carbonate calculi in
sheep. Although dietary excesses contri-
bute to certain types of urolithiasis,
calculus formation can rarely be recreated
experimentally by simple overfeeding.
The process of formation of urinary calculi
is more complex than a simple dietary
excess. However, recognition of associ-
ations between diet and some types of
urolithiasis has been useful in developing
preventive strategies.

Feeding practices can influence the
function of the kidney and may contribute
to calculus formation. In sheep fed grain
in a few large meals, there is a marked
reduction in urine volume and a marked
increase in urine concentration and
calcium excretion at the time of feeding.
These short-term changes in urine compo-
sition may be factors in the development of
uroliths.

The concentration of urine is an
important determinant of the concen-
tration of individual solutes in the urine.

Although it is difficult to induce urolithiasis
by restricting access to water, concentrated
urine is a risk factor for calculus formation.
Animals can be forced to produce con-
centrated urine because of lack of easy
access to water, a particular problem in
pastured animals, lack of familiarity with
water delivery systems and poor quality
of available water. Water deprivation can
be exacerbated by heavy fluid loss by
sweating in hot, arid climates.

Factors favoring concretion

Most calculi, and siliceous calculi in
particular, are composed of organic
matter as well as minerals. This organic
component is mucoprotein, particularly
its mucopolysaccharide fraction. It acts as
a cementing agent and favors the
formation of calculi when precipitates are
present. The mucoprotein content of
urine of feeder steers and lambs is
increased by heavy concentrate-low
roughage rations, by the feeding of
pelleted rations, even more so by
implantation with diethylstilbestrol and,
combined with a high dietary intake of
phosphate, may be an important cause of
urolithiasis in this class of livestock. These
high levels of mucoprotein in urine may
be the result of a rapid turnover of
supporting tissues in animals that are
making rapid gains in weight.

Miscellaneous factors in the
development of urolithiasis

Stasis of urine favors precipitation of
solutes, probably by virtue of the infection
that commonly follows, providing cellular
material for a nidus. Certain feeds,
including cottonseed meal and milo
sorghum, are credited with causing more
urolithiasis than other feeds. Alfalfa is
in an indeterminate position: by some
observers it is thought to cause the
formation of calculi, by others to be a
valuable aid in preventing their formation.
Pelleting appears to increase calculi
formation if the ration already has this
tendency.

Attempts to produce urolithiasis
experimentally by varying any of the
above factors are usually unsuccessful
and natural cases most probably occur as
a result of the interaction of several
factors. In feedlots a combination of high
mineral feeding and a high level of
mucoprotein in the urine associated with
rapid growth are probably the important
factors in most instances. In range
animals a high intake of mineralized
water, or oxalate or silica in plants, are
most commonly associated with a high
incidence of urinary calculi, but again
other predisposing factors, including
deprivation or excessive loss of water,
may contribute to the development of the
disease. Limited water intake at weaning

Diseases of the bladder, ureters and urethra

and in very cold weather may also be a
contributory factor.

Composition of calculi

The chemical composition of urethral
calculi varies and appears to depend
largely on the dietary intake of individual
elements. In semi-arid areas such as the
great plains of North America 1 and parts
of Australia, the dominant pasture grasses
have a high content of silica. Cattle and
sheep grazing these pastures have a high
prevalence of siliceous calculi. Calculi
containing calcium carbonate are more
common in animals on clover-rich pasture,
or when oxalate-containing plants abound.
Calcium, ammonium, and magnesium
carbonate are also common constituents
of calculi in cattle and sheep at pasture.

Sheep and steers in feedlots usually
have calculi composed of struvite, mag-
nesium ammonium phosphate. High
concentrations of magnesium in feedlot
rations also cause a high prevalence of
magnesium ammonium phosphate calculi
in lambs. 5 Experimental feeding of a
ration with a high magnesium content
increases the prevalence of calcium
apatite urolithiasis in calves and can be
prevented by supplementary feeding with
calcium. 4 Oxalate calculi are extremely
rare in ruminants but have been observed
in goats and induced experimentally in
feedlot cattle. Xanthine calculi in sheep
are recorded in some areas in New
Zealand where pasture is poor.

Estrogenic subterranean clover can
cause urinary tract obstruction in wethers in
a number of ways. Soft, moist, yellow calculi
containing 2-benzocoumarins, isoflavones
and indigotin-indirubin have been
observed. Calculi or unfonned sediments of
benzocoumarins (urolithins) and 4 '- 0 -
methylequol, either singly or in various
combinations with equol, formonentin,
biochanin A, indigotin and indirubin, also
occur. Obstruction is promoted by
estrogenic stimulation of squamous
metaplasia of the urethral epithelium,
accessoiy sex glandular enlargement and !
mucus secretion. Fhstures containing these ■
plants are also reputed to cause urinary j
obstruction by calculi consisting of calcium j
carbonate. Feedlot lambs receiving a j
supplement of stilbestrol (1 mg/kg of feed |
or 2 mg per lamb daily) developed urethral
obstruction believed to be caused primarily
by plugs of mucoprotein.The accessoiy sex
glands were also enlarged.

Risk factors for obstructive
urolithiasis

The risk factors important in the for-
mation of urinary calculi are also import-
ant in the development of obstructive
urolithiasis.

The size of individual calculi and
the amount of calculus material are

both important in the development of
urethral obstruction. Often the obstruc-
tion is caused by one stone, although an
aggregation of many small struvite calculi
often causes obstruction in sheep fed
high-concentrate rations.

Once calculi form, the most important
factor contributing to the occurrence of
obstruction is the diameter of the urethra.
Wethers (castrated lambs) and steers
(castrated cattle) are most commonly
affected because of the relatively small
diameter of the urethra in these animals.
Castration has a significant impact on the
diameter of the urethra in steers. When
the urethral diameter of late castrates
(6 months old) was compared to early
castrates (2 months), it was found to be
8% larger and would be able to expel a
calculus that was 13% larger than a
calculus passed by early castrates. 6 Bulls
can usually pass calculi that are 44%
larger than those that could be passed by
an early castrated steer.

Occurrence

Urethral obstruction may occur at any
site but is most common at the sigmoid
flexure in steers and in the vermiform
appendage or at the sigmoid flexure in
wethers or rams, all sites where the
urethra narrows. Urolithiasis is as com-
mon in females as in males, but obstruc-
tion rarely if ever occurs because of
the shortness and large diameter of the
urethra. Repeated attacks of obstructive
urolithiasis are not uncommon in wethers
and steers and at necropsy up to 200
calculi may be found in various parts of
the tract of one animal. However, generally,
a single calculus causes obstruction in
cattle whereas multiple calculi are com-
mon in sheep.

In North America obstructive
urolithiasis due to siliceous calculi is most
common in beef feeder cattle during the
fall and winter months. The calves are
weaned at 6-8 months and moved from
pasture to a feedlot where they are fed
roughage and grain. The incidence of
obstructive urolithiasis is highest during
the early part of the feeding period and
during cold weather, when the consump-
tion of water may be decreased.

Although the occurrence of obstructive
S urolithiasis is usually sporadic, with cases
1 occurring at irregular intervals in a group
of animals, outbreaks may occur affecting
: a large number of animals in a short time,
j In outbreaks it is probable that factors are
I present that favor the development
| of calculi, as well as the development of
| obstruction. For example, multiple cases of
i obstructive urolithiasis can occur in lambs
j within a few weeks of introducing a
concentrated ration. Obstructive urolithiasis
increases in occurrence with age but has

occurred in lambs as young as 1 month
of age.

PATHOGENESIS

Urinary calculi are commonly observed at
necropsy in normal animals, and in many
appear to cause little or no harm. Calculi
may be present in kidneys, ureters,
bladder, and urethra. In a few animals
pyelonephritis, cystitis, and urethral
obstruction may occur. Obstruction of
one ureter may cause unilateral hydro-
nephrosis, with compensation by the
contralateral kidney. The major clinical
manifestation of urolithiasis is urethral
obstruction, particularly in wethers and
steers. This difference between urolithiasis
and obstructive urolithiasis is an import-
ant one. Simple urolithiasis has relatively
little importance but obstructive urolithiasis
is a fatal disease unless the obstruction
is relieved. Rupture of the urethra or
bladder occurs within 2-3 days if the
obstruction is not relieved and the animal
dies of uremia or secondary bacterial
infection. Rupture of the bladder is more
likely to occur with a spherical, smooth
calculus that causes complete obstruction
of the urethra. Rupture of the urethra is
more common with irregularly shaped
stones that cause partial obstruction and
pressure necrosis of the urethral wall.

CLINICAL FINDINGS

Calculi in the renal pelvis or ureters are
not usually diagnosed antemortem
although obstruction of a ureter may be
detectable on rectal examination, especially
if it is accompanied by hydronephrosis.
Occasionally the exit from the renal pelvis
is blocked and the acute distension that
results may cause acute pain, accompanied
by stiffness of the gait and pain on pres-
sure over the loins. Calculi in the bladder
may cause cystitis and are manifested by
signs of that disease.

Obstruction of the urethra by a
calculus

! This is a common occurrence in steers and
| wethers and causes a characteristic
j syndrome of abdominal pain with kicking
I at the belly, treading with the hind feet and
j swishing of the tail. Repeated twitching of
j the penis, sufficient to shake the prepuce, is
often observed, and the animal may make
‘ strenuous efforts to urinate, accompanied
j by straining, grunting and grating of the
! teeth, but these result in the passage of only
I a few drops of bloodstained urine. A heavy
j precipitate of crystals is often visible on the
j preputial hairs or on the inside of the
j thighs. Some animals with urethral obstruc-
' tion will have a dry prepuce because of the
1 absence of urination, although this sign is
; not specific for urolithiasis.

568

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

The passage of a fle>«ble catheter up
the urethra, after relaxing the penis
by lumbosacral epidural anesthesia, by
pudendal nerve block or by administering
an ataractic drug, may make it possible to
locate the site of obstructions that are
anterior to the sigmoid flexure. However,
catheterization of the urethra from the
glans penis to the bladder is almost
impossible in cattle and ruminants
because of the urethral diverticulum with
its valve. 7 A precurved coronary catheter
has been used to catheterize the bladder
of calves and goats 8 but requires fluoro-
scopic guidance.

Cattle with incomplete obstruction -
'dribblers' - will pass small amounts of
bloodstained urine frequently. Occasion-
ally a small stream of urine will be voided
followed by a complete blockage. This
confuses the diagnosis. In these the
calculus is triangular in shape and allows
small amounts of urine to move past the
obstruction at irregular intervals. How-
ever, these are rare.

The entire length of the penis must be
palpated for evidence of a painful swell-
ing from the preputial orifice to the
scrotum, above the scrotum to locate
the sigmoid flexure and proximally up the
perineum as far as possible.

In rams, bucks, and wethers the
urethral process of the exteriorized
penis must be examined for enlargement
and the presence of multiple calculi.
Extrusion of the penis is difficult in
prepubertal sheep and goats because of
the presence of an attachment from the
prepuce to the glans penis; loss of this
attachment is mediated by testosterone
and is usually complete by the onset of
puberty/’ although separation may not
occur in castrated animals. 10 Penile extru-
sion is facilitated by xylazine sedation and
positioning the animals with lumbosacral
flexion. Abnormal urethral processes
should be amputated and in many
animals grit is detected during urethral
transection.

On rectal examination, when the size
of the animal is appropriate, the urethra
and bladder are palpably distended and
the urethra is painful and pulsates on
manipulation.

In rams with obstructive urolithiasis,
sudden depression, inappetence, stamping
the feet, tail swishing, kicking at the
abdomen, bruxism, anuria or the passage of
only a few drops of urine are common.
Clinical examination must include inspec-
tion of the ventral abdomen for edema,
inspection and palpation of the preputial
orifice for crystals, palpation of the penis in
the area of the sigmoid flexure, and
inspection and palpation of the urethral
process (vermiform appendage) of the
exteriorized penis.

Rupture of urethra or bladder

If the obstruction is not relieved, urethral
rupture or bladder rupture usually
occurs within 48 hours. With urethral
rupture, the urine leaks into the con-
nective tissue of the ventral abdominal
wall and prepuce and causes an obvious
fluid swelling, which may spread as far as
the thorax. This results in a severe
cellulitis and toxemia. The skin over the
swollen area may slough, permitting
drainage, and the course is rather more
protracted in these cases. When the
bladder ruptures there is an immediate
relief from discomfort but anorexia and
depression develop as uremia develops.
Two types of bladder rupture have been
described; multiple pinpoint perforations
in areas of necrosis or discrete tears in the
bladder wall. The site of leakage is almost
always on the dorsal aspect of the
bladder. Complete urethral obstruction
therefore results in urethral rupture or
bladder rupture and never both in the
same animal, because pressure is released
once rupture occurs.

A fluid wave is detectable on tactile
percussion and the abdomen soon
becomes distended. The animal may
continue in this state for as long as 2-3 days
before death occurs. Fibrin deposition
around the dorsal surface of the bladder
may be palpated per rectum in steers. In
rare cases death occurs soon after rupture
of the bladder as a result of severe internal
hemorrhage.

In rare cases calculi may form in the
prepuce of steers. The calculi are top-
shaped and, by acting as floating valves,
cause obstruction of the preputial orifice,
distension of the prepuce and infiltration
of the abdominal wall with urine. These
cases may be mistaken for cases of
| urethral perforation.

| CLINICAL PATHOLOGY

; Urinalysis

I Laboratory examinations may be useful in
j the diagnosis of the disease in its early
stages when the calculi are present in the
: kidney or bladder. The urine usually con-
tains erythrocytes and epithelial cells and
j a higher than normal number of crystals,
j sometimes accompanied by larger aggre-
i gations described as sand or sabulous
deposit. Bacteria may also be present if
i secondary invasion of the traumatic
| cystitis and pyelonephritis has occurred.

I Serum biochemistry

] Serum urea nitrogen and creatinine con- i
j centrations will be increased before either j
] urethral or bladder rupture occurs and i
j will increase even further afterwards. !
] Rupture of the bladder will result in
| uroabdomen. Because urine has a markedly
j low sodium and chloride concentration

and high osmolality relative to plasma,
equilibration of electrolytes and free water
into the abdomen will always result in
hyponatremia, hypochloremia, hyper-
phosphatemia, and hypo-osmolality in
serum, with the magnitude of the changes
reflecting the volume of urine in the
abdomen. Similar changes in serum bio-
chemistry are present in steers with
ruptured urethra, with the magnitude of the
changes being smaller than in steers with
ruptured bladder. 11 Interestingly, steers with
ruptured bladder or urethra typically have
serum potassium concentrations within the
normal range; 12 this result most probably
reflects the combined effects of increased
salivary potassium loss in the face of
hyponatremia and inappetance. 13

Abdominocentesis and needle aspirate
of subcutaneous tissue
Abdominocentesis is necessary to detect
uroperitoneum after rupture of the blad-
der or needle aspiration from the sub-
cutaneous swelling associated with
urethral rupture. However, it is often diffi-
cult to identify the fluid obtained from the
peritoneal cavity or the subcutaneous
tissues as urine other than by appearance
and smell, or by biochemical examination.
Generally, in uroperitoneum, substantial
quantities of fluid can be easily obtained
by abdominocentesis. Warming the fluid
may facilitate detection of the urine odor,
although this is a subjective and poorly
sensitive diagnostic test.

Ultrasonography

Ultrasonography is a useful aid for the
diagnosis of obstructive urolithiasis in
rams. 12 All parts of the urinary tract must be
examined for urinary calculi. The kidneys
are examined from the paralumbar fossa
and the bladder and urethra transrectally
The kidneys are examined for enlargement,
and the renal pelves, medullary pyramids
and urethra for dilatation. The size of the
bladder should be noted and its contents
examined. A ruptured bladder does not
always empty completely. In rams with
obstructive urolithiasis, the urethra and
bladder are markedly dilated. Because of
severe cystitis, the contents of the bladder
appear as multiple, tiny, unifonnly distri-
buted echoes. The renal pelves are com-
monly dilated. Uroperitoneum may also be
visualized.

NECROPSY FINDINGS

Calculi may be found in the renal pelvis or
bladder of normal animals, or of those
dying of other diseases. In the renal pelvis
they may cause no abnormality, although
in occasional cases there is accompanying
, pyelonephritis. Unilateral ureteral obstruc-
j tion is usually accompanied by dilatation
I of the ureter and hydronephrosis. Bilateral
obstruction causes fatal uremia. Calculi in

the bladder are usually accompanied by
varying degrees of chronic cystitis. The
urethra or urethral process may be
obstructed by one or more stones, or may
be impacted for up to 35 cm with a fine
sabulous deposit.

When rupture of the urethra has
occurred the urethra is eroded at the site
of obstruction and extensive cellulitis and
accumulation of urine are present in the
ventral abdominal wall. When the bladder
has ruptured the peritoneal cavity is
distended with urine and there is mild to
moderate chemical peritonitis. In areas
where urolithiasis is a problem it is an
advantage to determine the chemical
composition of the calculi.

DIFFERENTIAL DIAGNOSIS

Obstruction of the urethra in ruminant
animals is almost always caused by a
calculus and is characterized clinically by
anuria or dribbling, swishing of the tail,
abdominal pain with kicking at the
abdomen or stamping the feet, and a
progressively worsening condition
Nonobstructive urolithiasis may be
confused with pyelonephritis or cystitis,
and differentiation may be possible only by
rectal examination in the case of vesical
calculi or by radiographic examination in
smaller animals. Subsequent development
of hydronephrosis may enable a diagnosis
to be made in cattle. Ultrasonographic
examination is useful in sheep
A rectal examination, if possible, may
reveal distension of the bladder and
dilatation and pulsation of the urethra if
the bladder has not ruptured
In adults, rupture of the bladder is
usually the result of obstructive urolithiasis,
although other occasional causes of
urethral obstruction are observed
Rupture of the urethra in cattle is
characterized by diffuse swelling of the
subcutaneous tissues of the ventral body
wall and the skin is usually cooler than
normal. It must be differentiated from
other causes of swelling of the ventral
abdominal wall, including abscesses and
herniation of abdominal wall, which can
be determined by close physical
examination and needle aspiration
Dilatation of the urethral recess in
young cattle is characterized by a midline
perineal swelling and may resemble
pulsation of the perineal urethra in
obstructive urolithiasis . 8 The urethral recess
arises from the junction of the pelvic and
spongy parts of the urethra at the level of
the ischial arch. A fold of urethral mucosa
proximal to the recess acts as a valve to
prevent the retrograde flow of urine into
the pelvic urethra. An abnormally large
urethral recess has been described in a
calf . 8 In dilatation of the urethral recess,
during urination the proximal urethra
pulses and the swelling may enlarge
slightly. There is no urethral obstruction
and urine flows passively from the penis
for several minutes after the urethral
pulsation ceases. The dilatation can be
radiographed using contrast media

Diseases of the bladder, ureters and urethra

5

TREATMENT

The treatment of obstructive urolithiasis
is primarily surgical. Cattle or lambs with
obstructive urolithiasis that are near the
end of their feedlot feeding period and
close to being marketed can be slaughtered
for salvage if the result of an antemortem
inspection is satisfactory. Animals in the
early stages of obstruction before urethral
or bladder rupture will usually pass
inspection at an abattoir. The presence of
uremia warrants failure to pass inspec-
tion. Rams, bucks, and wethers should all
have their glans penis exteriorized and
inspected, and the urethral process
amputated.

It used to be thought that calculi
cannot be dissolved by medical means,
but recent studies suggest that adminis-
tration of specific solutions into the bladder
can rapidly dissolve most uroliths. Success-
ful outcomes have occurred following
instillation of 30-200 mL of an acetic acid
solution (Walpole's buffer, pH adjusted to
4.3-4.8) 14,15 or hemiacidrin solution
through a cystotomy catheter; 10 hemiacidrin
is an acidic gluconocitrate solution with
magnesium carbonate that is used for
dissolution of magnesium ammonium
phosphate and calcium phosphate uroliths
in humans. The advantage of hemiacidrin
is that it is reportedly less irritating to
urothelium than other acids of similar
pH. 10 The cystotomy tube can be placed
surgically or transcutaneously, using
abdominal ultrasound. The latter tech-
nique involves placement of a 12-French
sleeved trocar into the lumen of the
bladder, followed by removal of the trocar
and placement of a 10-French silicone
Foley catheter through the sleeve of the
trocar into the lumen of the bladder. The
balloon on the Foley catheter is then
inflated using 0.9% NaCl, the trocar
sleeve removed from the abdomen and
the Foley catheter secured to the
abdomen. 10 The cystotomy catheter
provides an alternative route for urine to
| leave the bladder and is allowed to
! continuously drip. The cystotomy catheter
I is occluded for 30 minutes to 2 hours after
j infusion to retain the solution in the
; bladder and urethra, after this time
the solution is drained from the bladder
via the cystotomy tube. 10,14,15

In early stages of the disease or in cases
i of incomplete obstruction, treatment with
j smooth muscle relaxants such as pheno-
; thiazine derivatives (aminopromazine,

! 0.7 mg/kg of BW) has been tried to relax
| the urethral muscle and permit passage of
j the obstructing calculus; 16 however treat-
; rnent efficacy is unknown. Animals
: treated medically should be observed
; closely to insure that urination occurs and
j that obstruction does not recur. However,
i field observations indicate that these

relaxants are ineffective, and it is difficult
to believe that smooth muscle relaxants
could be efficacious given that the urethral
and periurethral tissue contains very little
smooth muscle. 17 A more rational treat-
ment is infiltration of local anesthetic
around the origin of the retractor penile,
muscles 18 or a pudendal nerve block, which
would relax the retractor penis muscle
and straighten the sigmoid flexure,
thereby creating a wider and straighter
urethral passageway. 17

Normograde hydropulsion is only
occasionally successful, although it is
frequently used as part of the initial treat-
ment. This technique involves catheter-
ization of the urethral orifice with a
suitably sized urinary catheter, and
intermittent injection of 0.9% NaCl into
the urethra in an attempt to flush out the
calculi. Frequently, a gritty feeling is
detected during this procedure, and one
usually is left with the impression that the
procedure is creating additional urethral
trauma that may contribute to urethral
stricture. Normograde hydropulsion may
also pack small crystals more tightly into
the urethra. In young ruminants, it can be
difficult to exteriorize the glans penis and
identify the urethral orifice. Cystotomy
and retrograde hydropulsion appear
to have a higher success rate than
normograde hydropulsion. 2

Surgical treatment includes perineal
urethrostomy to relieve bladder pressure
and for the removal of calculi. This is a
salvage procedure and treated animals
can be sent to slaughter for salvage when
they have recovered sufficiently to pass
antemortem inspection. In a series of
85 cases of surgical treatment of urethral
obstruction in cattle, only 35% of animals
recovered satisfactorily. 7 In small rumi-
nants, which invariably have multiple
calculi, amputation of the urethral process
may restore urine flow but usually
provides only temporary relief, 2 and the
long-term prognosis in sheep and goats is
poor 10 because there is a high rate of
recurrence of obstruction with stricture
formation at the urethrostomy site. 2 If
perineal urethrostomy is unsuccessful,
tube cystotomy is indicated. Urethro-
scopy and laser lithotripsy have success-
fully dissolved uroliths in a small number
of small ruminants 20 and one steer 21 but
the technique is expensive and not widely
available. Prepubic urethrostomy has
been performed in a small number of
small ruminants that have undergone
stricture formation following perineal
urethrostomy, 17 whereas urinary bladder
marsupialization offers a simpler surgical
method for correction. 22 There is one
report of erection failure in a male goat as a
sequela to obstructive urolithiasis; erection
failure was attributed to vascular occlusion

570

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

of the corpus cavemosum penis. 23 Surgical
correction of urethral dilatation associated
with the urethral recess in cattle has been
described. 24

PREVENTION

A number of agents and management
procedures have been recommended in
the prevention of urolithiasis in feeder
lambs and steers. First, and probably most
important, the diet should contain an
adequate balance of calcium and phos-
phorus to avoid precipitation of excess
phosphorus in the urine. This is the major
difficulty in controlling urolithiasis in
feedlot ruminants, because their diets are
grain (and therefore phosphorus) -rich.
The ration should have a Ca:P ratio of
1.2:1, but higher calcium inputs (15-2.0:1)
have been recommended. Every practical
effort must be used to increase and
maintain water intake in feeder steers
that have just been moved into a feedlot
situation. The addition of salt at the level
of 4% of the total ration of feeder calves
has been shown experimentally to have
this effect on both steers and lambs.
Under practical conditions salt is usually
fed at a concentration of 3-5%, higher
concentrations causing lack of appetite. It
is thought that supplementary feeding
with sodium chloride helps to prevent
urolithiasis by decreasing the rate of
deposition of magnesium and phosphate
around the nidus of a calculus, but it is
possible that salt-related diuresis may
also play an important role. Feeding of
pelleted rations may predispose to the
development of phosphate calculi (such
as struvite or apatite) by reducing the
salivary secretion of phosphorus. 15 ' 20

The control of siliceous calculi in cattle
which are fed native range grass hay,
which may contain a high level of silica, is
dependent primarily on increasing the
water intake. The feeding of alfalfa hay is
considered to increase urine flow and
lower the incidence of urolithiasis but the
important reason may be that it contains j
considerably less silica. As in feedlot
animals, water intake can be promoted by
supplementing the ration with salt. For
yearling (300 kg) steers the daily con-
sumption of 50 g of salt does not prevent
the formation of siliceous calculi; at 200 g
daily intake the occurrence of calculi is
significantly reduced, and at 300 g daily
calculus formation is almost eliminated.
For calves on native range, providing
supplements ('creep feeds') containing up
to 12% salt is effective in eliminating
siliceous calculi. This effect is due to the
physical diluting effect of increased water
intake promoted by salt supplementation.

If the calves consume sufficient quantities
of salt to increase the water intake above
200 g/kg BW per day the formation

of siliceous calculi will be completely
suppressed. Since siliceous calculi form in
the last 60 days before weaning, it is
recommended that calves on range be
started on creep feed without salt well
before weaning and, once calves are
established on the supplement, that the
salt concentration be gradually increased
to 12%. It is usually necessary to increase
the salt gradually to this level over a
period of several weeks and incorporate it
in pellets to facilitate mixing.

An alkaline urine (pH > 7.0) favors the
formation of phosphate-based stones
(struvite, apatite) and calcium-carbonate-
based stones. Feeding an agent that
decreases urine pH will therefore protect
against phosphate-based stones. The
feeding of ammonium chloride (45 g/d to
steers and 10 g daily to sheep) may
prevent urolithiasis due to phosphate
calculi, but the magnitude of urine
acidification achieved varies markedly
depending on the acidogenic nature of
the diet. For this reason, urine pH should
be closely monitored when adding ammo-
nium chloride to the ration, because
clinically relevant metabolic acidosis,
depression and inappetence can result
from over-zealous administration rates.
For range animals, ammonium chloride
can be incorporated in a protein supple-
ment and fed at about two-thirds of the
above dosage. An acidic urine (pH < 7.0)
favors the formation of silicate stones, so
ammonium chloride manipulation of
urine pH is not indicated in animals at
risk of developing siliceous calculi. How-
ever, ammonium chloride may prevent
the formation of silica calculi in sheep; 3
this may have been due to the urine-
diluting effects of additional chloride
intake.

When the cause of urolithiasis is due
to pasture exposure, females can be used
to graze the dangerous pastures since
they are not as susceptible to developing
urinary tract obstruction. In areas where
the oxalate content of the pasture is high,
wethers and steers should be permitted
only limited access to pasture dominated
by herbaceous plants. Adequate water
supplies should be available and highly
saline waters should be regarded with
suspicion. Sheep on lush pasture com-
monly drink little if any water; apparently
because they obtain sufficient in the feed.
Although the importance of vitamin A in
the production of the disease has been
decried in recent years an adequate intake
should be insured, especially during
drought periods and when animals are
fed grain rations in feedlots. Deferment of
castration, by permitting greater urethral
dilatation, may reduce the incidence of
obstructive urolithiasis but the improve -
I ment is unlikely to be significant.

REVIEW LITERATURE

Oehme FW, Tillmann H. Diagnosis and treatment of
ruminant urolithiasis. J Am Vet Med Assoc 1965;
147:1331-1339.

Bailey CB. Silica metabolism and silica urolithiasis in
ruminants: a review. Can J Anim Sci 1981;
61 :219-235.

Larson BL. Identifying, treating, and preventing
bovine urolithiasis. Vet Med 1996; 91:366-377.

Van Metre DC et al. Obstructive urolithiasis in
ruminants: surgical management and prevention.
Compend Contin Educ Pract Vet 1996;
18:S275-S289.

REFERENCES

1. Bailey CB. Can J Anim Sci 1981; 61:219.

2. Haven ML et al. CornellVet 1993; 83:47.

3. Stewert SR et al. J Anim Sci 1991; 69:2225.

4. Kallfelz FA et al. CornellVet 1987; 77:33.

5. Poole DBR. IrVet J 1989; 42:60.

6. Marsh H, Safford JW.J Am Vet Med Assoc 1957;
342.

7. Gasthuys F et al. Vet Rec 1993; 133:522.

8. Anderson DE et al. Can Vet J 1993; 34:234.

9. Ashdown RR. J Agric Sci 1962; 58:65, 71.

10. Streeter RN et al. J Am Vet Med Assoc 2002;
221:546.

11. Donecker JM, Bellamy JEC. Can Vet J 1982;
23:355.

12. Braun U et al. Can Vet J 1992; 33:654.

13. Sockett D, Knight AP. Compend Contin Educ
Pract Vet 1984; 6:S311.

14. Cockcroft PD. Vet Rec 1993; 132:486.

15. Van Metre DC et al. Compend Contin Educ Pract
Vet 1996; 18:S275-S289.

16. Scheel EH, Raton IM. J Am Vbt Med Assoc 1960;
137:665.

17. Stone WC et al. J Am Vet Med Assoc 1997;
210:939.

18. Baxter GM et al. J Am Vet Med Assoc 1992;
200:517.

19. Van Weeren PR et al. Vet Q 1987; 9:76.

20. Halland SK et al. J Am Vet Med Assoc 2002;
220:1831.

21. Streeter RN et al. J Am Vet Med Assoc 2001;
219:640.

22. May KA et al.VetSurg 2002; 31:251.

23. Todhunter P ct al. J Am Vet Med Assoc 1996;
209:650.

24. Gasthys F et al.Vet Rec 1996; 138:17.

URO LITH IASIS IN HORSES

Urolithiasis occurs sporadically in horses.
The prevalence is low at about 0.04-0.5%
of all horse accessions or diagnoses. 1
Animals from about 5-15 years of age and
older are most commonly affected and
76% are males (27% intact, 49% geldings)
and 24% females. 1 The uroliths are most
commonly in the bladder (cystic) although
they also occur in the renal pelvis, ureters,
and urethra. 2 In most cases, there is a
single discrete stone, but a sandy sludge
accumulates in cases of paralysis of the
bladder. Almost all equine uroliths are
composed of calcium carbonate in the
form of calcite and their ultrastructure has
been examined. 3 ” 5

The factors that contribute to urolith
formation in horses are not understood.
Urine from healthy adult horses is
characterized by a substantial quantity of
mucoprotein, a high concentration of

Congenital defects of the urinary tract

minerals, considerable insoluble sabulous
material, and alkalinity. Equine urine is
normally supersaturated with calcium
carbonate and crystals of calcium carbonate
are usually present; 3 this is related in
some manner with the occurrence of
calcium carbonate uroliths in horses.
Nephrolithiasis may arise as a sequel to
degenerative or inflammatory processes
in the kidney in which inflammatory
debris serves as a nidus for calculus
formation. 6

The clinical findings of urolithiasis in
the horse include:

° Stranguria (straining to urinate)

• Pollakiuria (frequent passage of small
amounts of urine), hematuria and
dysuria (difficult urination)

° Incontinence resulting in urine
scalding of the perineum in females
or of the medial aspect of the
hindlimbs in males
Painful urination with hematuria
associated with cystitis
® Bacterial infection is common. 7

The bladder wall may be thickened and
large calculi in the bladder may be
palpable per rectum, just as the hand
enters the rectum. Large calculi may be
observed using transrectal ultrasonography 6
and cystoscopy. Calculi may also be pal-
pated in the ureters, per rectum, or
enlarged ureters may be present. 4

In males, urethral calculi may present
with signs of complete or partial obstruc-
tion that may be confused with colic of
gastrointestinal origin. Horses with
urethral obstructions make frequent
attempts to urinate but pass only small
amounts of blood-tinged urine. Unless
rupture has occurred, the bladder is
grossly enlarged. The calculus can be
located by palpation of the penile urethra
and by passage of a lead wire or catheter.
If a catheter or lead wire is passed, care
should be taken to prevent damage to the
urethral mucosa. Bladder rupture leads to
uroperitoneum but, if the rupture occurs
at the neck of the bladder, urine may
accumulate retroperitoneally and produce
a large, diffuse, fluid swelling that is
palpable per rectum. When rupture occurs
acute signs disappear and are replaced
by depression, immobility and pain on
palpation of the abdominal wall. The
heart rate rises rapidly and the tempera-
ture falls to below normal.

Urinalysis reveals evidence of erythro-
cytes, leukocytes, protein, amorphous
debris, and calcium carbonate crystals.

Renal calculi are frequently bilateral
and affected animals have often pro-
gressed to chronic renal failure by the
time of diagnosis without having displayed
signs of urinary tract obstruction. 6 A
history of chronic weight loss and colic in

a horse with renal failure indicates the
possible presence of renal calculi. Treat-
ment is supportive as for all cases of
chronic renal failure.

Treatment for cystic calculi is surgical
removal of the calculus and correction of
any defect in the bladder. Perineal
urethrotomy has been used for removal of
cystic calculi in a gelding. 8 Urethral calculi
in males are removed through the
external urethral orifice or by urethrotomy
at the site of obstruction. Recurrence of
cystic and urethral calculi is common in
the horse, which may be related to the
failure to remove all calculi. Some cystic
calculi can be removed with the aid of
electrohydraulic lithotripsy, 9 laser litho-
tripsy under endoscopic visualization 10 or
surgery. In large mares with bladder
calculi, it is possible to remove the calculi
manually by passing a very small hand
through the urethra into the bladder and
retrieving the calculi after administration
of epidural analgesia and sedation.
Percutaneous nephrostomy of the right
kidney under ultrasonic guidance has
been used for short-term diversion of
urine in a horse with ureteral calculi. 2
Ammonium chloride, at 200 mg/kg BW
orally twice daily and decreased at
biweekly intervals until a dosage of
60 mg/kg BW is reached, is recommended
to maintain the urine pH below 7.0.

REFERENCES

1. Laverty S et al.Vet Surg 1992; 21:56.

2. Byars TD et al. J Am Vet Med Assoc 1989; 195:499.

3. Newman RD et al. Am JVet Res 1994; 55:1357.

4. Diaz-Espincira M et al. J Equine Vet Sci 1995;
15:27.

5. Main TS. Res Vet Sci 1986; 40:288.

6. Ehncn SJ et al. J Am\fct Med Assoc 1990; 197:249.

7. Johnson PJ, Crenshaw KL.Vct Med 1990; 85:891.

8. Hanson RR, Poland HM. J Am Vet Med Assoc
1995; 207:418.

9. Eustace RA et al. Equine Vet J 1988; 20:221.

10. Judy CE, Galuppo LD. \fet Surg 2002; 31:245.

URETHRAL TEARS IN STALLIONS
AND GELDINGS

Urethral rents are lesions in the convex
surface at the level of the ischial arch in
geldings and stallions. The lesions
communicate with the corpus spongiosum
and cause hemorrhage at the end of
urination in geldings or during ejaculation
by stallions. 1 Stallions do not have
hematuria, despite having a lesion identical
to that in geldings, presumably because
of the lower pressure in the corpus
spongiosum of stallions at the end of
urination compared to that in geldings. 2
The disease is apparently caused by
contraction of the bulbospongiosus
muscle at the end of urination, with a con-
sequent increase in pressure in the corpus
spongiosum and expulsion of blood
through the rent. The cause of the rent

has not been determined. The diagnosis is
confirmed by endoscopic examination of
the urethra with visualization of the rent
in the urethral mucosa. Treatment of
the disease is by temporary subischial
urethrostomy and sexual rest. Sexual rest
alone was successful in one stallion. 1

REFERENCES

1 . Schumacher J et al.Vet Surg 1995; 24:250.

2. Taintor J et al. Equine \fet J 2004; 36:362.

URINARY BLADDER NEOPLASMS

Tumors of the urinary bladder are com-
mon only in cattle, where they are
associated with bracken poisoning, but
they do occur in other circumstances. For
example, 18 cows are recorded in one
series, with angioma, transitional epithelial
carcinoma and vascular endothelioma
being the most common tumors. Abattoir
surveys in Canada, the USA, and Australia
identified papillomas, lymphomas, aden-
omas, hemangiomas, and transitional cell
tumors occurring at low frequencies in
slaughter cattle. 1-3 Papillomas appear to
be associated with the bovine papilloma-
virus (BPV-5). Most bladder neoplasms
develop from focal areas of hyperplasia
within the transitional cell layer and
approximately 80% of these can be
classified as carcinomas while 17% are
papillomas. Because these neoplasms
arise from a common site, they can be
very similar in gross and histological
appearance and very difficult to differ-
entiate. 3,4 The immunoenzymatic labeling
of intermediate filaments in bovine
urinary bladder tumors is an accurate
indicator of histogenesis. 3

Six cases of bladder neoplasia are also
recorded in horses. 6 Clinical signs included
hematuria, weight loss, stranguria and the
secondary development of cystitis.

REFERENCES

1. Hcrenda Detal. Can\fet J 1990; 31:515.

2. Brobst DF, Olson C. Am J Vet Res 1963; 24:105.

3. Rimukcu AM. Bull WHO 1974; 50:43.

4. Skye DV. J Am Vet Med Assoc 1975; 166:596.

5. Gimcno EJ et al. J Comp Pathol 1994; 111:15.

6. Fischer AT et al. J Am Vet Med Assoc 1985;
186:1294.

Congenital defects of the
urinary tract

Congenital defects of the urinary tract are
not common in farm animals. The most
common congenital defect is uro-
peritoneum in foals following rupture of
the urinary bladder.

R ENA L HYPOPLASIA

Developmental abnormalities of the
kidneys are classified as renal agenesis,
hypoplasia and dysplasia, with agenesis

572

PART 1 GENERAL MEDICINE ■ Chapter 11: Diseases of the urinary system

and hypoplasia representing different
degrees of the same condition. Renal
hypoplasia is defined as a decrease in
total renal parenchyma of one-third or
more, with a proportionately greater loss
of medullary than cortical tissue. The
diagnosis of renal hypoplasia is straight-
forward in neonates but can be difficult
to differentiate from renal dysplasia in
adults.

Bilateral renal hypoplasia with or
without agenesis is recorded in Large
White piglets, the piglets being dead at
birth or dying in the first 3 months of life. 1
Clinical signs exhibited by older pigs
included lethargy, shivering, anorexia,
diarrhea and a slow rate of growth. The
disease was suspected to be inherited in a
simple autosomal recessive manner and
the basic defect appeared to be failure of
development of mesonephric mesenchyme.

Cases of bilateral renal hypoplasia
have been recorded in four horses. 2 The
four horses were 1 day to 3 years of age
and had common histories of stunting,
poor growth rate, anorexia, depression,
and lethargy. Evidence of chronic renal
failure was present on clinicopathological
examination. Transrectal and trans-
abdominal ultrasonography revealed
small kidneys and small renal medulla
and pelves and was considered a useful
diagnostic test.

RENAL DYSPLA SIA

Renal dysplasia is defined as disorganized
development of the renal parenchyma
due to anomalous differentiation. Histo-
logically, renal dysplasia is characterized
by persistence of abnormal mesenchymal
structures, including undifferentiated
cells, cartilage, immature collecting ductules,
and abnormal lobar organization.

Renal dysplasia with benign uretero-
pelvic polyps associated with hydro-
nephrosis has been recorded in a
4- month-old foal. 3 Renal dysplasia has
also been diagnosed in two adult horses
with weight loss, azotemia, hypercalcemia
and increased fractional clearance of
sodium. Ultrasonographic examination of
the kidneys revealed a poor distinction
between the cortex and medulla due to a
hyperechoic medulla, which was due to
fibrosis. 4 Histological changes in both
horses were indicative of interruption of
nephrogenesis after the initiation, but
before the complete differentiation, of the
metanephric blastema. Renal dysplasia is
also reported in foals, both as an apparent
spontaneous disease 5 and in foals born to
mares treated with sulfadimidine, pyri-
methamine, and folic acid during
pregnancy. 6

Congenital renal dysplasia has been
recorded in two successive years in a

Leicester sheep flock crossbred with
Suffolk and Swaledale rams. 7 Affected
lambs were born alive, were reluctant to
stand or move, sucked poorly and had
wet coats. Lambs improved with nursing
and provision of warmth, but none with
clinical signs at birth survived beyond
5 days after birth. At necropsy, the kidneys
were bilaterally small with fine intracortical
cysts and distinct cortical and medullary
zones. An inherited dominant trait with
complete penetrance is suspected.

Renal tubular dysplasia has been diag-
nosed in Japanese Black cattle (wagyu)
with renal failure, poor growth and long
hooves. 8 Calves were undersized at birth
and had repeated episodes of diarrhea
during the neonatal period. Calves began
to show signs of growth retardation from
2-5 months of age but had a normal
appetite. Clinicopathological findings
included azotemia, increased serum
phosphorus concentrations and oliguria.
At necropsy, the main lesion was
dysplasia of the proximal tubule epithelial
cells, with secondary interstitial fibrosis
with a reduction in the numbers of
glomeruli and tubules in older cattle. 9 An
autosomal recessive mode of inheritance
has been determined associated with a
deletion of the paracellin-1 gene on
chromosome l. 10 This gene encodes a
protein that is part of the tight junction of
renal epithelial cells, and this gene
deletion is considered to be the cause
for the renal tubular dysplasia. 9 Hetero-
zygotes are clinically normal and have
normal renal function.

POLYCYSTIC KIDNEYS

In most species this is a common
congenital defect. If it is extensive and
bilateral the affected animal is usually
stillborn or dies soon after birth. In some
cases, bilateral defects are compatible
with life and clinical signs may not
present until the residual nephron mass is
gradually exhausted and the animal is
adult. 11 If it is unilateral no clinical signs
appear because of compensatory activity
in the other kidney, but in an adult the
enormously enlarged kidney may be
encountered during rectal examination.

In adult horses, polycystic disease may
also be acquired rather than congenital. 12
The disease is rare, but affected animals
present in varying stages of chronic renal
failure. 13

A high incidence of renal defects has
been recorded in sucking pigs from sows
vaccinated during early pregnancy with
attenuated hog cholera virus; bilateral
renal hypoplasia has been observed as a
probably inherited defect in Large White
pigs. 14 Most polycystic kidneys in pigs
appear to be inherited in a polygenic

manner 15 and have no effect on the pig's
health or renal function. However, there is
a record of the defect in newborn pigs in
one herd in which it caused gross
abdominal distension due to moderate
ascites and gross cystic distension of the
kidneys and tract. There was no evidence
that the disease was inherited in this
instance and a toxic origin was surmised.

Isolated cysts occur in the kidneys of
all species and are of no clinical signifi-
cance. The increased availability of ultra-
sonographic examination of the kidneys
of animals facilitates antemortem identifi-
cation of these cysts. The cysts are usually
solitary and unilateral.

Congenital polycystic kidney
disease of lambs occurs as an autosomal
recessive trait. 16 The disease is recognized
in Romney, Perendale, and Coop worth
sheep in New Zealand. Lambs die at or
shortly after birth and there is no apparent
sex predisposition. Necropsy examination
reveals an abdomen distended by the
enlarged kidneys, which contain large
numbers of fluid-filled 1-5 mm cysts.
There are gross and histological abnor-
malities of the liver and pancreas. A
pathologically similar disease is reported
in a Nubian goat. 17

ECTOPIC URETER

Ectopic ureter has been recorded in cattle
and horses. 18 The condition may be
unilateral or bilateral with urinary
incontinence present since birth as the
major clinical manifestation. Reported
neurogenic causes of urinary incontinence
in horses include cauda equine neuritis,
herpesvirus-1 myelitis, Sudan grass
toxicosis, sorghum poisoning, trauma, and
neoplasia. Nonneurogenic causes of
urinary incontinence in horses include
ectopic ureter, cystitis, urolithiasis, hypo-
estrogenism, and abnormal vaginal
conformation. 19

The ectopic ureter opens into the
urogenital tract at a place other than the
bladder such as the cervix, urethra, or
vagina. The condition is often complicated
by ascending infections, hydronephrosis,
and dilatation of the ureter. Definite
diagnosis requires excretory urography or
endoscopy; visualization of the ureteral
openings during endoscopy can be
assisted by intravenous administration of
phenolsulfonphthalein (0.01 mg/kg BW) or
indigo carmine (0.25 mg/kg BW) to impart
a red or blue color, respectively, to the
urine being produced. Surgical treatment
involving ureterovesical anastomosis or
unilateral nephrectomy has been successful.

URETERAL DEFECT

Unilateral and bilateral ureteral defects
have been reported in newborn foals. 20

Congenital defects of the urinary tract

The clinical presentation is similar to
rupture of the urinary bladder but ureteral
defects may be more common in filly foals
than in colts. 21

PATENT URACHUS

Failure of the urachus to close at birth
occurs most commonly in foals and is
very rare in other species. Patent urachus
occurs as three syndromes in foals:
congenital and present at birth; acquired
and secondary to urachal infection or
inflammation; or secondary to severe
systemic illness, usually sepsis. As a result
of the patent urachus, which during intra-
uterine life drains urine into the allantoic
fluid, urine leaks from the umbilicus. The
urine flow varies from a continuous
stream during micturition to constant or
intermittent dribbling, or a continuous
moistening of the umbilical stalk. Healthy
foals with congenital patent urachus heal
in several days and no specific treatment is
required. Formerly, cauterization with
phenol or silver nitrate was practiced, but
this treatment has the potential to induce
necrosis and increases susceptibility to
infection.

Foals with patent urachus secondary to
umbilical disease usually have an enlarged
umbilicus and some have a purulent
discharge. Foals that have patent urachus
secondary to other umbilical disease
might require surgical correction, although
most respond to a 7-14- day course of
antimicrobials. Foals with patent urachus
secondary to systemic disease, usually
sepsis, should have their other disease
treated aggressively and the urachus
allowed to close spontaneously, which it
usually does. Ultrasonographic examin-
ation of the umbilicus of all foals with
patent urachus is essential to determine
the extent of disease and presence of
intra-abdominal disease. As with all sick
foals, the immune status of foals with
patent urachus secondary to umbilical or
systemic disease should be determined by
measurement of serum IgG concentration
and foals with low serum IgG concen-

tration should receive a transfusion.
Cystitis is an occasional sequel but
omphalitis and urachal abscess may also
develop as complications. Patent urachus
with a perforated urethra has been
recorded in a lamb. 22

Urachal abscess is discussed as a
subgroup of umbilical abscess in Chapter
3. When the infection is localized in the
urachus there are usually signs of cystitis,
especially increased frequency of
urination. 23

EVERSION OF THE BLADDER

Umbilical evagination of the bladder has
been reported in a neonatal filly. 24 The
bladder prolapsed through the umbilicus
such that the mucosa of the bladder was
outermost (bladder eversion). Bladder
eversion through the urethra into the
vagina and through the vulva occurs in
mares immediately after parturition. In this
instance care must be taken to not mistake
the everted bladder for uterine tissue. 25
Correction in both instances is surgical.

RUPTURE OF THE BLADDER

Rupture of the bladder is dealt with above,
under other causes of uroperitoneum in
foals.

URETHRAL DEFECT

An anomalous vas deferens caused a
chronic partial urethral obstruction in a 2-
year-old Limousin bull, resulting in
bilateral hydronephrosis, pyelonephritis
of the left kidney, and bilateral ureteral
dilatation. 26 There are two reports of a
ruptured urinary bladder in neonatal
calves apparently due to a congenital
urethral obstruction that was corrected by
passing a urethral catheter. Congenital
urethral obstruction with subsequent
hydronephrosis and uroperitoneum is
reported in a lamb. 27

URETHRAL ATRESIA

This is recorded rarely in calves and is
manifested by failure to pass urine and

distension of the patent portion of the
urethra. 28

HYP OSPADIAS

Imperfect closure of the external male
urethra in a series of newborn lambs is
recorded with other neonatal defects
including atresia ani and diaphragmatic
hernia. No genetic influence was suspected
and the cause was unidentified. 29

REFERENCES

1. Cordes DO, Dodd DC. Pathol Vet 1965; 2:37.

2. Andrews FM et al. J Am Vet Med Assoc 1986;
189:209.

3. Jones SL et al. J Am Vet Med Assoc 1994;
204:1230.

4. Ronen N et al. Vet Rec 1993; 132:269.

5. Zicker SC et al. J Am Vet Med Assoc 1990;
196:2001.

6. Toribio RE et al. J Am Vet Med Assoc 1998;
212:697.

7. O'Toole D et al. J Vet Diagn Invest 1993; 5:591.

8. OhbaY et al.VetRec 2001; 149:115.

9. SasakiYet al.VetRec 2002; 150:628.

10. Ohba Y et al. Vet Rec 2001; 149:153.

11. Ramsay G et al. Equine Vfet J 1987; 19:243.

12. Bertone JJ et al. J Am Vet Med Assoc 1987;
191:565.

13. Aguilera -Tejero E et al. EquineVet J 2000; 32:167.

14. Wells GAH et al.Vet Rec 1980; 106:532.

15. Wijeratne WVS, Wells GAH. Vet Rec 1980;
107:484.

16. Johnstone AC et al. New Zealand Vet J 2005;
53:307.

17. Krotec K et al.Vet Rithol 1996; 33:708.

18. Pringle JP et al. Can Vet J 1990; 31:26.

19. Johnson PJ et al. J Am Vet Med Assoc 1987;
191:973.

20. DiversTJ et al. J Am Vet Med Assoc 1988; 192:384.

21. Robertson JJ, Embertson RM. Vet Clin North Am
Equine Pract 1988; 4:359.

22. Adamu SS et al.VetRec 1991; 129:338.

23. Trent AM, Smith DF. J Am Vet Med Assoc 1984;
184:984.

24. Textor JA et al. J Am Vet Med Assoc 2001; 219:953.

25. Squire KR et al. J Am Vet Med Assoc 1992;
200 : 1111 .

26. Tyler JW et al. J Am Vet Med Assoc 1991, 198:871.

27. Yeruham I et al.Vet Rec 2003; 152:540.

28. Hylton WE, Trent AM. J Am Vet Med Assoc 1987;
190:433.

29. Dennis SM. Vet Rec 1979; 105:94.

PART 1 GENERAL MEDICINE

Diseases of the nervous system

INTRODUCTION 575

PRINCIPLES OF NERVOUS
DYSFUNCTION 576

Modes of nervous dysfunction 577

CLINICAL MANIFESTATIONS OF
DISEASE OF THE NERVOUS
SYSTEM 577

Altered mentation 577
Involuntary movements 578
Abnormal posture and gait 579
Paresis and paralysis 581
Altered sensation 582
Blindness 582

Abnormalities of the autonomic
nervous system 583

SPECIAL EXAMINATION OF THE
NERVOUS SYSTEM 583

The neurological examination 583
Signalment and epidemiology 583
History 583
Head 584

Posture and gait 587
Neck and forelimbs 589
Trunk and hindlimbs 590
Tail and anus 591

Palpation of the bony encasement of
the central nervous system 591
Collection and examination of
cerebrospinal fluid 591
Examination of the nervous system with
serum biochemical analysis 593

Introduction

This chapter presents the principles of
clinical neurology and their application to
large animal practice. In general, this
activity has not kept pace with the study
of neurology in humans and small
animals, although remarkable progress
has been made in equine neurology over
the last 20 years. To a large extent this
shortfall is due to the failure of large
animal clinicians to relate observed clinical
signs to a neuroanatomical location of
the lesion. In many cases this failure has
been because of adverse environmental
circumstances, or the large size or nature
of the animal, all of which adversely
impact the quality of the neurological
examination. It may be very difficult to do
an adequate neurological examination on
an ataxic belligerent beef cow that is still
able to walk and attack the examiner. An
aggressive, paretic bull in broad sunlight
can be a daunting subject if one wants
to examine the pupillary light reflex;

Examination of the nervous system with
imaging techniques 593
Rhinolaryngoscopy (endoscopy) and
ophthalmoscopy 594
Electroencephalography 594
Electromyography 594
Brainstem auditory evoked potentials 594
Intracranial pressure and cerebral
perfusion pressure 594

PRINCIPLES OF TREATMENT OF
DISEASES OF THE NERVOUS
SYSTEM 594

Elimination and control of infection 595
Decompression 595
Treatment of brain injury after head
trauma 595

Central nervous system stimulants 596
Central nervous system depressants 596

PATHOPHYSIOLOGICAL
MECHANISMS OF NERVOUS
SYSTEM DISEASE 596

DIFFUSE DISEASES OF THE
BRAIN* 596

Cerebral hypoxia 596
Increased intracranial pressure, cerebral
edema and brain swelling 597
Hydrocephalus 599
Encephalomalacia or the degenerative
diseases of the central nervous
system 602

Traumatic injury to the brain 604

ophthalmoscopic examination of the
fundus of the eye in a convulsing steer in
a feedlot pen can be an exasperating task.
Thus, at one end of the spectrum is the
clinical examination of pigs affected with
nervous system disease, which is limited
to an elementary clinical examination and
necropsy examination. 1 At the other end,
neurological examination of the horse
with nervous system disease is very
advanced. The global occurrence of bovine
spongiform encephalopathy has high-
lighted the importance of accurate clinical
diagnosis in adult cattle with neurological
abnormalities.

Discrete lesions of the central nervous
system resulting in well-defined neuro-
logical signs are not common in agri-
cultural animals. Many of the diseases are
characterized by diffuse lesions associated
with viruses, bacteria, toxins, nutritional
disorders and embryological defects, and
the clinical findings of each disease are
similar. Rather than attempting to localize
lesions in the nervous system, large-

12

FOCAL DISEASES OF THE BRAIN 606

Brain abscess 606
Otitis media/interna 607
Tumors of the central nervous
system 608

Central-nervous-system-associated
tumors 608

Metastatic tumors of the central
nervous system 608
Central-nervous-system-associated
masses 609

Coenurosis (gid, sturdy) 609

DISEASES OF THE MENINGES 609

Meningitis 609

TOXIC AND METABOLIC

ENCEPHALOMYELOPATHIES 611

PSYCHOSES OR NEUROSES 612

EPILEPSY 613

DISEASES OF THE SPINAL CORD 613

Traumatic injury 613
Spinal cord compression 61 5
Back pain in horses 617
Myelitis 617
Myelomalacia 617

DISEASES OF THE PERIPHERAL
NERVOUS SYSTEM 618

CONGENITAL DEFECTS OF THE
CENTRAL NERVOUS SYSTEM 619

animal practitioners more commonly
devote much of their time to attempting
to identify whether an animal has
meningoencephalitis, as in Histophilus
somni meningoencephalitis; whether it
has diffuse brain edema or increased intra-
cranial pressure, as in polioencephalo-
malacia; or whether the dysfunction is
at the neuromuscular level, as in hypo-
magnesemic tetany.

Radiographic examination, including
myelography, is not used routinely or
available as a diagnostic aid in large-
animal practice. The collection of cerebro-
spinal fluid (CSF) from the different
species and ages of large animal without
causing damage to the animal or con-
taminating the sample with blood is a
technique that few large- animal veteri-
narians have mastered. However, the
collection of CSF from the lumbosacral
cistern is not difficult if the animals are
adequately restrained, and the infor-
mation obtained from analysis of CSF can
be very useful in the differential diagnosis

576

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

of diseases of the brain and spinal cord. 2
Referral veterinary centers are now
providing detailed neurological examin-
ations of horses with nervous system
disease and the clinical and pathological
experience has expanded the knowledge
base of large -animal clinical neurology. 3

In spite of the difficulties, the large
animal practitioner has an obligation to
make the best diagnosis possible using
the diagnostic aids available. The principles
of large-animal neurology are presented
in this chapter and the major objective is
to recognize the common diseases of the
nervous system by correlating the clinical
findings with the location and nature of
the lesion. Accurate neuroanatomical
localization of the lesion(s) remains the
fundamental requirement for creating a
differential diagnosis list and diagnostic
and treatment plan.

A disease such as rabies has major
public health implications and it is impor-
tant for the veterinarian to be able to
recognize the disease as early as possible
and to minimize human contact. It is also
important to be able to recognize treat-
able diseases of the nervous system such
as polioencephalomalacia, listeriosis and
nervous ketosis, and to differentiate them
from untreatable and globally important
diseases such as bovine spongiform
encephalopathy.

The nontreatable diseases must also be
recognized as such, and slaughter for
salvage or euthanasia recommended if
necessary. There must be a major emphasis
on prognosis because it is inhumane and
uneconomic to hospitalize or continue to
treat an adult cow or horse with incurable
neurological disease for an indefinite
period. If they are recumbent the animals
commonly develop secondary compli-
cations such as decubitus ulcers and other
self-inflicted injuries because of repeated
attempts to rise. Very few diseases of the
nervous system of farm animals are
treatable successfully over an extended
period of time. This has become parti-
cularly important in recent years with the
introduction of legislation prohibiting the
slaughter of animals that have been
treated with antibiotics until after a certain
withdrawal period, which may vary from
5-30 days. This creates even greater
pressure on the clinician to make a rapid,
inexpensive and accurate diagnosis and
prognosis.

Because of limitations in the neuro-
logical examination of large animals,
there must be much more emphasis on
the history and epidemiological findings.
Many of the diseases have epidemiological
characteristics that give the clinician a
clue to the possible causes, thus helping
to narrow the number of possibilities. For
example, viral encephalomyelitis of horses

occurs with a peak incidence during the
insect season, lead poisoning is most
common in calves after they have been
turned out on to pasture, and polio-
encephalomalacia occurs in grain-fed
feedlot cattle.

The functions of the nervous system
are directed at the maintenance of the
body's spatial relation with its environ-
ment. These functions are performed by
the several divisions of the nervous system
including:

° The sensorimotor system, responsible
for the maintenance of normal
posture and gait

° The autonomic nervous system,
controlling the activity of smooth
muscle and endocrine glands, and
thereby the internal environment of
the body

°. The largely sensory system of special
senses

° The psychic system, which controls
the animal's mental state.

The nervous system is essentially a reactive
one geared to the reception of internal
and external stimuli and their translation
into activity and consciousness; it is
dependent upon the integrity of both the
afferent and efferent pathways. This
integrative function makes it often diffi-
cult to determine in a sick animal whether
abnormalities are present in the nervous
system, the musculoskeletal system or
acid-base and electrolyte status. Accord-
ingly, the first step when examining an
animal with apparent abnormalities in the
nervous system is to determine whether
other relevant systems are functioning
normally. In this way a decision to impli-
cate the nervous system is often made on
the exclusion of other systems.

The nervous system itself is not inde-
pendent of other organs and its functional
capacity is regulated to a large extent by
the function of other systems, particularly
the cardiovascular system. Hypoxia due to
cardiovascular disease commonly leads to
altered cerebral function because of the
dependence of the brain on an adequate
oxygen supply.

It is important to distinguish between
primary and secondary diseases of the
nervous system since both the prognosis
and the treatment will differ with the cause.

In primary disease of the nervous
system the lesion is usually an anatomical
one with serious, long-range conse-
quences.

In secondary disease the lesion, at
least in its early stages, is more likely to be
functional and therefore more responsive
to treatment, provided the defect in the
primary organ can be corrected.

The clinical findings that should arouse
suspicion of neurological disturbance

include abnormalities in the three main
functions of the system.

Posture and gait

An animal's ability to maintain a normal
posture and to proceed with a normal gait
depend largely upon the tone of skeletal
muscle but also upon the efficiency of the
postural reflexes. Abnormalities of posture
and gait are among the best indications of
nervous system disease because these
functions are governed largely by the
coordination of nervous activity. Besides
contributing to posture and gait, skeletal
muscle tone is characteristic in its own
right. However, its assessment in animals
is subject to great inaccuracy because of
our inability to request complete voluntary
relaxation by the patient. In humans it is a
very valuable index of nervous system
efficiency, but in animals it has serious
limitations. The most difficult step when
there is a defect of gait or posture is to
decide whether it originates in the skel-
eton, the muscles or the nerve supply.

Sensory perceptivity

Tests of sensory perception in animals can
only be objective, and never subjective as
they can be in humans, and any test used
in animals is based heavily on the integrity
of the motor system.

Mental state

Depression or enhancement of the psychic
state is not difficult to judge, particularly if
the animal's owner is observant and
accurate. The difficulty usually lies in
deciding whether the abnormality is due
to primary or secondary changes in the
brain.

Principles of nervous
dysfunction

Nervous tissue is limited in the ways in
which it can respond to noxious influences.
Because of its essentially coordinating
function, the transmission of impulses
along nerve fibers can be enhanced or
depressed in varying degrees, the extreme
degree being complete failure of trans-
mission. Because of the structure of the
system, in which nerve impulses are
passed from neuron to neuron by relays at
the nerve cells, there may also be exces-
sive or decreased intrinsic activity of
individual cells giving rise to an increase
or decrease in nerve impulses discharged
by the cells. The end result is the same
whether the disturbance be one of con-
duction or discharge and these are the
only two ways in which disease of the
nervous system is manifested. Nervous
dysfunction can thus be broadly divided
into two forms, depressed activity and
exaggerated activity. These can be further

Clinical manifestations of disease of the nervous system

subdivided into four common modes of
nervous dysfunction; excitation (irritation)
signs, release of inhibition signs, paresis
or paralysis due to tissue damage, and
nervous shock.

MODES OF NERVOUS
D YSFUNCT ION

Excitation (irritation) signs

Increased activity of the reactor organ
occurs when there is an increase in the
number of nerve impulses received either
because of excitation of neurons or because
of facilitation of passage of stimuli.

The excitability of nerve cells can be
increased by many factors, including
stimulant drugs, inflammation and mild
degrees of those influences that in a more
severe form may cause depression of
excitability. Thus early or mild hypoxia
may result in increased excitability while
sustained or severe hypoxia will cause
depression of function or even death of
the nerve cell.

Irritation phenomena may result
from many causes, including inflamma-
tion of nervous tissue associated with
bacteria or viruses, certain nerve poisons,
hypoxia and edema. In those diseases that
cause an increase in intracranial pressure,
irritation phenomena result from inter-
ference with circulation and the develop-
ment of local anemic hypoxia. The major
manifestations of irritation of nervous
tissue are tetany, local muscle tremor, and
whole body convulsions in the motor
system and hyperesthesia and paresthesia
in the sensory system. For the most part
the signs produced fluctuate in intensity
and may occur periodically as nervous
energy is discharged and reaccumulated
in the nerve cells.

The area of increased excitability may
be local or sufficiently generalized to affect
the entire body. Thus a local lesion in the
brain may cause signs of excitatory nervous
dysfunction in one limb and a more
extensive lesion may cause a complete
convulsion.

Release of inhibition signs

Exaggeration of normal nervous system
activity occurs when lower nervous centers
are released from the inhibitory effects of
higher centers. The classic example of
a release mechanism is experimental
decerebrate rigidity caused by transection
of the brain stem between the colliculi of
the midbrain. This results in an uninhibited
extensor tonus of all the antigravity
muscles. The head and neck are extended
markedly in a posture of opisthotonos,
and all four limbs in the quadruped are
extended rigidly. The tonic mechanism or
myotactic reflex involving the lower motor
neuron has been released from the effects

of the descending inhibitory upper motor
neuron pathways.

Cerebellar ataxia is another example of
inhibitory release. In the absence of
cerebellar control combined limb move-
ments are exaggerated in all modes of
action including rate, range, force, and
direction. In general, release phenomena
are present constantly while the causative
lesion operates, whereas excitatory pheno-
mena fluctuate with the building up and
exhaustion of energy in the nerve cells.

Paresis or paralysis due to tissue
damage

Depression of activity can result from
depression of metabolic activity of nerve
cells, the terminal stage being complete
paralysis when nervous tissue is destroyed.
Such depression of activity may result
from failure of supply of oxygen and other
essential nutrients, either directly from
their general absence or indirectly because
of failure of the local circulation. Infection
of the nerve cell itself may cause initial
excitation, then depression of function
and finally complete paralysis when the
nerve cell dies.

Signs of paralysis are constant and are
manifested by muscular paresis or paralysis
when the motor system is affected and by
hypoesthesia or anesthesia when the
sensory system is involved. Deprivation of
metabolites and impairment of function
by actual invasion of nerve cells or by
toxic depression of their activity produce
temporary, partial depression of function
that is completely lost when the neurons
are destroyed.

Nervous shock

An acute lesion of the nervous system
causes damage to nerve cells in the
immediate vicinity of the lesion but there
maybe, in addition, a temporary cessation
of function in parts of the nervous system
not directly affected. The loss of function
in these areas is temporary and usually
persists for only a few hours. Stunning is
the obvious example. Recovery from the
flaccid unconsciousness of nervous shock
may reveal the presence of permanent
residual signs caused by the destruction
of nervous tissue.

Determining the type of lesion is diffi-
cult because of the limited range of modes
of reaction to injury in the nervous system.
Irritation signs may be caused by bacterial
or virus infection, by pressure, by vascular
disturbance or general hypoxia, by
poisons and by hypoglycemia. It is often
impossible to determine whether the
disturbance is structural or functional.
Degenerative lesions produce mainly
signs of paresis or paralysis but unless
there are signs of local nervous tissue
injury, such as facial nerve paralysis, para-
plegia or local tremor, the disturbance

may only be definable as a general disturb-
ance of a part of the nervous system.
Encephalopathy is an all-embracing
diagnosis, but it is often impossible to go
beyond it unless other clinical data,
including signalment of the animal,
epidemiology and systemic signs, are
assessed or special tests, including radio-
graphic examination and examination of
the CSF, are undertaken.

Some information can be derived from
a study of the sign-time relationship in
the development of nervous disease. A
lesion that develops suddenly tends to
produce maximum disturbance of func-
tion, sometimes accompanied by nervous
shock. Slowly developing lesions permit a
form of compensation in that undamaged
pathways and centers may assume some
of the functions of the damaged areas.
Even in rapidly developing lesions partial
recovery may occur in time but the
emphasis is on maximum depression of
function at the beginning of the disease.
Thus a slowly developing tumor of the
spinal cord will have a different pattern of
clinical development from that resulting
from an acute traumatic lesion. Another
aspect of the rapidity of onset of the
lesion is that irritation phenomena are
more likely to occur when the onset is
rapid and less common when the onset
is slow.

Clinical manifestations of
disease of the nervous
system

The major clinical signs of nervous system
dysfunction include:

° Altered mentation
® Involuntary movements
0 Abnormal posture and gait
° Paresis or paralysis
° Altered sensation
° Blindness

° Abnormalities of the autonomic
nervous system.

ALTERED MENTATION

Excitation states

Excitation states include mania, frenzy,
and aggressive behavior, which are
manifestations of general excitation of the
cerebral cortex. The areas of the cortex
that govern behavior, intellect and person-
ality traits in humans are the frontal lobes
and temporal cortex. The clinical import-
ance of these areas, which are poorly
developed in animals, is not great. The
frontal lobes, temporal cortex and limbic
system are highly susceptible to influences
such as hypoxia and increased intracranial
pressure.

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PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Mania

In mania the animal acts in a bizarre way
and appears to be unaware of its surround-
ings. Maniacal actions include licking,
chewing of foreign material, sometimes
themselves, abnormal voice, constant
bellowing, apparent blindness, walking
into strange surroundings, drunken gait
and aggressiveness in normally docile
animals. A state of delirium cannot be
diagnosed in animals, but mental dis-
orientation is an obvious component of
mania as we see it.

Diseases characterized by mania
include:

° Encephalitis, e.g. the furious form of
rabies, Aujeszky's disease in cattle
(pseudorabies, mad itch)
o Degenerative diseases of the brain,
e.g. mannosidosis, early
polioencephalomalacia, poisoning by
Astragalus sp.

° Toxic and metabolic diseases of brain,
e.g. nervous ketosis, pregnancy
toxemia, acute lead poisoning,
poisoning with carbon tetrachloride,
and severe hepatic insufficiency,
especially in horses.

Frenzy

Frenzy is characterized by violent activity
and with little regard for surroundings.
The animal's movements are uncontrolled
and dangerous to other animals in the
group and to human attendants, and are
often accompanied by aggressive physical
attacks.

Examples of frenzy in diseases of the
nervous system include:

0 Encephalomyelitides, e.g. Aujeszky's
disease

o Toxic and metabolic brain disease, e.g.
hypomagnesemic tetany of cattle and
sheep, poisoning with ammoniated
roughage in cattle.

Examples of frenzy in diseases of other
body systems are:

o Acute pain of colic in horses
° Extreme cutaneous irritation, e.g.
photosensitization in cattle.

Apparently reasonless panic,
especially in individual horses or
groups of cattle, is difficult to
differentiate from real mania. A horse
taking fright at a botfly or a swarm of
bees, a herd of cattle stampeding at
night are examples.

Aggressive behavior

Aggression and a willingness to attack
other animals, humans and inert objects
is characteristic of: the early stages of
rabies and Aujeszky's disease in cattle; in
sows during postparturient hysteria; in
the later stages of chronic hypoxia in any
species; and in some mares and cows

with granulosa-cell tumors of the ovary.
The latter are accompanied by signs of
masculinization and erratic or continuous
estrus . 4 It is often difficult to differentiate
between an animal with a genuine change
in personality and one that is in pain or is
physically handicapped, e.g. pigs and
cattle with atlantoaxial arthroses.

Depressive states

Depressive mental states include somno-
lence, lassitude, narcolepsy/catalepsy,
syncope and coma. They are all mani-
festations of depression of cerebral cortical
function in various degrees and occur as a
result of those influences that depress
nervous system function generally, as well
as those that specifically affect behavior,
probably via the limbic system. It is not
possible to classify accurately the types
of depressive abnormality and relate
them to specific causes, but the common
occurrences in farm animals are listed
below.

Depression leading to coma
In all species this may result from:

0 Encephalomyelitis and
encephalomalacia

0 Toxic and metabolic diseases of the
brain such as uremia, hypoglycemia,
hepatic insufficiency, toxemia,
septicemia and most toxins that
damage tissues generally
° Hypoxia of the brain, as in peripheral
circulatory failure of milk fever
“ Heat stroke

° Specific poisons that cause

somnolence, including bromides,
Amitraz in horses, methyl alcohol,

Filix mas (male fern), kikuyu grass.

Syncope

The sudden onset of fainting (syncope)
may occur as a result of:

° Acute circulatory and heart failure
leading to acute cerebral hypoxia
° Spontaneous cerebral hemorrhage, a
most unlikely event in adult animals
" Traumatic concussion and contusion
0 Lightning strike, electrocution.

Narcolepsy (catalepsy)

Affected animals experience episodes of
uncontrollable sleep and literally 'fall'
asleep. The disease is recorded in Shetland
ponies and is thought to be inherited in
them, in other horses, and in cattle . 5

Compulsive walking or head-
pressing

Head-pressing is a syndrome charac-
terized by the animal pushing its head
against fixed objects, into a corner of a
pen, leaning into a stanchion or between
fence posts. Head -pressing should be
differentiated from compulsive walking,
where affected animals put their heads

down and walk slowly while appearing
blind. If they walk into an object they lean
forward and indulge in head-pressing; if
confined to a stall they will often walk
around the pen continuously or head-
press into a corner. The syndrome repre-
sents a change in behavior pattern due to
an unsatisfied compulsive drive charac-
teristic of a disorder of the limbic system.
Causes include:

•> Toxic and metabolic brain disease,
especially polioencephalomalacia and
hepatic encephalopathy
° Diseases manifested by increased
intracranial pressure
0 Encephalomyelitides.

Aimless wandering

A similar but less severe syndrome to
compulsive walking is aimless walking,
severe mental depression, apparent blind-
ness, with tongue protrusion and continu-
ous chewing movements, although the
animal is unable to ingest feed or drink
water. Causes include:

° Toxic and metabolic diseases of brain,
including poisoning by Helichrysum
sp. and tansy mustard
° Degenerative brain diseases, e.g.
nigropallidal encephalomalacia in
horses, ceroid lipofuscinosis in sheep,
hydrocephalus in the newborn.

INVOLUNTARY MOVEMENTS

Involuntary movements are due to invol-
untary muscle contractions, which include
gradations from fasciculations, shivering
and tremor, to tetany, seizures or con-
vulsions. Opisthotonos or 'backward tone'
is a sustained spasm of the neck and limb
muscles resulting in dorsal and caudal
extension of the head and neck with rigid
extension of the limbs.

Tremor

This is a continuous, repetitive twitching
of skeletal muscles, which is usually visible
and palpable. The muscle units involved
may be small and cause only local skin
movement, in which case the tremor is
described as fasciculations; or the muscle
units may be extensive, the movement
much coarser and sufficient to move the
extremities, eyes or parts of the trunk.
The tremor may become intensified when
the animal undertakes some positive
action, this usually being indicative of
cerebellar involvement and is the counter-
part of intention tremor in humans. True
tremor is often sufficiently severe to cause
incoordination and severe disability in
gait. Examples of causes of tremor include:

° Diffuse diseases of the cerebrum,
cerebellum, spinal cord
° Degenerative nervous system disease,
e.g. hypomyelinogenesis of the

Clinical manifestations of disease of the nervous system

newborn as in congenital tremor of
pigs and calves, poisoning by
Swainsona sp.

0 Toxic nervous system disease caused
by a large number of poisons,
especially poisonous plants and fungi,
Clostridium botulinum toxin in shaker
foal syndrome; metabolic disease such
as hyperkalemic periodic paralysis in
the horse; early stages of hypocalcemia
in the cow (fasciculations of the
eyelids and ears).

Tics

Tics are spasmodic twitching movements
made at much longer intervals than in
tremor, the intervals being usually at least
several seconds in duration and often
much longer. The movements are suffi-
ciently widespread to be easily visible and
are caused by muscles that are ordinarily
under voluntary control. They are rare in
large animals but may occur after traumatic
injury to a spinal nerve.

Tetany

Tetanus is a sustained contraction of
muscles without tremor. The most com-
mon cause is Clostridium tetani intoxi-
cation following localized infection with
the organism. The degree of muscular
contraction can be exaggerated by stimu-
lation of the affected animal and the
limbs are rigid and cannot be passively
flexed easily -'lead pipe' rigidity.

Myoclonus is a brief, intermittent
tetanic contraction of the skeletal muscles
that results in the entire body being rigid
for several seconds, followed by relaxa-
tion. Inherited congenital myoclonus
(hereditary neuraxial edema) of Polled,
Horned and crossbred Hereford calves
is a typical example. Affected calves are
bright and alert and can suck normally
but if they undertake a voluntary move-
ment or are handled, their entire body
becomes rigid for 10-15 seconds.

Convulsions

Convulsions, seizures, fits, or ictus are
violent muscular contractions affecting
part or all of the body and occurring for
relatively short periods as a rule, although
in the late stages of encephalitis they may
recur with such rapidity as to give the
impression of being continuous.

Convulsions are the result of abnormal
electrical discharges in forebrain neurons
that reach the somatic and visceral motor
areas and initiate spontaneous, parox-
ysmal, involuntary movements. These
cerebral dysrhythmias tend to begin and
end abruptly and they have a finite
duration. A typical convulsion may have a
prodromal phase or aura that lasts for
minutes to hours, during which the
animal is oblivious to its environment and
seems restless. The beginning of the con-

vulsion may be manifested as a localized
partial convulsion of one part of the body
that soon spreads to involve the whole
body, when the animal usually falls_ to the
ground thrashing rhythmically. Following
the convulsion there may be depression
and temporary blindness, which may last
for several minutes up to a few hours.

The convulsion may be clonic, the
typical 'paddling' involuntary movement
in which repeated muscle spasms alternate
with periods of relaxation. Tetanic or tonic
convulsions are less common and are
manifested by prolonged muscular spasm
without intervening periods of relaxation.
True tetanic convulsions occur only rarely,
chiefly in strychnine poisoning and in
tetanus, and in most cases they are a brief
introduction to a clonic convulsion.

Convulsions can originate from disturb-
ances anywhere in the prosencephalon,
including cerebrum, thalamus or even
the hypothalamus alone. However, the
initiating cause may be in the nervous
system outside the cranium or in some
other system altogether, so that con-
vulsions are therefore often subdivided
into intracranial and extracranial types.
Causes are many and include the following.

Intracranial convulsions are caused
by:

• Encephalomyelitis, meningitis

• Encephalomalacia

• Acute brain edema

« Brain ischemia, including increased
intracranial pressure

• Local lesions caused by trauma
(concussion, contusion), abscess,
tumor, parasitic injury, hemorrhage

« Inherited idiopathic epilepsy.

Extracranial convulsions are caused by
brain hypoxia, as in acute circulatory or
cardiac failure, and toxic and metabolic
diseases of the nervous system, including:

° Hepatic encephalopathy
° Hypoglycemia (as in newborn piglets
and in hyperinsulinism due to islet
cell adenoma of the pancreas as
described in a pony)

• Hypomagnesemia (as in lactation
tetany in cows and mares)

° Inorganic poisons, poisonous plants
and fungi. There are too many to give
a complete list but well-known
examples are the chlorinated
hydrocarbons, pluronics used in bloat
control in cattle, Clostridium spp.
intoxications, e.g. Clostridium
perfringens type D and Clostridium
sordellii, and subacute fluoroacetate
poisoning

° Congenital and inherited defects
without lesions, e.g. familial
convulsions and ataxia in Angus
cattle.

Involuntary spastic paresis

Involuntary, intermittent contractions of
large muscle masses may result in spas-
modic movements of individual limbs or
parts of the body. In most, contractions
occur when voluntary movement is
attempted. Diseases in this category are: ■

o Stringhalt and Australian stringhalt of
horses

° Inherited spastic paresis (Elso-heel) of
cattle

® Inherited periodic spasticity (stall-
cramp) of cattle

• Inherited congenital myotonia of
cattle

B Inherited myotonia of goats.

ABNORMAL POSTURE AND GAIT

Posture

Posture is evaluated with the animal at
rest. Abnormal postures may be adopted
intermittently by animals in pain but in
diseases of the nervous system the abnor-
mality is usually continuous and repeatable.
Deviation of the head and neck from the
axial plane or rotation of the head and
neck from the horizontal plane (head tilt)
and drooping of the lips, eyelids, cheeks
and ears, and opisthotonos and orthotonos
are examples, although the latter two are
often intermittent in that they occur as
part of a convulsive seizure. Head-
pressing and assumption of a dog-sitting
posture are further examples. Abnonnalities
of posture and gait are the result of lesions
of the brainstem, cerebellum, all levels of
the spinal cord, spinal nerve roots,
peripheral nerves, neuromuscular junc-
tions and muscles. The clinical emphasis
is on vestibular disease, cerebellar disease
and spinal cord disease. It is important to
recognize that cerebral lesions do not
cause abnormalities in posture and gait.

Vestibular disease

The vestibular system is a special proprio-
ceptive system that assists the animal to
maintain orientation in its environment
with respect to gravity. The system helps
to maintain the position of the eyes, trunk
and limbs in relationship to movements
and positioning of the head.

From the vestibular nuclei, the vesti-
bulospinal tracts descend ipsilaterally
through the length of the spinal cord. These
neurons are facilitatory to ipsilateral motor
neurons going to extensor muscles of the
limbs, are inhibitory to ipsilateral motor
flexor muscles and are inhibitory to contra-
lateral extensor muscles. The principal effect
of unilateral stimulation of this system on
the limbs is a relative ipsilateral extensor
tonus and contralateral flexor tonus, which
promotes ipsilateral support of the trunk
against gravity. Conversely, a unilateral
vestibular lesion usually results in ipsilateral

580

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

flexor and contralateral extensor tonus,
forcing the animal toward the side of the
lesion.

The nuclei of cranial nerves III, IV, and
VI, which control eye movement, are
connected with the vestibular system by
way of a brainstem tract - the medial
longitudinal fasciculus. Through this tract,
coordinated eye movements occur with
changes in positioning of the head.
Through these various pathways, the
vestibular system coordinates movements
of the eye, trunk, and limbs with head
movements and maintains equilibrium
of the entire body during motion and rest.

Signs of vestibular disease vary depend-
ing on whether there is unilateral or
bilateral involvement and whether the
disease involves peripheral or central
components of the system.

The vestibular influence on balance
can be affected:

•> At the inner ear
? Along the vestibular nerve or
0 At the vestibular nucleus in the
medulla.

Unilateral excitation or loss of function can
be caused by lesions at any of these points.

General signs of vestibular system
dysfunction are staggering, leaning,
rolling, circling, drifting sideways when
walking and a head tilt, and various
changes in eye position such as strabismus
and nystagmus. The walking in a circle
toward the affected side is accompanied
by increased tone in the contralateral
limbs, which is most easily observed in
the contralateral forelimb. Rotation or tilt
of the head occurs and severely affected
animals fall to the affected side.

When the lesion affects the inner ear,
as it may do in otitis media, the affected
side is turned down, the animal falls to
that side and there may be facial paralysis
on the same side if the lesion is extensive
and affects the seventh cranial nerve. In
the recumbent position, the affected side
is held to the ground, and if these animals
are rolled over to the opposite side they
quickly roll back to the affected side.
When the vestibular nuclei are affected,
which may occur in listeriosis, the animal
falls to the affected side.

Nystagmus and forced circling are
common when there is irritation of the
vestibular nucleus or the medial longi-
tudinal fasciculus.

Causes of vestibular disease include:

° Otitis media-interna with
involvement of the inner ear
0 Focal lesion at the vestibular nucleus,
e.g. listeriosis

0 Traumatic injury to the vestibular
apparatus in the horse caused by
fracture of the basisphenoid.

basioccipital and temporal bones in a
traumatic injury. The clinical signs
include lack of control of balance,
rotation of the head, circling to the
affected side, nystagmus and facial
paralysis.

In paradoxical vestibular syndrome

there is also head tilting, but circling in a
direction away from the side of the
lesion . 6 Deviation of the head and neck
must be distinguished from a head tilt.
Asymmetric lesions of the forebrain
such as a brain abscess, some cases of
polioencephalomalacia, verminous larval
migration or head trauma may cause
an animal to hold its head and neck
turned to one side, but there is no head
tilt and the circle is large in diameter.
In fact, the presence of a head tilt
(deviation of eyes away from a horizontal
plane) accompanied by a tight circle pro-
vide clinically useful methods of differen-
tiating a cerebral lesion from a vestibular
lesion.

Gait

Gait is assessed when the animal is
moving. Neurological gait abnormalities
have two components, weakness and
ataxia. Weakness (paresis) is evident
when an animal drags its limbs, has worn
hooves or has a low arc to the swing
phase of the stride. When an animal bears
weight on a weak limb, the limb often
trembles and the animal may even collapse
on that limb because of lack of support.
While circling, walking on a slope, and
walking with the head elevated, an animal
frequently will stumble on a weak limb
and knuckle over at the fetlock. During
manipulation of the limb, the clinician
will usually make the subjective obser-
vation that the muscle tone is reduced.

Ataxia

Ataxia is an unconscious, general pro-
prioceptive deficit causing incoordination
when the animal moves. Ataxia is
manifest as a swaying from side to side of
the pelvis, trunk and sometimes the
whole body (truncal sway). Ataxia may
also appear as a weaving of the affected
limb during the swing phase of the stride.
This often results in abducted or adducted
foot placement, crossing of the limbs or
stepping on the opposite foot.

Hypermetria is an increased range
of movement and is seen as an over-
reaching of the limbs with excessive joint
movement. Hypermetria without paresis
is characteristic of spinocerebellar and
cerebellar disease.

Hypometria is a decreased range of
movement that is characterized by a stiff
or spastic movement of the limbs with
little flexion of the joints, particularly the
carpal and tarsal joints.

Dysmetria is a term that includes both
hypermetria and hypometria, with goose-
stepping being the most common sign of
dysmetria. Dysmetria usually is caused by
a lesion in the cerebellum or cerebellar
pathway.

In equine degenerative myeloence-
phalopathy, there is dysmetria of the hind-
limbs and tetraparesis due to neuraxonal
dystrophy originating in the accessory
cuneate nuclei . 7 Severely affected horses
lift their feet excessively high and stamp
them to the ground.

Cerebellar disease

When cerebellar function is abnormal
there is ataxia, which is an incoordination
when the animal moves. In general terms
there are defects in the rate, range and
direction of movement. In typical cerebellar
diseases, ataxia of the limbs is common
and no weakness is evident. In true
cerebellar ataxia (e.g. cerebellar hypoplasia)
the affected animal stands with the legs
wide apart, sways and has a tendency to
fall. Ataxia of the head and neck are
characterized by wide, swinging, head
excursions, jerky head bobbing and an
intention tremor (nodding) of the head.

The head tremor may be the most
obvious sign in mild cases of cerebellar
hypoplasia in young foals. The limbs do
not move in unison, the movements are
grossly exaggerated, muscular strength is
usually preserved and there is a lack of
proper placement of the feet (hypermetria
and hypometria), so that falling is
common. The fault in placement is the
result of poor motor coordination and not
related in any way to muscle weakness or
proprioceptive deficit. Attempts to pro-
ceed to a particular point are usually
unsuccessful and the animal cannot
accurately reach its feed or drinking bowl.
Examples of cerebellar disease include:

° Inherited defects of cerebellar
structure or abiotrophy 8 in most
breeds of cattle and in Arabian horses
° Congenital cerebellar defects resulting
from maternal viral infections such as
bovine virus diarrhea (BVD) infection
in cattle

•’ Dysplastic disease of the cerebellum
of the horse

° Traumatic injury, e.g. by parasite
larvae such as Hijpoderma bovis, which
have caused unilateral cerebellar
ataxia in adult cattle
0 Tremorogenic mycotoxicoses and
ryegrasses

° Encephalomyelitis in which other
localizing signs also occur.

Spinal cord disease

Ataxia due to cerebellar dysfunction can
be difficult to differentiate from the
proprioceptive defects and partial motor

Clinical manifestations of disease of the nervous system

58

paralysis (weakness) that occur in animals
with spinal cord lesions and it is most
important that this differentiation be
made. Spinal cord disease, causing
varying degrees of weakness, and ataxia
are common in large animals. The weak-
ness is caused by damage to the upper or
lower motor neurons and the pro-
prioceptive deficit by damage to the
ascending sensory neurons. With a mild
or even moderate cervical spinal cord
lesion in an adult cow or horse, signs of
ataxia and weakness may be evident in
the pelvic limbs only and it can be difficult
to determine whether the thoracic limbs
are involved.

Close examination of the gait, posture
and postural reactions in the limbs,
together with a search for localizing
abnormalities, will often be productive in
localizing the lesion. Signs of weakness or
ataxia may be elicited by gently pushing
the hindquarters to one side or pulling
the tail to one side as the animal is walked
(the sway response) . The normal animal
resists these movements or steps briskly
to the side as it is pushed or pulled. The
weak animal can be easily pulled to one
side and may stumble or fall. The weak
animal may also tend to buckle or
collapse when strong pressure is applied
with the hand over the withers and loin
regions. The ataxic animal may sway to
one side, be slow to protract a limb, cross
its hindlegs or step on its opposite limb.

It is often difficult to distinguish paresis
from ataxia but in most instances it is
unimportant because of the close ana-
tomical relationship of the ascending
general proprioceptive and descending
upper motor neuron tracts in the white
matter of the spinal cord. These same
abnormal sway responses can be elicited
in the standing animal.

The ataxic animal may abduct the
outside pelvic limb too far as it is pushed
to one side or moved in a small circle. This
may appear as a hypermetric movement
similar to a stringhalt action and is
assumed to be a sign of a general pro-
prioceptive tract lesion. The pushed or
circled animal may keep a clinically affected
pelvic limb planted in one position on the
ground and pivot around it without
moving it. The same failure to protract the
limb may be seen on backing. It may even
force the animal into a 'dog-sitting'
posture.

Examples of ataxia due to spinal cord
disease include:

° Limited trauma to the spinal cord
° The early stages of a developing

compression lesion in the vertebral

canal

° Degenerative and inflammatory

diseases of the nervous system.

especially those causing enzootic
incoordination in horses and staggers
in sheep (both of them dealt with
under their respective headings)

° Functional diseases in toxic and
metabolic diseases of the nervous
system in which lesions have not yet
been identified and caused mainly by
poisons, especially plant materials.
Typical examples are poisoning by the
fungi Claviceps paspali, Diplodia spp.,
Acremonium lolii, the grass Phalaris
aquatica, the ferns Zamia and
Xanthorrhea spp. and herbaceous
plants such as Kallstroemia, Vida,
Baccharis, Solarium, Aesculus and
Ficus spp.

° Nutritional deficiency especially of
thiamin, occurring naturally in horses
poisoned by bracken and horsetail,
and experimentally in pigs
° Developmental defects including
congenital abnormalities and
abiotrophic abnormalities that
develop some time after birth.
Examples are Brown Swiss weavers
and Pietrain pig creepers.

In many of these diseases incoordination
and paresis are a stage in the development
of tetraplegia or paraplegia.

PARESIS AND PARALYSIS

The motor system comprises:

° The pyramidal tracts, which originate
in the motor cortex
° The extrapyramidal system, which
originates in the corpus striatum, red
nucleus, vestibular nucleus and roof
of the midbrain

.0 The peripheral nerves, which
originate in the ventral horn cells.

The pyramidal tracts are of minor impor-
tance in hoofed animals (ungulates),
reaching only to the fourth cervical seg-
ment. Accordingly, lesions of the motor
cortex in farm animals do not produce
any deficit of gait. Neither is there any
paresis, although in an acute lesion weak-
ness may be evident for the first day or
two. If the lesion is unilateral the paresis
will be on the contralateral side. This is in
marked contradistinction to the severe
abnormalities of posture and gait that
occur with lesions of the pons, medulla,
and spinal cord.

The main motor nuclei in these
animals are subcortical and comprise
the extrapyramidal system, and most
combined movements are controlled by
nerve stimuli originating in the tectal
nuclei, reticular nuclei, vestibular nuclei
and possibly red nuclei. The pyramidal
and extrapyramidal tracts comprise the
upper motor neurons, which reach to the
ventral horn cells of the spinal cord.

which cells together with their peripheral
axons form the lower motor neurons.
Paralysis is a physiological end result in all
cases of motor nerve injury, which if
severe enough is expressed clinically. The
type of paralysis is often indicative of the
site of the lesion.

A lesion of the upper motor neuron

causes:

° Spasticity with loss of voluntary

movement

0 Increased tone of limb muscles
° Increased spinal reflexes.

The spasticity of an upper motor neuron
lesion usually occurs with the affected
limb in extension. These are all release
phenomena resulting from liberation of
spinal reflex arcs from higher control.

A lesion of the lower motor neuron
causes:

° Paresis or paralysis with loss of

voluntary movement
° Decreased tone of the limb muscles
° Absence of spinal reflexes
° Wasting of the affected muscle

(neurogenic atrophy).

As injuries to specific peripheral nerves
are treated surgically, these are dealt with
in surgical textbooks and are not repeated
here.

A special fonn of paralysis is the Schiff-
Sherrington syndrome, which is com-
mon in dogs but recorded rarely in large
animals. It is caused by acute, severe,
compressive injury of the thoracolumbar
spinal cord and manifested by extensor
rigidity or hypertonia of the forelimbs and
hypotonic paralysis of the hindlimbs.
Neurons located in the lumbar spinal
cord are responsible for the tonic
inhibition of extensor muscle alpha motor
neurons in the cervical intumescence. The
cell bodies of these neurons are located in
the ventral gray column from L1-L7, with
a maximum population from L2-L4. Their
axons ascend to the cervical intumes-
cence. Acute severe lesions cranial to
these neurons and caudal to the cervical
intumescence will suddenly deprive the
cervical intumescence neurons of this
source of tonic inhibition, resulting in a
release of these latter neurons. This
results in extensor hypertonia observed in
the thoracic limbs which can function
normally in the gait and postural reactions,
except for the hypertonia.

The degree of paresis or paralysis
needs to be defined. Paralysis is identified
as an inability to make purposeful move-
ments. Thus convulsive, uncontrolled
movements as they occur in polio-
encephalomalacia may still fit a descrip-
tion of paralysis. Paresis, or weakness
short of paralysis, can be classified into
four categories:

582

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

8 Animals that cannot rise, nor support
themselves if helped up, but can make
purposeful movements in attempting
to rise

• Animals that cannot rise but can
support themselves if helped up
0 Animals that can rise but are paretic
and can move the limbs well and
stumble only slightly on walking
® Animals that move with difficulty and
have severe incoordination and
stumbling.

Probably the most difficult decision in
farm animal neurology is whether a
patient's inability to move is because of a
nervous or muscular deficit. For example,
the horse recumbent because of exer-
tional rhabdomyolysis often resembles a
horse with an injured spinal cord. Examples
of paresis and paralysis include:

0 Focal inflammatory, neoplastic,
traumatic lesions in the motor
pathway. These lesions usually
produce an asymmetric nervous
deficit

° Toxic and metabolic diseases of the

nervous system in their most severe
form, e.g. flaccid paralysis associated
with tickbite ( Ixodes holocyclus,
Ornithodoros sp.), poisoning, botulism,
snakebite. Comparable tetanic
paralyses include tetanus, lactation
tetany of mares, hypomagnesemic
tetany of cows and calves. In contrast
to inflammatory, neoplastic and
traumatic lesions in the motor
pathway, toxic and metabolic lesions
usually produce a symmetric
nervous deficit.

Neurogenic muscular atrophy

Destruction of the lower motor neurons
either within the vertebral canal or per-
ipheral to it causes neurogenic atrophy.
Whether or not the atrophy is visible
depends on how many neurons and there-
fore how many muscle fibers are affected.

A LTERE D SE NSATION

Lesions of the sensory system are rarely
diagnosed in animals, except for those
affecting sight and the vestibular apparatus,
because of the impossibility of measuring
subjective responses.

Thus, although animals must expe-
rience paresthesia, as in Aujeszky's disease
(pseudorabies) in cattle and sheep, the
animal's response of licking or scratching
does not make it possible to decide whether
the diagnosis should be paresthesia or
pruritus. Lesions of the peripheral sensory
neurons cause hypersensitivity or decreased
sensitivity of the area supplied by the
nerve. Lesions of the spinal cord may affect
only motor or only sensory fiber tracts or
both, or may be unilateral.

Although it is often difficult to decide
whether failure to respond to a normally
painful stimulus is due to failure to per-
ceive or inability to respond, certain tests
may give valuable information. The test
commonly used is pricking the skin with
a needle, or pinching the skin with a pair
of forceps, and observing the reaction. In
exceptional circumstances light stroking
may elicit an exaggerated response. The
'nibbling' reaction stimulated by stroking
the lumbar back of sheep affected
with scrapie is a striking example of
hypersensitivity.

In every test of sensitivity it must be
remembered that there is considerable
variation between animals and in an
individual animal from time to time, and
much discretion must be exercised when
assessing the response. In any animal
there are also cutaneous areas that are
more sensitive than others. The face and
the cranial cervical region are highly sensi-
tive, the caudal cervical and shoulder
regions less so, with sensitivity increasing
over the caudal thorax and lumbar region
to a high degree on the perineum. The
proximal parts of the limbs are much less
sensitive than the distal parts and sensi-
tivity is highest over the digits, parti-
cularly on the medial aspect.

Absence of a response to the appli-
cation of a painful stimulus to the limbs
(absence of the withdrawal reflex)
indicates interruption of the reflex arc,
absence of the reflex with persistence of
central perception, as demonstrated by
groaning or body movement such as
looking at the site of stimulus application,
indicates interruption of motor pathways
and that central perception of pain
persists. In the horse the response can be
much more subtle than in other species,
with movements of the ears and eyelids
being the best indicators of pain percep-
tion. Increased sensitivity is described
as hyperesthesia, decreased as hypo-
esthesia, and complete absence of sensi-
tivity is described as anesthesia. Special
cutaneous reflexes include the anal reflex,
in which spasmodic contraction of the
anus occurs when it is touched, and the
corneal reflex, in which there is closure of
the eyelids on touching the cornea. The
(cutaneous trunci) panniculus reflex is
valuable in that the sensory pathways,
detected by the prick of a pin, enter the
cord at spinal cord segments T1-L3, but
the motor pathways leave the cord only at
spinal cord segments C8, Tl, and T2. The
quick twitch of the superficial cutaneous
muscle along the whole back, which is the
positive response (panniculus reflex), is
quite unmistakable. Examination of the
eye reflexes and hearing are discussed
under examination of the cranial nerves
(see below).

BLINDNESS

Blindness is manifested as a clinical abnor-
mality by the animal walking into objects
that it should avoid.

The menace or blink reflex is used to
test the visual pathway. A threatening
gesture of the hand (or even better by
the index finger in a pointing manner)
toward the eye elicits immediate closure
of the eyelids. The hand must come close
enough to the eye without touching the
tactile hairs of the eyelids or creating a
wind which can be felt by the animal.
Some stoic, depressed or even excited
animals may not respond to a menace
reflex with closure of the eyelids; others
may keep the eyelids partially or almost
closed. It may be necessary to alert the
patient to the risk of injury by touching
the eyelids first. The menace reflex is a
learned reflex that is absent in neonates.

The most definitive test is to make the
animal walk an obstacle course and
place objects in front of it so that it must
step over the objects easily. A similar
procedure is the only way to test for night
blindness (nyctalopia). The area should
be dimly lit but the observer should be
able to see the obstructions clearly. A
decision that the animal is blind creates
a need for examination of the visual
pathways.

Central or peripheral blindness

Blindness may be central or peripheral.
Animals with forebrain lesions are centrally
blind, with depressed menace response in
one or both eyes while the pupillary light
reflexes are commonly intact. In periph-
eral blindness, such as hypovitaminosis-
A, the menace reflex is absent, and the
pupillary light reflexes are also absent.

Blindness can be caused by lesions
along the visual pathway, from the eye to
the cerebral cortex:

11 Diseases of the orbit including
keratoconjunctivitis, hypopyon,
cataract, panophthalmia, mixed ocular
defects inherited in white Shorthorn
and Jersey cattle, night blindness in
Appaloosa horses, sporadic cases of
blindness due to idiopathic retinal
degenerative disease in cattle
° Diseases of the retina including
retinal dysplasia of goats, lenticular
cataracts caused by poisoning with
hygromycin in pigs, 9 congenital ocular
malformations in calves after
intrauterine infection with BVD virus
(usually accompanied by cerebellar
defects)

° Diseases of the optic nerve and
chiasma, e.g. abscess of pituitary rete
mirabile, constriction of optic nerve by
diet deficient in vitamin A. Tumor of
pituitary gland, injury to the optic

Special examination of the nervous system

nerve, especially in horses after
rearing and falling backwards. There is
a sudden onset of unilateral or
bilateral blindness with no
ophthaliuological change until
3-4 weeks after the injury, when the
optic disc becomes paler and less
vascular 10

® Metabolic or ischemic lesions of
the cerebral cortex as in

polioencephalomalacia, cerebral
edema, hydrocephalus

° Localized infectious or parasitic
lesions caused by abscesses,
migrating larvae

° Functional blindness in which there
is complete, often temporary,
blindness in the absence of any
physical lesions. Causes are
acetonemia, pregnancy toxemia and
acute carbohydrate indigestion (hyper
D-lactatemia) of ruminants
° Specific poisonings causing
blindness include Filix mas (male
fern), Cheilanthes spp. (rockfern) and
rape. Stypandra spp. cause a specific
degeneration of the optic nerves. Lead
poisoning in cattle.

ABNORMALITIES OF THE
AUTONOMIC NERVOUS SYSTEM

Lesions affecting the cranial parasym-
pathetic outflow do so by involvement of
the oculomotor, facial, vagus, and glosso-
pharyngeal nerves or their nuclei and the
effects produced are discussed under
examination of the individual nerves.

In general, the lesions cause abnor-
mality of pupillary constriction, salivation
and involuntary muscular activity in the
upper part of the alimentary and res-
piratory tracts. Lesions of the spinal
sympathetic system interfere with normal
function of the heart and alimentary
tract. For the most part, affections of
the autonomic nervous system are of minor
importance in farm animals. Central
lesions of the hypothalamus can cause
abnonnalities of heat exchange, manifested
as neurogenic hyperthermia or hypo-
thermia and obesity, but they are also of
minor importance.

Some manifestations of autonomic
disease are important. Autonomic im-
balance is usually described as the
physiological basis for spasmodic colic of
horses; grass sickness of horses is charac-
terized by degenerative lesions in the
sympathetic ganglia; involvement of
the vagus nerve in traumatic reticulo-
peritonitis of cattle can lead to impaired
forestomach and abomasal motility and
the development of vagus indigestion.

Defects of sphincter control and motility
of the bladder and rectum may also be of
importance in the diagnosis of defects of

sacral parasympathetic outflow and the
spinal sympathetic system. The sacral
segments of the spinal cord are the critical
ones, and loss of their function will cause
incontinence of urine and loss of rectal
tone. The parasympathetic nerve supply
to the bladder stimulates the detrusor
muscle and relaxes the sphincter; the
sympathetic nerve supply has the reverse
function. A spinal cord lesion may cause
loss of the parasympathetic control and
result in urinary retention. Incontinence,
if it occurs, does so from overflow. When
the sympathetic control is removed
incontinence occurs but the bladder should
empty. Similar disturbances of defecation
occur. Both micturition and defecation are
controlled by medullary and spinal centers
but some measure of control is regained
even when the extrinsic nerve supply to
the bladder and rectum is completely
removed.

Special examination of the
nervous system

Veterinarians commonly include several
components of a neurological examina-
tion in a complete clinical examination.
Most often a diagnosis and differential
diagnosis can be made from considera-
tion of the history and the clinical findings.
However, if the diagnosis is uncertain it
may be necessary to conduct a complete
neurological examination, which may
uncover additional clinical findings
necessary to make a diagnosis and give a
prognosis.

The accuracy of clinical diagnosis of
neurological diseases in the horse is
high. 11 In a study of 210 horses in which a
definitive pathological diagnosis was
confirmed, the overall accuracy of clinical
diagnosis for all diseases was 0.95; the
accuracy ranged from 0.79-1.00, the sensi-
tivity varied from 0.73-0.95 and the
specificity varied from 0.88-1.00 for
individual disease categories. Some
neurological diseases are therefore under-
diagnosed while others are overdiagnosed.
The use of careful and thorough clinical
examinations and diagnostic techniques,
combined with confirmed pathological
diagnoses, will result in more accurate
diagnosis and therapy. Retrospective
studies of series of ataxic horses, for
example, will add to the body of knowl-
edge and improve diagnosis. 12

THE NEUROLOGICAL
EXA MINATION

The primary aim of the neurological
examination is to confirm whether or
not a neurological abnormality exists
and to determine the neuroanatomical

location of the lesion. 13 A clinicoana-
tomical diagnosis is necessary before one
can develop a list of differential diagnoses
and decided whether or not treatment is
possible. The format for a precise practical
examination procedure that is logical in
sequence, easy to remember with practice,
and emphasizes the need for an anatomical
diagnosis is outlined below. The rationale
for the sequence is that the examination
starts from a distance to assess posture
and mentation, and then proceeds to a
closer examination that may require
placing the animal in stocks or a chute.
The examination sequence is therefore
suitable for minimally handled beef cattle,
dairy cattle, horses, sheep, goats, and New
World camelids.The results of the neuro-
logical examination should be documented
and not left to memory. There are many
standard examination forms available that
outline each step in the examination and
provide for documentation of the results.

SIGNALMENT AND
EPIDEMIOLOGY

The age, breed, sex, use, and value of the
animal are all important considerations in
the diagnosis and prognosis of neuro-
logical disease. Some diseases occur more
frequently under certain conditions: for
example, lead poisoning in nursing beef
calves turned out to pasture in the spring
of the year. Histophilus somni meningoen-
cephalitis occurs most commonly in
feedlot cattle from 6-10 months of age
and hypovitaminosis-A occurs most
commonly in beef calves 6-8 months of
age after grazing dry summer pastures. In
the horse there are several clearly defined
diseases that affect the spinal cord
including cervical stenotic myelopathy,
degenerative myeloencephalopathy, pro-
tozoal myelitis, equine rhinopneumonitis
myelopathy, rabies polioencephalomye-
litis and equine motor neuron disease. 14
Some of these diseases have distinguish-
ing epidemiological characteristics that
are useful in diagnosis and differential
diagnosis. 9 The neurological examination
of the newborn foal is fraught with
hazards because of the different responses
elicited from those in adults. The differ-
ences relate mostly to the temporary
dysmetria of gait and exaggerated re-
sponses of reflexes.

HISTORY

Special attention should be given to the
recording of an accurate history. The
questioning of the owner should focus
on the primary complaint and when it
occurred and how it has changed over
time (the time-sign relationship). The
duration of signs, the mode of onset,
particularly whether acute with later

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

subsidence, or chronic with gradual
onset, the progression of involvement and
the description of signs that occur only
intermittently should be ascertained.
When the disease is a herd problem the
morbidity and mortality rates and the
method of spread may indicate an
intoxication when all affected animals
show signs within a very short period.
Diseases associated with infectious agents
may have an acute or chronic onset.
Neoplastic diseases of the nervous system
may begin abruptly but are often slowly
progressive. For some diseases, such as
epilepsy, consideration of the history may
be the only method of making a diag-
nosis. 13 Traumatic injuries have a sudden
onset and then often stabilize or improve.

When obtaining a history of convulsive
episodes an estimate should be made of
their duration and frequency. The pattern
is also of importance, and may be diag-
nostic, e.g. in salt poisoning in swine. The
occurrence of pallor or cyanosis during
the convulsion is of particular importance
in the differentiation of cardiac syncope
and a convulsion originating in the
nervous system.

HEA D

Behavior

The owner should be questioned about
the animal's abnormal behavior, which
can include bellowing, yawning, licking,
mania, convulsions, aggressiveness, head-
pressing, wandering, compulsive walking
and head-shaking. 16 Head-shaking may
be photic in origin and can be tested by
the application of blindfolds, covering the

eyes with a face mask and observing
the horse in total darkness outdoors. 17 In
one horse, head-shaking ceased with
blindfolding or night darkness outdoors,
and became less with the use of gray
lenses. Outdoor behavior suggested
efforts to avoid light.

Mental status

Assessment of mental status is based
on the animal's level of awareness or
consciousness. Coma is a state of complete
unresponsiveness to noxious stimuli.
Other abnormal mental states include
stupor, somnolence, debriousness, lethargy
and depression. Large animals that are
recumbent because of spinal cord disease
are commonly bright and alert unless
affected with complications, which may
cause fever and anorexia. Mature beef
cattle that are recumbent with a spinal
cord lesion and not used to being handled
may be quite aggressive and apprehensive.

Head position and coordination

Lesions of the vestibular system often
result in a head tilt. Lesions of the
cerebrum often result in deviation of the
head and neck. In cerebellar disease, there
may be jerky movements of the head,
which are exaggerated by increasing
voluntary effort. These fine jerky move-
ments of the head are called intention
tremors. Animals with severe neck pain
will hold their neck in a fixed position and
be reluctant to move the head and neck.
Head-shaking in horses has been associ-
ated with ear mite infestation, otitis
externa, cranial nerve dysfunction, cervical
injury, ocular disease, guttural pouch
mycosis, dental periapical osteitis and

vasomotor rhinitis. 16 However, idiopathic
head-shaking in the horse is often associ-
ated with evidence of nasal irritation,
sneezing and snorting, nasal discharge,
coughing and excessive lacrimation.

Cranial nerves

Abnormalities of cranial nerve (CN)
function assist in localizing a lesion near
or within the brainstem. Some of the infor-
mation on cranial nerve dysfunction is
presented in tabular form (Tables 12.1-12.6)
in addition to the more detailed examin-
ation described here.

Olfactory nerve (CN I)

Tests of smell are unsatisfactory in large
animals because of their response to food
by sight and sound.

Optic nerve (CN II)

The only tests of visual acuity applicable
in animals are testing the eye preservation
(menace) reflex: provoking closure of the
eyelids and withdrawal of the head by
stabbing the finger at the eye; and by
making the animal run a contrived obstacle
course. Both tests are often difficult to
interpret and must be carried out in such
a way that other senses are not used to
determine the presence of the obstacles
or threatened injury. In more intelligent
species, a good test is to drop some light
object such as a handkerchief or feather in
front of the animal. It should gaze at the
object while it is falling and continue to
watch it on the ground. The same method
can be applied to young ruminants, which
demonstrate normal vision by following
the examiner's moving hand at an age so
early that they have not yet developed a

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Principal sign

Secondary signs

Location of lesion

Example

Mania hysteria/hyperexcitability

Continuous, leading to paralysis;
aggression, convulsions

Cerebrum-limbic system

Peracute lead poisoning, rabies,
encephalitis

Intermittent, acetonuria, signs of
hepatic insufficiency

Cerebrum-limbic system

Hypoglycemia, hypoxia

Coma (recumbency with no

Gradual development. Hypothermia,

Cerebral-brainstem reticular

Hepatic insufficiency, uremia,

response to stimuli; dilated

peripheral vascular collapse.

formation (ascending reticular

toxemia, septicemia

pupils)

Clinicopathological tests

activating system)

Sudden onset. Normal temperature,

Cerebral-brainstem reticular

Accidental, severe blunt trauma

pulse/heart rate slow to normal,

formation (ascending reticular

with edema, concussion,

nose bleed, skin laceration, bruising
middle of forehead or poll

activating system)

contusion of brain

Narcolepsy/catalepsy.

With or without sudden loss of

Brainstem control of cerebral

Inherited in Shetland ponies,

Uncontrollable sleep

consciousness, intermittent falling
due to loss of voluntary motor
function

cortex

American miniature horses, and
Suffolk horses

Compulsive walking and

Apparent blindness, nystagmus

Cerebral-visual cortex and limbic

Increased intracranial pressure in

head-pressing, aggressive
behavior, grinding of teeth.

system

polioencephalomalacia

No ataxia

Apparent blindness, no nystagmus,

Cerebral-visual cortex and

Hepatic insufficiency (i.e.

hepatic insufficiency shown on
clinical pathology tests

limbic system

ammonia intoxication; in
pyrrolizidine poisoning)

Imbecility in neonate; lack of

Blindness

Cerebral cortex absent;

Intrauterine infection with

response to normal stimuli;
can walk, stand

hydrencephaly

Akabane or bovine virus
diarrhea (BVD) virus in calves

Special examination of the nervous system

585

^ ik’M

Principal sign

Secondary signs

Location of lesion

Example

Tremor (continuous repetitive

Moderate tetany

No specific focal lesion. Generalized

Congenital tremor of Herefords.

movements of skeletal muscles)

disease, e.g hypomyelinogenesis

Hypomyelinogenesis, shaker pigs,
lambs with Border disease

Intention tremor, sensory ataxia

Cerebellum

Cerebellar hypoplasia

With head rotation

Vestibular apparatus

Otitis media and interna. Fracture
of petrous temporal bone

Nystagmus

Usually with tetraparesis, impaired

Cerebellopontine and midbrain

Injury, increased intracranial

consciousness, abnormal pupils,
opisthotonos, facial palsy, dysphagia

areas

pressure, polioencephalomalacia,
listeriosis

Pendular nystagmus

No lesion

Benign sporadic occurrence in
dairy cattle, inherited in Finnish
Ayrshire bulls

Independent episodes

Focus of irritation in cerebral
cortex or thalamus, with spread of
excitation

Idiopathic or traumatic epilepsy

Convulsions

Continuous, leading to paralysis

Cerebral cortex

Increased intracranial pressure,
encephalitis

Intermittent, related to periods of
metabolic stress

Cerebral cortex

Hypomagnesemia (lactation
tetany); hypoglycemia (e.g. of
baby pigs)

Tenesmus (straining)

Later paralysis of anus, sometimes
tail head. Sexual precocity in male

Caudal cord segments and cauda
equina, stimulation of nerve cells,
later paralysis

Rabies, subacute local meningitis

Compulsive rolling

Compulsive walking and
head-pressing

Disturbance of balance, cannot stand,
must lie on one side. Nystagmus
(See Table 12.1)

Vestibular apparatus

Brain abscess, otitis media

menace reflex. Ophthalmoscopic examin-
ation is an integral part of an examination
of the optic nerve.

Oculomotor nerve (CN III)

This nerve supplies the pupilloconstrictor
muscles of the iris and all the extrinsic
muscles of the eyeball except the dorsal
oblique, the lateral rectus and the
retractor muscles. Loss of function of the
nerve results in pupillary dilatation and
defective pupillary constriction when the
light intensity is increased, abnormal
position (ventrolateral deviation) or
defective movement of the eyeballs and
palpebral ptosis.

The pupillary light reflex is best tested
by shining a bright point source of light
into the eye, which causes constriction of
the iris of that eye (direct pupillary reflex) .
Constriction of the opposite eye (consen-
sual pupillary light reflex) will also occur.
The consensual light reflex may be used
to localize lesions of the optic pathways.

Examination of the menace reflex (eye
preservation reflex to a menace) and the
results of the pupillary light reflex can be
used to distinguish between blindness due
to a lesion in the cerebral cortex (central
blindness) and that due to lesions in the
optic nerve or other peripheral parts of
the optic pathways (peripheral blindness).

As examples, in polioencephalomalacia
(central blindness) the menace reflex is
absent but the pupillary light reflex is
present. In the ocular form of hypo-

vitaminosis A (peripheral blindness) in
cattle the menace reflex is also absent, the
pupils are widely dilated and the pupillary
light reflex is absent. In polioencephalo-
malacia, the optic nerve, oculomotor
nucleus and oculomotor nerve are usually
intact but the visual cortex is not; in hypo-
vitaminosis A the optic nerve is usually
degenerate, which interferes with both
the menace and pupillary light reflexes.

Testing of ocular movements can be
carried out by moving the hand about in
front of the face. In paralysis of the
oculomotor nerve there may also be
deviation from the normal ocular axes and
rotation of the eyeball. There will be an
absence of the normal horizontal nys-
tagmus reaction with a medial jerk of the
eyeball in response to quick passive move-
ment of the head. Failure to jerk laterally
indicates a defect of the abducens nerve.

Trochlear nerve (CN IV)

This nerve supplies only the dorsal
oblique muscle of the eye so that external
movements and position of the eyeball
are abnormal (dorsolateral fixation) when
the nerve is injured. This is common in
polioencephalomalacia in cattle, resulting
in a dorsomedial fixation of the eyeball. In
other words, the medial angle of the pupil
is displaced dorsally when the head is
held in normal extension.

Trigeminal nerve (CN V)

The sensory part of the trigeminal nerve
supplies sensory fibers to the face and can

be examined by testing the palpebral
reflex and the sensitivity of the face. The
motor part of the nerve supplies the
muscles of mastication and observation of
the act of chewing may reveal abnormal
jaw movements and asymmetry of muscle
contractions. There may also be atrophy of
the muscles, which is best observed when
the lesion is unilateral.

Abducent nerve (CN VI)

Because the abducent nerve supplies motor
fibers to the retractor and lateral rectus
muscles of the eyeball, injury to the nerve
may result in protrusion and medial devi-
ation of the globe. This is not readily obser-
vable clinically. An inherited exophthalmos
and strabismus occurs in Jersey cattle.

Facial nerve (CN VII)

The facial nerve supplies motor fibers for
movement of the ears, eyelids, lips, and
nostrils, in addition to the motor path-
ways of the menace, palpebral, and corneal
reflexes. The symmetry and posture of the
ears, eyelids, and lips are the best criteria
for assessing the function of the nerve.
Ability to move the muscles in question
can be determined by creating a noise or
stabbing a finger at the eye. Absence of
the eye preservation reflex may be due
to facial nerve paralysis or blindness.
Facial paralysis is evidenced by ipsilateral
drooping of the ear, ptosis of the upper
eyelid, drooping of the lips and pulling
of the filtrum to the unaffected side. There
may also be drooling of saliva from the

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

;; r- ; ' A'. ;.-i '• 5;-, -

Principal sign

Secondary signs

Location of lesion

Example

Paresis (difficulty in rising,

Persistent recumbency, muscle tone

Loss of function in nervous tissue,

Lymphosarcoma affecting spinal

staggering gait, easily falling)

and reflexes variable depending on
site of lesion

e.g. spinal cord, may be upper or
motor neuron lesion

cord

General loss of muscle tone including

Depression of synaptic or

Milk fever, botulism, peracute

vascular, alimentary systems

neuromuscular transmission for
metabolic reasons or toxic reasons

coliform mastitis, tick paralysis

Flaccid paralysis

(1) Pelvic limbs only

Thoracic normal. Pelvic limbs flaccid,

Tissue destruction, myelomalacia

Paralytic rabies. Spinal cord local

no tone, or reflexes, no anal reflex,
urinary incontinence straining initially

at lumbosacral cord segments
L4 to end osteomyelitis, fracture

meningitis, vertebral body

Thoracic limbs normal. Pelvic limbs

Cord damage at thoracolumbar

Spinal cord local meningitis as

normal tone and reflexes, anal reflex
normal. No withdrawal reflex caudally

cord segments T3-L3

above, damage by vertebral
fracture, lymphosarcoma

(2) Thoracic and pelvic limbs

Flaccid paralysis, normal tone and

Cord damage at cervicothoracic

Fracture of vertebra

reflexes hindlimbs. Absent tone and
reflexes in front limbs. Atrophy only
in front. No withdrawal reflex caudally.
Intact perineal reflex

segments C6-T2

lymphosarcoma, abscess

Flaccid paralysis all four legs and neck.

Cord damage at upper cervical

Injury while running or falling,

Unable to lift head off ground. Normal
tone and reflexes all legs. Pain
perception persists. No withdrawal
reflex caudally

segments C1-C5

abscess or lymphosarcoma

Spastic paralysis (permanent,
no variation, all four limbs

Cranial nerve deficits trigeminal to
hypoglossal. Loss of central

Medulla, pons and midbrain

Abscess, listeriosis

in extension, increased tone,

perception of pain. Depression

exaggerated reflexes,
opisthotonos)

Tremor

Tremor (fine or coarse; no convulsions)

Red nucleus and reticular apparatus
and midbrain/basal ganglia area
tracts

Congenital disease of calves, e.g.
hypomyelinogenesis, neuraxial
edema

Tetany (all four limbs extended,
opisthotonos). Variable intensity

Intense hyperesthesia, prolapse 3rd eyelid

Decreased synaptic resistance
generally

Tetanus

modifiable by treatment

Exaggerated response to all external
stimuli, i.e. hyperesthesia

Increased neuromuscular
transmission

Hypomagnesemia

Paralysis of anus

No anal or perineal reflex. May be

Damage to spinal cord at

Injury or local meningitis, early

straining

segments S1-S3

rabies

Paralysis of tail

Flaccid tail with anesthesia

Injury to caudal segments

Injury or local meningitis, early
rabies

Opisthotonos

With spastic paralysis, tremor,
nystagmus, blindness

Cerebrum, cerebellum and
midbrain

Polioencephalomalacia, trauma

Part of generalized tetanic state
or convulsion

Neuromuscular transmission
defect, tetanus, hypomagnesemia

Tetanus

Falling to one side

Mostly with circling (see below).
Also with deviation of tail

No detectable lesion in spinal cord

Xanthorrhea hastile poisoning

commissures of the lips and in some cases j
a small amount of feed may remain in
the cheeks of the affected side. ;

The common causes of damage to the !
nerve are fracture of the petrous temporal j
bone, guttural pouch mycosis and
damage to the peripheral nerve at the
mandible. A common accompaniment is
injury to the vestibular nerve or center.

A diagnosis of central, as compared to
peripheral nerve involvement, can be
made by identifying involvement of
adjacent structures in the medulla
oblongata. Signs such as depression,
weakness and a head tilt would result,
and are frequently present in ruminants
and New World camelids with listeriosis.

Vestibulocochlear nerve (CN VIII)

The cochlear part of the vestibulocochlear
nerve is not easily tested by simple clinical

examination, but failure to respond
to sudden sharp sounds, created out
of sight and without creating air
currents, suggests deafness. The cochlear
portion can be tested electronically
(the brainstem auditory evoked response,
or BAER, test) to diagnose a lesion
of the auditory nerve, eliminating the
possibility of a central brain lesion.
Abnormalities of balance and carriage of
the head (rotation around the long axis
and not deviation laterally) accompany
lesions of the vestibular part of the
vestibulocochlear nerve, and nystagmus is
usually present.

In severe cases, rotation of the head is
extreme, the animal is unable to stand
and lies in lateral recumbency; moving to
achieve this posture is compulsive and
forceful. There is no loss of strength. In
some species there is a relatively common

occurrence of paralysis of the facial and
the vestibular nerves as a result of otitis
interna and otitis media. This does occur
in the horse but less commonly than
traumatic injury to the skull as a result of
falling.

Pendular nystagmus should not be
mistaken as a sign of serious neurological
disease. Pendular nystagmus is charac-
terized by oscillations of the eyeball that
are always the same speed and amplitude
and appear in response to a visual
stimulus, e.g. a flashing light. Pendular
nystagmus is observed most frequently in
Holstein-Friesian cattle (prevalence of
0.51% in 2932 Holstein-Friesian and
Jersey cows), 18 is not accompanied by
other signs and there is no detectable
histological lesion. A familial relation-
ship was observed in Ayrshire bulls in
Finland. 19

special examination ot tne nervous system

i; j.Ji HA D

Principal sign

Secondary signs

Location of lesion

Example

Circling

(1) Rotation of the head

Nystagmus, circles, muscle weakness,
falls easily, may roll, other cranial nerves
affected

Vestibular nucleus

Brain abscess, listeriosis

Nystagmus, walks in circles, falls

Inner ear (vestibular canals),

Otitis media, otitis interna,

occasionally, animal strong. Falls easily

7th cranial nerve, facial nerve

fracture petrous temporal bone

if blindfolded, sometimes facial paralysis

(horse)

(2) Deviation of the head

Deviation of head and gaze, compulsive

Cerebrum

Brain abscess in calf (infection

walking, depression. Can walk straight.

from dehorning or umbilicus)

Balance may be normal
Unable to walk straight. Facial paralysis,
other cranial nerve deficits, head may
be rotated

Medulla

Listeriosis

Cerebellar ataxia

Exaggerated strength and distance

Cerebellum

Inherited cerebellar hypoplasia in

of movement, direction wrong.

all species, especially Arabian

Flypermetria. Incoordination because

horses; Claviceps paspali

of exaggerated movement. No paresis

poisoning; Gomen disease a
probable plant poisoning;
destruction by a virus, especially
BVD in cattle; hematoma in the
fourth ventricle causes cerebellar
displacement. Idiopathic cerebellar
degeneration in adult cattle

Sensory ataxia

No loss of movement or strength but

Damage to sensory tracts in spinal

Cervical cord lesion.

timing movement wrong, legs get
crossed, feet badly placed when pivoting

cord

thoracolumbar if just pelvic limb

Sensorimotor ataxia

Weakness of movement, e.g. scuffing

Moderate lesion to spinal cord

Plant poisonings, e.g. sorghum.

toes, knuckling, incomplete flexion,

tracts

Cervical vertebral compression of

extension causes wobbly, wandering gait.

spinal cord. Degenerative

falls down easily, difficulty in rising

myelopathy

BVD, bovine viral diarrhea.

Glossopharyngeal nerve (CN IX) and
vagus nerve (CN X)

The glossopharyngeal nerve is sensory
from the pharynx and larynx, and the
vagus nerve is motor to these structures.
Dysfunction of these nerves is usually
accompanied by paralysis of these organs
with signs of dysphagia or inability to
swallow, regurgitation through the nostrils,
abnormality of the voice and interference
with respiration.

Because of the additional role of the
vagus nerve in supplying nerve fibers to
the upper alimentary tract, loss of vagal
nerve function will lead to paralysis of the
pharynx and esophagus. Parasympathetic
nerve fibers to the stomach are also
carried in the vagus and damage to them
could cause hypomotility of that organ.
The principal clinical finding in vagus
nerve injury is laryngeal and pharyngeal
paralysis.

Spinal accessory nerve (CN XI)

Damage to this nerve is extremely rare
and the effects are not documented.
Based on its anatomical distribution loss
of function of this nerve could be expected
to lead to paralysis of the trapezius,
brachiocephalic and sternocephalic muscles
and lack of resistance to lifting the head.

Hypoglossal nerve (CN XII)

As the motor supply to the tongue, the
function of this nerve can be best examined

by observing the motor activity of the
tongue. There may be protrusion, devia-
tion or fibrillation of the organ, all resulting
in difficulty in prehending food and
drinking water. The most obvious abnor-
mality is the ease with which the tongue
can be pulled out. The animal also has
difficulty in getting it back into its normal
position in the mouth, although diffuse
cerebral disease can also produce this
clinical sign. In lesions of some duration
there may be obvious unilateral atrophy.

j POSTURE AND GAIT

The examiner evaluates posture and gait

; to give a general assessment of brainstem,
spinal cord and peripheral nerve and
muscle function. Evaluation of posture
and gait consists of determining which
limbs are abnormal and looking for evi-
dence of lameness suggesting a muscu-
loskeletal gait abnormality. Weakness and
ataxia are the essential components of
gait abnormality. Each limb is examined
for evidence of these abnormalities. This
is done while the animal is standing still,
walking, trotting, turning tightly (pivoting)
and backing up. To detect subtle asym-
metry in the length of the stride, the
observer should walk parallel to or behind
the animal, step for step. If possible, the
gait should also be evaluated while the
animal is walking up and down a slope,

walking with the head and neck held
extended, while blindfolded and while
running free in an enclosure.

The best observations are made when
the animal is running free, preferably at a
fast gait, to avoid abnormalities resulting
from being led. Also, slight abnormalities
such as a high-stepping gait, slight
incoordination of movement, errors of
placement of feet, stumbling and failure
to flex joints properly are all better
observed in a free animal.

Weakness or paresis is evident when
; an animal drags its limbs, has worn hooves
I or has a low arc to the swing phase of the
stride. When an animal bears weight on a
; weak limb, the limb often trembles and the
animal may even collapse on that limb
because of lack of support. While circling,
walking on a slope and walking with the
head held elevated, an animal frequently
will stumble on a weak limb and knuckle
over on the fetlock.

The presence of weakness in the limbs
of horses or cattle can be determined by
pulling the tail while the animal is
walking forward. A weak animal is easily
pulled to the side and put off stride. While
the animal is circling, the examiner can
; pull on the lead rope and tail simulta-
: neously to assess strength. Ease in pulling
the animal to the side occurs because of
weakness due to lesions of descending
upper motor neuron pathway, the ventral

rHHI 1 UClMCttML IVICLm.ll'JE

i-napier iz: Diseases or tne nervous system

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Principal sign

Secondary signs

Location of lesion

Example

Blindness (bumps into objects)

Pupillary dilatation. No pupillary light reflex.

Optic nerve (examine

Vitamin A deficiency. Pituitary rete

No menace reflex

fundus of eye)

mirabile abscess. Congenital
retinal dysplasia of goats

Peripheral blindness or night
blindness

Retina

Nutritional deficiency of vitamin A
Inherited defect of Appaloosa
foals

Central blindness

Pupil normal size. Pupillary light reflexes
normal

Cerebral cortex

Polioencephalomalacia, lead
poisoning

Abnormal dilatation of

Absence of pupillary light reflex. Can

Motor path of oculomotor nerve

Snakebite, atropine poisoning,

pupils (mydriasis)

see - does not bump into objects

milk fever

Absent pupillary light reflex. No vision.
Retinal damage on ophthalmoscopic
examination

Retinal lesion

Toxoplasmosis, trauma,
ophthalmitis

Absent pupillary light reflex. No vision.
Retina normal

Optic nerve atrophy and fibrosis

Avitaminosis A in cattle

Abnormal constriction of
pupil (miosis)

Diarrhea, dyspnea

Failure to activate acetylcholine

Organophosphate poisoning

Blindness, coma, semicoma, spastic paralysis

Diffuse lesion

Polioencephalomalacia, acute lead
poisoning

Horner's syndrome.

Hemilateral sweating and temperature

Damage to cranial thoracic and

Mediastinal tumor. Guttural pouch

Drooping upper eyelid.

rise side of face and upper neck.

cervical sympathetic trunk

mycosis. Neoplastic space-

miosis, enophthalmos
Nystagmus

Unilateral exophthalmus; nasal obstruction
See Table 12.2

occupying lesions of the cranium
involving the periorbit;
perivascular injection around
jugular vein or normal intravenous
injection of xylazine hydrochloride
in normal horses, melanoma at
the thoracic inlet in a horse

Abnormal position of eyeball

Dorsomedial deviation of eyeball

Trochlear (4th)

Polioencephalomalacia

and eyelids

Eyelid

Ventrolateral fixation

Facial (7th)
Oculomotor (3rd)

Listeriosis

Protrusion and medial deviation

Abducent (6th)

Abscess/tumor, e g. bovine viral
leukosis

No palpebral reflex

Deficit sensory branch of 5th nerve

Trauma

Absence of menace response

Absence of pupillary light
reflex

Facial nerve (provided vision is
present)

Oculomotor (provided vision is
present)

Listeriosis

Principal sign

Secondary signs

Location of lesion

Example

Inability to prehend or

Facial (nasal septal) hypalgesia

Sensory branch of trigeminal (5th)

Poisoning by Phalaris aquatica in

inability to chew

dysfunction

cattle. Local medullary lesion

Inappropriate movements of tongue

Hypoglossal (12th) nerve dysfunction

Poisoning by Phalaris aquatica in
cattle. Listeriosis, local medullary
lesion

Inappropriate movements of lips

Facial (7th) nerve dysfunction

Traumatic injury to petrous
temporal bone, otitis media and
interna, listeriosis, guttural pouch

mycosis

Inadequate chewing movements of jaw

Motor branch of the trigeminal

Poisoning by Phalaris aquatica in

(5th) nerve dysfunction

cattle, listeriosis

Inability to swallow

Regurgitation through nose and mouth,

Glossopharyngeal (9th) nerve

Abscess or tumor adjacent to

(in absence of physical

inhalation into lungs causing aspiration

dysfunction. Also vagus (10th).

nerve. Listeriosis, abscess in

foreign body; in

pneumonia

Nuclei in medulla

medulla

pharyngeal paresis or
paralysis)

Inappropriate swallowing movements

Globus pallidus and substantia nigra

Poisoning Centaurea sp.

horn gray matter level with the limb or
peripheral nerves or muscle. With lower
motor neuron lesions, the weakness is
often so marked that it is easy to pull an
animal to the side while it is standing or
walking. In contrast, a weak animal with a

lesion of the upper motor neuron path-
ways will often fix the limb in extension,
reflexly, when pulled to one side. It resists
the pull and appears strong.

Severe weakness in all four limbs,
but with no ataxia and spasticity, suggests

neuromuscular disease. Obvious weakness
in only one limb is suggestive of a periph-
eral nerve or muscle lesion in that limb.

Ataxia is an unconscious, general
proprioceptive deficit causing poor
coordination when moving the limbs and

the body. It results in swaying from side to
side of the pelvis, trunk and sometimes
the entire body. It may also appear as a
weaving of the affected limb during the
swing phase. This often results in abducted
or abducted foot placement, crossing of
the limbs or stepping on the opposite
foot, especially when the animal is circling
or turning tightly. Circumduction of the
outside limbs when turning and circling is
also considered a proprioceptive deficiency.
Walking an animal on a slope, with the
head held elevated, often exaggerates
ataxia, particularly in the pelvic limbs.
When a weak and ata^c animal is turned
sharply in circles, it leaves the affected
limb in one place while pivoting around
it. An ataxic gait may be most pronounced
when an animal is moving freely, at a trot
or canter, especially when attempting to
stop. This is when the limbs may be wildly
abducted or adducted. Proprioceptive
deficits are caused by lesions affecting the
general proprioceptive sensory pathways,
which relay information on limb and body ]
position to the cerebellum (unconscious
proprioception) and to the thalamus and
cerebral cortex (conscious proprioception).

Knuckling the flexed foot while the
animal stands on the dorsum to deter-
mine how long the animal leaves the foot
in this state before returning it to a
normal position is a test for conscious
proprioception in dogs and cats. The test
has not been useful in horses and adult
cattle but is useful in sheep, goats. New
World camelids, and calves. Depressed
animals will often allow the foot to rest on
the dorsum for prolonged periods.
Crossing the limbs and observing how
long the animal maintains a crosslegged
stance has been used to test conscious
proprioception.

Hypermetria is used to describe a lack
of direction and increased range of
movement, and is seen as an overreaching
of the limbs with excessive joint move-
ment. Hypermetria without paresis is
characteristic of spinocerebellar and
cerebellar disease.

Hypometria is seen as stiff or spastic
movement of the limbs with little flexion
of the joints, particularly the carpal and
tarsal joints. This generally is indicative of
increased extensor tone and of a lesion
affecting the descending motor or ascend-
ing spinocerebellar pathways to that limb.

A hypometric gait, particularly in the
thoracic limbs, is best seen when the
animal is backed up or when it is
maneuvered on a slope with the head
held elevated. The thoracic limbs may
move almost without flexing.

Dysmetria is a term that incorporates
both hypermetria and hypometria. Animals
with severe cerebellar lesions may have a
high-stepping gait but have limited

Special examination of the nervous system

589

movement of the distal limb joints,
especially in thoracic limbs.

The degree of weakness, ataxia,
hypometria and hypermetria should be
graded for each limb. The types of gait
abnormalities and the degree of weakness
reflect various nervous and musculoskeletal
lesions. Generally, with focal, particularly
compressive, lesions in the cervical spinal
cord or brainstem, neurological signs are
one grade more severe in the pelvic limbs
than in the thoracic limbs. Thus, with a
mild, focal, cervical spinal cord lesion
there may be more abnormality in the
pelvic limbs with no signs in the thoracic
limbs. The anatomical diagnosis in such
cases may be a thoracolumbar, cervical, or
diffuse spinal cord lesion.

A moderate or severe abnormality in
the pelvic limbs, and none in the thoracic
limbs, is consistent with a thoracolumbar
spinal cord lesion. With a mild and a
severe change in the thoracic and the
pelvic limb gaits respectively, one must
consider a severe thoracolumbar lesion
plus a mild cervical lesion, or a diffuse
spinal cord disease.

Lesions involving the brachial
intumescence (spinal cord segments
C6-T2) with involvement of the gray
matter supplying the thoracic limbs, and
diffuse spinal cord lesions may both result
in severe gait abnormality in the thoracic
limbs and the pelvic limbs.

A severely abnormal gait in the
thoracic limbs, with normal pelvic limbs,
indicates lower motor neuron involvement
of the thoracic limbs; a lesion is most
likely to be present in the ventral gray
columns at spinal cord segments C6-T2
or thoracic limb peripheral nerves of
muscle.

Gait abnormalities can occur in all four
limbs, with lesions affecting the white
matter in the caudal brainstem, when
head signs, such as cranial nerve deficits,
are used to define the site of the lesion.
Lesions affecting the cerebrum cause no
change in gait or posture.

I

s

I

!

!

;

:

j

i

i

i

:

i

j

i

NECK AND FORELIMBS

If a gait abnormality was evident in the
thoracic limbs and there was no evidence
of brain involvement, then examination of
the neck and forelimbs can confirm
involvement of the spinal cord, peripheral
nerves (spinal cord segments C1-T2) or
thoracic limb muscles. The neck and
forelimbs are examined for evidence of
gross skeletal defects, asymmetry of
the neck and muscle atrophy. The neck
should be manipulated from side to side
and up and down to detect any evidence
of resistance or pain. Localized unilateral
sweating of the neck and cranial shoulder
is evidence of Horner's syndrome , 20 in

which there are varying degrees of ptosis,
prolapse of the third eyelid, miosis,
enophthalmos and increased temperature
of the face, neck and shoulder. The syn-
drome is associated with lesions affecting
the descending sympathetic fibers in the
white matter of the spinal cord or gray
matter in the cranial thoracic segments,
thoracocervical sympathetic trunk,
cervical vagosympathetic trunk or cranial
cervical ganglion and its pre- and post-
ganglionic fibers.

Sensory perception from the neck
and forelimbs is assessed using a painful
stimulus such as a blunt needle or forceps.
The local responses as well as the cerebral
responses are noted when the skin over
the shoulders and down the limbs is
pricked.

Gait deficits are evaluated by making
the horse or halter-broken ruminant
perform a series of movements. Such
exercises should include walking and
trotting in a straight line, in large circles,
in tight circles, backing on a level ground
and on a slight slope, walking and trotting
over curbs or low obstacles, walking in
straight lines and circles, and walking on
a slope with the head held elevated.
The sway reaction for the thoracic limb
is assessed by pushing against the
shoulders and forcing the animal first to
resist and then to take a step laterally. This
can be done while the animal is standing
still and walking forward. Pulling the tail
and lead rope laterally at the same time
will assess the strength on each side of
the body. Making the animal turn in a
tight circle by pulling the lead rope and
tail at the same time will indicate strength;
an adult horse should be able to pull the
examiner around and should not pivot on
a limb or be pulled to the side. Pressing
down with the fingers on the withers of a
normal animal causes some arching,
followed by resistance to the downward
pressure. An animal with weakness in the
thoracic limbs may not be able to resist
this pressure by fixing its vertebral
column but will arch its back more than
normal and often buckle in the thoracic
limbs.

In smaller farm animal species, other
postural reactions can be performed.
These include wheelbarrowing and the
hopping response test. The spinal reflexes
are assumed to be intact in animals that
are ambulating normally.

If a large mature horse, cow or pig has
a gait abnormality, it is very rare to cast
the animal to assess the spinal reflexes.
However, spinal reflexes are usually
examined in calves, sheep, and goats.

A recumbent animal that can use its
thoracic limbs to sit up in the dog-sitting
position may have a lesion caudal to
spinal cord segment T2. If a recumbent

590

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

animal cannot attain a dog-sitting position,
the lesion may be in the cervical spinal
cord. In lambs aged between 4 and
10 weeks with thoracic vertebral body
abscesses extending into the epidural
space causing spinal cord compression,
the thoracic limbs are normal and the
lambs frequently adopt a 'dog-sitting'
position and move themselves around
using the thoracic limbs only. 21 Lambs
with a cervical spinal cord lesion are unable
to maintain sternal recumbency and have
paresis of all four limbs.

However, mature cattle with the
downer cow syndrome secondary to
hypocalcemia may be unable to use both
the thoracic and pelvic limbs. If only the
head, but not the neck, can be raised off
the ground, there may be a severe cranial
cervical lesion. With a severe caudal cervical
lesion, the head and neck can usually be
raised off the ground but thoracic limb
function is decreased and the animal is
unable to maintain sternal recumbency.

Assessment of limb function is done
by manipulating each limb separately, in
its free state, for muscle tone and sensory
and motor activity. A limb that has been
lain upon for some time cannot be
properly evaluated because there will be
poor tone from the compression. A flaccid |
limb, with no motor activity, indicates a j
lower motor lesion to that limb. A severe !
upper motor neuron lesion to the thoracic i
limbs causes decreased, or absent, voluntary '■
effort, but there is commonly normal or j
increased muscle tone in the limbs. This is !
due to release of the lower motor neuron, j
which reflexly maintains normal muscle !
tone from the calming influence of the
descending upper motor neuron pathways, j

The tone of skeletal muscle may be ;
examined by passively flexing and
extending the limbs and moving the neck ;
from side to side and up and down. ;
Increased muscle tone, spasticity or
tetany may be so great that the limb
cannot be flexed without considerable
effort. If the spastic-extended limb does
begin to flex but the resistance remains,
this is known as'lead-pipe' rigidity, which
is seen in tetanus. If after beginning to flex
an extended spastic limb, the resistance
suddenly disappears ('clasp-knife release')
this suggests an upper motor neuron lesion,
as occurs in spastic paresis in cattle.

Flaccidity, or decreased muscle tone,
indicates the presence of a lower motor
neuron lesion with interruption of the
spinal reflex arc.

Localized atrophy of muscles may
be myogenic or neurogenic and the differ-
ence can be detennined only by electro-
myography, a technique not well suited to
large-animal practice. If the atrophic
muscle corresponds to the distribution of
a peripheral nerve it is usually assumed

that the atrophy is neurogenic. In addition,
neurogenic atrophy is usually rapid (will
be clinically obvious in a few days) and
much more marked than either disuse or
myogenic atrophy.

Spinal reflexes of the thoracic limbs

These include the flexor reflex, the biceps
reflex and the triceps reflex. The flexor
reflex is tested by stimulation of the skin
of the distal limb and observing for
flexion of the fetlock, knee, elbow, and
shoulder. The reflex arc involves sensory
fibers in the median and ulnar nerves,
spinal cord segments C6-T2 and motor
fibers in the axillary, musculocutaneous,
median and ulnar nerves. Lesions cranial
to spinal cord segment C6 may release
this reflex from the calming effect of the
upper motor neuron pathways and cause
an exaggerated reflex with rapid flexion of
the limb, and the limb may remain
flexed for some time. A spinal reflex may
be intact without cerebral perception.
Cerebral responses to the flexor reflex
include changes in the facial expression,
head movement toward the examiner and
vocalization. Conscious perception of the
stimulus will be intact only as long as the
afferent fibers in the median and ulnar
nerves, the dorsal gray columns at spinal
cord segments C6-T2 and the ascending j
sensory pathways in the cervical spinal j
cord and brainstem are intact.

The laryngeal adductory reflex is of j
special interest in the examination of j
ataxic horses. In normal horses a slap on j
the saddle region just caudal to the j
withers causes a flickering adductory j
movement of the contralateral arytenoid j
cartilage that is visible by an endoscope. j
Reflex muscle contraction can be palpated j
on the dorsolateral surfaces of the larynx. ;
The reflex is absent when there is damage j
to afferent tracts up the spinal cord, j
when there is damage to the recurrent j
laryngeal nerves, and in tense or frightened j
horses. Elicitation of the reflex is called ;
the slap test.

TRUNK AND HINDLIMBS

If examination of the posture, gait, head,
neck or thoracic limbs reveals evidence of a
lesion, then an attempt should be made to
explain any further signs found during
examination of the trunk and hindlimbs
that could have been caused by the lesion. If
there are only signs in the trunk and
hindlimbs, then the lesion(s) must be either
between spinal cord segments T2 and S2 or
in the trunk and pelvic limb nerves or
muscles. It must be remembered that a
subtle neurological gait in the pelvic limbs
may be anywhere between the midsacral
spinal cord and the rostral brainstem.

The tmnk and hindlimbs are observed
and palpated for malformations and

asymmetry. Diffuse or localized sweating,
the result of epinephrine release and
sympathetic denervation, is often present
in horses affected with a severe spinal
cord injury.

Gentle pricking of the skin over the
trunk and over the lateral aspects of the
body wall on both sides, including on
either side of the thoracolumbar vertebral
column, will test-stimulate the cutaneous
trunci reflex. The sensory stimulus travels
to the spinal cord in thoracolumbar spinal
nerves at the level of the site of stimulation.
These impulses are transmitted up the
spinal cord to spinal cord segments
C8-T1, where the lateral thoracic nerve is
stimulated, causing contraction of the
cutaneous trunci muscle, which is seen as
a flicking of the skin over the tmnk.
Lesions anywhere along this pathway will
result in suppression or absence of this
reflex caudal to the site of the lesion.
Degrees of hypalgesia and analgesia
have been detected caudal to the sites
of thoracolumbar spinal cord lesions,
especially if they are severe. In mature
cattle with fractured thoracolumbar
vertebrae associated with traumatic injury
or vertebral body abscesses in calves,
the site of the lesion may be able to be
localized with this reflex. Sensory per-
ception of pinpricking the tmnk and
hindlimbs may also be absent caudal to
the lesion.

The sway reaction for the pelvic
limbs involves pushing against the pelvis
and pulling on the tail with the animal
standing still and walking forward. An
animal which is weak in the pelvic limbs
will be easily pulled and pushed laterally,
especially while walking. Proprioceptive
deficits can be observed as overabduction
and crossing of the limbs when a step is
taken to the side.

Pinching and pressing down on the
thoracolumbar or sacral paravertebral
muscles with the fingers causes a normal
animal to extend slightly, then fix, the
thoracolumbar vertebral column. It also
resists the ventral motion and usually
does not flex the thoracic or pelvic limbs.
A weak animal usually is not able to resist
the pressure by fixing the vertebral
column and thus it overextends the back
and begins to buckle in the pelvic limbs.

In the recumbent animal, examination
of the pelvic limbs includes the pelvic
limb spinal reflexes, the degree of
voluntary effort and the muscle tone
present. Observing the animal attempting
to rise on its own or following some
coa)«ng will help to assess the pelvic limbs.
The flexor spinal reflex is performed by
pricking the skin and observing the
flexion of the limb; central perception of
the painful stimulus is also noted. The
afferent and efferent pathways for this

Special examination of the nervous system

reflex are in the sciatic nerve and involve
spinal cord segments L5-S3.

The patellar reflex is evaluated by
placing the animal in lateral recumbency
and supporting the limb in a partly flexed
position. The intermediate patellar ligament
(horses) or patellar ligament (ruminants,
pigs, New World camelids) is then tapped
with a heavy metal plexor. This results in
extension of the stifle joint. The sensory
and motor fibers for this reflex are in the
femoral nerve, and the spinal cord
segments are L4 and L5. The patellar
reflex is hyperactive in newborn farm
animals. The gastrocnemius reflex and the
cranial tibial reflex are not evaluated
because they cannot be reliably induced.

The spinal cord of the calf has more
control of basic physical functions than in
humans, dogs and horses. For example,
calves are able to retain control of the
pelvic limb in spite of experimentally
induced lesions that cause hemiplegia in
dogs and humans. Also transection of the
spinothalamic tract in the calf cord does
not produce an area of hypalgesia or
analgesia on the contralateral side as such
a lesion would do in a human. 22

Skin sensation of the pelvic limbs
should be assessed independently from
reflex activity. The femoral nerve is
sensory to the skin of the medial thigh
region, the peroneal nerve to the dorsal
tarsus and metatarsus, and the tibial
nerve to the plantar surface of the
metatarsus.

TAIL AND ANUS

Tail tone is evaluated by lifting the tail and
noting the resistance to movement. A
flaccid tail, with no voluntary movement,
is indicative of a lesion of the sacrococcygeal
spinal cord segments, nerves, or muscles.
Decreased tone in tail can be detected
with severe spinal cord lesions cranial to
the coccygeal segment.

The perineal reflex is elicited by lightly
pricking the skin of the perineum and
observing reflex contraction of the anal
sphincter and clamping down of the tail.
The sensory fibers are contained within
the perineal branches of the pudendal
nerve (spinal cord segments S1-S3).
Contraction of the anal sphincter is
mediated by the caudal rectal branch of
the pudendal nerve, and tail flexion is
mediated by the sacral and coccygeal
segments and nerves (spinal cord
segments SI -Co). An animal with a flaccid
tail and anus, due to lower motor neuron
lesion, will not have an anal or tail reflex.
However, it may still have normal
sensation from the anus and tail provided
that the sensory nerves and spinal cord
and brainstem white matter nociceptive
pathways are intact.

Observation of defecation and urination
movements and postures contributes
to knowledge of the state of the cauda
equina. Thus neuritis of the cauda equina
is characterized by flaccid paralysis and
analgesia of the tail, anus and perineum,
rectum and bladder. There is no paresis
or paralysis of the hindlimbs unless
lumbosacral segments of the cord are
damaged.

PALPATION OF THE BONY
ENCASEMENT OF THE CENTRAL
NERVOUS SYSTEM

Palpable or visible abnormalities of the
cranium or spinal column are not com-
monly encountered in diseases of the
nervous system but this examination
should not be neglected. There may be
displacement, abnormal configuration or
pain on deep palpation. These abnor-
malities are much more readily palpable
in the vertebral column and if vertebrae
are fractured. Abnormal rigidity or flexi-
bility of the vertebral column, such as occurs
in atlanto-occipital malformations in
Arabian horses and cattle, may also be
detectable by manipulation.

COLLECTION AND EXAMINATION
OF CEREBROSPINAL FLUID

The collection and laboratory analysis of
CSF from farm animals with clinical
evidence of nervous system disease can
provide useful diagnostic and prognostic
information. 2

CSF is formed mostly from the choroid
plexuses of the lateral ventricles by the
ultrafiltration of plasma and the active
transport of selected substances across
the blood-brain barrier. The CSF in the
ventricular system flows caudally and
diffuses out of the lateral aperture in the
fourth ventricle to circulate around the
brain and spinal cord. The presence of
CSF in the subarachnoid space separates
the brain and spinal cord from the bony
cranium and vertebral column, which
reduces trauma to the underlying delicate
nervous tissue. CSF also has excretory
functions with the removal of products of
cerebral metabolism.

Collection of cerebrospinal fluid

CSF can be collected from lumbosacral
cistern with sedation (horses) or restraint
(ruminants) and the atlanto-occipital
cistern (cisterna magna) using injectable
general anesthesia. For collection it is
necessary to puncture the subarachnoid
space in either the lumbosacral space or
cisterna magna. Although there is no
substantial difference between the com-
position of lumbosacral or cisternal CSF
samples unless there is a compressive
lesion of the spinal cord, the general

policy is to sample as close to the lesion as
possible. CSF should be collected into a
sterile tube and there is no need to add an
anticoagulant, even in samples visibly
contaminated with blood. Cytology should
be performed as soon as possible after
collection (ideally within 15 min) because
the cells rapidly degenerate.

Collection from the lumbosacral cistern
The lumbosacral site is preferred because
general anesthesia is not required. CSF
can be collected from the lumbosacral
cistern with relative ease provided that
adequate restraint can be achieved and
the anatomical landmarks can be identified.
CSF can be collected from the standing
or recumbent animal. If recumbent, the
animal should be placed in sternal
recumbency with hips flexed and the pelvic
limbs extended alongside the abdomen.
This widens the lumbosacral space to
permit correct placement of the spinal
needle.

The site for collection is the midpoint
of the lumbosacral space, which can
be identified as the midline depression
between the last palpable dorsal lumbar
spine (L6 in cattle, goats and horses; L6 or
L7 in sheep and pigs; L7 in New World
camelids) and the first palpable sacral
dorsal spine (usually S2). In well con-
ditioned animals, these landmarks cannot
always be identified; in which case the
site is identified as the midpoint of a line
connecting the caudal aspect of the tuber
coxae. The site is clipped, surgically
prepared and 1-2 mL of local anesthetic is
administered subcutaneously. Sterile
surgical gloves should be worn. Hypo-
dermic spinal needles with stilettes are
recommended because ordinary needles
commonly plug with tissue. The length
and gauge of needle depends on the size
of the animal, but 15 cm (6 in) 18-gauge
needles are needed for adult horses and
cattle. The following guide is recommended
(Table 12.7).

Provided the animal is well restrained
and care is exercised in introducing the
needle, little difficulty should be en-
countered. For collection from the lumbo-
sacral space the needle is slowly advanced

M>ta fe/. ijf&ife .

tturnTloXo^fetc) Stlky 2Jl@es 2?l h«ll l.ftttvfef : V, -

Species and body
weight

Length (cm) and
gauge of needle

Lambs <30 kg

2.5 and 20

Ewes 40-80 kg

4.0 and 20

Rams > 80 kg

5.0 and 20

Calves < 100 kg

4.0 and 20

Calves 100-200 kg

5.0 and 18

Cattle > 200 kg

10.0-15.0 and 18

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

perpendicular or up to 15° caudal to
perpendicular to the plane of the vertebral
column. The needle must be introduced
in a perfectly vertical position relative to
the plane of the animal's vertebral
column because of the danger of entering
one of the lateral blood vessels in the
vertebral canal. Changes in tissue resist-
ance can be felt as the needle point passes
sequentially through the subcutaneous
tissue, interarcuate ligament, then the
sudden 'pop' due to the loss of resistance
as the needle point penetrates the
ligamentum flavum into the epidural
space. Once the needle point has pen-
etrated the dorsal subarachnoid space,
CSF will well up in the needle hub within
2-3 seconds. Failure to appreciate the
changes in resistance as the needle moves
down may result in puncture of the conus
medullaris, which may elicit an immediate
pain response and some discomfort.
Movement of the pelvic limbs may dis-
lodge the needle point, with the risk of
causing local trauma and hemorrhage
in the leptomeninges, which results in
blood in the sample. Repeated CSF taps
of the lumbosacral space may make it
more difficult to obtain an adequate
sample volume because of fibrosis of
epidural tissue. 23

Careful aspiration with a syringe
attached to the needle held between the
thumb and index finger is usually required
to obtain a sample of 2-3 mL, which is
sufficient for laboratory analysis. This
can be facilitated by firmly resting the
forearms and wrists on the animal's back.
Failure to obtain fluid is usually due to
incorrect direction of the needle, in which
the case the bony landmarks of the
lumbosacral space (depression) must be
rechecked and, with the needle correctly
realigned, the procedure repeated. In
animals with a vertebral body abscess and
neurological disease confined to the hind
limbs, CSF may be difficult to obtain from
the lumbosacral space because flow is
occluded. In these circumstances, if a
sample is obtained, the CSF protein may
be increased as a result of stagnation of
CSF distal to the lesion with exudation or
transudation of protein from the lesion
(Froin's syndrome ). 24

Collection from the atlanto-occipital
cistern (cisterna magna)

This site is preferred for intracranial
lesions because the fluid is produced in
the subarachnoid space and flows caudally
down the spinal cord. 25 However, this site
is rarely used because of the inherent risk
of needle penetration of the brainstem.
Xylazine at 0.20 mg/kg body weight (BW)
intramuscularly is effective in providing
adequate sedation and analgesia for this
procedure in cattle. A general anesthetic

(such as combined intravenous adminis-
tration of xylazine and ketamine) is
recommended for horses.

The site is prepared as with the lumbo-
sacral cistern. Ventriflexion of the head
and neck of cattle enlarges the space of
the cisterna magna and allows easy entry
using a stiletted spinal needle inserted at a
point created by the transection of the
transverse line of the cranial rim of the
wing of the atlas and the dorsal midline.
The needle is advanced carefully and
steadily and the tip is directed rostrally
towards the symphysis of the lower jaw.
The needle point goes through the skin,
ligamentum nuchae and leptomeninges.
In most mature cattle of body weight over
500 kg, a 20-gauge, 10 cm (4 in) spinal
needle will enter the cisterna magna at
5-7 cm after going through the ligamentum
nuchae, which provides some increased
resistance. When the needle point punc-
tures the leptomeninges, the animal may
move its head slightly. At that point the
needle is advanced only 1-2 mm and the
stilette is then removed. If the end
of the needle is in the cisterna magna,
CSF will flow out of the needle freely and
the manometer can be attached and the
pressure measured.

Cerebrospinal fluid pressure

The CSF pressure can be determined by
the use of a manometer attached to the
spinal needle. Normal CSF pressures
of the cisterna magna in cattle and
xylazine/ketamine-anesthetized horses
range from 5-15 cm (uncertain reference
point) and 28 ± 4 cm (referenced to the
right atrium), respectively, using 0.9%
NaCl solution in a manometer. 26 When
the fluid system is properly connected,
occlusion of both jugular veins causes a
marked rise in CSF pressure; this is called
Queckenstedt's test. The Queckenstedt
test involves bilateral jugular vein
compression; this results in a sudden
increase in intracranial subarachnoid
pressure that is transmitted to the cranial
subarachnoid space. The resultant CSF
pressure wave is transmitted to the lumbar
area (when obtaining CSF from the
lumbosacral space) in the absence of an
obstruction in the spinal subarachnoid
space, thereby resulting in an increased
flow of CSF.

Variations in CSF pressure are not of
much use in clinical diagnosis except in
hypovitaminosis A, and measurement of
CSF pressure is only indicated in animals
with signs of cerebral disease (abnormal
mentation). Care is needed in interpreting
results because the pressure is greatly
affected by voluntary movement such
as tenesmus. CSF pressure is increased
in a number of diseases, including polio-
encephalomalacia, bacterial meningitis, and

hypovitaminosis A. Xylazine given intra-
venously causes a decrease in intracranial
pressure in healthy conscious horses. 27
Epidural pressure of cattle changes with
change in position from standing to
lateral recumbency to dorsal recumbency,
and epidural pressure is positive in
laterally recumbent animals. 23 Although
the effect of epidural pressure on CSF
pressure has not been evaluated in large
animals, it is likely that CSF pressure is
also affected by position.

Analysis of cerebrospinal fluid

Analysis of CSF has greater diagnostic
value than hematology in animals with
nervous system disease. CSF can be
examined for the presence of protein,
cells and bacteria. 2 The white blood cell
count in normal animals is usually less
than 5 cells/pL but a report exists of
higher counts (12-200 cells/pL) in sheep. 28
An increase in CSF leukocyte count above
5 cells/pL is termed a pleocytosis and
is categorized as mild (6-49 cells/pL),
moderate (50-200 cells/pL) or marked
(> 200 cells/pL). The differential white cell
count comprises mostly lymphocytes
and monocytes; there are no erythrocytes
in normal animals. Samples that show
visible turbidity usually contain large
numbers of cells (>500 cells/pL) and
much protein. In cattle, protein concen-
trations range from 23-6 mg/dL, sodium
concentrations from 132-144 mmol/L,
potassium 2. 7-3. 2 mmol/L, magnesium
1.8-2. 1 mEq/L and glucose concentrations
37-51 mg/dL 29 In the horse, the reference
values for CSF are similar. 30 Neonatal
foals under 3 weeks of age have higher
CSF protein concentrations than do adult
horses. Glucose concentrations peak in
the first 48 hours after birth, then
decrease to adult values by the second
week of life. Concentrations of sodium
and potassium are not affected by age
and are similar to values reported for adult
horses and ponies.

With bacterial infections of the nervous
system the CSF concentration of protein
will be increased and the white blood cell
count increased up to 2000 cells/pL with
more than 70% neutrophils. 28 A neutrophilic
pleocytosis is considered 95-100% indi-
cative of an inflammatory process within
the central nervous system. 28 Theoretically,
the CSF glucose concentration will be
decreased and CSF lactate concentration
will be increased in animals with bacterial
meningitis because of bacterial metabolism,
but these are unreliable signs and usually
do not provide additional information to
that provided by determination of CSF
leukocyte and protein concentrations.
Bacteria may also be cultured from the
CSF. Because meningoencephalitis may
occur concurrently or following acute

diarrhea in calves under a few weeks of
age, the evaluation of CSF should be
considered in calves that remain depressed
and inactive following rehydration and
treatment. 31

The creatine kinase and lactate dehy-
drogenase activities in CSF have been
examined as an aid in the differentiation
of some neurological diseases. However,
creatine kinase activity is considered to be
unreliable; contamination of the sample
with epidural fat and dura may increase
CSF creatine kinase activity in the horse. 32
Insufficient information is available to
evaluate the clinical utility of CSF lactate
dehydrogenase activity in large animals.

The CSF glucose concentration is
usually 60-80% of serum glucose concen-
tration; this steady state value reflects
facilitated transport across the blood-brain
barrier, absence of binding proteins for
glucose in CSF and nervous tissue metab-
olism of glucose. 29 However, sudden
changes in plasma glucose concentrations
are not immediately reflected in CSF
glucose concentrations, because CSF turns
over at around 1% per minute. Typically, a
lag time of up to 3 hours is needed for
CSF glucose concentration to be in
equilibrium with plasma glucose concen-
trations. Hyperglycemia as a result of the
stress of handling and restraint may there-
fore not be reflected by an increased CSF
glucose concentration.

Blood contamination of CSF can make
interpretation difficult. A formula has
been developed that 'corrects' the CSF
values for the degree of blood contami-
nation, based on the red blood cell count
in CSF (RBC csl .) and blood (RBC bk)0d ),
whereby the corrected value for
substance X in CSF (X correclcd , where X is a
concentration or activity) is derived from
the measured value of X in CSF (X CSF )
and blood (X btood ) and applying the
following formula:

^corircli'd ~ X CSF — (^blood ^

RBCcs/RB Cuoai) ■ 33

Calculation of a 'corrected' value rarely
provides additional insight into the CSF
analysis and is not commonly practiced
in large animals.

Protein fractionation of CSF is not
routinely performed because it requires
sensitive electrophoresis methodology or
species-specific radial immunodiffusion
assays. However, calculation of the
albumin quotient and IgG index may
be informative in specific neurologic
diseases. 34,35 Theoretically, these calcu-
lations can differentiate four blood-brain
permeability patterns; nonnal blood-brain
barrier permeability (normal albumin
quotient and IgG index); intrathecal IgG
production with normal blood-brain
barrier permeability (normal albumin

Special examination of the nervous system

quotient and increased IgG index);
increased blood-brain barrier permeability
without intrathecal IgG production
(increased albumin quotient and normal
IgG index) and increased blood-brain
barrier permeability with intrathecal
production of IgG (increased albumin
quotient and increased IgG index).
The albumin quotient is calculated from
the albumin concentration in CSF (ALB CSF )
and serum (ALB scrum ), whereby:

Albumin Quotient = (ALB CSF ) x

100/(ALB sm J.

The normal value for albumin quotient
in the adult horse is less than 2.2 34,36 but
the mean is 0.4 to 0.5 in cattle and adult
llamas. 29,35 Because CSF protein is most
commonly derived by disturbance of
the blood-brain barrier and inflammation
(resulting in an increased CSF albumin
concentration), an increased CSF protein
concentration is usually accompanied
by an increased albumin quotient.

In animals suspected to have increased
immunoglobulin production in the central
nervous system (a rare occurrence, and
almost always accompanied by disturbance
of the blood-brain barrier), the IgG index
can be calculated from the IgG concen-
tration in CSF (IgG CSF ) and serum
(IgG scrum ), and the albumin concentration
in CSF (ALB csf ) and serum (ALB scrurn ),
whereby:

IgG Index = (IgG csr /(IgG wrt/in) ^

(ALB scnm / ALB CS rd) ■

An IgG index of more than 0.3 is suspected
to indicate intrathecal IgG production in
the adult horse. 34

This formula corrects the CSF IgG con-
centration for an increased permeability of
the blood-brain barrier, and therefore
theoretically provides a more sensitive
method for detecting local production of
I IgG within the central nervous system.
Calculating the albumin quotient and IgG
index is expensive and rarely provides
additional information to that provided
by CSF protein concentration alone, and
for this reason is not commonly performed
in large animals.

In summary, collection and analysis
of CSF from the lumbosacral region
provides a practical, safe and informative
diagnostic tool in conscious large animals
with neurological disease. Analysis of
CSF in animals with central nervous
system disease has greater diagnostic
value than analysis of the leukon or
serum biochemical analysis. Routine
assessment of CSF should include total
protein concentration, erythrocyte count,
leukocyte count and leukocyte differential
count. Other analytical procedures on
CSF can be performed in specific diseases
related to the nervous system.

EXAMINATION OF THE NERVOUS
SYSTEM WITH SERUM
BIOCHEMICAL ANALYSIS

Arterial plasma ammonia concentration

In animals suspected of having hepatic
encephalopathy, measurement of the
arterial plasma ammonia concentration
provides a clinically useful diagnostic test
and a means of monitoring the response
to treatment. In monogastrics, ammonia
is produced by bacterial degradation of
amines, amino acids, and purines in the
gastrointestinal tract, by the action of
bacterial and intestinal urease on urea in
the gastrointestinal tract and by the
catabolism of glutamine by enterocytes. 37
In ruminants, ammonia is derived pre-
dominantly from bacterial metabolism in
the rumen and catabolism of amino acids
in tissue. Absorbed ammonia is normally
converted to urea by the liver and to
glutamine by the liver, skeletal muscle,
and brain. In the presence of hepatic
dysfunction, ammonia is inadequately
metabolized, resulting in high plasma
ammonia concentrations. Ammonia is a
direct neurotoxin that alters inhibitory and
excitatory neurotransmission in the brain.

Hyperammonemia can be used as a
specific indicator of hepatic dysfunction.
Nonnal values for arterial plasma ammonia
concentration are less than 29 pmol/L in
adult cattle 37 but may reach higher values
in the immediate periparturient period.
Arterial values are higher than venous
values, and are preferred for analysis.

Blood gas analysis and serum electrolyte
determination should be routinely under-
taken in animals with clinical signs of
encephalopathy, in order to rule out
metabolic causes of cerebral dysfunction.

EXAMINATION OF THE NERVOUS
SYSTEM WITH IMAGING
TECHNIQUES

Radiography

Examination of the bony skeleton of the
head and vertebral column to detect
abnormalities which are affecting the
nervous system of large animals is being
used more commonly in referral centers.
Conventional diagnostic radiography
remains the best method for the initial
evaluation of trauma to the brain and
spinal cord. The injection of contrast
media into the CSF system (myelography)
is used for the detection of spinal cord
compression but is rarely indicated in
large animals because spinal cord
depression surgery is rarely performed. In
cases of peripheral nerve injury the radio-
graph of the appropriate limb may reveal
the presence of a fracture or space-
occupying lesion that has caused dys-
function of the peripheral nerve.

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Computed tomography

Computed tomography (CT) of the skull
has several advantages over radiography
because structures are viewed in cross
section without superimposition . 38 The
development of computer software and
technology allows a large amount of
information to be obtained from a CT
examination. Numerous diseases of the
head of the horse, including those of
the brain, can be diagnosed using this
technique, but the limiting factors are the
weight of the patient, accessibility for
large animals and the need for general
anesthesia. In general, CT provides an
excellent image of skeletal defects. CT has
been used for the antemortem diagnosis
of many conditions in foals and horses,
and otitis interna in calves . 39

Magnetic resonance imaging

Magnetic resonance imaging (MRI) scan-
ning uses nuclear magnetic resonance to
create cross sectional images based on the
magnetic properties of tissues. In general,
MRI provides an excellent image of soft
tissue defects, but the limiting factors are
the weight of the patient, accessibility for
large animals and the need for general
anesthesia. MRI has been used for the
antemortem diagnosis of many neuro-
logical conditions in foals and horses 40
and cerebellar hypoplasia in a calf . 41

RHINOLARYNGOSCOPY
(ENDOSCOPY) AND
OPHTHALMOSCOPY

Endoscopy (rhinolaryngoscopy) is now
a routine technique for the examination
of horses with suspected laryngeal
hemiplegia . 3 Ophthalmoscopy for the
examination of the structures of the eye
is important in the diagnosis of diseases
affecting the optic nerve such as in
vitamin A deficiency, and the optic disc
edema (papilledema) associated with
diffuse cerebral edema.

ELECTR OENCEPHALOG RAPHY

Electroencephalography (EEC) has not
been utilized to any significant degree
in large animals. The EEC requires
sophisticated equipment, a quiet dim
environment free from electrical inter-
ference and a quiet patient that has
minimal muscular activity. Because of
the difficulty in obtaining quality record-
ings in a conscious large animal, it is
preferred that the animal is anesthetized
for the recording, which may confound
interpretation of the EEC pattern depend-
ing on the anesthetic protocol. Electro-
encephalography has therefore been
primarily used as an antemortem or
research tool in large animals, and its use
will probably remain as a complementary

test to other neurological examinations
and diagnostic tests at referral institutions . 42

Recommendations have been made in
order to standardize EEG techniques
for animals; these typically involve meticu-
lous preparation of the recording sites on
the scalp, and placement of electrodes
over the left and right frontal areas, the
left and right occipital areas, the vertex
area and a reference electrode is placed
behind the tip of the nose . 20 However, the
addition of other recording sites increases
the ability to localize a focal lesion . 42
Neurological disease is associated with
changes in either EEG frequency or
amplitude, or both, with frequency
changes being a more reliable indicator of
disease. In general, focal EEG abnor-
malities indicate a focal lesion in the cortex,
whereas diffuse EEG abnormalities indicate
diffuse cortical or subcortical lesions or
focal subcortical lesions.

Electroencephalography has been used
to study epilepsy in goats and cattle, con-
genital hydranencephaly and hydro-
cephalus in cattle, scrapie in sheep,
thiamine-responsive polioencephalo-
malacia in cattle 43 and bovine spongiform
encephalopathy in cattle. When performed
under controlled conditions, EEG has
been shown to be a useful diagnostic tool
for the early diagnosis of equine intracranial
diseases , 42 with adequate sensitivity and
specificity.

ELECTROMYOGRAPHY

Electromyographic needle examination
(EMG) is a technique that records the
electrical activity generated by single
muscle fibers and the summated electrical
activity of muscle fibers in individual
motor units . 44 The technique involves
inserting a recording needle into the muscle
of interest and recording the resultant
EMG. Typically, animals are unsedated
and restrained in stocks or a chute.
Abnormal EMG signals include short-
duration and low-amplitude motor unit
action potentials, which indicate diseased
muscle fibers of early or incomplete
reinnervation after denervation. Other
abnormalities include the presence of
fibrillation potentials, positive sharp
waves and complex repetitive discharges
that occur when the skeletal cell membrane
becomes unstable because of denervation
or myopathy . 44

Electromyography provides a more
practical diagnostic test than EEG, and
is especially useful for evaluating peripheral
nerve injury and diagnosing hyperkalemic
periodic paresis in horses. Electro-
myography can discriminate between
neurogenic or myogenic disorders, and
nerve conduction studies can differentiate
axonal loss from demyelination. In

addition, repetitive stimulation can provide
information regarding neuromuscular
transmission.

Electromyography has been coupled
with transcranial magnetic stimulation to
induce magnetic motor evoked potentials
in the horse . 45 This provides a useful non-
invasive evaluation of cervical spinal cord
dysfunction in horses that evaluates the
integrity of the descending motor tracts.

BRAINSTEM AUDITORY EVOKED
POTENTIALS

The brainstem auditory evoked potential
(BAEP) is a recording of the electrical
activity of the brainstem following an
acoustic stimulation . 46 The use of the
BAEP is well documented in human
medicine as a diagnostic aid and has been
used in dogs to evaluate deafness. The
BAEP is obtained by recording neuro-
electrical activity from generators in the
auditory pathway immediately following
an acoustic click stimulus, and BAEP
waveforms for horses and ponies have
been recorded . 47 Such recordings can be
useful in evaluating horses suspected to
have deafness, vestibular disease or brain-
stem disease, and to monitor the response
to treatment . 48

INTRACRANIAL PRESSURE AND
CEREBRAL PERFUSION PRESSURE

Intracranial pressure has been measured
in neonatal foals , 49 although the clinical
utility of such measurements has not
been demonstrated. Increases in intra-
cranial pressure can cause decreases in
cerebral perfusion pressure and irre-
versible injury to the central nervous
system.

Principles of treatment of
diseases of the nervous
system

Treatment of disease of the nervous
system presents some particular problems
because of the failure of nervous tissue in
the brain and spinal cord to regenerate
and because of the impermeability of the
blood-brain barrier to many antimicrobial
agents, antiprotozoal agents, and anthel-
mintics.

When peripheral nerves are severed,
regeneration occurs if the damage is not
extensive but no specific treatment, other
than surgical intervention, can be provided
to facilitate repair. When neurons are
destroyed in the brain and spinal cord no
regeneration occurs and the provision of
nervous system stimulants can have no
effect on the loss of function that occurs.
The emphasis in the treatment of diseases

Principles of treatment of diseases of the nervous system

of the nervous system must be on
prevention of further damage. On occasion
this can be done by providing specific or
ancillary treatments.

ELIMINATION AND CONTROL OF
INFECTION

Most of the viral infections of the nervous
system are not susceptible to chemo-
therapeutics. Some of the larger organisms
such as Chlamydia spp. are susceptible
to broad-spectrum antimicrobial agents
such as the tetracyclines and chlor-
amphenicol.

Bacterial infections of the central
nervous system are usually manifestations
of a general systemic infection as either
bacteremia or septicemia. Treatment of
such infections is limited by the existence
of the blood-brain and blood-CSF
barriers, which prevent penetration of
some substances into nervous tissue and
into the CSF. Very little useful data exist
on the penetration of parenterally ad-
ministered antibiotics into the central
nervous system of either normal farm
animals or those in which there is inflam-
mation of the nervous system.

In humans it is considered that most
antimicrobials do not enter the sub-
arachnoid space in therapeutic concen-
trations unless inflammation is present,
and the degree of penetration varies
among drugs. Chloramphenicol is an
exception; levels of one-third to one-half
of the blood level are commonly achieved
in normal individuals. The relative
diffusion of Gram-negative antimicrobial
agents from blood into CSF in humans is
shown in Table 12.8.

The most promising antimicrobial
agents for the treatment of bacterial menin-
gitis in farm animals are the third-
generation cephalosporins, trimetho-
prim-sulfonamide combinations and
gentamicin. 50

In most instances of bacterial encep-
halitis or meningitis in farm animals it is

Table 12.8 Relative di
‘‘negativeantimicrobia

ffusion of Gram-’ .
15 "

Excellent with or

Good only with

without inflammation

inflammation

Sulfonamides

Ampicillin

Third-generation

Carbenicillin

cephalosporins

Cephalothin

(cefoperazone,

Cephaloridine

cefotaxime)

Minimal or not good

No passage with

with inflammation

inflammation

Tetracycline

Polymyxin B

Streptomycin

Colistin

Kanamycin

Gentamicin

likely that the blood-brain barrier is not
intact and that parenterally administered
drugs will diffuse into the nervous
tissue and CSF. Certainly, the dramatic
beneficial response achieved by the early
parenteral treatment of Histophilus somni
meningoencephalitis in cattle using
intravenous oxytetracycline, intramuscular
penicillin or a broad-spectrum antibiotic
suggests that the blood-brain barrier
may not be a major limiting factor when
inflammation is present. Another example
of an antibiotic that does not normally
pass the blood-brain barrier well but
is able to do so when the barrier is
damaged is penicillin in the treatment
of listeriosis. When cases of bacterial
meningoencephalitis fail to respond to
antimicrobial agents, to which the
organisms are susceptible, other reasons
should also be considered. Often the
lesion is irreversibly advanced or there is a
chronic suppurative process which is
unlikely to respond.

Intrathecal injections of antimicrobial
agents have been suggested as viable
alternatives when parenteral therapy
appears to be unsuccessful. Flowever,
there is no evidence that such treatment
is superior to appropriate parenteral
therapy. In addition, intrathecal injections
can cause rapid death and therefore are
not recommended.

DECOMPRESSION

Increased intracranial pressure probably
occurs in most cases of inflammation of
the brain but it is only likely to be severe
enough to cause physical damage in acute
cerebral edema, space-occupying lesions
such as abscesses, and hypovitaminosis A.
In these circumstances some treatment
should be given to withdraw fluid from
the brain tissue and decrease the
intracranial pressure.

One treatment that may be attempted
is the combination of mannitol and
corticosteroids used in man and in small
animals. Mannitol given as a 20% solu-
tion intravenously over a 30-60-minute
period is a successful intracranial decom-
pressant with an effect lasting about
4 hours; the effect can be prolonged by
the intravenous administration of dexa-
methasone 3 hours after the mannitol. The
treatment has been used in calves with
polioencephalomalacia, combined with
thiamin, with excellent results to relieve
the effects of acute cerebral edema. The
dose rates have been those recommended
for dogs and are very expensive: mannitol
2 g/kg BW, dexamethasone 1 mg/kg BW,
both intravenously. There are dangers
with mannitol: it should not be repeated
often; it must not be given to an animal in
shock; it should be given intravenously

slowly. Dexamethasone on its own is
safe and has a good effect but does
not decompress sufficiently. Hypertonic
glucose given intravenously is dangerous
because an initial temporary decom-
pression is followed after a 4-6-hour
interval by a return to pretreatment C^F
pressure when the glucose is metabolized.

TREATMENT OF BRAIN INJURY
AFTER HEAD TRAUMA

The principles of treatment of animals
exhibiting neurological abnormalities
after a traumatic event are derived from
the results of large, controlled, multi-
center clinical trials in human beings.
Similar studies have not been performed
in large animals. The general principles
are: 1) stabilize the patient by ensuring a
patent airway, obtaining vascular access
and attending to wounds, 2) specific
treatment for hyperthermia as brain
defects may result in an inability to
regulate core temperature, 3) prevent or
treat systemic arterial hypotension, 4)
optimize oxygen delivery, 5) ensure
adequate ventilation by placing in sternal
recumbency whenever possible, 6)
decrease pain, 7) monitor plasma glucose
concentration and maintain euglycemia,
and 8) prevent or treat cerebral edema
by having the head elevated or by the
intravenous administration of a hyper-
osmolar agent (hypertonic saline, 7.2%
NaCl, 2mL/kg BW every 4 hours for
5 infusions; 20% mannitol as a series of
bolus infusions of 0.25 to 1 g/kg BW every
4-6 hours, the latter is an expensive
treatment). Intravenous catheterization
should be confined to one jugular vein
and the neck should not be bandaged in
an attempt to minimize promotion of
cerebral edema by jugular venous hyper-
tension. Seizures should be treated when
they occur by administering diazepam,
midazolam, phenobarbital, or pentobarbital.

Many anecdotal treatments have been
used in large animals, but evidence
attesting to their efficacy is clearly lacking.
Amongst the more popular empiric anti-
oxidant treatments are dimethyl sulfoxide
(1 g/kg BW as a 10% solution in 0.9%
NaCl) administered intravenously or by
nasogastric tube every 12 h, vitamin E
(a-tocopherol, 50IU/kg BW administered
orally every day), vitamin C (ascorbic acid,
20 mg/kg BW administered orally every
day), and allopurinol (5 mg/kg BW admin-
istered orally every 12 h). Corticosteroids
have also been advocated; promoted
treatments include an anti-inflammatory
dose of dexamethasone (0.05 mg/kg BW
every day) or a high dose of methyl-
prednisolone sodium succinate (30 mg/kg
BW initial bolus, followed by continuous
infusion of 5.4 mg/kg BW per hour for

16

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

24M8 h); the latter treatment is prohibi-
tively expensive in large animals and must
be given within 8 hours of the traumatic
event to be effective. Intravenous mag-
nesium sulfate (50 mg/kg BW) in the first
5-10 L of intravenous fluids has also been
advocated on the basis that it inhibits
several aspects of the secondary injury
cascade.

CENTRAL NERVOUS SYSTEM
STIMULANTS

These substances are used to excess in
many instances. They exert only a transitory
improvement in nervous function and are
indicated only in nervous shock and after
anesthesia or other short-term reversible
anoxias such as cyanide or nitrate poison-
ing. It is unlikely that terminal respiratory
Mure caused by anoxia over a long period,
and in which anoxia is likely to continue,
will respond permanently to their use.

CENTRAL NERVOUS SYSTEM
DEPR ESSA NTS

Animals with convulsions should be
sedated to avoid inflicting traumatic injuries
on themselves. Most of the general anes-
thetic agents in common use will satis-
factorily control convulsions, and allow
some time to examine the animal pro-
perly, assess the diagnosis and institute
specific therapy if possible.

REVIEW LITERATURE

Mayhew IG. Large animal neurology. A handbook for
veterinary clinicians. Philadelphia, PA: Lea &
Febiger, 1989.

Summers BA., Cummings JF. de Lahunta A.Veterinary
neuropathology. St Louis, MO: Mosby, 1995.
Tucker RL, Fardl E. Computed tomography and
magnetic resonance imaging of the equine head. Vet
Clin North Am Equine Pract 2001; 17:131-144.
Saegerman C, Claes L, Dcwaelc A et al. Differential
diagnosis of neurologically expressed disorders in
Western European cattle. Rev Sci Tech Off Int Epiz
2003; 22:83-102.

Wijnberg ID, van der Kolk JH, Franssen H, Breukink
HJ. Needle electromyography in the horse
compared with its principles in man: a review.
Equine Vet J 2003; 35:9-17.

Constable PD. Clinical examination of the ruminant
nervous system. Vet Clin North Am Food Anim
Pract 2004; 20:215-230.

MacKay RJ. Brain injury after head trauma: patho-
physiology, diagnosis, and treatment. Vet Clin
North Am Equine Pract 2004; 20:199-216.

Scott PR. Diagnostic techniques and clinicopathologic
findings in ruminant neurologic disease. Vet Clin
North Am Food Anim Pract 2004; 20:215-230.

REFERENCES

1. Done S. In Pract 1995; 17:318.

2. Scott PR. BrVet J 1995; 151:603.

3. Tyler CM ct al. AustVet J 1993; 70:445.

4. Perino LJ et al. Equine Pract 1985; 7:14.

5. Strain GM et al. J Am Vet Med Assoc 1984;
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6. Roeder BL et al. Compend Contin Educ Pract Vet
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7. Beech J. Am J Vet Res 1987; 48:109.

8. De Lahunta A. Can J Vet Res 1990; 54:65.

9. Fayer R et al. J Vet Intern Med 1990; 4:54.

10. Martin L et al. EquineVet J 1986; 18:133.

11. Mayhew IG. J Vet Intern Med 1991; 5:332.

12. Nappert G et al. Can Vet J 1989; 30:802.

13. Mayhew IG. Large animal neurology: A
handbook for veterinary clinicians. Philadelphia,
PA: Lea & Febiger, 1989.

14. Cummings JF et al. Cornell Vet 1990; 80:357.

15. Strain GM et al. J Am Vet Med Assoc 1987; 191:833.

16. Lane JG, MairTS. EquineVet J 1987; 19:331.

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19. Nurmio P et al. NordVet Med 1982; 34:130.

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22. Cash WC et al. J Vet Med A 1986; 33:491.

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24. Scott PR, Will RG. BrVet J 1991; 147:582.

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26. Foreman JH et al. J Vet Intern Med 2004; 18:223.

27. Moore RM, Trims CM.AmJVet Res 1992; 53:1558.

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30. Furr MO, Bender H. Am J Vet Res 1994; 55:781.

31. Scott PR, Penny CD. Vet Rec 1993; 133:119.

32. Jackson C et al. J Vet Intern Med 1996; 10:246.

33. Wilson JW, Stevens JB. J AmVet Med Assoc 1977;
171:256.

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36. Foreman JH et al. J Vet Intern Med 2004; 18:223.

37. Mudron P et al. Vet Med Czech 2004; 49:187.

38. Tietje S et al. EquineVet J 1996; 28:98.

39. Van Biervliet J et al. J Vet Intern Med 2004; 18:907.

40. SpoormakersTJPet al. EquineVet J 2003; 35:146.

41. Gordon PJ, Dennis R.Vet Rec 1995; 137:671.

42. LacombeVA et al. J Vet Intern Med 2001; 15:385.

43. Suzuki M et al. Jpn JVet Sci 1990; 52:1077.

44. Wijnberg ID et al. J Vet Intern Med 2003; 17:185.

45. Nollet H et al. EquineVet J 2004; 36:51.

46. Mayhew IG, Washbourne JR. Br Vet J 1992;
148:315.

47. Mayhew IG, Washbourne JR. Vet J 1997; 153:107.

48. Mayhew IG, Washbourne JR. Br Vet J 1990;
146:509.

49. Kortz GD ct al. Am JVet Res 1995; 56:1351.

50. Jamison JM, Prescott JF. Compend Contin Educ
Pract Vet 1988; 10:225.

Pathophysiological
mechanisms of nervous
system disease

Etiology of nervous system disease

There are many different causes of nervous
system disease in large domestic animals.

° Infectious causes include bacteria,
viruses, fungi, and helminth,
arthropod and protozoan parasites
° Exogenous substances such as lead,
salt, selenium, organophosphate
insecticides, feed additives such as
urea, poisonous plants and many
other chemicals are common causes
« Endogenous substances such as
products of disease in other body
systems or of abnormal metabolism
such as bacterial toxins, ammonia and
carbon dioxide can cause
abnormalities of the nervous system

° Metabolic and nutritional causes
include ischemia secondary to
cardiopulmonary disease,
hypoglycemia, hypomagnesemia,
copper deficiency in pregnant
animals, and hyper D-lactatemia in
calves with neonatal diarrhea and
adult ruminants with grain overload
° Acidemia associated with diarrhea can
cause mental depression and ataxia
° Traumatic and physical injuries to the
brain or spinal cord are common
° Neoplasms of the nervous system in
large animals are uncommon, with
the exception of spinal
lymphosarcoma in adult cattle due to
enzootic bovine leukosis
° Idiopathic diseases account for several
diseases of the spinal cord of horses
° Malfonnation occurs primarily in the
developing fetus and results in
congenital nervous system disease,
which is usually present at birth. Many
different teratogens can cause
congenital defects. In some cases of
inherited disease, the clinical signs are
not manifest until some time after birth.

Responses of central nervous system
to injury

The central nervous system may respond
to injury by morphological changes that
include cerebral edema and brain swelling,
inflammation, and demyelination. Malfor-
mations occur when the central nervous
system is affected during fetal life.

The remainder of this chapter will
present the general clinical aspects of the
diseases of the nervous system according
to anatomical sites. The salient features of
the etiology, pathogenesis, clinical findings,
diagnosis, and treatment of these clinico-
anatomical diseases are described. The
objective is to generalize about the clinical
findings that are common or typical of
diseases affecting each of the major
anatomical sites of the brain and spinal
cord. Cerebral hypoxia and ischemia,
hydrocephalus and cerebral edema are
common to many diseases of the nervous
system, and are described here.

Diffuse diseases of the
brain*

CEREBRAL HYPOX IA

Cerebral hypoxia occurs when the supply
of oxygen to the brain is reduced for any
reason. An acute or chronic syndrome

* In the following discussion of diseases of the brain,
the terms 'irritation', 'release', 'paralysis' and 'nervous
shock' are used to describe groups of signs. These
terms are used in accordance with their definitions
under the principles of nervous dysfunction.

Diffuse diseases of the brain

59

develops depending on the acuteness of
the deprivation. Initially there are irritation
signs followed terminally by signs of loss
of function.

ETIOLOGY

All forms of hypoxia, including anemic,
anoxic, histotoxic, and stagnant forms
cause some degree of cerebral hypoxia
but signs referable to cerebral dysfunction
occur only when the hypoxia is severe.
The hypoxia of the brain may be secondary
to a general systemic hypoxia or be
caused by lesions restricted to the cranial
cavity.

Cerebral hypoxia secondary to
general hypoxia

o Poisoning by hydrocyanic acid or
nitrite

° Acute heart failure in severe copper
deficiency in cattle
2 Anesthetic accidents
° Terminally in pneumonia, congestive
heart failure

0 During or at birth in foals, neonatal
maladjustment syndrome in foals, or
intrapartum hypoxia in calves and
lambs due to prolonged parturition.

Cerebral hypoxia secondary to
intracranial lesion

0 In increased intracranial pressure
0 In brain edema.

PATHOGENESIS

The central nervous system is extremely
sensitive to hypoxia, and degeneration
occurs if the deprivation is extreme and
prolonged for more than a few minutes.
The effects of the hypoxia vary with the
speed of onset and with the severity.
When the onset is sudden there is usually
a transitory period during which excitation
phenomena occur and this is followed by
a period of loss of function. If recovery
occurs, a second period of excitation
usually develops as function returns. In
more chronic cases the excitation phase is
not observed, the signs being mainly
those of loss of function. These signs
include dullness and lethargy when
deprivation is moderate, and uncon-
sciousness when it is severe. All forms of
nervous activity are depressed but the
higher centers are more susceptible than
medullary centers and the pattern of
development of signs may suggest this.

CLINICAL FINDINGS

Acute and chronic syndromes occur
depending on the severity of the hypoxia.
Acute cerebral hypoxia is manifested by a
sudden onset of signs referable to
paralysis of all brain functions, including
tetraparesis and unconsciousness. Muscle
tremor, beginning about the head and
spreading to the trunk and limbs, followed
by recumbency, clonic convulsions and

death or recovery after further clonic
convulsions is the most common pattern,
although affected animals may fall to the
ground without premonitory signs. In
chronic hypoxia there is lethargy,
dullness, ataxia, weakness, blindness and
in some cases muscle tremor or convul-
sions. In both acute and chronic hypoxia
the signs of the primary disease will also
be evident. Cerebral hypoxia of fetal calves
is thought to be a cause of weakness and
failure to suck after birth, leading to the
eventual death of the calf from starvation.
Such hypoxia can occur during the birth
process, especially if it is difficult or delayed,
or during late pregnancy.

CLINICAL PATHOLOGY AND
NECROPSY FINDINGS

There is no distinctive clinical pathology
or characteristic necropsy lesion other
than those of the primary disease.

DIFFERENTIAL DIAGNOSIS

Clinically there is little to differentiate
cerebral hypoxia from hypoglycemia or
polioencephalomalacia in which similar
signs occur. Irritation and paralytic signs
follow one another in many poisonings
including lead and arsenic and in most
diffuse diseases of the brain including
encephalitis and encephalomalacia. The
differential diagnosis of cerebral hypoxia
depends upon the detection of the cause
of the hypoxia.

TREATMENT

An increase in oxygen delivery is essential
and can usually only be provided by
removing the causative agent. A respiratory
stimulant (such as doxapram) may be
advantageous in acute cases and artificial
respiration may be necessary and effective.

INCREASED INTRACRANIAL
PRESSURE, CEREBRAL EDEMA,
AND BRAIN SWELLING

Diffuse cerebral edema and brain swelling
usually occur acutely and cause a general
increase in intracranial pressure. Cerebral
edema is rarely a primary disease, but
commonly an accompaniment of other
diseases. Cerebral edema is commonly a
transient phenomenon and may be
fatal but complete recovery or recovery
with residual nervous signs also occurs. It
is manifested clinically by blindness,
opisthotonos, muscle tremor, paralysis,
and clonic convulsions.

ETIOLOGY

Diffuse cerebral edema and brain swelling
may be vasogenic, when there is increased
permeability of capillary endothelium,
cytotoxic when all the elements of brain
tissue, glia, neurons and endothelial cells

undergo swelling. Causes include the
following.

Vasogenic edema

0 Brain abscess, neoplasm, hemorrhage,
lead encephalopathy, purulent
meningitis

c Minor edema after most traumatic
injuries, in many encephalitides and
many poisonings, including propylene
glycol in the horse; probably
contributes to the pathogenesis
° Accidental intracarotid injection of
promazine in horses

° Leukoencephalomalacia in horses due
to fumonisin consumption 1,2
° Septicemia in neonatal foals . 3

Cytotoxic edema

° Hypoxia

° Polioencephalomalacia of ruminants
(thiamine deficiency or sulfur
toxicosis)

0 Salt poisoning of swine.

Interstitial edema

° Hydrocephalus.

PATHOGENESIS

Cerebral edema and brain swelling

This disease is potentially life-threatening
because of the limited ability for accom-
modation of increased volume within the
confines of the dura and the cranium. The
central nervous system parenchyma does
not possess a lymphatic system, and the
interstitial space between cells, especially
in the gray matter, is much narrower than
in other tissues. When central nervous
system edema develops, of necessity it
largely accumulates within cells, although
interstitial fluid will form if cells lyse or if
the edema is severe.

Cerebral edema commonly occurs to
some degree in all pathological states,
whether degenerative or inflammatory,
traumatic or neoplastic. Edema around
chronic, focal lesions such as abscesses,
parasitic cysts and primary or metastatic
tumors in white matter often produces
marked swelling. Cerebral hemispheric
swelling compresses the underlying brain-
stem, flattening the rostral colliculi and
distorting the aqueduct. As the swollen
brain expands and fills the confines of the
calvaria, some regions are prone to
herniation. If this occurs, the accompany-
ing blood vessels are likely to become
occluded, which may result in hemor-
rhage or infarction. Commonly with brain
swelling, the caudal lobe of the cerebellar
vermis protrudes as a flattened lip over
the medulla oblongata toward the foramen
magnum.

In vasogenic edema the primary
insult is to the wail of cerebral capillaries,
allowing the escape of plasma fluid and
proteins under the hydrostatic pressure of
the circulation. The inciting vascular

18

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

injury may be brain or spinal cord trauma,
vasculitis, a neoplasm or a cerebrovascular
accident. Vasogenic edema affects pre-
dominantly the white matter, where fluid
accumulates within the cytoplasm of
astrocytes and spreads in the interstitial
spaces. Vasogenic edema moves over very
long distances and from one hemisphere
to the other via the corpus callosum. A
chronic epidural abscess involving the
frontal lobe can produce sufficient brain
swelling from vasogenic edema to induce
herniation of the occipital cortex beneath
the tentorium cerebelli.

Cytotoxic edema results from an injury
to a glial cell that disturbs osmoregulation
of that cell by depletion of energy stores
and failure of energy-dependent ionic
pumps. This leads to cell swelling with
fluid, and differs from edema in other
tissues in which fluid accumulation is
interstitial. Cytotoxic edema reflects a
specific cellular insult and may result from
ischemia or hypoxia, nutritional deficiency,
an intoxication cr an inherited metabolic
abnormality. Brain swelling from cytotoxic
edema is less dramatic than that seen in
vasogenic edema. It may affect just the gray
matter, just the white matter, or both.

The extracellular fluid volume in
vasogenic edema is increased by the
edema fluid, which is a plasma filtrate
containing plasma protein. In cytotoxic
edema it is the cellular elements themselves
that increase in size. In hypoxia this is
because of failure of the adenosine
triphosphate (ATP) -dependent sodium
pump within the cells. As a result sodium
accumulates within the cells and water
follows to maintain osmotic equilibrium.
In polioencephalomalacia and salt poison-
ing the edema of the brain is primary. In
salt poisoning in pigs there is an increase
in concentration of cations in brain tissue
with a sudden passage of water into the
brain to maintain osmotic equilibrium.
The cause of the edema in polio-
encephalomalacia of ruminants, associated
with a thiamin inadequacy, is unknown.
When promazine is injected accidentally
into the carotid artery of the horse it
produces a vasogenic edema and infarc-
tion generally, but especially in the
thalamus and corpora quadrigemina on
the injected side. The vasogenic edema
surrounding an abscess is localized and is
not evident in the white matter.

Cerebral edema and cerebellar
herniation has been described in four
neonatal foals admitted to an intensive
care unit for treatment. 3 All foals had
septicemia. It was suggested that hypo-
glycemia, hypoxia, or the alterations in
cerebral blood flow associated with
septicemia might have initiated injury to
cell membranes, resulting in vascular
damage and subsequent edema. It is

hypothesized that cerebellar herniation
occurs in neonatal foals with sepsis
because of the inelastic nature of the
dural folds and the anatomical rigidity of
the neonatal equine skull. This is in
contrast to the human infant, in whom
cerebral edema occurs in bacterial
meningitis but cerebral or cerebellar
herniation is not normally a feature. The
relatively small brain of the newborn foal
is only 1% of total body mass compared
to the human infant which is 12% and in
which the brain is enclosed within a large
but relatively thin calvarium with sutures
that, in the preterm infant at least, can be
separated by excess internal pressure. 4

An increase in intracranial pressure
occurs suddenly and, as in hydrocephalus,
there is a resulting ischemic anoxia of the
brain due to compression of blood vessels
and impairment of blood supply. This may
not be the only factor that interferes with
cerebral activity in polioencephalomalacia
and salt poisoning. The clinical syndrome
produced by the rapid rise in intracranial
pressure is manifested by involuntary
movements such as tremor and convulsions
followed by signs of weakness. If the
compression of the brain is severe enough
and of sufficient duration, ischemic necrosis
of the superficial layers of the cortical gray
matter may occur, resulting in permanent
nervous defects in those animals that
recover. Opisthotonos and nystagmus are
commonly observed and are probably due
to the partial herniation of the cerebellum
into the foramen magnum.

CLINICAL FINDINGS

Although the rise of intracranial pressure
in diffuse edema of the brain is usually
more acute than in hydrocephalus, the
development of clinical signs takes place
over a period of 12-24 hours and nervous
shock does not occur. There is central
blindness, and periodic attacks of abnor-
mality occur in which opisthotonos,
nystagmus, muscle tremor, and con-
vulsions are prominent.

In the intervening periods the animal is
dull, depressed, and blind, and optic disc
edema may be present. The involuntary
signs of tremor, convulsions, and opistho-
tonos are usually not extreme but this varies
with the rapidity of onset of the edema.
Because of the involvement of the brain-
stem, in severe cases muscle weakness
appears, the animal becomes ataxic, goes
down and is unable to rise, and the early
signs persist. Clonic convulsions occur ter-
minally and animals that survive may have
residual defects of mentality and vision.

CLINICAL PATHOLOGY

Clinicopathological observations will
depend on the specific disease causing
the edema.

NECROPSY FINDINGS

Microscopically the gyri are flattened and
the cerebellum is partially herniated into
the foramen magnum with consequent
distortion of its caudal aspect. The brain
has a soft, swollen appearance and tends
to sag over the edges of the cranium
when the top has been removed. Caudal
portions of the occipital lobes herniate
ventral to the tentorium cerebelli.

DIFFERENTIAL DIAGNOSIS

Diffuse b.rain edema causes a syndrome
not unlike that of encephalitis although
there are fewer irritation phenomena.
Differentiation from encephalomalacia and
vitamin A deficiency may be difficult if the
history does not give a clue to the cause of
the disease. Metabolic diseases, particularly
pregnancy toxemia,: hypomagnesemic
tetany of calves and lactation tetany, : .
resemble it closely, as do some cases of
acute ruminal impaction, In the history of
each of these diseases there are
distinguishing features that aid in making a
tentative diagnosis. Some of the
poisonings, particularly lead, organic
mercurials and arsenicals and
enterotoxemia associated with Clostridium
perfringens type D produce similar nervous
signs and gut edema of swine may be
mistaken for diffuse cerebral edema.

TREATMENT

Decompression of the brain is desirable in
acute edema. The treatment will depend
in part on the cause; the edema associated
with polioencephalomalacia will respond
to early treatment with thiamin. In general
terms, edema of the brain responds to
parenteral treatment with hypertonic
solutions and corticosteroids. Hypertonic
solutions are most applicable to cytotoxic
edema and corticosteroids to vasogenic
edema. This is in addition to treatment for
the primary cause of the disease. Mannitol
at 2 g/kg BW and dexamethasone at
1 mg/kg BW, both intravenously, are
recommended. The mannitol is given
intravenously as a 20% solution followed
3 hours later by the dexamethasone, also
intravenously. Diuretics usually produce
tissue dehydration too slowly to be of
much value in acute cases, but they may
be of value as an adjunct to hypertonic
solutions or in early or chronic cases. The
removal of CSF from the cisterna magna
in an attempt to provide relief may cause
complications. In some cases the removal
of 25-75 mL of CSF provides some tem-
porary relief but the condition becomes
worse later because portions of the
swollen brain herniate into the foramen
magnum. There is no published infor-
mation available on how much fluid can
be safely removed and recommendations
cannot therefore be made.

Diffuse diseases of the brain

59

REFERENCES

1. Smith GW et al. Am J Vet Res 2002; 63:538.

2. Foreman JH et al. JVet Intern Med 2004; 18:223.

3. Kortz GD et al. Equine Vet J 1992; 24:63.

4. Wiggles worth JS. Equine Vet J 1992; 24:6.

HYDROCEPHALUS

Obstructive hydrocephalus may be con-
genital or acquired and is manifested in
both cases by a syndrome referable to a
general increase in intracranial pressure.
Irritation signs of mania, head-pressing,
muscle tremor and convulsions occur
when the onset is rapid, and signs of
paralysis including dullness, blindness
and muscular weakness are present when
the increased pressure develops slowly.

ETIOLOGY

Obstructive hydrocephalus may be con-
genital or acquired but in both instances it
is due to defective drainage or absorption
of CSF. In the congenital disease there is
an embryological defect in the drainage
canals and foramina between the individual
ventricles or between the ventricles and
the subarachnoid space, or in the absorptive
mechanism, the arachnoid villi.

Congenital hydrocephalus

Causes are:

® Alone, with lateral narrowing of the
mesencephalon

8 Inherited defects of Hereford,

Holstein, Ayrshire and Jersey
cattle

° Inherited combined defects with
chondrodysplasia, or in white
Shorthorn cattle combined with
hydrocephalus, microphthalmia and
retinal dysplasia

0 Virus infections of the fetus suggest
themselves as possible causes of
embryological defects in the drainage
system, but there are no verified
examples of this. The cavitation of
brain tissue and subsequent
accumulation of fluid,
hydranencephaly, which occurs after
infection with bluetongue virus in
lambs and Akabane virus in calves, is
compensatory, not obstructive
° Vitamin A deficiency may contribute
° Other occurrences, sometimes at high
levels of prevalence, but without
known cause.

Acquired hydrocephalus

Causes include:

° Hypovitaminosis A in young growing
calves causing impaired absorption of
fluid by the arachnoid villi
° Cholesteatoma in choroid plexuses of
the lateral ventricles in the horse.
These may produce an acute,
transient hydrocephalus on a number
of occasions before the tumor reaches

sufficient size to cause permanent
obstruction

° Other tumor or chronic inflammatory
lesion obstructing drainage from the
lateral ventricles.

PATHOGENESIS

Increased intracranial pressure in the
fetus and before the syndesmoses of the
skull have fused causes hydrocephalus
with enlargement of the cranium. After
fusion of the suture lines the skull acts as
a rigid container and an increase in the
volume of its contents increases intracranial
pressure. Although the increase in volume
of the contents may be caused by the
development of a local lesion such as an
abscess, tumor, hematoma or cestode
cyst, which interferes with drainage of
the CSF, the more common lesion is a
congenital defect of CSF drainage.

Clinical and pathological hydrocephalus
has been produced experimentally in
animals by creating granulomatous
meningitis. The clinical signs included
depression, stiffness of gait, recumbency
and opisthotonus with paddling con-
vulsions. The general effects in all cases
are the same, the only difference being
that local lesions may produce localizing
signs as well as signs of increased intra-
cranial pressure. These latter signs are
caused by compression atrophy of nervous
tissue and ischemic anoxia due to
compression of blood vessels and impair-
ment of blood supply to the brain.

In congenital hydrocephalus the signs
observed are usually those of paralysis of
function, while acquired hydrocephalus,
being more acute, is usually manifested
first by irritation phenomena followed
by signs of paralysis. Edema of the optic
papilla is a sign of increased intracranial
pressure and may be detected ophthal-
moscopically. Bradycardia occurs in-
constantly and cannot be considered to
be diagnostic.

CLINICAL FINDINGS

In acquired hydrocephalus there is, in
most cases, a gradual onset of general
paresis. Initially there is depression, dis-
inclination to move, central blindness, an
expressionless stare and a lack of precision
in acquired movements. A stage of
somnolence follows and is most marked
in horses. The animal stands with half-
closed eyes, lowered head and a vacant
expression and often leans against or
supports itself upon some solid object.
Chewing is slow, intermittent and in-
complete and animals are often observed
standing with food hanging from their
mouths. The reaction to cutaneous stimu-
lation is reduced, and abnormal postures
are frequently adopted. Frequent stum-
bling, faulty placement of the feet and
incoordination are evidenced when the

animal moves, and circling may occur in
some cases. Bradycardia and cardiac
arrhythmia have been observed.

Although the emphasis is on depres-
sion and paresis, signs of brain irritation
may occur, particularly in the early stages.
These signs often occur in isolated'
episodes during which a wild expression,
charging, head-pressing, circling, tremor
and convulsions appear. These episodes
may be separated by quite long intervals,
sometimes of several weeks' duration. In
vitamin A deficiency in calves blindness and
papilledema are the early signs and an
acute convulsive stage occurs terminally.

Congenitally affected animals are
usually alive at birth but are unable to
stand and most die within 48 hours. The
cranium is sometimes domed, the eyes
protrude and nystagmus is often evident.
Meningocele is an infrequent accompani-
ment.

CLINICAL PATHOLOGY

Examination of the composition and
pressure of the CSF will be of value. The
fluid is usually normal biochemically
and cytologically but the pressure is
increased. A marked increase in serum
muscle enzyme activity has been observed
in calves with congenital hydrocephalus,
due probably to an accompanying
muscular dystrophy. Convulsions, if they
occur, may contribute to this increase.

NECROPSY FINDINGS

The cranium may be enlarged and soft in
congenital hydrocephalus. The ventricles
are distended with CSF under pressure
and the overlying cerebral tissue is thinned
if the pressure has been present for some
time.

DIFFERENTIAL DIAGNOSIS

Congenital hydrocephalus resembles
vitamin A deficiency in newborn pigs,
toxoplasmosis and hydranencephaly if
there is no distortion of the cranium.
Acquired hydrocephalus needs to be
differentiated from other diffuse diseases
of the brain, including encephalitis and
encephalomalacia, and from hepatic
dystrophies, which resemble it very closely.
In these latter diseases there may be other
signs of diagnostic value, including fever in
encephalitis and jaundice in hepatic
dystrophy. In most cases it is necessary to
depend largely on the history and
recognition of individual disease entities.

ENCEPHALITIS

Encephalitis is, by definition, inflammation
of the brain but in general usage it includes
those diseases in which inflammatory
lesions occur in the brain, whether there
is inflammation of the nervous tissue
or primarily of the vessel walls. Clinically,
encephalitis is characterized initially

600

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

by signs of involuntary movements,
followed by signs caused by loss of
nervous function. The meninges and
spinal cord may be involved in an
encephalitis, causing varying degrees of
meningoencephalomyelitis.

ETIOLOGY

Many encephalitides of large animals are
associated with viruses but other infectious
agents are also common. Some causes are
as follows.

All species

‘ 3 Viral infections - rabies, pseudorabies,
Japanese B encephalitis, West Nile
virus encephalomyelitis
0 Bacterial infections of neonatal farm
animals

0 Toxoplasmosis, which is not a
common cause in any species
° Sarcocystosis

° Verminous encephalomyelitis -

migration of larvae of parasitic species
that normally have a somatic
migration route, e.g. Micronema
deletrix, Setaria spp.
Paraelaphostrongylus tenuis

Cattle

° Bovine spongiform encephalopathy
0 Viral infections - bovine malignant
catarrh, sporadic bovine
encephalomyelitis and bovine herpes
virus

° Bacterial infections including Listeria
monocytogenes, Histophilus somni
(formerly Haemophilus somnus ),'
heartwater, clostridial infections
following dehorning of calves 2
3 Migration of Hypodenna bovis

occasionally to brain and spinal cord

Sheep
0 Scrapie

0 Viral infections - louping ill, visna
(associated with Maedi-visna virus) 3
° Thrombotic meningoencephalitis
associated with H. somni (formerly
Histophilus ovi s) in lambs 1,4
0 Bacterial meningoencephalitis in
lambs 2-4 weeks of age s
° Migration of Oestrus ovis

Goats
° Scrapie

0 Caprine arthritis-encephalitis virus

New World camelids
° Bacterial infection due to
L. monocytogenes

Pigs

0 Bacterial infections - as part of
systemic infections with Salmonella
and Erysipelas spp., rarely
L. monocytogenes

° Viral infections - hog cholera, African
swine fever, encephalomyocarditis,
swine vesicular disease,

hemagglutinating encephalomyelitis j
virus, porcine encephalomyelitis virus j

Horses

° Viral infections - infectious equine
encephalomyelitis, Borna disease,
equine herpes virus, equine infectious
anemia, eastern, western and West
Nile equine encephalomyelitides,
rarely louping ill virus
° Protozoal encephalomyelitis 6
° Verminous encephalomyelitis due to
Strongylus vulgaris in horses and
Draschia megastoma. Angiostrongylus
cantonensis, which normally migrates
through the central nervous system of
the rat, has been found as a cause of
verminous encephalomyelitis in foals 7

PATHOGENESIS

Compared to other extraneural tissues,
the inflammatory response mounted by
the nervous system is unique. The central
nervous system is in a sequestered and
immunologically dormant state within
the body. The capillary endothelial blood-
brain barrier restricts free access by
blood constituents. The central nervous
system lacks specialized dendritic antigen-
presenting cells, and the intrinsic
expression by central nervous system cells
of major histocompatibility complex
molecules, especially class II, is low. There
is no lymphatic system within nervous
tissue, but cells and antigens within the
central nervous system drain into the
circulation and to the cervical lymph
nodes.

The central nervous system has unique
populations of cells consisting of paren-
chymal cells, which are neurons, and
neuroglia. The neuroglia are supporting
cells and are subdivided into macroglia
and microglia: the macroglia are

astrocytes and oligodendrocytes; the
third glial cell type is a microglial cell.
The brain and spinal cord are enclosed by
meninges (dura, arachnoid and pia),
which provide protection, a compartment
for CSF circulation (the subarachnoid
space), support for blood vessels and a
sheath for the cranial and spinal nerves.
Within the brain and spinal cord are the
ventricular system and central canal,
which are lined by ependymal cells and
the choroid plexuses, which produce the
CSF. Circulation of the CSF moves from
the lateral, third and fourth ventricles into
the central canal or through lateral
apertures at the cerebellomedullary angle
into the subarachnoid space of the brain.
CSF in the subarachnoid space drains via
specialized arachnoid granulations into
intracranial venous sinuses, with some
draining into venous plexuses associated
with cranial and spinal nerves. CSF may
also cross the ventricular surface into the
adjacent parenchyma.

The histological characteristics of
central nervous system inflammation are:

o Perivascular cuffing
° Gliosis

3 Neuronal satellitosis and

neuronophagia.

A perivascular compartment, actual or
potential, exists around all central
nervous system arteries, arterioles, venules
and veins. A characteristic feature of
central nervous system inflammation is
perivascular cuffing, the accumulation
of leukocytes of one or multiple types
in the perivascular space. All perivascular
cuffing results in vasculitis of some de-
gree. In bacterial diseases, polymorpho-
nuclear cells predominate with a minor
component of mononuclear cells. In
general, viral diseases are characterized
by lymphocyte-rich cells with some
plasma cells and monocytes; some
arbovirus infections cause a polymorpho-
nuclear cell response. In immune-
mediated diseases, there are mixtures of
polymorphonuclear and mononuclear
cells. In thrombogenic diseases such as
thrombotic meningoencephalitis, vascular
occlusion precludes the development of
cuffing around injured vessels.

Gliosis is the increased prominence of
glial cells, resulting from cytoplasmic
swelling and the acquisition of more cell
processes, from cell proliferation, or both.
Either of the macroglia (oligodendrocytes
or astrocytes) or microglia may participate
in gliosis.

Neuronal satellitosis occurs when
oligodendrocytes react and proliferate in
response to degenerating neurons which
may be infected by a virus.

Neuronophagia is the progressive
degeneration of the neuron characterized
by its piecemeal division and phagocytosis,
eventually leaving a dense nodule of glial
cells and fragments of the former neuron.
Details of the form, functions and roles of
astrocytes in neurological disease have
been reviewed. 8

Primary demyelination is charac-
teristic of only a small number of inflam-
matory neurological diseases and is
associated with only a few viruses. The
inflammatory neuraxial diseases of large
animals include visna in sheep and caprine
arthritis-encephalitis. The demyelinating
process may be initiated directly by the
infectious agent alone or by an immuno-
logical response initiated by the agent.

With the exception of the viruses of
bovine malignant catarrh and equine
herpesvirus 1, which exert their effects
principally on the vasculature, those viruses
that cause encephalitis do so by invasion
of cellular elements, usually the neurons,
and cause initial stimulation and then
death of the cells. Those bacteria that

Diffuse diseases of the brain

601

cause diffuse encephalitis also exert their
effects primarily on vascular endothelium.
L. monocytogenes does so by the formation
of microabscesses. In some diseases, such
as meningoencephalitis in cattle associated
with H. somni, the lesions may be present
in the brain and throughout the spinal
cord. 9

Entrance of the viruses into the
nervous tissue occurs in several ways.
Normally the blood-brain barrier is an
effective filtering agent but when there is
damage to the endothelium infection
readily occurs. The synergistic relationship
between the rickettsias of tick-borne fever
and the virus of louping ill probably has
this basis. Entry may also occur by
progression of the agent up a peripheral
nerve trunk, as occurs with the viruses
of rabies and pseudorabies and with
L. monocytogenes. Entry via the olfactory
nerves is also possible.

The clinical signs of encephalitis are
usually referable to a general stimulatory
or lethal effect on neurons in the brain.
This may be in part due to the general
effect of inflammatory edema and in part
to the direct effects of the agent on nerve
cells. In any particular case one or other of
these factors may predominate but the
tissue damage and therefore the signs are
generalized. Clinical signs are often
diverse and can be acute or chronic,
localized or diffuse, and progressive or
reversible. Because of diffuse inflammation
in encephalitis, the clinical signs are
commonly multifocal and asymmetric.
This is not the case in listeriosis, in which
damage is usually localized in the
pons-medulla. Localizing signs may
appear in the early stages of generalized
encephalitis and remain as residual
defects during the stage of convalescence.
In calves with thromboembolic men-
ingoencephalitis due to H. somni, prolonged
recumbency may be associated with
widespread lesions of the spinal cord.
Visna is a demyelinating encephalitis, and
caprine leukoencephalomyelitis is both
demyelinating and inflammatory and also
invades other tissues including joints and
lung.

In verminous encephalomyelitis,

destruction of nervous tissue may occur in
many parts of the brain and in general the
severity of the signs depends upon the
size and mobility of the parasites and the
route of entry. One exception to this
generalization is the experimental 'visceral
larva migrans' produced by Toxocara cams
in pigs when the nervous signs occur at a
time when lesions in most other organs
are healing. The signs are apparently
provoked by a reaction of the host to
static larvae rather than trauma due to
migration. Nematodes not resident in
nervous tissues may cause nervous signs

due possibly to allergy or to the formation
of toxins.

CLINICAL FINDINGS

Because the encephalitides are associated
with infectious agents they are often
accompanied by fever, anorexia, depression
and increased heart rate. This is not
the case in the very chronic diseases
such as scrapie and bovine spongiform
encephalopathy. In those diseases asso-
ciated with agents that are not truly
neurotropic, there are characteristic signs,
which are not described here.

The clinical findings that can occur in
encephalitis are combinations of:

° Subtle to marked changes in

behavior
° Depression
° Seizures
° Blindness
° Compulsive walking
° Leaning on walls or fences
° Circling
° Ataxia.

Bacterial meningoencephalitis in lambs
2-4 weeks of age is characterized by lack
of suck reflex, weakness, altered gait
and depression extending to stupor, but
hyperesthesia to auditory and tactile
stimuli. 5 Opisthotonus is common during
the terminal stages.

There may be an initial period of
excitement or mania. The animal is
easily startled and responds excessively
to normal stimuli. It may exhibit vicious-
ness and uncontrolled activity including
blind charging, bellowing, kicking and
pawing. Self-mutilation may occur in
diseases such as pseudorabies. Mental
depression, including head-pressing, may
occur between episodes.

Involuntary movements are variable in
their occurrence or may not appear at
all. When they do occur they include con-
vulsions, usually clonic, and may be
accompanied by nystagmus, champing of
the jaws, excessive frothy salivation and
muscle tremor, especially of the face and
limbs. In cattle with malignant catarrhal
fever, there is severe depression for a few
days followed by the onset of tremors
associated with the terminal encephalitis.
Unusual irritation phenomena are the
paresthesia and hyperesthesia of pseu-
dorabies and scrapie.

Signs caused by loss of nervous
function follow and may be the only signs
in some instances. Excessive drooling
and pharyngeal paralysis are common
in rabies. In horses with equine
encephalomyelitis, feed may be left
hanging from the mouth, although
swallowing may not be impaired. The loss
of function varies in degree from paresis
with knuckling at the lower limb joints, to

spasticity of the limbs with resultant
ataxia, to weakness and recumbency.
Recumbency and inability to rise may be
the first clinical finding encountered as in
many cases of meningoencephalitis
associated with H. somni. Hypermetria, a
staggering gait and apprehensiverfess
progressing to belligerency may occur in a
disease such as bovine spongiform
encephalopathy.

Clinical signs referable to certain
anatomical sites and pathways of the brain
and spinal cord are manifested by deviation
of the head, walking in circles, abnor-
malities of posture, ataxia and incoordi-
nation but these are more commonly
residual signs after recovery from the acute
stages. Progressive ascending spinal cord
paralysis, in which the loss of sensation and
weakness occur initially in the hindlimbs
followed by weakness in the forelimbs,
occurs commonly in rabies. Residual
lesions affecting the cranial nerves do not
commonly occur in the encephalitides,
except in listeriosis and protozoal
encephalitis of horses, both infections
predominating in the caudal brainstem.

An acute hemorrhagic necrotizing
encephalitis following dehorning calves
has been described. 2 Affected calves were
found dead or moribund within a few
days following dehorning using a gouge.
A secondary clostridial infection was
suspected.

In the horse with cerebral nematodiasis
due to S. vulgaris the clinical signs are
referable to migration of the parasite in
the thalamus, brainstem and cerebellum.
There is incoordination, leaning and
head-pressing, dysmetria, intermittent
clonic convulsions, unilateral or bilateral
blindness and paralysis of some cranial
nerves. The onset may be gradual or
sudden. The clinical diagnosis is extremely
difficult because examination of CSF
and hematology are of limited value. A
pathological diagnosis is necessary. In foals
with neural angiostrongylosis, tetraparesis
was the end result of progressive and
multifocal neurological disease. 7

CLINICAL PATHOLOGY

Clinical pathology may be of considerable
assistance in the diagnosis of encephalitis
but the techniques used are for the most
part specific to the individual diseases.

Hemogram

In the horse, complete and differential
blood counts and serum chemistry profiles
are recommended for most neurological
cases.

Serology

Acute and convalescent sera can be
submitted when a specific infectious
disease is suspected for which a serologic
diagnosis is possible.

602

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Cerebrospinal fluid

Laboratory examination of CSF for cellular
content and pathogens may also be
indicated. In bacterial meningoencephalitis
of young lambs, analysis of CSF
obtained from the lumbosacral space
reveals a highly significant increase in
protein concentration with neutrophilic
pleocytosisd

NECROPSY FINDINGS

In some of the commonly occurring
encephalitides there are no gross lesions
of the brain apart from those that occur in
other body systems and that are typical of
the specific disease. In other cases, on
transverse section of the brain, extensive
areas of hemorrhagic necrosis may be
visible, as in meningoencephalitis in cattle
due to H. somnus. Histological lesions vary
with the type and mode of action of the
causative agent. Material for laboratory
diagnosis should include the fixed brain
and portions of fresh brain material for
culture and for transmission experiments.

TREATMENT

Specific treatments are dealt with under
each disease. Antimicrobials are indicated
for bacterial meningoencephalomyelitis.
Generally the aim should be to provide
supportive treatment by intravenous fluid
and electrolyte therapy or stomach tube
feeding during the acute phase. Sedation

during the excitement stage may prevent
the animal from injuring itself, and nervous
system stimulants during the period of
depression may maintain life through the
critical phase. Although there is an
increase in intracranial pressure, the
removal of CSF is contraindicated because
of the deleterious effects of the procedure
on other parts of the brain.

REVIEW LITERATURE

Montgomery DL. Astrocytes: form, function, and role
in disease. Vet Pathol 1994; 31: 145-167.

Summers BA., Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.

REFERENCES

1. Ahrens AO et al. Int J Syst Evol Microbiol 2003;
53:1449.

2. Nation PN, CalderWA. Can Vet J 1985; 26:378.

3. Duffel SJ.Vet Rec 1984; 115:547.

4. Cassidy JP et al. \fct Rec 1997; 140:193.

5. Scott PR et al. Vet Rec 1994; 135:154.

6. Boy MG et al. J Am Vet Med Assoc 1990; 196:632.

7. Geiser DR et al. Compend Contin Educ PractVet
1988; 10:740.

8. Montgomery DL. Vet Pathol 1994; 31:145.

9. Yamaski H et al. J Comp Pathol 1991; 105:303.

ENCEPHALOMALACIA OR THE
DEGENERATIVE DISEASES OF THE
CENTRAL NERVOUS SYSTEM

The degenerative diseases of the brain are
grouped together under the name en-
cephalomalacia. By definition encepha-
lomalacia means softening of the brain. It
is used here to include all degenerative
changes. Leukoencephalomalacia and
polioencephalomalacia refer to softening of
the white and gray matter respectively.
Abiotrophy is the premature degeneration
of neurons due to an inborn metabolic error
of development and excludes exogenous
insults of neurons. The underlying cellular
defect in most abiotrophies is inherited. The
syndrome produced in most degenerative
diseases of the nervous system is essentially
one of loss of function.

ETIOLOGY

Some indication of the diversity of causes
of encephalomalacia and degenerative
diseases of the nervous system can be
appreciated from the examples which
follow but many sporadic cases occur in
which the cause cannot be defined.

All species

° Hepatic encephalopathy thought to be
due to high blood levels of ammonia
associated with advanced liver disease. 1
This is recorded in experimental
pyrrolizidine alkaloid poisoning in
sheep, in hepatic arteriovenous
anomaly and thrombosis of the portal
vein in the horse. Congenital
portocaval shunts are also a cause
° Abiotrophy involving multisystem
degenerations in the nervous system
as focal or diffuse lesions involving

DIFFERENTIAL DIAGNOSIS

The diagnosis of encephalitis cannot
depend entirely on the recognition of the
typical syndrome because similar
syndromes may be caused by many other
brain diseases. Acute cerebral edema and
focal space-occupying lesions of the cranial
cavity, and a number of poisonings,
including salt, lead, arsenic, mercury,
rotenone and chlorinated hydrocarbons all
cause similar syndromes, as do
hypovitaminosis A, hypoglycemia,
encephalomalacia and meningitis.

Fever is common in encephalitis but is
not usually present in rabies, scrapie, or
bovine spongiform encephalopathy; but it
may occur in the noninflammatory diseases
if convulsions are severe.

Generally, the clinical diagnosis rests
upon the recognition of the specific
encephalitides and the elimination of the
other possible causes on the basis of the
history and clinical pathology, especially in
poisonings, and on clinical findings
characteristic of the particular disease. In
many cases a definite diagnosis can only
be made on necropsy. For differentiation of
the specific encephalitides reference should
be made to the diseases listed under
Etiology, above.

Infestation with nematode larvae causes
a great variety of signs depending on the
number of invading larvae and the amount
and location of the damage.

the axons and myelin of neuronal
processes. 2 These include a multifocal
encephalopathy in the Simmental
breed of cattle in New Zealand and
Australia, 2 and progressive
myeloencephalopathy in Brown Swiss
cattle, known as 'weavers' because of
their ataxic gait (see below and
Chapter on Inherited Defects)

° Poisoning by organic mercurials and,
in some instances, lead; possibly also
selenium poisoning; a bilateral
multifocal cerebrospinal poliomalada
of sheep in Ghana
• Cerebrovascular disorders

corresponding to the main categories
in humans are observed in animals,
but their occurrence is chiefly in pigs
and their clinical importance is minor
° Congenital hypomyelinogenesis and
dysmyelinogenesis are recorded in
lambs (haiiy shakers), piglets
(myoclonia congenita) and calves
(hypomyelinogenesis congenita). All
are associated with viral infections in
utero. Equine herpesvirus-1 infections
in horses cause ischemic infarcts
° Cerebellar cortical abiotrophy in
calves and lambs. 2 " 4

Ruminants

0 Bovine spongiform encephalopathy
° Plant poisons, e.g. Astragalus spp.,
Oxytropis spp., Swainsona spp., Vicia
spp., Kochia scoparia
° Focal symmetrical encephalomalacia
of sheep, thought to be a residual
lesion after intoxication with
Clostridium perfringens type D toxin
0 Polioencephalomalacia caused by
thiamin inadequacy in cattle and
sheep and sulfur toxicosis in cattle;
poliomalada of sheep caused possibly
by an antimetabolite of nicotinic acid
° Progressive spinal myelopathy of
Murray Grey cattle in Australia 2
° Spongiform encephalopathy in
newborn polled Hereford calves
similar to maple syrup urine disease 2
° Neuronal dystrophy in Suffolk sheep 2
° Shakers in horned Hereford calves
associated with neuronal cell body
chromatolysis 2

° The abiotrophic lysosomal storage
diseases - progressive ataxia of
Charolais cattle, mannosidosis,
gangliosidosis, globoid cell
leukodystrophy of sheep
° The inherited defect of Brown Swiss
cattle known as 'weavers', and
presented elsewhere, is a degenerative
myeloencephalopathy 5
° Swayback and enzootic ataxia due to
nutritional deficiency of copper in lambs
° Prolonged parturition of calves
causing cerebral hypoxia and the
weak calf syndrome

Diffuse diseases of the brain

61

o Idiopathic brainstem neuronal
chromatolysis in cattle 6
f Bovine bonkers due to the

consumption of ammoniated forages
o Inherited neuronal degeneration in
Angora goats. 2

Horses

° Leukoencephalomalacia caused by
feeding moldy corn infested with
Fusarium moniliforme, which produces
primarily fumonisin B : and, to a lesser
extent, fumonisin B 2 7-10
• Nigropallidal encephalomalacia
caused by feeding on yellow star
thistle ( Centaurea solstitialis)

° Poisoning by bracken and horsetail
causing a conditioned deficiency of
thiamin

° Ischemic encephalopathy of neonatal
maladjustment syndrome of foals
° Equine degenerative

myeloencephalopathy; 11 may be
associated with a vitamin E deficiency.

Ruminants and horses
Neurotoxic mycotoxins
Swainsonine and slaframine produced by
Rhizoctonia leguminicola cause mannose
accumulation and parasympathomimetic
effects. Lolitrems from Acremonium lolii
and paspalitrems from Claviceps paspali
are tremorgens found in grasses. 7

Pigs

° Leukoencephalomalacia in mulberry
heart disease

0 Subclinical attacks of enterotoxemia
similar to edema disease
° Poisoning by organic arsenicals, and
salt.

PATHOGENESIS

The pathogenesis of the degenerative
diseases can be subdivided into:

° Metabolic and circulatory disorders
0 Intoxications and toxic-infectious
diseases

° Nutritional diseases
° Hereditary, familial, and idiopathic
degenerative diseases . 12

Metabolic and circulatory

Hepatic encephalopathy is associated
with acquired liver disease and the resultant
hyperammonemia and other toxic factors
are considered to be neurotoxic. Disorders
of intermediary metabolism result in the
accumulation of neurotoxic substances
such as in maple syrup urine disease of
calves. Lysosomal storage diseases are
caused by a lack of lysosomal enzymes
which results in an accumulation of cellular
substrates and affecting cell function.
Central nervous system hypoxia and
ischemia impair the most sensitive
elements in brain tissue especially neurons.
Severe ischemia results in necrosis of
neurons and glial elements and areas of

infarcts. Gas- anesthesia-related neuro-
logical disease occurs in animals that
have been deprived of oxygen for more
than 5 minutes.

The hypoxia is lethal to neurons
and upon recovery from the anesthetic
affected animals are blind and seizures
may occur. The typical lesion consists of
widespread neuronal damage. Post-
anesthetic hemorrhagic myelopathy and
postanesthetic cerebral necrosis in horses
are typical examples. Hypoglycemia occurs
in neonates deprived of milk and in
acetonemia and pregnancy toxemia and
clinical signs of lethargy, dullness
progressing to weakness, seizures and
coma have been attributed to hypo-
glycemia. However, there are no studies
of the central nervous system in farm
animals with hypoglycemia and the
effects, if any, on the nervous tissue are
unknown.

Intoxications and toxic-infectious
diseases

A large number of poisonous substances
including poisonous plants, heavy metals
(lead, arsenic, mercury), salt poisoning,
farm chemicals, antifreeze, herbicides and
insecticides can directly affect the nervous
system when ingested by animals. They
result in varying degrees of edema of the
brain, degeneration of white and gray
matter and hemorrhage of both the
central and peripheral nervous system.
Toxic-infectious diseases such as edema
disease of swine and focal symmetrical
encephalomalacia of sheep are examples
of endotoxins and exotoxins produced by
bacterial infections which have a direct
effect on the nervous system resulting in
encephalomalacia.

Nutritional diseases

Several nutritional deficiencies of farm
animals can result in neurological disease:

° Vitamin A deficiency affects bone
growth, particularly remodeling of the
optic nerve tracts, and CSF
absorption. The elevated CSF pressure
and constriction of the optic nerve
tracts results in edema of the optic
disc and wallerian-type degeneration
of the optic nerve resulting in
blindness

° Copper deficiency in pregnant ewes
can result in swayback and enzootic
ataxia of the lambs. Copper is an
integral element in several enzyme
systems such as ceruloplasmin and
lysyl oxidase, and copper deficiency
affects several organ systems. The
principal defect in swayback appears
to be one of defective myelination
probably caused by interference with
phospholipid formation. However,
some lesions in the newborn are more

m

extensive, and show cavitation with
loss of axons and neurons rather than
simply demyelination. In the brain,
there is a progressive gelatinous
transformation of the white matter,
ending in cavitation that resembles
porencephaly or hydranencephaly. In ,
the spinal cord the lesions are
bilateral and it is suggested that the
copper deficiency has a primary
axonopathic effect

0 Thiamine deficiency in ruminants can
result in polioencephalomalacia or
cerebrocortical necrosis. Thiamine,
mainly as thiamine diphosphate
(pyrophosphate), has an important role
as a coenzyme in carbohydrate
metabolism especially the pentose
pathway. Diffuse encephalopathy may
occur characterized by brain edema
and swelling, resulting in flattening of
the gyri, tentorial herniation and
coning of the cerebellar vermis.

Bilateral areas of cerebral cortical
laminar necrosis are widespread.

Hereditary, familial, and idiopathic
degenerative diseases

A large number of neurological diseases
of farm animals are characterized by
abnormalities of central myelinogenesis.

In most instances the underlying ab-
normality directly or indirectly affects
the oligodendrocyte and is reflected in
the production of central nervous system
myelin of diminished quantity or quality
or both. Many of these are inherited
and are manifest from or shortly after birth.

They include leukodystrophies, hypo-
myelinogenesis, spongy degeneration, and
related disorders. 12 Neuronal abiotrophy,
motor neuron diseases, neuronal dystrophy
and degenerative encephalomyelopathy of
horses and cattle are included in this group.

Polioencephalomalacia and
leukoencephalomalacia
Polioencephalomalacia appears to be, in
some cases at least, a consequence of
acute edematous swelling of the brain
and cortical ischemia. The pathogenesis
of leukoencephalomalacia appears to be
related to vasogenic edema as a result
of cardiovascular dysfunction and an
inability to regulate cerebral blood
flow. Whether the lesion is in the gray
matter (polioencephalomalacia) or in the
white matter (leukoencephalomalacia)
the syndrome is largely one of loss of
function although as might be expected
irritation signs are more likely to occur
when the gray matter is damaged.

CLINICAL FINDINGS

Weakness of all four limbs is accompanied
by:

0 Dullness or somnolence
° Blindness

PARTI GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

0 Ataxia
° Head-pressing
• Circling
= Terminal coma.

In the early stages, particularly in ruminant
polioencephalomalacia, there are invol-
untary signs including muscle tremor,
opisthotonos, nystagmus, and convulsions.

In equine leukoencephalomalacia,
which may occur in outbreaks, initial
signs include anorexia and depression. 3 In
the neurotoxic form, which is most
common, the anorexia and depression
progresses to ataxia, circling, apparent
blindness, head-pressing, hyperesthesia,
agitation, delirium, recumbency, seizures,
and death. An early and consistent sign
in affected horses is reduced proprio-
ception of the tongue, manifest as delayed
retraction of the tongue to the buccal
cavity after the tongue has been extended. 10
In the hepatotoxicosis form, clinical
findings include icterus, swelling of the
lips and nose, petechiation, abdominal
breathing and cyanosis. Horses with either
syndrome may be found dead without
any premonitory signs.

In many of the leukoencephalomalacias,
the course may be one of gradual pro-
gression of signs, or more commonly
a level of abnormality is reached and
maintained for a long period, often
necessitating euthanasia of the animal.
For example, equine degenerative
myeloencephalopathy is a diffuse de-
generative disease of the equine spinal
cords and caudal portion of the brainstem
and primarily affects young horses.
There is an insidious onset of symmetrical
spasticity, ataxia, and paresis. Clinical
signs may progress slowly to stabilize
for long periods. All four limbs are affected,
but the pelvic limbs are commonly more
severely affected than the thoracic limbs.
There is no treatment for the disease, no
spontaneous recovery and, once affected,
horses remain atactic and useless for any
athletic function.

CLINICAL PATHOLOGY

There are no clinicopathological tests
specific for encephalomalacia but various
tests may aid in the diagnosis of some of
the specific diseases mentioned above
under Etiology.

NECROPSY FINDINGS

Gross lesions including areas of softening,
cavitation and laminar necrosis of the cortex
may be visible. The important lesions are
described under each of the specific
diseases.

TREATMENT

The prognosis depends on the nature of the
lesion. Early cases of thiamine-deficiency-
induced polioencephalomalacia can recover
completely if treated with adequate

DIFFERENTIAL DIAGNOSIS

The syndromes produced by
encephalomalacia resemble very closely _
those caused by most lesions that elevate
intracranial pressure. The onset is quite
sudden and there is depression of
consciousness and loss of motor function.
One major difference is that the lesions
tend to be nonprogressive and affected
animals may continue to survive in an
impaired state for long periods.

levels of thiamin. Encephalomalacia due
to sulfur-induced polioencephalomalacia
and lead poisoning is more difficult
to treat, \bung calves with acquired in
utero hypomyelinogenesis and horses
with myelitis associated with equine
herpesvirus-1 infection can make complete
recoveries.

REVIEW LITERATURE

De Lahunta A. Abiotrophy in domestic animals: a
review. Can J Vet Res 1990; 54: 65-76.

Summers BA., Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis: Mosby, 1995.

Cebra CK, Cebra ML. Altered mentation caused by
polioencephalomalacia, hypernatremia, and lead
poisoning. Vet Clin North Am Food Anim Pract
2004; 20: 287-302.

REFERENCES

1. Maddison JE. JVet Intern Med 1992; 6:341.

2. De Lahunta A et al. Can JVet Res 1990; 54:65.

3. Wilkins PA et al. CornellVet 1994; 84:53.

4. Woodman MP et al.Vet Rec 1993; 132:586.

5. Toenniessen JG, Morin DE. Compend Contin
Educ PractVetl995; 17:271.

6. Stewart WB. Vet Rec 1997; 140:260.

7. Plumlee KH, Galey FD. J Vet Intern Med 1994;
8:49.

8. Uhlinger C. J Am Vet Med Assoc 1991; 198:126.

9. Smith GW et al. Am J Vet Res 2002; 63:538.

10. Foreman JH et al. JVet Intern Med 2004; 18:223.

11. Dill SG et al. Am JVet Res 1990; 51:1300.

12. Summers BA et al. Veterinary neuropathology. St
Louis: Mosby, 1995.

TRAUMATIC INJURY TO THE
BRAIN

The effects of trauma to the brain vary
with the site and extent of the injury
but initially nervous shock is likely to
occur followed by death, recovery, or the
persistence of residual nervous signs.

ETIOLOGY

Traumatic injury to the brain may result
from direct trauma applied externally, by
violent stretching or flexing of the head
and neck or by migration of parasitic
larvae internally. Recorded causes include
the following:

° Direct trauma, an uncommon cause
because of the force required to
damage the cranium. Accidental
collisions, rearing forwards, falling
over backwards after rearing are the
usual reasons

° Fferiorbital skull fractures in horses
caused by direct traumatic injury
commonly from collision with gate
posts 1

0 Cerebral injury and cranial nerve
injury, accounted for in a large
percentage of neurological disease in
horses. 2 Young horses under 2 years of
age seem most susceptible to injuries
of the head

• Injury by heat in goat kids achieved
with prolonged application of a hot
iron used for debudding
0 Pulling back violently when tethered
causing problems at the atlanto-
occipital junction

° Animals trapped in bogs, sumps,
cellars, and waterholes and dragged
out by the head; recumbent animals
pulled on to trailers suffering dire
consequences to the medulla and
cervical cord, although the great
majority of them come to surprisingly
little harm

0 The violent reaction of animals to
lightning stroke and electrocution
causing damage to central nervous
tissue; the traumatic effect of the
electrical current itself also causing
neuronal destruction
° Spontaneous hemorrhage into the
brain - rare but sometimes occurring
in cows at parturition, causing
multiple small hemorrhages in the
medulla and brainstem
° Brain injury at parturition, recorded in
lambs, calves, and foals and possibly a
significant cause of mortality in the
former.

PATHOGENESIS

The initial reaction in severe trauma or
hemorrhage is nervous shock. Slowly
developing subdural hematoma, a common
development in humans, is accompanied
by the gradual onset of signs of a space-
occupying lesion of the cranial cavity
but this seems to be a rare occurrence in
animals. In some cases of trauma to the
head, clinical evidence of injury to the
brain may be delayed for a few days
until sufficient swelling, callus formation
or displacement of the fracture fragments
has occurred. Trauma to the cranial vault
may be classified, from least to most
severe, as concussion, contusion, lacer-
ation, and hemorrhage.

Concussion

Concussion is usually a brief loss of
consciousness which results from an
abrupt head injury which produces an
episode of rapid acceleration/deceleration
of the brain.

Contusion

With a more violent force, the brain is
contused. There is maintenance of structure

but loss of vascular integrity, resulting in
hemorrhage into the parenchyma and
meninges relative to the point of impact.
Bony deformation or fracture of the calvaria
result in two different kinds of focal
lesions:

o Direct (coup) contusions immediately
below the impact site
c Indirect (contrecoup) contusions to
the brain at the opposite point of the
skull. Contrecoup hemorrhages result
from tearing of leptomeningeal and
parenchymal blood vessels.

Laceration

The most severe contusion is laceration
where the central nervous system tissue is
physically torn or disrupted by bony
structures lining the cranium or by
penetrating objects such as bone fragments.
Focal meningeal hemorrhage is a common
sequel to severe head injury. Subdural
hematomas usually follow disruption of
bridging cerebral veins that drain into the
dural venous sinuses but subarachnoid
hemorrhages are more common. The
importance of these hemorrhages is that
they develop into space-occupying
masses that indent and compress the
underlying brain. Progressive enlargement
of the hematoma can result in secondary
effects such as severe, widespread brain
edema, areas of ischemia, herniations,
midline shift, and lethal brainstem
compression.

In birth injuries the lesion is principally
one of hemorrhage subdurally and under
the arachnoid.

Experimental traumatic
craniocerebral missile injury

Traumatic insult of the brains of sheep
with a .22 caliber firearm results in a
primary hemorrhagic wound track with
indriven bone fragments and portions of
muscle and skin. 3 There is crushing and
laceration of tissues during missile
penetration, secondary tracks due to bone
and bullet fragments, widely distributed
stretch injuries to blood vessels, nerve
fibers and neurons as a consequence of
the radial forces of the temporary cavity
that develops as a bullet penetrates tissue,
marked subarachnoid and intraventricular
hemorrhage, and distortion and displace-
ment of the brain. The lesions are
consistently severe and rapidly fatal.

CLINICAL FINDINGS

The syndrome usually follows the pattern
of greatest severity initially with recovery
occurring quickly but incompletely to a
point where a residual defect is evident,
this defect persisting unchanged for a
long period and often permanently. This
failure to improve or worsen after the initial
phase is a characteristic of traumatic
injury.

Diffuse diseases of the brain

With severe injury there is cerebral
shock in which the animal falls uncon-
scious with or without a transient clonic
convulsion. Consciousness may never be
regained but in animals that recover it
returns in from a few minutes up to
several hours. During the period of
unconsciousness, clinical examination
reveals dilatation of the pupils, absence of
the eye preservation and pupillary light
reflexes, and a slow, irregular respiration,
the irregularity being phasic in many
cases. There may be evidence of bleeding
from the nose and ears and palpation of
the cranium may reveal a site of injury.
Residual signs vary a great deal, blindness
is present if the optic cortex is damaged;
hemiplegia may be associated with
lesions in the midbrain; traumatic epilepsy
may occur with lesions in the motor
cortex.

Fracture of the petrous temporal
bone is a classic injury in horses caused
by rearing and falling over backwards.
Both the facial and the vestibular nerves
are likely to be damaged so that at first
the animal may be unable to stand and
there may be blood from the ear and
nostril of the affected side. When the
animal does stand the head is rotated
with the damaged side down. There may
be nystagmus, especially early in the
course of the disease. The ear, eyelid, and
lip on the affected side are also paralyzed
and sag. Ataxia with a tendency to fall is
common. Some improvement occurs in
the subsequent 2 or 3 weeks as the horse
compensates for the deficit, but there is
rarely permanent recovery. An identical
syndrome is recorded in horses in which
there has been a stress fracture of the
petrous temporal bone resulting from a
pre-existing inflammation of the bone.
The onset of signs is acute but
unassociated with trauma.

Fracture of the basisphenoid and/or
basioccipital bones is also common.
These fractures can seriously damage the
jugular vein, carotid artery and glosso-
pharyngeal, hypoglossal and vagus nerves.
The cavernous sinus and the basilar artery
may also be damaged and lead to massive
hemorrhage within the cranium. Large
vessels in the area are easily damaged by
fragments of the fractured bones, causing
fatal hemorrhage. A midline fracture of the
frontal bones can also have this effect.

Other signs of severe trauma to the
brain include opisthotonos with blindness
and nystagmus and, if the brainstem
has been damaged, quadriplegia. There
may also be localizing signs, including
head rotation, circling and falling back-
wards. Less common manifestations of
resulting hemorrhage include bleeding
into the retropharyngeal area, which may
cause pressure on guttural pouches and

the airways and lead to asphyxia. Bleed-
ing may take place into the guttural
pouches themselves.

Newborn lambs affected by birth
injury to the brain are mostly dead at
birth, or die soon afterwards. Surviving
lambs drink poorly and are very suscept-
ible to cold stress. In some flocks it may
be the principal mechanism causing
perinatal mortality.

CLINICAL PATHOLOGY

Radiography of the skull is important to
detect the presence and severity of frac-
tures, .which may have lacerated nervous
tissue. CSF should be sampled from the
cerebellomedullary cistern and examined
for evidence of red blood cells. Extreme
care must be taken to ensure that blood
vessels are not punctured during the
sampling procedure as this would con-
found the interpretation of the presence
of red blood cells. The presence of heme
pigments in the CSF suggests the pre-
sence of pre-existing hemorrhage; the
presence of eosinophils or hypersegmented
neutrophils suggests parasitic invasion.

NECROPSY FINDINGS

In most cases a gross hemorrhagic lesion
will be evident but in concussion and
nematodiasis the lesions may be detect-
able only on histological examination.

DIFFERENTIAL DIAGNOSIS

Unless a history of trauma is available
diagnosis may be difficult.

TREATMENT

In those animals that recover conscious-
ness within a few hours or earlier, the
prognosis is favorable and little or no
specific treatment may be necessary
other than nursing care. When coma
lasts for more than 3-6 hours the prog-
nosis is unfavorable and slaughter for
salvage or euthanasia is recommended.
Treatment for edema of the brain as
previously outlined may be indicated
when treatment for valuable animals is
requested by the owner. Animals that are
still in a coma 6-12 hours following treat-
ment are unlikely to improve and
continued treatment is not warranted.

REVIEW LITERATURE

Summers BA, Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: 1995, Mosby.
MacKay RJ. Brain injury after head trauma: patho-
physiology, diagnosis, and treatment. Vet Clin
North Am Equine Pract2004; 20:199-216.

REFERENCES

1. Wright JD et a l.AustVet J 1991; 68:58.

2. Tyler CM et al. AustVet J 1993; 70:445.

3. Finnie JW. J Comp Fhthol 1993; 108:93.

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Focal diseases of the brain

BRAIN A B SCESS

Abscesses of the brain occur most com-
monly in young farm animals under
1 year of age and rarely in older animals.
Brain abscesses produce a variety of
clinical signs depending on their location
and size. Basically the syndrome pro-
duced is one of a space-occupying lesion
of the cranial cavity with some motor
irritation signs. Localized or diffuse
meningitis is also common, along with
the effects of the abscess.

ETIOLOGY

Abscesses in the brain originate in a
number of ways. Hematogenous infec-
tions are common, but direct spread
from injury to the cranium or via the
nasopharynx may also occur.

Hematogenous spread

The lesions may be single, but are often
multiple, and are usually accompanied
by meningitis. The infection usually
originates elsewhere.

; I Actinobacillus mallei from glanders
lesions in lung

Streptococcus zooepidemicus var. equi as
a complication of strangles in horses
o Corynebacterium pseudotuberculosis in a
goat causing an encapsulated abscess
in the left cerebellar peduncles 1
c Actinomyces bovis and Mycobacterium
bovis from visceral lesions in cattle
' Fusobacterium necrophorum from
lesions in the oropharynx of calves
Pseudomonas pseudomallei in
melioidosis in sheep
- Staphylococcus aureus in tick pyemia of
lambs

-> Systemic fungal infections such as
cryptococcosis may include
granulomatous lesions in brain. 2

Local spread

'■ Via peripheral nerves from

oropharynx, the one specific disease is
listeriosis in ruminants and New
World camelids

» Multifocal meningoencephalitis
associated with lingual arteritis
induced by barley spikelet clusters 3
0 Space-occupying lesions of facial and
vestibulocochlear nerves and
geniculate ganglion secondary to
otitis media in calves 4
Abscesses of rete mirabile of pituitary
gland secondary to nasal septal
infection after nose-ringing in cattle. 5
Arcanobacterium (Actinomyces or
Corynebacterium) pyogenes is the most
common isolate and several other
species of bacteria that cause chronic
suppurative lesions have been
recovered. 5 Similar abscesses, usually

containing A. pyogenes, occur in the
pituitary gland itself
° Extensions from local suppurative
processes in cranial signs after
dehorning, from otitis media. The
lesions are single, most commonly
contain A. pyogenes and are
accompanied by meningitis.

PATHOGENESIS

Infectious agents can invade the central
nervous system by four routes:

• Retrograde infection via peripheral
nerves

° Direct penetrating injuries
° Extension of adjacent suppurative
lesions

° By way of the systemic circulation.

Single abscesses cause local pressure
effects on nervous tissue and may produce
some signs of irritation, including head-
pressing and mania, but the predominant
effect is one of loss of function due to
destruction of nerve cells. Multiple
abscesses have much the same effect but
whereas in single abscesses the signs
usually make it possible to define the
location of the lesion, multiple lesions
present a confusing multiplicity of signs
and variation in their severity from day to
day, suggesting that damage has occurred
at a number of widely distributed points
and at different times.

The pituitary abscess syndrome has
an uncertain pathogenesis. The pituitary
gland is surrounded by a complex mesh of
intertwined arteries and capillary beds
known as the rete mirabile, which has
been identified in cattle, sheep, goats,
and pigs but not horses. This extensive
capillary network surrounding the pituitary
gland makes it susceptible to localization
by bacteria that originate from other
sources of infection. Nose-ringing of
cattle may result in septic rhinitis,
which could result in infection of the
dural venous sinus system, which com-
municates with the subcutaneous veins
of the head. Bacteria may also reach the
rete mirabile by way of lymphatics of
the nasal mucosa and cribriform plate.
Cranial nerve deficits occur as a result of
the extension of the abscess into the
adjacent brainstem.

CLINICAL FINDINGS

General signs include mental depression,
clumsiness, head-pressing, and blindness,
often preceded or interrupted by transient
attacks of motor irritation including excite-
ment, uncontrolled activity, and con-
vulsions. A mild fever is usually present but
the temperature may be normal in some
cases.

The degree of blindness varies de-
pending on the location of the abscess
and the extent of adjacent edema and

meningoencephalitis. The animal may be
blind in one eye and have normal eyesight
in the other eye or have normal eyesight in
both eyes. Unequal pupils and abnormali-
ties in the pupillary light reflex, both direct
and consensual, are common. Uveitis, iris
bombe, and a collection of fibrin in the
anterior chamber of an eye may be present
in some cases of multiple meningo-
encephalitis in cattle. 3 Nystagmus is com-
mon when the lesion is near the vestibular
nucleus; strabismus may also occur.

Localizing signs depend on the
location of lesions and may include
cerebellar ataxia, deviation of the head
with circling and falling, hemiplegia or
paralysis of individual or groups of cranial
nerves often in a unilateral pattern. In the
later stages there may be papilledema.
In calves with lesions of the facial and
vestibulocochlear nerves and geniculate
ganglion, clinical signs may include
drooping of the ears and lips, lifting of the
nose, slight unilateral tilting of the head
and uncontrolled saliva flow. Inability to
swallow may follow and affected calves
become dehydrated.

These localizing signs may be inter-
mittent, especially in the early stages, and
may develop slowly or acutely.

Pituitary gland abscesses are most
common in ruminants, primarily cattle
2-5 years of age, 5 but are relatively rare. The
most common history includes anorexia,
ataxia, depression, and drooling from the
mouth with inability to chew and swallow.
The most common clinical findings are
depression, dysphagia, dropped jaw, blind-
ness, and absence of pupillary light reflexes.
Terminally, opisthotonos, nystagmus,
ataxia, and recumbency are common.
Characteristically, the animal stands with
a base-wide stance, with its head and neck
extended and its mouth not quite closed;
there is difficulty in chewing and swallow-
ing, and drooling of saliva. Affected animals
are usually nonresponsive to external
stimuli. Cranial nerve deficits are common,
usually asymmetrical, multifocal and pro-
gressive. These include reduced tone of the
jaw, facial paralysis, strabismus, and a head
tilt. There may also be ptosis and prolapse of
the tongue. Bradycardia has been recorded
in about 50% of cases. 5 Terminally there is
opisthotonos, nystagmus, and loss of
balance, followed by recumbency.

CLINICAL PATHOLOGY
Cerebrospinal fluid

Leukocytes, protein, and bacteria may be
present in the CSF, but only when the
abscess is not contained.

Hematology

In pituitary gland abscessation there
may be hematological evidence of chronic
infection including neutrophilia, hyper-
proteinemia, and increased fibrinogen, 5

although it is unlikely that a pituitary
abscess itself is sufficiently large enough
to induce these changes.

Imaging

Radiographic examination will not detect
brain abscesses unless they are calcified
or cause erosion of bone. Computed
tomography has been used to diagnose a
brain abscess in the horse. 6

Electroencephalography

Electroencephalographs assessment of
central blindness due to brain abscess in
cattle has been reported. 7

NECROPSY FINDINGS

The abscess or abscesses may be visible
on gross examination and if superficial are
usually accompanied by local meningitis. 8
Large abscesses may penetrate to the ven-
tricles and result in a diffuse ependymitis.
Microabscesses may be visible only
on histological examination. A general
necropsy examination may reveal the
primary lesion.

DIFFERENTIAL DIAGNOSIS

Brain abscess is manifested by signs of
involuntary movements and loss of function,
which can occur in many other diseases of
the brain, especially when local lesions
develop slowly. This occurs more frequently
with tumors and parasitic cysts but it may
occur in encephalitis. The characteristic
clinical findings are those of a focal or
multifocal lesion of the brain, which include:

• Localizing signs of hemiparesis and
ataxia

• Postural reaction deficit

• Vestibular signs, including head tilt and
positional nystagmus

• Cranial nerve deficits.

There may be evidence of the existence of a
suppurative lesion in another organ, and a
high cell count and detectable infection in
the CSFto support the diagnosis of abscess.
Fever may or may not be present. The only
specific disease in which abscess occurs is
listeriosis, in which the lesions are largely
confined to the medulla oblongata and the
characteristic signs include circling and
unilateral facial paralysis. Occasional cases
may be associated with fungal infections,
including cryptococcosis. Toxoplasmosis is an
uncommon cause of granulomatous lesions
in the brain of most species.

Many cases of brain abscess are similar
to otitis media but there is, in the latter,
rotation of the head, a commonly
associated facial paralysis and an absence
of signs of cerebral depression.

The pituitary gland syndrome in cattle
must be differentiated from listeriosis,
polioencephalomalacia, lead poisoning,
other brain abscesses and
thrombomeningoencephalitis. In sheep and
goats, Paraelaphostrongylus tenuis
infection and caprine arthritis
encephalomyelitis syndrome may resemble
the pituitary gland abscess syndrome.

Focal diseases ot the brain

TREATMENT

Parenteral treatment with antimicrobials
is indicated but the results are generally
unsatisfactory because of the inaccessi-
bility of the lesion, with the clear excep-
tion being listeriosis. Treatment of pituitary
gland abscess is not recommended,
and an antemortem diagnosis is rarely
obtained.

REVIEW LITERATURE

Perdrizet JA, Dinsmore P. Pituitary abscess syndrome.
Compend Contin Educ Pract Vet 1986;
8:S311-S318.

Summers BA, Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.
Morin DE. Brainstem and cranial nerve abnormalities:
Listeriosis, otitis media/interna, and pituitary
abscess syndrome. Vet Clin North Am Food Anim
Pract 2004; 20:243-274.

REFERENCES

1. Glass ENetal. Cornell Vet 1993; 83:275.

2. Teuscher E et al. ZentralblVet Med A 1984; 31:132.

3. Sorden SD, Radostits OM. Can Vet J 1996; 37:227.

4. Van der Lugt JJ, Jordaan P.Vet Rec 1994; 134:579.

5. Perdrizet JA, Dinsmore P. Compend Contin Educ
Pract Vet 1986; 8:S311.

6. Allen JR et al. Equine Vet J 1987; 19:552.

7. Strain GM et al. Cornell Vet 1987; 77:374.

8. Summers BA, Cummings JF, de Lahunta A.
Veterinary neuropathology. St Louis, MO: Mosby,
1995.

OTJTJS MEDIA/INTERNA

Infection of the middle ear (otitis media)
occurs in young animals of all species but
especially dairy calves and pigs, to a lesser
extent feedlot cattle and lambs, and rarely
foals. The infection may gain entrance
from the external ear (e.g. caused by ear
mite infestation) or hematogenously, but
the spread is chiefly an ascending infec-
tion of the eustachian tubes in a young
animal from a respiratory tract infection.
Extension of infection into the inner ear
leads to otitis interna.

Pigs

Otitis media was present in 68% of 237 pigs
i that were slaughtered because of illness. 1
j It is suggested that otitis media in pigs
develops first as an acute inflammation in
1 the auditory tube and then extends to
: other parts of the ear and brain. When
abscesses form at the ventrum of the
brainstem, the vestibulocochlear nerve is
usually involved in the lesion. 1 Infection
in the ear may extend into the brain by
I following the auditory nerve. Perilymph
filling the scala vestibuli and scala
tympani is also a possible tract for the
extension of the infection because there is
a communication between the perilymph-
filled spaces of the bonylabyrinth and the
subarachnoid space.

Calves and lambs

j The peak of occurrence in calves and
lambs is 1-4 weeks of age. The highest
: prevalence is in suckling dairy calves

and weaned cattle and sheep in feedlots,
where the disease is probably secondary
to respiratory tract infection. Outbreaks
of otitis media/interna have occurred in
beef calves from 6-10 weeks of age on
pasture with their dams; mixed cultures
of Escherichia coli, Pseudomonas spp., and
Acinetobacter spp. were isolated. 2 Otitis
media/interna in suckling dairy calves
can also occur in outbreaks, and Myco-
plasma bovis is frequently isolated from
the middle and inner ears of affected
calves. 3

The onset of clinical signs commonly
includes dullness, fever, inappetence,
tachypnea, and a purulent discharge from
the affected ear accompanied by rotation
of the head (in otitis interna) and droop-
ing of the ear a few days later due
to involvement of the facial nerve in the
inflammation. 2 Deep palpation at the
base of the ears may elicit a pain
response. 3

Rotation of the head, with the affected
side down and facial paralysis may occur
on the same side, and walking in circles
with a tendency to fall to the affected side
is common. In most cases the animals are
normal in other respects, although
depression and inappetence can occur in
advanced cases.

Horses

Otitis media/interna occurs in horses 4,5
and two clinical syndromes have been
described.

The first syndrome is primary otitis
media characterized by abnormal behavior,
including head tossing, head shaking, and
ear rubbing. 4 Violent, uncontrollable
behavior includes throwing themselves
on the ground, rolling, and thrashing. This
may progress to involve the bony
structures of the temporal and proximal
stylohyoid bones, resulting in a degener-
ative arthritis and eventual fusion of the
temporohyoid bone.

The second syndrome is characterized
by an acute onset of neurologic deficits.

I Commonly, there is vestibulocochlear
nerve and often facial nerve dysfunction
i characterized by head tilt to the side of
; the lesion, nystagmus with the slow
component to the affected side and
; weakness of the extensor muscles on the
affected side resulting in an ataxia or
reluctance or refusal to stand. Horses that
can stand often will lean on walls for
support of the affected side.

Definitive diagnosis is dependent on
either a positive tympanocentesis or, in
the majority of cases, bony proliferation
of the temporal bone and proximal
part of the stylohyoid bone, or lysis of
the tympanic bulla, as determined by
radiography 4 or computed tomography. 3
This can be visualized using endoscopy of

8

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases oT tne nervous system

the auditory tube diverticula in horses
with otitis media/interna. 5 In some cases,
the tympanic membrane is ruptured,
which can be seen using an otoscope. 5

Tympanocentesis is done under
general anesthesia in horses or sedation
in ruminants by directing a 15 cm needle
through the tympanic membrane visualized
with the aid of an otoscope. The tech-
nique is somewhat difficult because of the
long and angled external auditory canal.
Sterile 0.9% NaCl (0.5-1 mL) is injected
into the tympanic cavity and then, after a
few seconds, withdrawn. A positive tap
consists of withdrawal of a cloudy or
yellow fluid, which on analysis may con-
tain evidence of pus and can be sampled
for culture and antimicrobial susceptibility.

. zz . -.. . -- ;v, ■ . -;-57 L

DIFFERENTIAL DIAGNOSIS

The disease needs to be differentiated
from otitis externa, in which the head may
be carried in a rotated position, but usually
intermittently, and this is accompanied by
head shaking and the presence of exudate
and an offensive smell in the ear canal,
and from cerebral injury or abscess, and
similar lesions of the upper cervical cord.

All of these are characterized by deviation
of the head, not rotation. At necropsy the
tympanic bulla contains pus, and a variety
of organisms, such as staphylococci,
streptococci, Pasteurella haemolytica, and
Neisseria catarrhalis, may be isolated.

TREATMENT

Treatment consists of broad-spectrum
antimicrobials daily for 4 weeks, and anti-
inflammatory agents. The prognosis with
treatment with fluoroquinolones is very
good in calves, although a 50% mortality
rate has been reported in calves that were
not treated with other antimicrobial
agents. 6 The use of lincomycin at 6.5 mg/kg
BW combined with spectinomycin at
10 mg/kg BW intravenously twice daily for
5 days has been reported to be successful
for the treatment of otitis media in beef
calves. 2 Anecdotal reports exist in cattle of
the use of a knitting needle to rupture the
tympanic membrane, with rapid resolution
of the head tilt because of the decreased
pressure in the middle ear. Bilateral
tympanic bulla osteotomy has been per-
formed in an affected calf, resulting in a
rapid resolution of the head tilt. 3

REVIEW LITERATURE

Duarte ER, Hamdan JS. Otitis in cattle, a n etiological
review. J Vet Med B 2004; 51:1-7.

Morin DE. Brainstem and cranial nerve abnormalities:
listeriosis, otitis media/interna, and pituitary
abscess syndrome. Vet Clin North Am Food Anim
Pract 2004; 20:243-273.

REFERENCES

1. Shimada A et al.Vet Fhthol 1992; 29:337.

2. Henderson JP, McCullough WP. Vet Rec 1993;
132:24.

3. Van Biervliet Jet al.JVet Intern Med 2004; 18:907. j

4. Blythe LL et al. ProcAnnu Conv Am Assoc Equine I
Pract 1991; 36:517.

5. Hassel DM et al. J Am Vet Med Assoc 1995; j
207:1081.

| 6. Walz PH et al.JVet Intern Med 2004; 18:907.

j

TUMORS OF THE CENTRAL
i NERVOUS SYSTEM

j Primary tumors of the central nervous j
! system are extremely rare in farm i
j animals. They produce a syndrome indi-
; cative of a general increase in intracranial 1
I pressure and local destruction of nervous
' tissue. Tumors of the peripheral nervous
system are more common.

| ETIOLOGY

; The reader is referred to the review I
> literature for a summary of available refer-
! ences on the tumors of the central
nervous system of farm animals, which
include:

Meningeal tumors in cattle 1
Equine papillary ependymoma. 2

PATHOGENESIS

The development of the disease parallels
that of any space-occupying lesion, with
the concurrent appearance of signs of
increased intracranial pressure and local
tissue destruction. Many lesions found
incidentally at necropsy may not have had
any related clinical findings.

CLINICAL FINDINGS

The clinical findings are similar to those
caused by a slowly developing abscess
and localizing signs depend on the
location, size, and speed of development
of the tumor. Clinical signs are usually
representative of increased intracranial
pressure, including opisthotonos, convul-
sions, nystagmus, dullness, head-pressing,
and hyperexcitability. Common localizing
signs include circling, deviation of the head,
disturbance of balance. Lesions close to
the pituitary gland may cause diabetes
insipidus and Cushing's syndrome. 3 A
17-year-old horse with an ependymoma
had an 18-month history of slowly pro-
gressive ataxia culminating in a sudden
loss of ability to control the pelvic limbs,
with dog-sitting, spinning, and falling. 4

CLINICAL PATHOLOGY

There are no positive findings in clinico-
pathological examination which aid in
diagnosis.

NECROPSY FINDINGS

The brain should be carefully sectioned
after fixation if the tumor is deep-seated.

TREATMENT

There is no treatment.

REVIEW LITERATURE

Summers BA, Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.

DIFFERENTIAL DIAGNOSIS

Differentiation is required from the other
diseases in which space-occupying lesions
of the cranial cavity occur. The rate of
development is usually much slower in
tumors than with the other lesions.

REFERENCES

1. Josephson GKA, Little PB. CanVet J 1990; 31:700.

2. Carrigan MJ et al.Vet Pathol 1996; 33:77.

3. Green EM, Hunt EL. Compend Contin Educ Pract
Vet 1985; 7:S249.

4. Summers BA, Cummings JF, de Lahunta A.
Veterinary Neuropathology. St Louis, MO Mosby,
1995.

CENTRAL-NERVOUS-SYSTEM-
ASSOCIATED TUMORS

The pituitary gland (hypophysis)

consists of the adenohypophysis (pars
distalis, intermedia, tuberalis) and the
neurohypophysis (pars nervosa). Tumors
of the pituitary gland occur in the horse. 1
Cushing's syndrome in horses almost
invariably originates from an adenoma of
the pars intermedia of the pituitary
gland. 1 Initially, these animals exhibit only
one remarkable sign, namely, hirsutism.
Horses with Cushing's disease only do
not manifest polyuria and polydipsia.
Major sequelae of an adenoma of the pars
intermedia of the pituitary gland are type
2 diabetes mellitus and laminitis. Diagnosis
of an adenoma of the pars intermedia of
the pituitary gland in the horse mainly
depends on dynamic endocrinological
function tests. The sensitivity of the
adrenocorticotropin (ACTH) test is about
80%. 1

REVIEW LITERATURE

Summers BA, Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.

REFERENCE

1 . Van der Kolk JH e t al. Domestic Anim Endocrinol
1995; 12:35.

METASTATIC TUMORS OF THE
CENTRAL NERVOUS SYSTEM

Many primary tumors of non-nervous
tissue have the potential for metastasis to
the central nervous system.

Ocular squamous cell carcinoma of

cattle may invade the cranium
through the cribriform plate
Lymphomas of cattle may metastasize
to the central nervous system with
either a multicentric distribution or
occasionally as the only lesion. Most
commonly bovine lymphoma occurs as
an epidural mass in the vertebral canal.
Intracranial lymphoma usually involves
the leptomeninges or the choroid
plexus. Clinical signs are related to the
progressive compression of the

Diseases of the meninges

61

1

nervous tissue at the site of the mass.

Lymphoma in the horse has occurred

in the epidural space with spinal cord

compression.

CENTRAL-NERVOUS-SYSTEM-
ASSOCIATED MASSES

Cholesterinic granulomas, also known as
cholesteatomas may occur in up to 20% of
older horses without any clinical effects. 1
However, they can be associated with
significant neurological disease. Affected
horses are commonly obese. 1 Cholesterinic
granulomas occur in the choroid plexus of
the fourth ventricle or in the lateral
ventricles and mimic cerebrocortical
disease. It has been suggested that choles-
terol granulomas result from chronic
hemorrhage into the plexus stroma but the
underlying pathogenesis is unknown.

Brownish nodular thickening of the
plexuses with glistening white crystals is
a common incidental finding in mature
and aged horses. Occasionally, deposits
in the plexuses of the lateral ventricles
are massive and fill the ventricular space
and cause secondary hydrocephalus
due to the build up of CSF behind the
mass. CSF maybe xanthochromic with an
elevated total protein. 1

Clinical findings include episodes of
abnormal behavior such as depression and
bolting uncontrollably, running into fences
and walls. 2 Some horses exhibit profound
depression, somnolence, and reluctance to
move. 1 Secures have also been reported. 1
Other clinical findings reported include
decreased performance, aggression, head
tilt, incoordination, intermittent con-
vulsions, hindlimb ataxia progressing to
recumbency, intermittent circling in one
direction, and spontaneous twitching along
the back and flank. There are often serious
changes in temperament, with previously
placid animals becoming violent and
aggressive. In others there are outbursts of
frenzied activity followed by coma. The
horse may be normal between attacks
and these may be precipitated by moving
the head rapidly.

These signs are referable to cerebro-
cortical disease and the differential diag-
nosis of cholesterol granulomas must
include diffuse cerebral encephalopathy
due to abscess, tumor, toxicosis, metabolic
disease, encephalomyelitis, trauma, and
hydrocephalus. At necropsy, large chol-
esterol granulomas are present in the
choroid plexus.

REFERENCES

1. Jackson CA et al.Vet Rec 1994; 135:228.

2. Duff S. Vet Rec 1994; 135:288.

COENUROSIS (GID, STURDY)

Coenurosis is the disease caused by
invasion of the brain and spinal cord by

the intermediate stage of Taenia multiceps. \
The syndrome produced is one of !
localized, space-occupying lesions of the j
central nervous system. In most countries j
the disease is much less common than it j

used to be and relatively few losses occur. \

1

ETIOLOGY j

The disease is associated with Coenurus |
cerebralis, the intermediate stage of the j
tapeworm T. multiceps, which inhabits !
the intestine of dogs and wild Canidae. !
j The embryos, which hatch from eggs j
ingested in feed contaminated by the j
feces of infested dogs, hatch in the !
intestine and pass into the bloodstream. ;
j Only those embryos that lodge in the !
| brain or spinal cord survive and continue j
! to grow to the coenurid stage. C. cerebralis j
i can mature in the brain and spinal cords !
| of sheep, goats, cattle, horses, and wild j
ruminants, and occasionally humans, but j
clinical coenurosis is primarily a disease j
of sheep and occasionally cattle. Infection ■
in newborn calves, acquired prenatally, >
has occasionally been observed.

] PATHOGENESIS

i The early stages of migration through ;
: nervous tissue usually passes unnoticed, but
in heavy infections an encephalitis may be
; produced. Most signs are caused by the
; mature coenurus, which may take
6-8 months to develop to its full size
of about 5 cm. The cyst-like coenurus
; develops gradually and causes pressure on
nervous tissue, resulting in its irritation and
eventual destruction. It may cause sufficient
| pressure to rarefy and soften cranial bones.

CLINICAL FINDINGS

In acute outbreaks due to migration of
larval stages, sheep show varying degrees
of blindness, ataxia, muscle tremors,
nystagmus, excitability, and collapse.
Sheep affected with the mature coenurus
show an acute onset of irritation
phenomena including a wild expression,
salivation, frenzied running and convul-
sions. Deviation of the eyes and head
may also occur. Some animals may die in
this stage but the greater proportion
go on to the second stage of loss of
function phenomena, the only stage in
most affected animals. The most obvious
sign is slowly developing partial or
complete blindness in one eye. Dullness,
clumsiness, head-pressing, ataxia, in-
complete mastication and periodic epi-
leptiform convulsions are the usual signs.
Papilledema may be present. Localizing
signs comprise chiefly deviation of the
head and circling; there is rotation of the
head with the blind eye down, and
deviation of the head with circling in the
direction of the blind eye. 1

In young animals local softening of the
cranium may occur over a superficial cyst

and rupture of the cyst to the exterior may
follow, with final recovery. When the
spinal cord is involved there is a gradual
development of paresis and eventually
inability to rise. Death usually occurs after
a long course of several months.

CLINICAL PATHOLOGY

Clinicopathological examinations are not
generally used in diagnosis in animals
and serological tests are not sufficiently
specific to be of value. Radiological exam-
inations are helpful in defining the
location of the cyst, especially if there is
a prospect of surgical intervention. 1

NECROPSY FINDINGS

Thin-walled cysts may be present any-
where in the brain but are most com-
monly found on the external surface of
the cerebral hemispheres. In the spinal
cord the lesions are most common in
the lumbar region but can be present in
the cervical area. Local pressure atrophy
of nervous tissue is apparent and soften-
ing of the overlying bone may occur.

The condition needs to be differentiated
from other local space-occupying lesions of
the cranial cavity and spinal cord, including
abscess, tumor, and hemorrhage. In the
early stages the disease may be confused
with encephalitis because of the signs of
brain irritation. Clinically there is little
difference between them and, while
clinical signs and local knowledge may lead
to a presumptive diagnosis, demonstration
of the metacestode is essential.

TREATMENT AND CONTROL

Surgical drainage of the cyst may make
it possible to fatten the animal for
slaughter, and surgical removal with
complete recovery is possible in a majority
of cases. The life cycle can be broken most
satisfactorily by control of mature tape-
worm infestation in dogs. Periodic treat-
ment of all farm dogs with a tenicide is
essential for control of this and other
more pathogenic tapeworms. Carcasses
of livestock infested with the intermediate
stages should not be available to dogs.

REVIEW LITERATURE
Skerritt GC, Stallbaumer MF. Diagnosis and
treatment of coenuriasis (gid) in sheep. Vet Rec
1984; 115:399.

REFERENCE

1. Tirgari M et al.Vet Rec 1987; 120:173.

Diseases of the meninges

MENINGITIS

Inflammation of the meninges occurs
most commonly as a complication of

PART 1 GENERAL meuiune ■ unapter iz.-. Diseases ot ine nervous system

a pre-existing disease. Meningitis is usually
associated with a bacterial infection and is
manifested clinically by fever, cutaneous
hyperesthesia, and rigidity of muscles.
Although meningitis may affect the spinal
cord or brain specifically, it commonly
affects both and is dealt with here as a
single entity. Meningoencephalitis is com-
mon in neonatal farm animals. Primary
bacterial meningitis is extremely rare in
adult farm animals, with the exception of
listeriosis and Histophilus somni (formerly
Haemophilus somnus) infection, although
the latter is more a vasculitis than a primary
meningitis. The possibility of immuno-
deficiency should be considered in adult
horses with bacterial meningitis. 1

ETIOLOGY

Most significant meningitides are
bacterial, although most viral encepha-
litides have some meningitic component.

Cattle

• Viral diseases - bovine malignant
catarrh, sporadic bovine
encephalomyelitis
Bacterial diseases - listeriosis,

H. somni, chronic lesions elsewhere in
the body possibly associated with
meningitis in adult animals; 2 rarely
tuberculosis.

Horses

0 Strangles, Pasteurella haemolytica (also
donkeys and mules), Streptococcus suis,
Streptococcus equi, Actinomyces spp.
Klebsiella pneumonia, coagulase-
negative staphylococci,
Sphingobacterium multivorum,
Cnjptococcus neoformans.

Sheep

1 Melioidosis, S. aureus (tick pyemia) in
newborn lambs

Pasteurella multocida in lambs
Mannhemia (Pasteurella) haemolytica in
lambs.

Pigs

Glasser's disease, erysipelas,
salmonellosis; S. suis type 2 in weaned
and feeder pigs.

Young animals generally
Streptococcal and coliform septicemias
are probably the commonest causes of
meningitis in neonatal farm animals.
The infection may originate from an
omphalophlebitis, bacteremia, 3 or bacte-
rial translocation across the gastroin-
testinal tract in neonates less than 24 h
of age or with enteritis. Septicemia occurs
in all species, especially calves, and may be
accompanied by polysynovitis, endocarditis,
and hypopyon. The causative bacteria are
usually a mixed flora. 4

Hematogenous infection occurs from
other sites also. In neonatal animals, some
of the common infections are:

° Calf - £. coli. The disease occurs most
commonly in calves under several
days of age and can occur in less than
24 hours after birth. Failure of transfer
of colostral immunoglobulins is a
common contributing factor
° Piglet - Streptococcus zooepidemicus,

S. suis type 1

0 Lamb - S. zooepidemicus.

PATHOGENESIS

Inflammation of the meninges causes
local swelling and interference with
blood supply to the brain and spinal
cord but as a rule penetration of the
inflammation along blood vessels and
into nervous tissue is of minor import-
ance and causes only superficial
encephalitis. Failure to treat meningitis
associated with pyogenic bacteria often
permits the development of a fatal
choroiditis, with exudation into CSF, and
ependymitis. There is also inflammation
! around the nerve trunks as they pass
| across the subarachnoid space. The signs
I produced by meningitis are thus a
| combination of those resulting from
! irritation of both central and peripheral
| nervous systems. In spinal meningitis
I there is muscular spasm with rigidity of
the limbs and neck, arching of the back
and hyperesthesia with pain on light
touching of the skin. When the cerebral
i meninges are affected, irritation signs,

I including muscle tremor and convulsions,
are the common manifestations. Since
meningitis is usually bacterial in origin,
fever and toxemia can be expected if the
lesion is sufficiently extensive.

Defects of drainage of CSF occur in
both acute and chronic inflammation
of the meninges and produce signs of
increased intracranial pressure. The signs
are general although the accumulation of
fluid may be localized to particular sites
such as the lateral ventricles.

CLINICAL FINDINGS

Acute meningitis usually develops suddenly
and is accompanied by fever and toxemia
in addition to nervous signs. Vomiting is
common in the early stages in pigs. There
is trismus, opisthotonos, and rigidity of
the neck and back. Motor irritation signs
include tonic spasms of the muscles of the
neck causing retraction of the head,
muscle tremor and paddling movements.
Cutaneous hyperesthesia is present in
varying degrees, even light touching of
the skin causing severe pain in some
cases. There may be disturbance of
consciousness manifested by excitement
or mania in the early stages, followed by
drowsiness and eventual coma.

Blindness is common in cerebral
meningitis but not a constant clinical
finding. In young animals, ophthalmitis

with hypopyon may occur, which sup-
ports the diagnosis of meningitis. The
pupillary light reflex is usually much
slower than normal. Examination of the
fundus of the eyes may reveal evidence
of optic disk edema, congestion of the
retinal vessels and exudation.

In uncomplicated meningitis the res-
piration is usually slow and deep,
and often phasic in the form of
Cheyne-Stokes breathing (a breathing
pattern characterized by a period of
apnea followed by a gradual increase in
the depth and rate of respiration) or
Biot's breathing (a breathing pattern
characterized by unpredictable irregularity).
Terminally there is quadriplegia and
clonic convulsions.

The major clinical finding of meningo-
encephalitis in calves under 2 weeks of
age was depression which progressed
rapidly to stupor but the mental state
changed to hyperesthesia, opisthotonos
and seizures in unresponsive terminal
cases. 3 Meningoencephalitis should be
considered in calves that have been
treated for the effects of diarrhea with
fluid therapy but fail to respond and
remain depressed.

In a series of 32 cases of meningitis in
neonatal calves, the mean age at admis-
sion was 6 days (range, 11 hours-
30 days). The major clinical findings were
lethargy (32/32), recumbency (32/32),
anorexia and loss of the suck reflex
(26/32), and stupor and coma (21/32). 3
The frequency of other clinical findings
were as follows: opisthotonos (9/32),
convulsions (7/32), tremors (6/32), and
hyperesthesia (6/32). The case fatality rate
was 100%.

Although meningitis in farm animals
is usually diffuse, affecting particularly
the brainstem and upper cervical cord,
it may be quite localized and produce
localizing signs, including involvement
of the cranial or spinal nerves. Localized
muscle tremor, hyperesthesia and rigidity
may result. Muscles in the affected area
are firm and board -like on palpation.
Anesthesia and paralysis usually develop
caudal to the meningitic area. Spread
of the inflammation along the cord is
usual. Reference should be made to the
specific diseases cited under Etiology
for a more complete description of their
clinical manifestations.

In newborn calves, undifferentiated
diarrhea, septic arthritis, omphalophlebitis
and uveitis are frequent concurrent
clinical findings. Bacterial meningitis has
been reproduced experimentally in calves,
resulting in typical clinical signs con-
sisting of convulsions, depression, circling
and falling to one side, ataxia, propulsive
walking, loss of saliva, tremors, recum-
bency, lethargy, and nystagmus. 6

Toxic and metabolic encephalomyelopathies

6

CLINICAL PATHOLOGY
Cerebrospinal fluid

CSF collected from the lumbosacral
space or cisterna magna in meningitis
contains elevated protein concentrations,
has a high cell count and usually
contains bacteria. 4,7 The collection of
CSF from the lumbosacral space of
calves has been described under the
section on Special examination of the
nervous system. 7 Culture and deter-
mination of drug sensitivity of the
bacteria is advisable because of the low
concentrations of antimicrobial agents
achieved in CSF. In a series of meningitis
in neonatal calves, the CSF revealed
pleocytosis (mean 4000 leukocytes/pL;
range, 130-23 270 leukocytes/pL),
xanthochromia, turbidity and a high
total protein concentration. 5

Hematology

The hemogram usually reveals a marked
leukocytosis, reflecting the severity of the
systemic illness secondary to septicemia.

NECROPSY FINDINGS

Hyperemia, the presence of hemorrhages,
and thickening and opacity of the
meninges, especially over the base of
the brain, are the usual macroscopic
findings. The CSF is often turbid and
may contain fibrin. A local superficial
encephalitis is commonly present.
Additional morbid changes are described
under the specific diseases and are
often of importance in differential diag-
nosis. In neonatal calves with meningitis,
lesions of septicemia are commonly
present at necropsy and E. coli is the most
commonly isolated organism.

DIFFERENTIAL DIAGNOSIS

TREATMENT

The infection is usually bacterial, and
parenteral treatment with antimicrobial

agents is necessary. Large doses daily
for several days are required. The levels of
antimicrobial agents that are achieved in
the meninges and CSF following parenteral
administration to farm animals are not
known. Presumably, the blood-brain and
blood-CSF barriers are not intact in
meningitis and minimum inhibitory con-
centrations of some drugs may be
achieved.

Antimicrobial agents

The injection of antimicrobial agents
into the cerebromedullary cistern or into
the lumbosacral space is not recommended.
If parenteral treatment with the anti-
microbial of choice, determined by a
susceptibility test, does not result in
a beneficial response in 3-5 days the
prognosis is unfavorable.

The choice of antimicrobial agent
will depend on the suspected cause of
the meningitis. The common antibiotics,
such as penicillin and oxytetracycline,
are effective for the treatment of meningo-
encephalitis in cattle due to H. somni when
treatment is begun early. Neonatal strepto-
coccal infections also respond beneficially
to penicillin when treated early before
irreparable injury has occurred.

The response to therapy will depend
on the causative pathogen and the
severity of the inflammation present.
Some cases of meningitis, such as that in
swine associated with S. suis type 2,
commonly do not respond to treatment
when clinical signs are obvious. Conversely,
the meningoencephalitis in cattle associ-
ated with H. somni will respond dramatically
if treatment is begun as soon as clinical
signs are apparent. The prognosis in
meningitis associated with infection with
E. coli is unfavorable. In a series of 32 cases
admitted to a veterinary teaching hospital,
even after intensive therapy the case
fatality rate was 100%. 5

Cephalosporins

Based on recent experiences in human
medicine, the most promising anti-
microbials for the treatment of meningitis
in fann animals, particularly the neonates,
may be the new third-generation
cephalosporins, which resist hydrolysis by
beta -lactamases, have enhanced penetra-
tion into the CSF and are bactericidal at
very low concentrations. 4 Clinical experi-
ence with these agents in the treatment of
neonatal meningitis has been very
encouraging. The aminoglycosides are
also indicated in the treatment of
meningitis in newborn animals. 5
Moxalactam and cefotaxime are used
widely for the treatment of Gram-
negative bacillary meningitis in human
and ceftazidime is equally effective. 4
Trimethoprim-sulfonamide combinations,
with or without gentamicin, which is

Hyperesthesia, severe depression, muscle
rigidity, and blindness are the common
clinical findings in cerebral meningitis but it
is often difficult to differentiate meningitis
from encephalitis and acute cerebral
edema. Examination of the CSF is the only
means of confirming the diagnosis before
death. Analysis of CSF is very useful in the
differential diagnosis of diseases of the
nervous system of ruminants . 7 8 Details are
presented under Examination of CSF in the
section on Special examination of the
nervous system. Subacute or chronic
meningitis is difficult to recognize clinically.
The clinical findings may be restricted to
recumbency, apathy, anorexia, slight
incoordination if forced to walk and some
impairment of the eyesight. Spinal cord
compression is usually more insidious in
onset and is seldom accompanied by fever;
hyperesthesia is less marked or absent and
there is flaccidity rather than spasticity.

synergistic with the former, are also
recommended. The principles of the
pharmacotherapeutics of bacterial menin-
gitis in farm animals have been reviewed. 4

REVIEW LITERATURE

Fecteau G, George LW. Bacterial meningitis and
encephalitis in ruminants, Vet Clin North Am
Food Anim Pract 2004; 20:363-378.

Scott PR. Diagnostic techniques and clinicopathologic
findings in ruminant neurologic disease. Vet Clin
North Am Food Anim Pract 2004; 20:215-230.

REFERENCES

1. Ffellegrini-Masini A et al. J Am Vet Med Assoc
2005; 227:114.

2. Scott PR et al. Vet Rec 1993; 133:623.

3. Scott PR, Penny CD. Vet Rec 1993; 133:119.

4. Jamison JM, Prescott JF. Compend Contin Educ
PractVet 1988; 10:225.

5. Green SL, Smith LL. J Am Vet Med Assoc 1992;
201:125.

6. Nazifi S et al. J Vet Med A 1997; 44:55.

7. Scott PR. BrVet J 1992; 148:15.

8. Scott PR. BrVet J 1995; 151:603.

Toxic and metabolic
encephalomyelopathies

A very large number of poisons, especially
poisonous plants and farm chemicals, and
some metabolic defects cause abnormal-
ities of function of the nervous system.
Those plants that cause degenerative
nervous system disease are listed under
encephalomalacia; those that cause no
detectable degenerative change in tissue
are listed here.

A partial list of toxins and metabolic
errors or imbalances that can cause
nervous system dysfunction are as follows.

Abnormalities of consciousness and
behavior

Hypoglycemia and ketonemia of
pregnancy toxemia (with degenerative
lesions in some) and acetonemia
o Depression due to strong ion

(metabolic) acidosis associated with
diarrhea and dehydration, particularly
in neonatal animals

° Hypomagnesemia of lactation tetany
« Hyper-D-lactatemia in neonatal calves
with diarrhea and adult ruminants
with grain overload
0 High blood levels of ammonia in
hepatic insufficiency
0 Unspecified toxic substances in
uremic animals

■ Exogenous toxins, including carbon
tetrachloride, hexachloroethane, and
trichloroethylene

° Plants causing anemic and histotoxic
hypoxia, especially plants causing
cyanide or nitrite poisoning
° Poison plants, including Helichrysum
spp., tansy mustard, male fern, kikuyu
grass (or a fungus, Myrothecium sp. on
the grass).

2

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Abnormality characterized by tremor
and ataxia

'■ Weeds, including Conium spp.
(hemlock), Eupatorium spp.

(snakeroot), Sarcostemma spp..
Euphorbia spp. and Karwinskia spp.
f Bacterial toxins in shaker foal
syndrome (probably)

« Fungal toxins, e.g. Acremonium lolii,
the fungus of ryegrass staggers.

Convulsions

Metabolic deficits, including
hypoglycemia (piglets, ewes with
pregnancy toxemia), hypomagnesemia
(of whole milk tetany of calves,
lactation tetany, cows and mares)
Nutritional deficiencies of vitamin A
(brain compression in calves and
pigs), pyridoxine (experimentally in
calves)

Inorganic poisons, including lead
(calves), mercury (calves), farm
chemicals such as organic arsenicals
(pigs), organophosphates, chlorinated
hydrocarbons, strychnine, urea,
metaldehyde

si Bacterial toxins, including Clostridium
tetani, Clostridium perfringens type D
o Fungal toxins, e.g. Claviceps purpurea
' Grasses, including Wimmera ryegrass
(. Lolium rigidum) or the nematode on
it, Echinopogon ovatus
p Pasture legumes - lupines
Weeds - Qenanthe spp. (hemlock
water dropwort), Indigophera spp. (in
horses), Cicuta spp. (water hemlock),
Albizia tanganyinicus, Sarcostemma spp.
and Euphorbia spp.
p Trees - laburnum, oleander,
supplejack ( Ventilago spp.).

Ataxia apparently due to
proprioceptive defect

■' Grasses - Phalaris tuberosa (aquatica)
(and other Phalaris spp.), Lolium
rigidum, Echinopogon ovatus
Weeds - Romulea bulbocidum,
sneezeweed (. Helenium spp.),
Indigophera spp., Iceland poppy
(1 Papaver nudicaule), Gomphrena spp.,
Malva spp., Stachys spp., Ipomoea spp.,
Solanum esuriale

Trees - Kalmia spp., Erythrophloeum
spp., Eupatorium rugosum
<■ Ferns - Xanthorrhea spp., Zamia spp.
Induced thiamin deficiency caused by
bracken and horsetail poisoning.

Involuntary spastic contraction of
large muscle masses

This includes, for example, Australian
stringhalt caused by Arctotheca calendula
(flatweed).

Tremor, incoordination, and
convulsions

There is an additional long list of plants
that cause diarrhea and nervous signs,

especially ataxia, together, but whether
the latter are due to the former or caused
by neurotoxins is not identified.

The nervous signs include tremor,
incoordination, and convulsions.

Paresis or paralysis

Many of the toxic substances and meta-
bolic defects listed above cause paresis
when their influence is mild and paralysis
when it is severe. Some of the items
appear in both lists. Because an agent
appears in one list and not the other is
not meant to suggest that it does not
cause the other effect. It is more likely that
it occurs in circumstances that are almost
always conducive to the development of a
mild syndrome (or a severe one, as the
case may be).

Psychoses or neuroses

Psychoses or neuroses are extremely rare
in farm animals, although the vices of
crib-biting and weaving in horses could
be included in this category.

Crib-biting and windsucking
Crib-biting is an acquired habit in
which the horse grasps an object, usually
the feed box or any solid projection,
with the incisor teeth, then arches the
neck and, by depressing the tongue and
elevating the larynx, pulls upwards and
backwards and swallows air, emitting
a loud grunt at the same time. This results
in erosion of the incisor teeth, inter-
mittent bouts of colic and flatulence.
Crib-biting must be distinguished from
chewing wood due to boredom and

from pica due to a mineral deficiency.
Some horses perform similarly but do
not actually seize the object with their
teeth; they just rest their teeth or their
chin on it.

Wind sucking is the vice in which the
horse flexes and arches the neck and
swallows air and grunts but there is no
grasping of objects.

Grasping is the seizing of an object
with the teeth but without swallowing of
air.

Kicking, pawing, circling, weaving

Persistent kicking of the stall, in the
absence of pruritic lesions of the lower
limbs, continuous circling of a stall, pawing
of the floor with a forefoot and weaving,
standing at the window looking out while
rocking from one forefoot to the other
and swinging the head and neck to the
same side, are all neurotic vices caused by
boredom in active horses. The extreme
case is the animal that bites itself and
causes cutaneous and subcutaneous
mutilation.

Farrowing hysteria

Hysteria in sows at farrowing is a
common occurrence. This syndrome
occurs most commonly in gilts. Affected
animals are hyperactive and restless
and they attack and savage their piglets
as they approach the head during the
initial teat sucking activity after birth.
Serious and often fatal injuries result.
Cannibalism is not a feature.

When the syndrome occurs, the
remaining piglets and freshly born
piglets should be removed from the
sow and placed in a warm environment
until parturition is finished. The sow
should then be tested to see if she will
accept the piglets. If not, ataractic or
neuroleptic drugs should be administered
to allow initial sucking, after which the
sow will usually continue to accept the
piglets.

Azaperone (2 mg/kg BW) is usually
satisfactory and pentobarbital sodium
administered intravenously until the pedal
reflex is lost has been recommended.
Promazine derivatives are effective but
subsequent incoordination may result in a
higher crushing loss of piglets. The piglets'
teeth should be clipped.

Affected gilts should be culled sub-
sequently as the syndrome may recur at
subsequent farrowing. Where possible,
gilts should be placed in their farrowing
accommodation 4-6 days before parturition
and the farrowing environment should be
kept quiet at the time of parturition.

Tail-biting, ear-chewing, snout-
rubbing

The incidence of cannibalism has in-
creased with intensification of pig rearing

Disturbance of function at

neuromuscular junctions eg.:
hypocalcemia, hypomagnesemia,
hypokalemia (as in downer cows),
tetanus, botulism and hypoglycemia
of pregnancy toxemia in cows and
ewes, and tick paralysis.
Hypophosphatemia has not been
demonstrated to be a definitive cause
of weakness in cattle
Nutritional deficiency, but including
only experimentally induced
deficiency of nicotinic and
pantothenic acids: biotin and choline,
cause posterior paresis and paralysis
in pigs and calves

Toxic diseases of the nervous system,
including disease associated with
many chemicals used in agriculture,
e.g.: piperazine, rotenone, 2,4-D and
2,4,5-T, organophosphates,
carbamates, chlorinated
hydrocarbons, propylene glycol,
metaldehyde, levamisole, toluene,
carbon tetrachloride, strychnine, and
nicotine sulfate.

Diseases of the spinal cord

613

and it is now a significant problem in
many pig-rearing enterprises. Tail-biting
is the most common and occurs in
groups of pigs, especially males, from
weaning to market age. Ear-chewing is
less common and is generally restricted
to pigs in the immediate postweaning
and early growing period, although both
syndromes may occur concurrently. The
incidence of ear-chewing has increased
with the practice of docking piglet tails
at birth.

Tail-biting usually begins with one
or two pigs sucking or chewing the
tails of pen mates. Initially the practice
causes no resentment but as the tail
becomes raw and eroded, pain is shown.
Rarely, if the offending agonists are
removed at this stage, the problem will
not progress. Generally the raw eroded
tail becomes attractive to other indivi-
duals within the group and the vice
spreads within the group to involve the
majority of pigs. Most of the tail may
eventually be removed, leaving a raw
bleeding stump.

Productivity is affected by severe lesions
and sequelae such as spinal abscessation
with paralysis and abscessation or pyemia
with partial or total carcass condemnation
are not uncommon.

Ear-biting occurs in similar fashion.
The lesions are usually bilateral and
most commonly involve the ventral part
of the ear. Lesions from bite wounds may
also occur on the flanks of pigs. There
is frequently an association with mange
infestation with both of these vices.

A syndrome of snout-rubbing to pro-
duce eroded necrotic areas on the flanks
of pigs has been described. Affected pigs
were invariably colored, although both
white and colored pigs acted as agonists.

The causes of these forms of
cannibalism in pigs are poorly understood
but they are undoubtedly related to an
inadequate total environment. Affected
groups are usually more restless and
have heightened activity. Factors such as a
high population density, both in terms of
high pen density and large group size,
limited food and competition for food,
low protein and inadequate nutrition, bore-
dom and inadequate environment in
terms of temperature, draft and venti-
lation have been incriminated in pre-
cipitating the onset of these vices.

When a problem is encountered each
of these factors should be examined
and corrected or changed if necessary.
Prevention is through the same measures.
Chains or tires are frequently hung for
displacement activity but are not parti-
cularly effective.

The problem may recur despite all
attempts at prevention. Also for economic
reasons it is not always possible to

implement the radical changes in
housing and management that may be
necessary to avoid the occurrence of these
vices. Because of this, the practice of
tipping or docking the piglets' tails at
birth has become common as a method
of circumventing the major manifestation
of cannibalism.

Epilepsy

Seizures occur most frequently in
conjunction with other signs of brain
disease. The syndrome of inherited,
recurrent seizures, which continues
through life with no underlying morpho-
logical disease process, is true epilepsy,
which is extremely rare in farm animals.
Familial epilepsy has been recorded
in Brown Swiss cattle and is described
under that heading in Chapter 12.

Residual lesions after encephalitis
may cause symptomatic epileptiform
seizures but there are usually other
localizing signs. A generalized seizure
is manifested by an initial period of
alertness, the counterpart of the aura
in human seizures, followed by falling
in a state of tetany, which gives way after
a few seconds to a clonic convulsion with
paddling, opisthotonos and champing of
the jaws. The clonic convulsions may last
for some minutes and are followed by a
period of relaxation. The animal is
unconscious throughout the seizure, but
appears normal shortly afterwards.

Some seizures may be preceded by
a local motor phenomenon such as
tetany or tremor of one limb or of the face.
The convulsion may spread from
this initial area to the rest of the body.
This form is referred to as jacksonian
epilepsy and the local sign may indicate the
whereabouts of the local lesion or point of
excitation. Such signs are recorded very
rarely in dogs and not at all in farm animals.
The seizures are recurrent and the animal is
normal in the intervening periods.

Diseases of the spinal cord

TRAUMATIC INJURY

Sudden severe trauma to the spinal
cord causes a syndrome of immediate,
complete, flaccid paralysis caudal to the
injury because of spinal shock. This is
so brief in animals as to be hardly
recognizable clinically. Spinal shock is
soon followed by flaccid paralysis in the
area supplied by the injured segment
and spastic paralysis caudal to it.

ETIOLOGY

Trauma is the most common cause of
monoplegia in large animals. There are

varying degrees of loss of sensation,
paresis, paralysis, and atrophy of muscle.

Physical trauma

° Animals falling off vehicles, through
barn floors

° Osteoporotic or osteodystrophic
animals, especially aged brood mare's
and sows, spontaneously while
jumping or leaning on fences
° Spondylosis and fracture of

thoracolumbar vertebrae in old bulls
in insemination centers
° Cervical vertebral fractures account for
a large percentage of spinal cord
injuries in horses 1

0 Trauma due to excessive mobility of
upper cervical vertebrae may
contribute to the spinal cord lesion in
wobbles in horses

0 Dislocations of the atlanto-occipital
joint are being reported increasingly
° Stenosis of the cervical vertebral canal
at C2.-C4 in young rams, probably as
a result of head-butting 2
° Fracture of T1 vertebra in calves
turning violently in an alleyway wide
enough to admit cows
° Vertebral fractures in 7-10-month-old
calves escaping under the head gate
of chute and forcefully hitting their
backs (just cranial to the tuber coxae)
on the bottom rail of the gate 3
° Vertebral fractures in neonatal calves
associated with forced extraction
during dystocia 2,4

° Lightning strike may cause tissue
destruction within the vertebral canal.

Parasitic invasion

0 Cerebrospinal nematodiasis, e.g.
Paraelaphostrongylus tenuis, Setaria
spp. in goats and sheep, Stephanurus
dentatus in pigs. P. tenuis in moose,
causing moose sickness
" Toxocara canis experimentally in pigs
° Strongylus vulgaris in horses and
donkeys

° Hypoderma bovis larvae in cattle.

Local ischemia of the spinal cord

° Obstruction to blood flow to the cord
by embolism, or of drainage by
compression of the caudal vena cava,
e.g. in horses during prolonged dorsal
recumbency under general
anesthesia; 5 in pigs due to
fibrocartilaginous emboli, probably
originating in injury to the nucleus
pulposus of an intervertebral disk. 5

PATHOGENESIS

The lesion may consist of disruption of
nervous tissue or its compression by dis-
placed bone or hematoma. Minor degrees
of damage may result in local edema or
hyperemia or, in the absence of macro-
scopic lesions, transitory injury to nerve
cells, classified as concussion. The initial

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

response is that of spinal shock, which
affects a variable number of segments on
both sides of the injured segment and is
manifested by complete flaccid paralysis.
The lesion must affect at least the ventral
third of the cord before spinal shock
occurs. When the shock wears off the
effects of the residual lesion remain.
These may be temporary in themselves
and completely normal function may
return as the edema or the hemorrhage is
resorbed. In sheep, extensive experi-
mental damage to the cord may be
followed by recovery to the point of being
able to walk, but not sufficiently to be of
any practical significance.

Traumatic lesions usually affect the
whole cross-section of the cord and pro-
duce a syndrome typical of complete
transection. Fhrtial transection signs are
more common in slowly developing
lesions. Most of the motor and sensory
functions can be maintained in 3-month-
old calves with experimental left
hemisection of the spinal cord. 6

In a retrospective study of dystocia-
related vertebral fractures in neonatal
calves, all the fractures were located
between the 11th thoracic vertebra and
the fourth lumbar vertebra, with 77%
occurring at the thoracolumbar junction. 4
All but one case was associated with
a forced extraction using unspecified
(53%), mechanical (28%) or manual
(17%) methods of extraction. Traction
is most commonly applied after the
fetus has entered the pelvic canal.
Manual traction varies from 75 kg press-
ure applied by one man to 260 kg applied
by three or more men. The forces applied
in mechanical traction vary from 400 kg
for a calf puller to over 500 kg for a tractor.
The transfer of these forces to the
vertebrae and to the physeal plates at the
thoracolumbar junction could readily
cause severe tissue damage. In a pros-
pective study of vertebral fractures in
newborn calves, all fractures were located
at the thoracolumbar area, especially the
posterior epiphysis of T13. 2

CLINICAL FINDINGS

Spinal shock develops immediately
after severe injury and is manifested
by flaccid paralysis (reflex loss) caudal to
a severe spinal cord lesion. There is a con
current fall in local blood pressure
due to vasodilatation and there may be
local sweating. Stretch and flexor
reflexes and cutaneous sensitivity disap-
pear but reappear within a half to
several hours, although hypotonia may
remain. The extremities are affected in
most cases and the animal is unable to
rise and may be in sternal or lateral
recumbency. The muscles of respiration
may also be affected, resulting in

interference with respiration. The body
area supplied by the affected segments
will eventually show flaccid paralysis,
disappearance of reflexes and muscle
wasting - a lower motor neuron lesion.

When the injury is caused by invasion
by parasitic larvae there is no stage of
spinal shock but the onset is acute,
although there may be subsequent
increments of paralysis as the larva moves
to a new site.

Neonatal calves with dystocia-related
vertebral fractures are weak immediately
after birth or remain recumbent and
make no effort to rise.

Sensation may be reduced at and caudal
to the lesion and hyperesthesia may be
observed in a girdle-like zone at the cranial
edge of the lesion as a result of irritation of
sensory fibers by local inflammation and
edema. Because of interference with the
sacral autonomic nerve outflow there may
be paralysis of the bladder and rectum,
although this is not usually apparent in
large animals. The vertebra] column should
be examined carefully for signs of injury.
Excessive mobility, pain on pressure, and
malalignment of spinous processes may
indicate bone displacements or fractures.
Rectal examination may also reveal
damage or displacement particularly in
fractures of vertebral bodies and in old bulls
with spondylosis.

Residual signs may remain when the
shock passes off. This usually consists
of paralysis, which varies in extent and
severity with the lesion. The paralysis
is apparent caudal to and at the site of
the lesion. The reflexes return except at
the site of the lesion. There is usually no
systemic disturbance but pain may be
sufficiently severe to cause an increase
in heart rate and prevent eating.

Recovery may occur in 1-3 weeks if
nervous tissue is not destroyed but
when extensive damage has been done to
a significantly large section of the cord
there is no recovery and disposal is
advisable. In rare cases animals that
suffer a severe injury continue to be
ambulatory for up to 12 hours before
paralysis occurs. In such instances it may
be that a fracture occurs but displacement
follows at a later stage during more active
movement. Recovered animals may be
left with residual nervous deficits or
with postural changes such as torticollis.

Fracture of the cervical vertebrae in
horses

In horses fracture/dislocation of cranial
cervical vertebrae occurs fairly commonly.
Affected animals are recumbent and
unable to lift the head from the ground.
However, they may be fully conscious
and able to eat and drink. It may be poss-
ible to palpate the lesion, but a radiograph

is usually necessary. Lesions of the caudal
cervical vertebrae may permit lifting 0 f
the head but the limbs are not moved
voluntarily. In all cases the tendon and
withdrawal reflexes in the limbs are
normal to supernormal.

Spondylosis in bulls

Old bulls in artificial insemination centers
develop calcification of the ventral vertebral
ligaments and subsequent spondylosis or
rigidity of the lumbar area of the vertebral
column. When the bull ejaculates vigor-
ously the calcified ligaments may fracture
and this discontinuity may extend upward
through the vertebral body. The ossification
is extensive, usually from about T2-L3, but
the fractures are restricted to the midlumbar
region. There is partial displacement of
the vertebral canal and compression of the
cord. The bull is usually recumbent
immediately after the fracture occurs but
may rise and walk stiffly several days later.
Arching of the back, slow movement, trunk
rigidity and sometimes unilateral lameness
are characteristic signs. Less severe degrees
of spondylosis have been recorded in a high
proportion of much younger (2-3-year old)
bulls, but the lesions do not appear to cause
clinical signs.

CLINICAL PATHOLOGY

Radiologic examination may reveal the
site and extent of the injury. CSF obtained
from the lumbosacral space may reveal
the presence of red blood cells, suggesting
pre-existing hemorrhage.

NECROPSY FINDINGS

The abnormality is always visible on
macroscopic examination. In neonatal
calves with dystocia-related vertebral
fractures, hemorrhage around the kidneys,
around the adrenal glands and in the
perivertebral muscles is a common find-
ing and a useful indicator that a thora-
columbar fracture is present. In addition to
the vertebral fracture, subdural and epi-
dural hemorrhage, myelomalacia, spinal
cord compression, severed spinal cord,
and fractured ribs are common findings.

DIFFERENTIAL DIAGNOSIS

Differentiation from other spinal cord
diseases is not usually difficult because of
the speed of onset and the history of
trauma, although spinal myelitis and
meningitis may also develop rapidly. Other
causes of recumbency may be confused
with trauma especially if the animal is not
observed in the immediate predinical
period. In most diseases characterized by
recumbency, such as azoturia, acute rumen
impaction and acute coliform mastitis,
there are other signs to indicate the
existence of a lesion other than spinal cord
trauma. White muscle disease in foals is
characterized by weakness and the serum
creatine kinase activity will be increased.

Diseases of the spinal cord

615

TREATMENT

Treatment is expectant only, surgical treat-
ment rarely being attempted. Large doses of
corticosteroids or nonsteroidal anti-
inflammatory agents are recommended to
minimize the edema associated with the
spinal cord injury. Careful nursing on deep
bedding with turning at 3-hourly intervals,
massage of bony prominences and periodic
slinging may help to carry an animal
with concussion or other minor lesion
through a long period of recumbency.
In cattle especially, recumbency beyond
a period of about 48 hours is likely
to result in widespread necrosis of the
caudal muscles of the thigh and recovery in
such cases is improbable. A definitive diag-
nosis of a vertebral fracture with paralysis
usually warrants a recommendation for
euthanasia.

REVIEW LITERATURE

Divers TJ. Acquired spinal cord and peripheral nerve
disease. Vet Clin North Am Food Anim Pract 2004;
20, 231-242.

REFERENCES

1. Tyler CM et al. AustVet J 1993; 70:445.

2. Agerholm JS et al. Acta Vet Scand 1993; 34:379.

3. Edwards JF et al. J Am Vet Med Assoc 1995;
207:934.

4. Schuh JCL, Killeen JR. Can Vet J 1988; 29:830.

5. Johnson RC et al. CornellVet 1988; 78:231.

6. Troyer DL et al. ProgVet Neurol 1994; 5:98.

SPINAL CORD COMPRESSION

The gradual development of a space-
occupying lesion in the vertebral canal
produces a syndrome of progressive weak-
ness and paralysis. A pre-existing inflam-
matory or neoplastic lesion of the vertebral
body may result in spontaneous fracture
of the vertebral body and compression of
the spinal cord.

ETIOLOGY

Compression of the spinal cord occurs
from space-occupying lesions in the
vertebral canal, the common ones being
as follows.

Tumors

Tire most commonly occurring tumor in
animals is lymphomatosis, which the nerve
trunks and invades the vertebral canal,
usually in the lumbosacral region and less
commonly in the brachial and cervical areas
This tumor is particularly common in adult
cattle with multicentric lymphosarcoma
due to bovine leukosis virus infection.

Rare tumors include: fibrosarcomas,
metastases, plasma cell myeloma, angioma,
melanoma in a horse, 1 hemangiosarcoma
in a horse, 2 neurofibroma and lympho-
sarcoma, e.g. in horses, vascular hamartoma
in a goat. 3

Vertebral body or epidural abscess

Vertebral body abscesses (osteomyelitis)
occur most commonly in neonatal farm

animals generally in association with a
chronic suppurative lesion elsewhere in
the body.

0 Docking wounds in lambs, bite
wounds in pigs and chronic
suppurative pneumonia in calves are
common occurrences
® Polyarthritis and endocarditis may
also be present

• Compression of the spinal cord is
caused by enlargement of the
vertebral body abscess into the
vertebral canal and there may or may
not be deviation of the vertebral canal
and its contents

® The original site of infection may have
resolved when the clinical signs
referable to the spinal cord abscess
appear

• Hematogenous spread may also occur
from Arcanobacterium (Actinomyces or
Corynebacterium) pyogenes in cattle,
Actinomyces bovis in cattle with lumpy
jaw, Corynebacterium pseudotuberculosis
in sheep

® Epidural abscesses causing

compression of the spinal cord and
not associated with vertebral bodies
also occur in lambs. 4

Bony lesions of vertebra

° Exostoses over fractures with no
displacement of vertebral bodies
® Similar exostoses on vertebral bodies
of lambs grazing around old lead
mines

0 Hypovitaminosis A in young growing
pigs causing compression of the nerve
roots passing through the vertebral
foramina

° Congenital deformity or fusion of the
atlanto-occipital-axial joints in calves,
foals and goats (see Congenital
defects, below)

° Congenital spinal stenosis of calves. 5

Rarely there is protrusion of an inter-
vertebral disc, identifiable by myelogram,
and progressive paresis and ataxia also
occur rarely in diskospondy litis in horses.
Cervical pain is a more common sign in
the latter. The degenerative lesions in
disks in the neck of the horse resemble
the Hansen type 2 disk prolapses in dogs.

Adult sows and boars may have
degeneration of intervertebral disks and
surrounding vertebral osteophytes. Less
commonly ankylosing spondylosis, arthrosis
of articular facets, defects in annulus
fibrosus and vertebral end plates, and
vertebral osteomyelitis or fracture. These
lesions of diskospondylitis cause lameness
in boars and sows rather than compression
of cord and paresis/ paralysis.

These are not to be confused with the
many extravertebral causes of posterior
lameness or paralysis in adult pigs, which

are discussed in Chapter 13 on the
musculoskeletal system.

Vertebral subluxation

Cervicothoracic vertebral subluxation in
Merino sheep in Australia. 6

Ataxia in horses

This is a major problem and is dealt
with more extensively under the heading
of enzootic incoordination of horses. For
purposes of comparison the diseases
involved are listed here:

® Nonfatal fractures of the skull
(basisphenoid, basioccipital, and
petrous temporal bones)
s Nonfatal cervical fractures
® Atlanto-occipital instability
• Stenosis of cranial vertebral orifice of
C3-C7; 7 this may be effective as a
compression mechanism only if the
vertebrae adopt exaggerated positions
® Abnormal growth of interarticular
surfaces

0 Dorsal enlargement of caudal
vertebral epiphyses and bulging of
intervertebral disks
® Formation and protrusion of false
joint capsules and extrasynovial
bursae

® Spinal myelitis due to parasitic
invasion or equine herpesvirus-1
virus, even louping-ill virus and
probably others

° Spinal abscess usually in a vertebral
body

® Cerebellar hypoplasia - most
commonly the inherited version in
Arabian foals

0 Degenerative myelomalacia/
myelopathy - cause unknown
0 Fusion of occipital bone with the
atlas, which is fused with the axis
° Hypoxic-ischemic neuromyopathy in
aortic-iliac thrombosis
° Tumors of the meninges.

PATHOGENESIS

The development of any of the lesions
listed above results in the gradual appear-
ance of motor paralysis or hypoesthesia,
depending on whether the lesion is
ventrally or dorsally situated. In most
cases there is involvement of all motor
and sensory tracts but care is necessary in
examination if the more bizarre lesions
are to be accurately diagnosed. There may
be hemiparesis or hemiplegia if the lesion
is laterally situated. Paraparesis or para-
plegia is caused by a bilateral lesion in the
thoracic or lumbar cord and monoplegia
by a unilateral lesion in the same
area. Bilateral lesions in the cervical
region cause tetraparesis to tetraplegia
(quadriplegia).

In horses with chronic compressive
myelopathy (wobbles), compression of
the spinal cord results in necrosis of white

616

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

matter, and some focal loss of neurons. 8-9
With time, secondary wallerian-like
neuron fiber degeneration in ascending
white matter tracts cranial to the focal
lesion and in descending white matter
tracts caudal to the lesion occurs. Astro-
cytic gliosis is a prominent and persistent
alteration of the spinal cord of horses
with chronic cervical compressive myelo-
pathy and is associated with nerve fiber
degeneration at the level of the
compression and in well-delineated areas
of ascending and descending nerve fiber
tracts. It is possible that the persistent
astrocytic gliosis may prevent, or slow,
recovery of neurological function in
affected horses.

Vertebral osteomyelitis in young
calves occurs most commonly in the
thoracolumbar vertebrae and less com-
monly in the cervical vertebrae. The
abscess of the vertebral body gradually
enlarges and causes gradual compression
of the spinal cord, which causes varying
degrees of paresis of the pelvic limbs
and ataxia. 10 The abscess may extend
into adjacent intervertebral spaces and
result in vertebral arthritis with lysis
of the articular facets. The onset of paresis
and paralysis may be sudden in cases
of abscessation or osteomyelitis of the
vertebrae, which may fracture and
cause displacement of bony fragments
into the vertebral canal with compression
and traumatic injury of the spinal cord.
Vertebral body abscesses between T2 and
the lumbar plexus will result in weakness
of the pelvic limbs and normal flexor
withdrawal reflexes of the pelvic limbs.
Lesions at the site of the lumbar plexus
will result in flaccid paralysis of the
pelvic limbs.

CLINICAL FINDINGS

Varying degrees of progressive weakness
of the thoracic limbs or pelvic limbs
may be the initial clinical findings. With
most lesions causing gradual spinal
cord compression, difficulty in rising is
the first sign, then unsteadiness during
walking due to weakness, which may be
more marked in one of a pair of limbs.
The toes are dragged along the ground
while walking and the animal knuckles
over on the fetlocks when stand-
ing. Finally the animal can rise only
with assistance and then becomes
permanently recumbent. These stages
may be passed through in a period of
4-5 days.

The paralysis will be flaccid or spastic
depending on the site of the lesion and
reflexes will be absent or exaggerated
in the respective states. The 'dog-sitting /
position in large animals is compatible
with a spinal lesion caudal to the second
thoracic vertebral segment. Calves with

vertebral osteomyelitis caudal to T2 are
usually able to sit up in the 'dog-sitting'
position, they are bright and alert and will
suck the cow if held up to the teat. In
some cases, extensor rigidity of the thoracic
limbs resembles the Schiff-Sherrington
syndrome and indicates a lesion of the
thoracic vertebrae.

Lesions involving the lumbar plexus
will result in flaccid paralysis of the
pelvic limbs and an absence of the flexor
withdrawal reflexes. Lesions involving
the sacrococcygeal vertebrae will cause
a decrease in tail tone, decreased or
absent perineal reflex and urinary bladder
distension.

Pain and hyperesthesia may be

evident before motor paralysis appears.
The pain may be constant or occur only
with movement. In vertebral body
osteomyelitis in the horse, vertebral column
pain and a fever may be the earliest
clinical abnormalities. With neoplasms of
the epidural space, the weakness and
motor paralysis gradually worsen as the
tumor enlarges.

Considerable variation in signs
occurs depending on the site of the
lesion. There may be local hyperesthesia
around the site of the lesion and
straining to defecate may be pronounced.
Retention of the urine and feces may
occur. There is usually no detectable
abnormality of the vertebrae on physical
examination.

In the wobbler horse, circumduction
of the limbs with ataxia is typical. The
ataxia is usually pronounced in the
pelvic limbs, and weakness is evident
by toe dragging and the ease with which
the horse can be pulled to one side while
walking. Ataxia with hypometria is often
evident in the thoracic limbs, especially
while walking the horse on a slope and
with the head elevated.

Calves with congenital spinal stenosis
are usually unable to stand or can do so
only if assisted. There are varying degrees
of weakness and ataxia of the pelvic
limbs. They are bright and alert and will
suck the cow if assisted. Those that
survive for several weeks will sometimes
assume the 'dog-sitting 7 position.

CLINICAL PATHOLOGY

Radiographic examination of the vertebral
column should be carried out if the ani-
mal is of a suitable size. Myelography is
necessary to demonstrate impingement
on the spinal cord by a stenotic vertebral
canal. Myelography using the contrast
medium Iopamidol has been done in
neonatal calves for the detection of spinal
cord compression causing paresis. 11 The
contrast medium was introduced through
the foramen magnum under general
anesthesia.

The cerebrospinal fluid may show
a cellular reaction if there is some invasion
of the spinal canal.

NECROPSY FINDINGS

Gross abnormalities of the vertebrae
and the bony spinal canal are usually
obvious. Those diseases of the spinal cord
characterized by degeneration without
gross changes require histological tech-
niques for a diagnosis.

DIFFERENTIAL DIAGNOSIS

Differentiation between abscess, tumor
and exostosis in the vertebral canal is
usually not practicable without
radiographic examination. Vertebral
osteomyelitis is difficult to detect
radiographically, particularly in large
animals, because of the overlying tissue. In
bovine lymphosarcoma there are frequently
signs caused by lesions in other organs. A
history of previous trauma may suggest
exostosis. The history usually serves to
differentiate the lesion from acute trauma.

• Spinal myelitis, myelomalacia and
meningitis may resemble cord
compression but are much less
common. They are usually associated
with encephalitis, encephalomalacia
and cerebral meningitis respectively

• Meningitis is characterized by much
more severe hyperesthesia and muscle
rigidity

• Rabies in the dumb form may be
characterized by a similar syndrome but
ascends the cord and is fatal within a
6-day period.

In the newborn there are many congenital
defects in which there is defective
development of the spinal cord. Most of
them are not characterized by compression
of the cord, the diminished function being
caused in most cases by an absence of
tissue. Spina bifida, syringomyelia and
dysraphism are characterized by
hindquarter paralysis or, if the animal is able
to stand, by a wide-based stance and
overextension of the legs when walking.
Some animals are clinically normal.

A generalized degeneration of
peripheral nerves such as that described
in pigs and cattle causes a similar clinical
syndrome; so does polyradiculoneuritis.
A nonsuppurative ependymitis,
meningitis and encephalomyelitis, such
as occurs in equine infectious anemia, may
also cause an ataxia syndrome in horses.

Paresis or paralysis of one limb
(monoplegia) is caused by lesions in the
ventral gray matter, nerve roots, brachial
and lumbosacral plexus, and peripheral
nerves and muscles of the limbs.

TREATMENT

Successful treatment of partially collapsed
lumbar vertebra by dorsal laminectomy
has been performed in a calf and in
horses, but in farm animals treatment
is usually not possible and in most cases
slaughter for salvage is recommended.

Diseases of the spinal cord

617

REVIEW LITERATURE

Jeffcott LB, Dalin G. Bibliography of thoracolumbar
conditions in the horse. Equine Vet J 1983;
15:155-157.

Divers TJ. Acquired spinal cord and peripheral nerve
disease. Vet Clin North Am Food Anim Pract 2004;
20:231-242.

references

1. Schott HC et al. J Am Vet Med Assoc 1990;
196:1820.

2. Newton-Clarke MJ et al. Vet Rec 1994; 135:182.

3. Middleton JR et al. Vet Rec 1999; 144:264.

4. Scott PR, Will RG. BrVet J 1991; 147:582.

5. Doige CE et al.Vet Pathol 1990; 27:16.

6. Hill BD et al. AustVet J 1993; 70:156.

7. Tomizawa N et al. J Vet Med Sci 1994; 56:227.

8. Yovich JV et al. AustVet J 1991; 68:326.

9. Yovich JV et al. AustVet J 1991; 68:334.

10. Rashmir-Raven A et al. Prog Vet Neurol 1991;
2:197.

11. Bargai U.Vet Radiol Ultrasound 1993; 34:20.

BA CK PAIN IN HORSES

The subject of back pain, and its relation-
ship to lameness, is a very important
one in horses. There is often a lesion in
the vertebral canal and by pressing
on the cord or peripheral nerves it causes
gait abnormalities that suggest the
presence of pain, or they actually cause
pain. Spondylosis, injury to dorsal spinous
processes, and sprain of back muscles are
common causes of the same pattern of
signs. Because these problems are largely
orthopedic ones, and therefore surgical,
their exposition is left to other authorities.

It is necessary in horses to differentiate
spinal cord lesions from acute nutritional
myodystrophy, and subacute tying-up
syndrome. Those diseases are characterized
by high serum creatine kinase and aspartate
aminotransferase activities.

REVIEW LITERATURE

Jeffcott LB, Dalin G. Bibliography of thoracolumbar
conditions in the horse. Equine Vet J 1983;
15:155-157.

MY ELITIS

Inflammation of the spinal cord is
usually associated with viral encephalitis.
The signs are referable to the loss of
function, although there may be signs
of irritation. For example, hyperesthesia
or paresthesia may result if the dorsal
root ganglia are involved. This is par-
ticularly noticeable in pseudorabies and
to a lesser extent in rabies. Paralysis
is the more usual result. There are
no specific myelitides in farm animals.
Listeriosis is sometimes confined in its
lesion distribution to the spinal cord
in sheep. Viral myelitis associated
with equine herpesvirus- 1 (the equine
rhinopneumonitis virus) is now com-
monplace and equine infectious anemia
and dourine include incoordination
and paresis in their syndromes. In goats,
caprine arthritis encephalitis is principally

a myelitis, involving mostly the white
matter.

Equine protozoal myeloencephalitis

causes multifocal lesions of the central
nervous system, mostly the spinal cord. 1
The most accurate diagnosis is based
on histological findings:

° Necrosis and mild to severe,
nonsuppurative myeloencephalitis
0 Infiltration of neural tissue by
mononuclear cells

® Sometimes giant cells, neutrophils,
and eosinophils

0 Infiltration of perivascular tissue by
mononuclear cells including
lymphocytes and plasma cells.

Equine protozoal myeloencephalitis is
caused primarily by Sarcocystis neurona,
which has the opossum ( Didelphis
virginiana) as the definitive host, raccoons
as the most likely intermediate host,
with the horse acting as a dead end
host. 1 Occasional cases of protozoal
myeloencephalitis in horses are associ-
ated with Neospora hughesi.

Myelitis associated with Neosporum
caninum infection in newborn calves
has been described. 2 Affected calves
were recumbent and unable to rise but
were bright and alert. Histologically
there was evidence of protozoal myelitis.

MYELOMALACIA

Myelomalacia occurs rarely as an entity
separate from encephalomalacia. One re-
corded occurrence is focal spinal polio-
malacia of sheep and in enzootic ataxia
the lesions of degeneration are often
restricted to the spinal cord. In both
instances there is a gradual development
of paralysis without signs of irritation and
with no indication of brain involvement.
Progressive paresis in young goats may be
associated with the virus of caprine
arthritis encephalitis and other unidentified,
possibly inherited causes of myelomalacia. 3

Degeneration of spinal cord tracts
has also been recorded in poisoning by
Phalaris aquatica in cattle and sheep,
by sorghum in horses, by 3-nitro-
4-hydroxyphenylarsonic acid in pigs
and by selenium in ruminants; the lesion
is a symmetrical spinal poliomalacia.
Fbisoning of cattle by plants of Zamia spp.
produces a syndrome suggestive of
injury to the spinal cord but no lesions
have been reported. Pantothenic acid
or pyridoxine deficiencies also cause de-
generation of spinal cord tract in swine.

A disease of obscure etiology in sheep
with spinal cord degeneration is
Murrurrundi disease. A spinal myelino-
pathy, possibly of genetic origin is
recorded in Murray Grey calves. 4 Affected
animals develop ataxia of the hindlegs,

| swaying of the hindquarters and collapse
j of one hindleg with falling to one side,
j Clinical signs become worse over an
j extended period.

j Sporadic cases of degeneration of
j spinal tracts have been observed in pigs.

| One outbreak is recorded in the littdrs
j of sows on lush clover pasture. The
piglets were unable to stand, struggled
! violently on their sides with rigid exten-
j sion of the limbs and, although able to
drink, usually died of starvation. Several
; other outbreaks in pigs have been attributed
to selenium poisoning.

An inherited lower motor neuron
disease of pigs has been recorded. 5
Clinical findings of muscular tremors,
paresis or ataxia developed at 12-59 days
of age. There is widespread degeneration
of myelinated axons in peripheral nerves
and in the lateral and ventral columns
of lumbar and cervical segments of the
spinal cord. Axonal degeneration is
present in ventral spinal nerve roots
and absent in dorsal spinal nerve
roots when sampled at the same lumbar
levels.

Equine degenerative myelo-
encephalopathy of unknown etiology
affects young horses and has been
recorded in the USA, Canada, the UK,
and Australia. 6 The major clinical signs
are referable to bilateral leukomyelopathy
involving the cervical spinal cord. There
is abnormal positioning and decreased
strength and spasticity of the limbs as
a result of upper motor neuron and general
proprioceptive tract lesions. Hypalgesia,
hypotonia, hyporeflexia, muscle atrophy,
or vestibular signs are not present and
there is no evidence of cranial nerve,
cerebral or cerebellar involvement clinically.
Abnormal gait and posture are evident,
usually initially in the pelvic but
eventually also in the thoracic limbs.
There are no gross lesions but histo-
logically there is degeneration of neuronal
processes in the white matter of all spinal
cord funiculi, especially the dorsal spin-
ocerebellar and sulcomarginal tracts. The
lesion is most severe in the thoracic
segments. The disease is progressive and
there is no known treatment.

Equine motor neuron disease affects
horses from 15 months to 25 years of age
of many different breeds. 7,8 Progressive
weakness, short-striding gait, trembling,
long periods of recumbency, and trem-
bling and sweating following exercise
are characteristic clinical findings. The
weakness is progressive and recumbency
is permanent. Appetites remain normal
or become excessive. At necropsy, degener-
ation and/or loss of somatic motor
neurons in the spinal ventral horns and
angular atrophy of skeletal muscle fibers
are characteristic. 7

8

PART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

Sporadic cases of spinal cord damage
in horses include hemorrhagic myelo-
malacia following general anesthesia 9
and acute spinal cord degeneration fol-
lowing general anesthesia and surgery. 10
Following recovery from the anesthesia,
the horse is able to assume sternal
recumbency but not able to stand. 10 A
hemorrhagic infarct assumed to be due
to cartilage emboli, and a venous mal-
formation causing spinal cord destruction
have also occurred in the horse. The
disease must be differentiated from
myelitis and spinal cord compression
caused by space-occupying lesions of the
vertebral canal, and cervical, vertebral
malformation/malarticulation.

REFERENCES

1. Fayer R et al. J Vet Intern Med 1990; 4:54.

2. Rirish SM et al. J Am Vet Med Assoc 1987;
191:1599.

3. Lancaster MJ et al. AustVet J 1987; 64:123.

4. Richards RB, Edwards JR. Vet Pathol 1986; 23:35.

5. O'Toole D et al. J Vet Diagn Invest 1994; 6:230.

6. Mayhew IG et al. JVet Intern Med 1987; 1:45.

7. Step DL et al. J Am Vet Med Assoc 1993; 202:26.

8. Cummings JF et al. CornellVet 1990; 80:357.

9. Lerche E et al. CornellVet 1993; 83:267.

10. Lam KHK et al. Vet Rec 1995; 136:329.

Diseases of the peripheral
nervous system

The peripheral nervous system consists
of cranial and spinal nerve components.
As such, the peripheral nervous system
includes the dorsal and ventral nerve
roots, spinal ganglia, spinal and specific
peripheral nerves, cranial nerves and
their sensory ganglia, and the peripheral
components of the autonomic nervous
system. 1

ETIOLOGY

There are several different causes of
peripheral nervous system disease.

Inflammatory

Polyneuritis equi, also known as
neuritis of the cauda equina or cauda
equina syndrome, is a rare and slowly
progressive demyelinating granulomatous
disease affecting peripheral nerves in
the horse. 2 Polyneuritis equi is charac-
terized by signs of lower motor neuron
lesions, primarily involving the perineal
region but also affecting other peripheral
nerves, especially the 5th and 7th cranial
nerves. The 8th, 9th, 10th and 12th cranial
nerves also may be involved. Clinical signs
of perineal region paresis/paralysis pre-
dominate, manifest as varying degrees of
hypotonia, hypalgesia and hyporeflexia of
the tail, anus and perineal region. Degrees
of urinary bladder paresis and rectal dila-
tation are also present. Differential diag-
noses include sacral or coccygeal trauma,

equine herpes myeloencephalopathy,
equine protozoal myeloencephalitis, rabies
and equine motor neuron disease 2

Cranial neuritis with guttural
pouch mycosis and empyema in the
horse may cause abnormalities of swallow-
ing, laryngeal hemiplegia and Homer's
syndrome if the glossopharyngeal and
vagal nerves are involved in the inflam-
matory process of the guttural pouch. 1

Degenerative

Equine laryngeal hemiplegia, often
called roaring, is a common disease of
the horse in which there is paralysis of
the left cricoarytenoid dorsalis muscle
resulting in an inability to abduct the
arytenoid cartilage and vocal fold, which
causes an obstruction in the airway
during inspiration. Endoscopic examina-
tion reveals asymmetry of the glottis. On
exercise, inspiratory stridor develops as
the airflow vibrates a slack and adducted
vocal fold. The abnormality is due to
idiopathic distal degeneration of axons in
the left recurrent laryngeal nerve (see
more details in Chapter 10).

Traumatic

Injection injuries to peripheral nerves

may result from needle puncture, the
drug deposited, pressure from an abscess
or hematoma, or fibrous tissue around the
nerve. 1 The sciatic nerve has been most
commonly affected in cattle because
historically most intramuscular injections
were given deep in the hamstring muscles.
Young calves were particularly susceptible
because of the small muscle masses.
Current recommendations in cattle are
that intramuscular injections should be
administered cranial to the shoulder.

Femoral nerve paralysis in calves
occurs in large calves born to heifers with
dystocia. The injury occurs when calves in
anterior presentation fail to enter the
birth canal because their stifle joints
become engaged at the brim of the pelvis.
Traction used to deliver these calves
causes hyperextension of the femur and
stretching of the quadriceps muscle and
its neural and vascular supplies. In most
cases the right femoral nerve is affected.
Such calves are unable to bear weight on
the affected leg within days after birth, the
quadriceps muscle is atrophied and the
patella can be luxated easily. The patellar
reflex is absent or markedly reduced in
the affected limb because this reflex
requires an intact femoral nerve and
functional quadriceps muscle. Varying
degrees of rear limb paresis result,
accompanied by varying degrees of hind
limb gait abnormality. 3,4 Skin analgesia
maybe present over the proximal lateral
to cranial to medial aspect of the tibia. 3 At
rest, the affected leg is slightly flexed and
the hip on the affected side is held slightly

lower. 4 During walking, the animal has
difficulty in advancing the limb normally
because the limb collapses when weight-
bearing. In severe cases of muscle
atrophy, the patella is easily luxated both
medially and laterally. Injury to the
femoral nerve is relatively easy to
clinically identify, and there is usually no
need to perform electromyographic
studies of atrophied quadriceps muscle in
order to document denervation.

Calving paralysis is common in heifers
that have experienced a difficult calving.
Affected animals are unable to stand
without assistance; if they do stand, the
hind limbs are weak and there is marked
abduction and inability to adduct. It has
always been erroneously thought that
traumatic injury of the obturator nerves
during passage of the calf in the pelvic
cavity was the cause of the paresis; however,
detailed pathological and experimental
studies have demonstrated that most
calving paresis/paralysis is due to damage
to the sciatic nerved -8 Experimental tran-
section of the obturator nerves does not
result in paresis. The tenm obturator nerve
paralysis should only be used for post-
parturient cattle with an inability to adduct
one or both hindlimbs, and calving paralysis
in the preferred descriptive tenn for hind
limb paresis/paralysis occurring in the
immediate postparturient period.

Damage to the sciatic nerve results
in rear limb weakness and knuckling of
the fetlocks; the latter clinical sign is
an important means for differentiating
sciatic nerve damage from obturator
nerve damage. The patellar reflex in
ruminants with sciatic nerve damage is
normal or increased, because the reflex
contraction of the quadriceps muscle
group by the femoral nerve is unopposed
by the muscles of the hindlimb innervated
by the sciatic nerve.

The peroneal nerve is most frequently
damaged by local trauma to the lateral
stifle, where the peroneal nerve runs in
a superficial location lateral to the head
of the fibular bone. Damage to the
peroneal nerve leads to knuckling over
of the fetlock joint due to damage to
the extensor muscles of the distal limb,
resulting in the dorsal aspect of the hoof
resting on the ground when the animal is
standing. Full weight can be borne on the
affected limb when the digit is placed in
its normal position, but immediately
upon walking the digit is dragged. There
is a loss of skin sensation on the anterior
aspect of the metatarsus and digit.

Damage to the tibial nerve causes mild
hyperflexion of the hock and a forward
knuckling of the fetlock joint. Tibial nerve
damage is very rare, and most cases
described as tibial nerve damage are
actually sciatic nerve damage.

Congenital defects of the central nervous system

619

Metabolic and nutritional
Pantothenic acid deficiency may occur
in pigs fed diets based solely on corn
(maize). Affected animals develop a
goose -stepping gait due to degenerative
changes in the primary sensory neurons
of the peripheral nerves.

Toxic

Heavy metal poisoning including lead
and mercury poisoning in horses has

been associated with clinical signs of
degeneration of peripheral cranial nerves
but these are not well documented.

Tumors

A multicentric schwannoma causing
chronic ruminal tympany and forelimb
paresis has been recorded in an aged
cow. 9 Neoplastic masses were present
throughout the body and both right and
left brachial plexi were involved. The
peripheral nerves of each brachial plexus
were enlarged. Large tumor masses
were present on the serosal surfaces of
the esophagus, pericardial sac and
epicardium, within the myocardium,
endocardium and the ventral branches of
the first four thoracic spinal nerves. A
large mass was present in the anterior
mediastinum near the thoracic inlet.

Autonomic nervous system
Grass sickness in the horse occurs
exclusively in the UK and is characterized
by a peracute to chronic alimentary tract
disease of horses on pasture (hence the
name). Gastrointestinal stasis is partial or
complete. Peracute cases are in shock and
in a state of collapse with gastric refluxing.
Acute, subacute and chronic cases also
occur. Degenerative changes occur in the
autonomic ganglia, especially the celiac-
mesenteric, stellate, thoracic sympathetic
chain, ciliary, cranial and caudal cervical,
the craniospinal sensory ganglia and
selected nuclei in the central nervous
system. 9 The etiology is unknown.

REVIEW LITERATURE

Summers BA, Cummings BA, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.
Constable PD. Clinical examination of the ruminant
nervous system. Vet Clin North Am Food Anim
Pract2004; 20:185-214.

Divers TJ. Acquired spinal cord and peripheral nerve
disease. Vet Clin North Am Food Anim Pract 2004;
20:231-242.

REFERENCES

1. Summers BA, Cummings BA, de Lahunta A.
Veterinary neuropathology. St Louis, MO: Mosby,
1995.

2. Vatistas N, Mayhew J. J Pract 1995; 17:26.

3. Tryphonas L et al. J Am Vet Med Assoc 1974;
164:801.

4. Paulsen DB et al. Bovine Pract 1981; 2:14-26.

5. Vaughan LC.VetRec 1964; 76:1293.

6. Cox VS et al. Am J Vet Res 1975; 36:427.

7. Cox VS, Breazile JE. Vet Rcc 1973; 93:109.

8. CoxVS, Onapito JS. Bovine Pract 1986; 21:195.

9. Reek SF et al. Vet Rec 1997; 140:504.

Congenital defects of the
central nervous system

The pathogenesis of congenital defects,
including those of the central nervous
system, has been dealt with in general
terms in Chapter 3. Inheritance, nutrition,
virus infection in early pregnancy and
some toxins can all play a part in
the genesis of these defects and the
purpose of this section is to guide the
diagnostician through the recognition
of the defect to the possible causes. How-
ever, many such cases occur sporadically
and a specific cause cannot be identified.

Although most developmental defects
are present at birth there are a few
that appear later in life, especially the abio-
trophic diseases, in which an essential
metabolic process (essential, that is. for
cellular structure and function) is missing
and the tissue undergoes degeneration.

The diseases to be identified are listed
under the headings of the principal
clinical signs and syndromes that they
produce. Many affected neonates are
weak and die either during birth or soon
afterwards so that they tend to be diag-
noses for pathologists rather than clini-
cians. There may be an unintentional bias
toward more clinically conspicuous
diseases in the following material. The
reader is referred to the review literature
for details of specific congenital defects.

Defects with obvious structural
errors

Hydrocephalus, sporadic or inherited,
with obvious enlargement of the
cranium

° Meningocele with protrusion of a
fluid-filled sac through the open
fontanelle in the cranial vault. The
defect is inherited in some pigs
Hydrocephalus with spina bifida
combination - the Arnold-Chiari
syndrome - in cattle
9 Hydrocephalus with congenital
achondroplasia (bulldog calf
syndrome)

« Cranium bifidum (may include
meningocele) of pigs
=■ Ventral meningomyelocele in a filly
foal 1

° Microphthalmia - in microcephaly the
cranium is usually of normal size
Some cases of failure of closure of
neural tube, e.g. spina bifida in
lambs 2 There is a defect in the skin
and dorsal arch of the vertebra in the
lumbosacral area in some cases
c Exophthalmos with or without
strabismus, an inherited form in
Jersey and Shorthorn cattle does not
appear until the animal is more than
6 months of age

o Neurofibromas occurring as

enlargements on peripheral nerves
and seen as subcutaneous swellings.
They are passed from cow to calf
i. Persistent cloaca and caudal spinal
agenesis in calves 3

« Hydranencephaly, porencephaly and
other structural defects due to
intrauterine infection with Akabane,
Bluetongue, Cache Valley and
Wesselsbron viruses.

Diseases characterized by congenital
paresis/paralysis

? Enzootic ataxia due to nutritional
deficiency of copper. It may also
develop later, within the first month
of postnatal life

° Inherited congenital posterior
paralysis of calves, and of pigs
9 Congenital spinal stenosis of calves 4
° Spina bifida, sometimes accompanied
by flexion and contracture and
atrophy of hindlegs; most are
stillborn. In rare cases the affected calf
is ambulatory 3

9 Spinal dysraphism in Charolais and
Angus calves, syringomyelia and
hydromyelia in calves
" Tetraparesis, tetraplegia, progressive
ataxia with head deviation in foals
with congenital occipitoatlanto-axial
malformations. A familial tendency to
the defects occurs in Arab and non-
Arabian horses. Additional signs
include stiffness of the neck, palpable
abnormalities at the site and a
clicking sound on passive movement.
Foals may be affected at birth or
develop signs later. The defect is
identifiable radiographically
« A congenital dysplasia of the atlanto-
occipital joint with excessive mobility
is recorded in Angora goats and
causes a compressive myelopathy.
Devon calves may be affected by the
same deformity 1 ’ and similar ones
have been recorded in calves that
were recumbent at birth 3 and others
in which ataxia developed
subsequently'

More widespread malacic changes
have been recorded in the spinal cord
of calves but without the specific
etiology being determined.

Neurogenic arthrogryposis and
muscle atrophy

9 Akabane virus infection of calves,
kids, possibly lambs, in utero
° There are many other causes of

arthrogryposis listed under congenital
abnormalities of joints but they are
not known to be neurogenic.

Spasms of muscle masses

Inherited spastic paresis (Elso-heel) of
calves

RART 1 GENERAL MEDICINE ■ Chapter 12: Diseases of the nervous system

° Inherited periodic spasticity (stall-
cramp).

Diseases characterized by cerebellar
ataxia

0 Inherited cerebellar hypoplasia of
calves, Arabian foals, lambs
° Cerebellar hypoplasia and

hypomyelinogenesis in calves from
cows infected with BVD virus and
possibly Akabane virus during
pregnancy

0 Cerebellar hypoplasia in piglets after
hog cholera vaccination of dams
% Inherited cerebellar ataxia in pigs and
foals

° Familial convulsions and ataxia of
Angus cattle

° Mannosidosis of cattle
° Intracranial hemorrhage in newborn
foals, discussed in more detail under
Neonatal maladjustment syndrome
° Spinal cord hypoplasia in Akabane
virus infection in ruminants.

Diseases characterized by tremor

13 Congenital paresis and tremor of piglets
0 Inherited congenital spasms of cattle
° Inherited neonatal spasticity (Jersey
and Hereford cattle) develops at
2-5 days old

° Border disease (hairy shakers) in
lambs due to BVD virus
0 Inherited neuraxial edema (now
inherited congenital myoclonus) of
polled Hereford cattle and congenital
brain edema of Herefords
° Myoclonia congenita as a result of
infection with hog cholera or
Aujeszky's disease viruses
0 Tremor with rigidity due to

hydranencephaly and porencephaly in
calves infected in utero with BVD
virus

0 Shaker calves' in Herefords.

Disease characterized by convulsions

0 Brain injury during birth in calves and
lambs

J Brain compression due to

hypovitaminosis A in calves and pigs

° Neonatal maladjustment syndrome
(barkers and wanderers) in
Thoroughbred foals

° Congenital toxoplasmosis in calves,
bluetongue virus infection in lambs

0 Tetanic convulsion in inherited
neuraxial edema (now inherited
congenital myoclonus) of Hereford
calves, but only when lifted to
standing position

° Inherited idiopathic epilepsy of Brown
Swiss cattle

0 Familial convulsions and ataxia of
Angus cattle

0 Inherited narcolepsy/catalepsy in
Shetland ponies and Suffolk horses
(not really a convulsion)

° Doddler calves.

Diseases characterized by imbecility

3 Microencephaly in calves, probably
inherited, with no abnormality of the
cranium, but the cerebral
hemispheres, cerebellum and
brainstem are reduced in size and the
corpus callosum and fornix are absent

° Microcephaly recorded in sheep;
many are dead at birth, viable ones
are unable to stand, blind,
incoordinate and have a constant
tremor

° Anencephaly in calves with absence
of cerebral hemispheres, rostral
midbrain, occurs sporadically in calves

° Hydranencephaly associated with
Akabane virus infection of calf, kid,
and possibly lamb in utero

° Congenital porencephaly in lambs
after intrauterine infection with
bluetongue virus.

Ocular abnormalities

° Spontaneous microphthalmia and
anophthalmia in calves, usually of
unknown cause

° Congenital lenticular cataracts in
cattle and lambs

° Blindness developing after birth in
gangliosidosis of cattle and ceroid
lipofuscinosis of sheep

i

° Constriction of optic nerve by vitamin
A deficiency causing blindness in
calves and pigs

° Constriction of optic nerve and

blindness with BVD virus infection in
calves in utero

° Inherited exophthalmos with
strabismus of cattle
° Familial undulatory nystagmus
(pendular nystagmus).

Defects conditioned by inheritance
but not present at birth

0 Cerebellar atrophy (abiotrophy) in
calves and foals; a probably inherited
cerebellar abiotrophy in sheep aged
3.5-6 years

c Inherited idiopathic epilepsy of
Jerseys and Shorthorns
° Mannosidosis of cattle
° Gangliosidosis of cattle
c Bovine generalized glycogenosis
° Multifocal symmetrical necrotizing
encephalomyelopathy (Leigh's
disease) in Angus, Simmental, and
Limousin cattle 7

0 Globoid cell leukodystrophy of sheep
° Ceroid lipofuscinosis of sheep
• Inherited myotonia of goats
° Progressive ataxia of Charolais cattle
° Inherited citrullinemia of calves
° Inherited maple syrup urine disease.

REVIEW LITERATURE

Done JT. Developmental disorders of the nervous
system in animals. AdvVet Sci 1976; 20:69.

Cho DY, Leipold HW. Congenital defects of the
bovine central nervous system. Vet Bull 1977;
47:489.

Summers BA, Cummings JF, de Lahunta A. Veterinary
neuropathology. St Louis, MO: Mosby, 1995.
Washburn KE, Streeter RN. Congenital defects of the
ruminant nervous system. Vbt Clin North Am
Food Anim Pract 2004; 20:413^J34.

REFERENCES

1. Harmelin A et al. J Comp Pathol 1993; 109:93.

2. Davies IH. Vet Rec 1993; 132:90.

3. Dean CE et al.Vet Pathol 1996; 33:711.

4. Doigc C. E et al.Vet Pathol 1990; 27:16.

5. Boyd JS, McNeil PE. Vet Rec 1987; 120:34.

6. McCoy DJ et al. Cornell Vet 1986; 76:277.

7. Philbey AW, Martel KS. AustVet J 2003; 81:226.

PART 1 GENERAL MEDICINE

Diseases of the musculoskeletal system

PRINCIPAL MANIFESTATIONS OF
MUSCULOSKELETAL DISEASE 621

Lameness 621

Abnormal posture and movement 621
Deformity 621
Spontaneous fractures 625
Painful aspects of lameness 625
Economics of lameness in food-
producing animals 625
Examination of the musculoskeletal
system 625

DISEASES OF MUSCLES 626

Myasthenia (skeletal muscle asthenia)
626

Diseases of the organs of support,
including muscles, bones, and joints, have
much in common in that the major
clinical manifestations of diseases that
affect them are lameness, failure of sup-
port, insufficiency of movement and
deformity. Insufficiency of movement
affects all voluntary muscles, including
those responsible for respiratory move-
ment and mastication, but lameness and
failure of support are manifestations of
involvement of the limbs.

Various classifications of the diseases
of the musculoskeletal system, based on
clinical, pathological and etiological differ-
ences, are in use, but the simplest is that
which divides the disease into degener-
ative and inflammatory types.

0 The degenerative diseases of muscles,
bones and joints are distinguished as:
myopathy, osteodystrophy and
arthropathy, respectively
The inflammatory diseases are
myositis, osteomyelitis and arthritis.

Principal manifestations of
musculoskeletal disease

LAMENESS

Lameness is an abnormal gait or loco-
motion characterized by limping
(claudication) or not bearing full weight
on a leg, usually associated with pain
in the musculoskeletal system. Lameness
must be distinguished from ataxia, which
is an abnormal gait characterized by lack
of coordination of muscular action, usually
because of a lesion of the central or
peripheral nervous system.

Weakness is the inability to maintain
a normal posture and gait, usually

Myopathy 626
Myositis 631

DISEASES OF BONES 632

Osteodystrophy 632
Hypertrophic pulmonary
osteoarthropathy (Marie's disease,
achropachia ossea) 635
Osteomyelitis 635

DISEASES OF JOINTS 637

Arthropathy (osteoarthropathy,
degenerative joint disease) 637
Arthritis and synovitis 642

because of a lesion of muscle or generalized
weakness due to an abnormal systemic
state such as shock, hypocalcemia, or
starvation.

Because of the difficulty inherent in
the differentiation of diseases causing
lameness, and other abnormalities of gait
and posture, a summary is presented in
Table 13.1. It does not include lameness in
racing horses, which is described in text-
books on lameness in horses, or diseases
of the nervous system that interfere with
normal movement and posture. These are
discussed in Chapter 12.

ABNORMAL POSTURE AND
MOVEMENT

As a group, diseases of the musculo-
skeletal system are characterized by
reduced activity in standing up and
moving, and the adoption of unusual
postures. Abnormal movements include
limpness, sagging or stiffness and lack of
flexion. Abnormal postures include per-
sistent recumbency, including lateral
recumbency. There may be signs of pain
on standing, moving or palpation. There is
an absence of signs specifically referable
to the nervous system. For example, there
are no signs of brain damage and the
spinal cord reflexes are present but may
be only partly elicitable (the sensory
pathway is intact but the motor response
maybe diminished). Differentiation from
diseases of the nervous system and from
each other may be aided by specific
biochemical, radiological or hematological
findings that indicate the system involved.
Specific epidemiological findings may
indicate the location of the lesion (which
may be secondary) in muscle, bones, or
joints, as set out in Table 13.1.

CONGENITAL DEFECTS OF MUSCLES,
BONES, AND JOINTS 648

Fixation of joints 648
Hypermobility of joints 648
Weakness of skeletal muscles 648
Congenital hyperplasia of
myofiber 648

Obvious absence or deformity of
specific parts of the musculoskeletal
system 648

DEFORMITY

Atypical disposition, shape or size of a
part of the musculoskeletal system con-
stitutes a deformity. This may occur in a
number of ways, and be caused by the
following.

Muscle and tendon defects

° Congenital hypermobility of joints,
inherited and sporadic
° Congenital flexed or stretched

tendons of limbs causing contracture
of joints or hyperextension
° Inherited congenital splayleg of pigs
° Muscle hypertrophy (doppelender,
culard) of cattle

° Acquired asymmetric hindquarters of
pigs.

Joint defects

° Inherited congenital ankylosis of
cattle causing fixation of flexion
° Joint enlargement of rickets and
chronic arthritis.

Defects of the skeleton

° Dwarfism - inherited miniature

calves, achondroplastic dwarves; short
legs of inherited congenital
osteopetrosis; nutritional deficiency of
manganese; acorn calves
° Giant stature - inherited prolonged
gestation, not really giantism, only
large at birth

° Asymmetry - high withers, low pelvis
of hyena disease of cattle
0 Limbs - complete or partial absence,
inherited or sporadic amputates;
curvature of limbs in rickets; bowie or
bentleg of sheep poisoned by
Trachymene sp.

° Head - inherited and sporadic
cyclopean deformity; inherited
probatocephaly (sheep's head) of

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

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Principal manifestations of musculoskeletal disease

calves; inherited moles, bulldog
calves; acquired atrophic rhinitis of
pigs.

SPONTANEOUS FRACTURES

Spontaneous fractures occur uncommonly
in farm animals and pre-existing diseases
are usually present, which include the
following:

o Nutritional excess of phosphorus
causing osteodystrophia in horses
o Nutritional deficiency of calcium
causing osteodystrophia in pigs
o Nutritional deficiency of phosphorus
or vitamin D in ruminants causing
rickets and/or osteomalacia;
hypervitaminosis A may contribute to
this

o Nutritional deficiency of copper
■ Chronic fluorine intoxication.

PAINFUL ASPECTS OF LAMENESS

Musculoskeletal pain can be caused by
lacerations and hematomas of muscle,
myositis and space-occupying lesions of
muscle. Osteomyelitis, fractures, arthritis,
joint dislocations, sprains of ligaments
and tendons are also obvious causes of
severe pain. Among the most painful of
injuries are swollen, inflammatory lesions
of the limbs caused by deep penetrating
injury or in cattle by extension from
footrot. Amputation of a claw, laminitis
and septic arthritis are in the same
category. Ischemia of muscle and gener-
alized muscle tetany, as occurs in electro-
immobilization, also appear to cause pain.

Research on the pathophysiology and
pharmacology of pain associated with
lameness in animals indicates that the
thresholds to painful stimuli change in
response to pain and this change is seen
as an indication of an alteration in nerve
function or in nociceptive processing at
higher levels. In flocks of sheep with
severe lameness due to foot rot, affected
sheep had a lower threshold to a mechan-
ical nociceptive stimulus than matched
controls and their thresholds remained
low when tested 3 months later, after the
apparent resolution of the foot lesions. 1
Thus hyperalgesia persisted in severely
lame sheep for at least 3 months. It is
suggested that N-methyl-D-aspartate
receptors are involved in the development
of this long-term hypersensitivity. Similar
findings have been reported in dairy
heifers affected with claw lesions during
the peripartum period. 2

Relief of musculoskeletal pain

Several aspects about relieving pain in
agricultural animals are important. Cost
has always been a deterrent to the use of
local anesthetics and analgesics but, with
changing attitudes, the need to control

pain is more apparent. Treatment of the
causative lesion is a major priority but the
lesion may be painful for varying lengths
of time. Relief and the control of pain
should be a major consideration. Details
on the use of analgesics are presented in
Chapter 2.

ECONOMICS OF LAMENESS IN
FOOD-PRODUCING ANIMALS

Diseases of the musculoskeletal system
and feet that cause lameness cause major
economic losses. A survey of the inci-
dence and prevalence of lameness in
cattle on 37 dairy farms in the UK in
1989-91 found a mean annual incidence
of 54.6 new cases per 100 cows (farm
range 11-170%) and a mean annual
prevalence of 21% (farm range 2-54%). 3
Loss of production occurs because animals
that are in pain have difficulty moving
around and do not eat and milk normally.
Reproductive performance may be reduced
because of failure to come into heat
normally. The culling rate may be higher
than is desirable because so many of the
; lesions of the feet and legs are incurable.

1 The direct monetary costs for the
j treatment of lame animals are not high, but
i the actual treatment of either individual
: animals or groups of animals is time-
' consuming and laborious. The condem-
nation of animals to slaughter because of
; lesions of the musculoskeletal system also
1 contributes to the total economic loss.
When lameness is a herd problem not
only are the economic losses increased
but clinical management becomes very
difficult.

The epidemiological factors which
contribute to lameness include:

; Injuries due to floor surfaces
Ftersistently wet, unhygienic ground
conditions

Overcrowding and trampling during
transportation and handling
Nutritional inadequacies
Undesirable skeletal conformation
Failure to provide regular foot-
trimming.

Certain breeds may be more susceptible
to diseases of the feet and legs than others.
Osteoarthritis occurs most commonly in
old animals. Diseases of the legs of daily
cattle occur most commonly at the time of
parturition and during the first 50 days of
lactation. Diseases of the feet of dairy
cattle occur most commonly in days
50-150 of the lactation period. Often the
etiology is complex and a definitive
etiological diagnosis cannot be made. This
makes clinical management difficult and
often unrewarding.

REFERENCES

( 1 . Ley SJ et al.Vet Rec 1995; 137:85.

2. Whay HR et al. Vet J 1997; 154:155.

3. Clarkson MJ et al.Vet Rec 1996; 138:563.

EXAMINATION OF THE
MUSCULOSKE LETAL SYSTEM

The clinical examination of the musculo-
skeletal system and the feet of farm
animals would include the following
special examinations.

Analysis of gait and conformation

Inspection of the gait of the animal is
necessary to localize the site of lameness.
Evaluation of its conformation may pro-
vide clues about factors that may contribute
to lameness. Details on the examination
of farm animals for lameness are available
in textbooks on lameness in horses and
cattle.

Close physical examination

A close detailed physical examination of
the affected area is necessary to localize
the lesion. This includes passive move-
ments of limbs to identify fractures, dis-
locations and pain on movement. Muscles
can be palpated for evidence of enlarge-
ment, pain, or atrophy.

Radiography

j Radiography is useful for the diagnosis of
! diseases of bones, joints and soft tissue
swelling of limbs, which cannot be easily
defined by physical examination. Detailed
radiographic information about the joint
! capsule, joint cavity or articular cartilage
I can be obtained using negative (air),

1 positive or double contrast arthrography.
Ultrasonographic imaging can be used to
differentiate the pathological changes in
the soft tissue structures of digital flexor
tendon sheaths of cattle. 1

Ultrasonography

Ultrasonography is used extensively in
dogs and horses for the visualization of
soft tissue structures of the joint. Most
veterinary practices have an ultrasound
machine that is used for small-animal
imaging or transrectal pregnancy diagnosis
in cattle and horses. 2 Ultrasonography is
cheaper, faster and provides important
information compared to radiography; it
is also less invasive and cheaper than joint
fluid aspiration and analysis.

The ultrasonographic anatomy of the
elbow, carpal, fetlock, and stifle joints of
clinically normal sheep using a 7.5 MHz
linear transducer with a stand-off pad has
been described. 2 The anatomical structures
that could be consistently identified in
normal ovine joints included bone, articular
cartilage, ligaments and tendons. In sheep
with chronic arthritis/synovitis, the gross
thickening of the joint capsule is visible as a
hyperechoic band up to 20 mm thick.

The ultrasonographic examination
of the stifle region in cattle has been

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

described. 3 The homogeneously echogenic
patellar and collateral ligaments, the
combined tendon of the long digital
extensor and peroneus tertius muscles,
the popliteal tendon, the anechoic articular
cartilage of femoral trochlea, the echogenic
menisci and the hyperechoic bone
surfaces were imaged successfully. The
boundaries of the joint pouches became
partially identifiable only when small
amounts of anechoic fluid were present in
the medial and lateral femorotibial joint
pouches. The main indication for ultra-
sonography of the bovine stifle is evalu-
ation of acute septic and traumatic
disorders of the region, when specific
radiographic signs are often nonspecific
or absent. The cruciate ligaments could
not be imaged in live cattle. The cruciate
ligaments are identifiable in the horse, in
which flexion of the hindlimb is a routine
procedure necessary for identification of
these structures.

The ultrasonographic examination of
the carpal region in cattle has been
described. 4 The main indication is the
evaluation of septic and traumatic dis-
orders of the carpal joints and tendon
sheaths. Each tendon and tendon sheath
in carpal region must be scanned
separately. The use of a stand-off pad is
recommended as it permits adaptation of
the rigid transducer to the contours of the
carpus. The carpal joint pouches and
tendon sheath lumina are not clearly
defined in healthy cattle. Thus the ability
to image these structures indicates the
presence of synovial effusion.

Ultrasonography is a valuable diag-
nostic aid for septic arthritis. Joint effusion,
which is one of the earliest signs of septic
arthritis, the accurate location of soft
tissue swelling, the extent and character
of joint effusion and involvement of
concurrent periarticular synovial cavities
or other soft tissue structures can be
imaged by ultrasonography. 5 The ultra-
sonogram can image the presence of
small, hyperechogenic fragments within
the joint, appearing very heterogeneous.
Normal synovial fluid is anechoic and
appears black on the sonogram. A cloudy
appearance is usually associated with the
presence of pus. 6

Muscle biopsy

A muscle biopsy may be useful for
microscopic and histochemical evaluations.

Arthrocentesis

Joint fluid is collected by needle puncture
of the joint cavity (arthrocentesis) and
examined for the presence of cells, bio-
chemical changes in the joint fluid and
the presence of infectious agents. The
techniques and application of arthro-
centesis for some of the joints commonly
sampled in the horse have been reviewed.

Arthroscopy

Special endoscopes are available for
inspection of the joint cavity and articular
surfaces (arthroscopy). Diagnostic and
surgical arthroscopy is now commonplace
in specialized equine practice. Surgical
arthroscopy is rapidly replacing conven-
tional arthrotomy for the correction of
several common surgical conditions
of the musculoskeletal system of the
horse. Accurate quantification of equine
carpal lesions is possible when the
procedure is performed by an experienced
arthroscopist. 7 Convalescent time follow-
ing surgery is decreased and the cosmetic
appearance improved compared to
arthrotomy. The arthroscopic anatomy of
the intercarpal and radiocarpal joints of
the horse have been described. A synovial
membrane biopsy can be examined histo-
logically and for infectious agents and
may yield useful diagnostic information.

Serum biochemistry and enzymology

When disease of bone or muscle is
suspected, the serum levels of calcium,
phosphorus, alkaline phosphatase and
the muscle enzymes creatinine phospho-
kinase (CPK) and aspartate amino-
transferase (AST), also known as serum
glutamic oxaloacetic transaminase (SGOl),
may be useful. The muscle enzymes are
sensitive indicators of muscle cell damage;
the serum levels of calcium, phosphorus
and alkaline phosphatase are much less
sensitive indicators of osteodystrophy.

Nutritional history

Because the most important osteo-
dystrophies and myopathies are nutritional
in origin a complete nutritional history
must be obtained. This should include an
analysis of the feed and determination of
the total amount of intake of each nutrient,
including the ratio of one nutrient to
another in the diet.

Environment and housing

When outbreaks of lameness occur in
housed cattle and pigs the quality of the
floor must be examined to evaluate the
possibility of floor injuries.

REFERENCES

j 1. Kofler J.Vfet Rec 1996; 139:36.
j 2. Macrae AI, Scott PR. Vet J 1999; 158:135.

3. Kofler J. Vfet J 1999; 158:21.

4. Kofler J.VetJ 2000; 159:85.

5. Kofler J. BrVet J 1996; 152:683.

6. Munroe GA,Cauvin ER. BrVet J 1994; 150:439.

7. Hurtig MB et al. Vet Surg 1 985; 14:93.

Diseases of muscles

MYASTHENIA (SKELETAL MUSCLE
ASTHENIA)

The differential diagnosis of paresis,
paralysis and incoordination should

include a consideration of skeletal muscle
weakness unrelated to primary neurogenic
hypotonia or to permanent muscle injury,
including myopathy and myositis. Most of
the syndromes that fall into this group of
myasthenia have been described in detail
elsewhere in this book and are referred
to briefly here only to complete the list of
abnormalities of skeletal muscle that
affect gait and posture. Unlike myopathy
and myositis, they are reversible states.

The common causes of myasthenia in
farm animals are:

0 Ischemia in iliac thrombosis in the
horse and after recumbency in cows
with parturient paresis. The end stage
is myonecrosis and not reversible
° Metabolic effect on muscle fibers -
causes include hypokalemia,
hypocalcemia and possibly
hypophosphatemia (in parturient
paresis of dairy cows), hypomagnesemia
(in lactation tetany), hypoglycemia of
newborn pigs and lactic acidemia after
engorgement on grain
13 Toxins - general toxemia is a cause.
Also, many plant toxins exert an effect
on skeletal muscle activity. Although
in most cases the mode of the action
of the toxin is unknown, the toxins
have been listed as neurotoxins.

MYOPATHY

The term myopathy describes the non-
inflammatory degeneration of skeletal
muscle that is characterized clinically by
muscle weakness and pathologically by
hyaline degeneration of the muscle fibers.
The serum levels of some muscle enzymes
are elevated and myoglobinuria is a com-
mon accompaniment.

ETIOLOGY AND EPIDEMIOLOGY

The most important myopathies in fama
animals are due to nutritional deficiencies
of vitamin E and selenium and the effects
of unaccustomed exercise. In humans, in
contrast, the muscular dystrophies occur
as inherited defects of muscle or degener-
ative lesions caused by interruption of their
nerve supply. The skeletal myopathies can
be classified into primary and secondary
myopathies.

i A retrospective analysis of the case
j records in a veterinary teaching hospital
over a 9-year period revealed that the
most common myopathy in horses was
exercise-associated muscle disorder (69%).
The remainder were postexhaustion
syndrome (9%), infectious myopathies
(10.5%), immunological myopathy (6.0%),
nutritional myopathy (4.5%) and hyper-
kalemic periodic paralysis (1.5%).'

The major causes of myopathy in farm
animals and their epidemiological deter-
minants are as follows.

Diseases of muscles

Enzootic nutritional muscular
dystrophy

A nutritional deficiency of vitamin E and /
or selenium is a common cause in young
calves, lambs, foals, and piglets. Factors
enhancing or precipitating onset include:
rapid growth, highly unsaturated fatty
acids in diet and unaccustomed exercise.
The disease also occurs in adult horses.

Exertional or postexercise
rhabdomyolysis

This is not known to be conditioned
by vitamin E (selenium deficiency) and
occurs as equine paralytic myoglobinuria
(tying-up syndrome, azoturia) in horses
after unaccustomed exercise or insufficient
training. 1 It also occurs in sheep chased
by dogs, in cattle after running wildly for
several minutes and as capture myopathy
during capture of wildlife. An acute
myopathy of undetermined etiology
occurred in horses at grass in Scotland. 2
The horses were not in training, creatine
kinase levels were elevated and the urine
was dark brown; most of them died
and the muscles affected were those of
posture and respiration rather than
movement. 2

Equine polysaccharide storage myo-
pathy is a metabolic disease being recog-
nized with increasing frequency in many
breeds of horse. 3 It occurs in Quarter-
Horse-related breeds and more recently
has been recognized in draught horse
breeds. It is thought to be due to an
inherited metabolic defect affecting carbo-
hydrate metabolism (see Ch. 28).

Metabolic

Hyperkalemic periodic paralysis occurs in
certain pedigree lines of North American
show Quarter Horses.

Degenerative myopathy

This occurs in newborn calves, sheep and
goats affected by Akabane virus infected
in utero.

Inherited myopathies
The porcine stress syndrome, which is
discussed under that heading, now
includes herztod pale, soft, exudative pork
encountered at slaughter and malignant
hyperthermia following halothane anes-
thesia. Certain blood types in pigs have
been used as predictors of stress suscepti-
bility and malignant hyperthermia in
Pietrain pigs is genetically predetermined.
Most of these myopathies of pigs thus
have an inherited basis and the stress of
transportation, overcrowding and handling
at slaughter precipitates the lesion and
rapid death.

Congenital myopathy of Braunvieh-
Brown Swiss calves is thought to be
inherited. 4 Affected calves become pro-
gressively weak and recumbent within
2 weeks of birth. 4

Doubling-muscling in cattle and
splaylegs of newborn pigs are also
considered to be inherited. A dystrophy-
like myopathy in a foal has been
described and is similar to human
muscular dystrophy. 5 Dystrophy of the
diaphragmatic muscles in adult Meuse-
Rhine-Yessel cattle is thought to be
inherited. Xanthosis occurs in the
skeletal and cardiac muscles of cattle
and is characterized grossly by a green
iridescence.

Toxic agents

This is caused by poisonous plants,
including Cassia occidentalis, Karwinskia
humboldtiana, Ixioloena spp., Geigeria spp.
and lupins. A special case is enzootic
calcinosis of all tissues, especially muscle,
and the principal signs are muscular. It
is caused by poisoning by Solatium
malacoxylctn, Tricetum spp., and Cestrum spp.

Ischemia

Ischemic myonecrosis occurs in the thigh
muscles of cattle recumbent for about
48 hours or more and is discussed in
detail under the heading Downer cow
syndrome. Iliac thrombosis in horses is an
important cause of ischemic myopathy
and has been reported in calves.

Neurogenic

Neurogenic muscular atrophy occurs
sporadically due to traumatic injury and
subsequent degeneration or complete
severance of the nerve supply to skeletal
muscle. The myopathy in arthrogryposis
associated with the Akabane virus is
thought to be due to lesions of the lower
motor neurons supplying the affected
muscles. It has been suggested that cattle
with muscular hypertrophy may be more
susceptible to the effects of exercise and
the occurrence of acute muscular dystrophy.
Suprascapular nerve paralysis in the horse
(sweeney) is a traumatic neuropathy
resulting from compression of the nerve
against the cranial edge of the scapula.

Neoplasms

Neoplasms of striated muscle are
uncommon in animals. Rhabdomyo-
sarcomas are reported in the horse,
affecting the diaphragm and causing loss
of body weight, anorexia and respiratory
distress.

PATHOGENESIS
Primary myopathy

The characteristic change in most cases of
primary myopathy varies from hyaline
degeneration to coagulative necrosis,
affecting particularly the heavy thigh
muscles and the muscles of the diaphragm.
Myocardial lesions are also commonly
associated with the degeneration of
skeletal muscle and when severe will
cause rapid death within a few hours or

days. The visible effects of the lesions are
varying degrees of muscle weakness,
muscle pain, recumbency, stiff gait,
inability to move the limbs and the
development of respiratory and circulatory
insufficiency.

In primary nutritional muscular dys-
trophy associated with a deficiency of
vitamin E and/or selenium there is lipo-
peroxidation of the cellular membranes of
muscle fibers resulting in degeneration
and necrosis. The lesion is present only in
muscle fibers and the histological and
biochemical changes which occur in the
muscle are remarkably similar irrespective
of the cause. Variations in the histological
lesion occur but indicate variation in the
severity and rapidity of onset of the
change rather than different causes.

Myoglobinuria

Because of the necrosis of muscle,
myoglobin is excreted in the urine and
myoglobinuric nephrosis is an import-
ant complication, particularly of acute
primary myopathy. The degree of myo-
globinuria depends on the severity of the
lesion, acute cases resulting in marked
myoglobinuria, and on the age and
species of animal affected. Adult horses
with myopathy may liberate large quan-
tities of myoglobin, resulting in dark
brown urine. Yearling cattle with myopathy
release moderate amounts and the urine
may or may not be colored; calves with
severe enzootic nutritional muscular
dystrophy may have grossly normal urine.
In all species the renal threshold of
myoglobin is so low that discoloration
of the serum does not occur.

Muscle enzymes

An important biochemical manifestation
of myopathy is the increased release of
muscle cell enzymes that occurs during
muscle cell destruction. CPK and serum
glutamic oxaloacetate transaminase are
both elevated in myopathy and CPK,
particularly, is a more specific and reliable
indication of acute muscle damage.
Increased amounts of creatinine are
also released into the urine following
myopathy.

Exertional rhabdomyolysis

In exertional rhabdomyolysis in horses
there is enhanced glycolysis with depletion
of muscle glycogen, the accumulation of
large amounts of lactate in muscle and
blood and the development of hyaline
degeneration of myofibers. Affected
muscle fibers are richer in glycogen in the
acute stage of 'tying-up' than in the late
stages, suggesting an increased glycogen
storage in the early phase of the disease
compared with normal healthy horses.
During enforced exercise there is local
muscle hypoxia and anaerobic oxidation

part 1 titNhKAL MtuiLiNt ■ <_naprer u: uiseases ot tne muscuiosiceieiai sysiem

resulting in the accumulation of lactate
and myofibrillar degeneration. The
pathogenesis of postanesthetic myositis
in horses is uncertain. 6 A significant
postischemic hyperemia occurs in horses
that develop postanesthetic myopathy. 6
Postanesthetic recumbency can occur in
the horse with polysaccharide storage
myopathy. 7

Types of muscle fiber affected

In most animals skeletal muscle is
composed of a mixture of fibers with differ-
ent contractile and metabolic charac-
teristics. Fibers with slow contraction
times have been called slow twitch or
type I fibers and those with fast con-
traction time are fast twitch or type II.
Histochemically, types I and II fibers can
be differentiated by staining for myo-
fibrillar ATPase. Type II fibers can be
subgrouped into type IIA and IIB on the
basis of acid preincubations. 8 Several
different characteristics of these muscle
fibers have been studied in the horse.
There are variations in the percentage
of each type of fiber present and in
composition of muscle fibers dependent
on genetic background, age, and stage of
training. 8 There are also variations in the
muscle fibers within one muscle 9 and
between different muscles. 10 The histo-
chemical characteristics of equine muscle
fibers have been examined: 11,12

0 Type I fibers are characterized by
strong aerobic capacity, compared
with type IIA

° Type IIA fibers are more glycolytic and
have strong aerobic and moderate to
strong anaerobic capacities
Type IIB fibers are characterized by a
relatively low aerobic and a relatively
high anaerobic capacity and are
glycolytic. 11

The histochemical staining characteristics
of normal equine skeletal muscle have
been examined and serve as a standard
for comparison with data obtained from
skeletal muscles with lesions. 12

Secondary myopathy due to
ischemia

In secondary myopathy due to ischemia
there may be multiple focal areas of
necrosis, which causes muscle weakness
and results in an increase of muscle
enzymes in the serum. The degree of
regeneration with myofibers depends on
the severity of the lesion. Some regener-
ation occurs but there is considerable
tissue replacement. In aortic and iliac
thrombosis in calves under 6 months of
age the thrombosis results in acute-to-
chronic segmental necrosis of some
skeletal muscles and coagulation necrosis
in others. 13

Neurogenic atrophy of muscle

In neurogenic atrophy there is flaccid
paralysis, a marked decrease in total
muscle mass and degeneration of myo-
fibers, with failure to regenerate unless
the nerve supply is at least partially
restored.

CLINICAL FINDINGS

The nutritional myopathies associated with
a deficiency of vitamin E and/or selenium
occur most commonly in young growing
animals and may occur in outbreak form,
particularly in calves and lambs. The details
are presented under the heading of vitamin
E and selenium deficiency.

Primary myopathy

In general terms, in acute primary
myopathy there is a sudden onset of weak-
ness and pseudoparalysis of the affected
muscles, causing paresis and recumbency
and, in many cases, accompanying
respiratory and circulatory insufficiency.
The affected animals will usually remain
bright and alert but may appear to be in
pain. The temperature is usually normal
but may be slightly elevated in severe cases
of primary myopathy. Cardiac irregularity
and tachycardia may be evident, and
myoglobinuria occurs in adult horses
and yearling cattle. The affected skeletal
muscles in acute cases may feel swollen,
hard and rubbery but in most cases it is
difficult to detect significant abnormality
by palpation. Acute cases of primary
myopathy may die within 24 hours after
the onset of signs.

Acute nutritional myopathy

While acute nutritional myopathy in
horses occurs most commonly in foals
from birth to 7 months of age, acute
dystrophic myodegeneration also occurs
in adult horses. There is muscle stiffness
and pain, myoglobinuria, edema of the
head and neck, recumbency and death in
a few days. A special occurrence of
myopathy has been recorded in suckling
Thoroughbred foals up to 5 months of
age. The disease occurs in the spring and
summer in foals running at pasture with
their dams and is unassociated with
excessive exercise. In peracute cases there
is a sudden onset of dejection, stiffness,
disinclination to move, prostration and
death 3-7 days later. Lethargy and stiff-
ness of gait are characteristic of less acute
cases. There is also a pronounced swelling
and firmness of the subcutaneous tissue at
the base of the mane and over the gluteal
muscles. There may be excessive salivation,
desquamation of lingual epithelium and
board-like firmness of the masseter
muscles. The foals are unable to suck
because of inability to bend their necks.
Spontaneous recovery occurs in mild
cases but most severely affected foals die.

Severe nutritional myopathy of the
masseter muscles in a 6-year-old Quarter
Horse stallion has been described. 14 The
masseter muscles were swollen and
painful, and there was exophthalmos and
severe chemosis with protrusion of the
third eyelids. The mouth could be opened
only slightly and masticatory efforts were
weak. Serum enzymology supported a
diagnosis of nutritional muscular dys-
trophy, and the concentrations of vitamin
E and selenium in the blood and feed
were lower than normal.

Tying-up

In tying-up in horses there is a very sudden
onset of muscle soreness 10-20 minutes
following exercise. There is profuse
sweating and the degree of soreness
varies from mild, in which the horse
moves with a short, shuffling gait, to
acute, in which there is a great disincli-
nation to move at all. In severe cases,
horses are unable to move their hindlegs,
and swelling and rigidity of the croup
muscles develops. Myoglobinuria is
common.

Postanesthetic myositis

In postanesthetic myositis affected horses
experience considerable difficulty during
recovery from anesthesia. Recovery is
prolonged and when initial attempts are
made to stand there is lumbar rigidity,
pain and reluctance to bear weight. 7
Some affected horses will be able to stand
in within several hours if supported in a
sling. 7 The limbs may be rigid and the
muscles firm on palpation. In severe cases
the temperature begins to rise - reminiscent
of malignant hyperthermia. Other clinical
findings include anxiety, tachycardia,
profuse sweating, myoglobinuria and
tachypnea. Death may occur in 6-12 hours.
Euthanasia is the only course for some
horses. In the milder form of the syndrome,
affected horses are able to stand, but are
stiff and in severe pain for a few days.

Exertional rhabdomyolysis

In horses, the clinical findings are variable
and range from poor performance to
recumbency and death. Signs may be
mild and resolve spontaneously within
24 hours or severe and progressive.

The usual presentation is a young
(2-5-year-old) female racehorse with
recurrent episodes of stiff gait after
exercise. The horse does not perform to
expectation and displays a short-
stepping gait that may be mistaken for
lower leg lameness. The horse may be
reluctant to move when placed in its stall,
be apprehensive and anorexic, and fre-
quently shift its weight. More severely
affected horses may be unable to continue
to exercise, have hard and painful

Diseases of muscles

muscles (usually gluteal muscles), sweat
excessively, be apprehensive, refuse to
walk and be tachycardic and tachypneic.
Affected horses may be hyperthermic.
Signs consistent with abdominal pain are
present in many severely affected horses.
Deep red urine (myoglobinuria) occurs
but is not a consistent finding. Severely
affected horses may be recumbent and
unable to rise.

Many different manifestations of
equine polysaccharide storage myopathy
occur 3 All manifestations are related to
dysfunction, which results in pain, weak-
ness, segmental fiber necrosis, stiffness,
spasm, atrophy or any combination of the
above. The muscles most severely affected
are the powerful rump, thigh and
back muscles, including gluteals, semi-
membranosus, semitendinosus and
longissimus.

In exertional rhabdomyolysis in sheep
chased by dogs, affected animals are
recumbent, cannot stand, appear exhausted
and myoglobinuria is common. Death
usually follows. A similar clinical picture
occurs in cattle that have run wildly for
several minutes.

Hyperkalemic periodic paralysis

Initially there is a brief period of myotonia
with prolapse of the third eyelid. In severe
cases, the horse becomes recumbent and
the myotonia is replaced by flaccidity.
Sweating occurs, and generalized muscle
fasciculations are apparent, with large
groups of muscle fibers contracting
simultaneously at random. The animal
remains bright and alert and responds to
noise and painful stimuli. In milder cases,
affected horses remain standing and
generalized muscle fasciculations are
prominent over the neck, shoulder and
flank. There is a tendency to stand base-
wide. When the horse is asked to move, the
limbs may buckle and the animal appears
weak. The horse is unable to lift its head,
usually will not eat and may yawn
repeatedly early in the course of an epi-
sode. The serum potassium levels are
elevated above normal during the episodes.

Secondary myopathy due to
ischemia

In secondary myopathy due to ischemia,
e.g. the downer cow syndrome, the
affected animal is unable to rise and the
affected hindlegs are commonly directed
behind the cow in the frogleg attitude.
The appetite and mental attitude are
usually normal. No abnormality of the
muscles can be palpated. With supportive
therapy, good bedding and the prevention
of further ischemia by frequent rolling of
the animal, most cows will recover in a
few days.

In calves with aortic and iliac artery
thrombosis there is an acute onset of

paresis or flaccid paralysis of one or both
pelvic limbs. 13 Affected limbs are hypo-
thermic and have diminished spinal
reflexes and arterial pulse pressures.
The diagnosis can be defined using
angiography. Affected calves die or are
euthanized because treatment is not
undertaken.

Neurogenic atrophy

With neurogenic atrophy there is marked
loss of total mass of muscle, flaccid para-
lysis, loss of tendon reflexes and failure of
regeneration. When large muscle masses
are affected, e.g. quadriceps femoris in
femoral nerve paralysis in calves at birth,
the animal is unable to bear normal
weight on the affected leg.

Dystrophy of the diaphragmatic
muscles

In dystrophy of the diaphragmatic muscles
in adult Meuse-Rhine-Yessel cattle there
is loss of appetite, decreased rumination,
decreased eructation and recurrent bloat.
The respiratory rate is increased with
forced abdominal respirations, forced
movement of the nostrils and death from
asphyxia in a few weeks.

Severe diaphragmatic necrosis in a
horse with degenerative myopathy due to
polysaccharide storage myopathy has
been described. 15 Affected horses may
have severe respiratory distress and
respiratory acidosis, and do not respond
to supportive therapy.

CLINICAL PATHOLOGY
Muscle-derived serum enzymes

The serum levels of the muscle enzymes
are characteristically elevated following
myopathy due to release of the enzymes
from altered muscle cell membranes.
Creatine kinase (CK) is a highly specific
indication of both myocardial and skeletal
muscle degeneration. Plasma CK activity
is related to three factors: the amount and
rate of CK released from an injured
muscle into plasma, its volume of distri-
bution and its rate of elimination. 16 CK
has a half-life of about 4-6 hours and,
following an initial episode of acute
myopathy, serum levels of the enzyme
may return to normal within 3-4 days if
no further muscle degeneration has
occurred. Levels of AST are also increased
following myopathy but, because the
enzyme is present in other tissues such as
liver, it is not a reliable indicator of pri-
mary muscle tissue degeneration.

Because AST has a longer half-life
than CK, the levels of AST may remain
elevated for several days following acute
myopathy. The daily monitoring of both
CK and AST levels should provide an
indication of whether active muscle
degeneration is occurring. A marked drop
in CK levels and a slow decline in

AST levels suggests that no further
degeneration is occurring whereas a
constant elevation of CK suggests active
degeneration.

In acute nutritional muscular dystrophy
in calves, lambs, and foals the CK levels
will increase from normal values of
below 100 IU/L to levels ranging from
1000-5000IU/L and even higher. The
levels of CK in calves will increase from a
normal of 50IU/L to approximately
5000IU/L within a few days after being
placed outdoors followed by unconditioned
exercise. There is some preliminary
investigation into quantification of the
amount of skeletal damage in cattle based
on the amount of CK activity. 16

The measurement of serum levels of
glutathione peroxidase is a useful aid in
the diagnosis of myopathy due to selenium
deficiency.

In downer cows with ischemic necrosis
of the thigh muscles, the CK and AST
levels will be markedly elevated and will
remain elevated if muscle necrosis is
progressive in cows that are not well
bedded and rolled from side to side
several times daily to minimize the degree
and extent of ischemic necrosis.

High levels of CK (1000 IU/L and
greater) usually indicate acute primary
myopathy. Levels from 500-1000 IU/L
may be difficult to interpret in animals
recumbent for reasons other than primary
myopathy. This will necessitate a careful
reassessment of the clinical findings,
history and epidemiology.

In horses with acute exertional rhabdo-
myolysis (paralytic myoglobinuria) the CK
levels will range from 5000-10 000 IU/L.
Following vigorous exercise in uncon-
ditioned horses, the CK and AST levels
will rise as a result of increased cell
membrane permeability associated with
the hypoxia of muscles subjected to
excessive exercise. Lactate dehydrogenase
(LDH) has also been used as a bio-
chemical measurement of the degree of
physical work done by horses in training.
With progressive training in previously
unconditioned horses there is no signifi-
cant change between rest and exercise in
the levels of serum CK, AST, and LDH. In
horses with postanesthetic myositis the
CK levels may exceed 100 000 IU/L, the
serum calcium is decreased and the serum
inorganic phosphorus is increased. In
naturally occurring cases of exertional
rhabdomyolysis in horses the most
consistent acid-base abnormality may be
a hypochloremia rather than metabolic
acidosis as has been assumed.

Muscle biopsy

Investigation of the structural and bio-
chemical alterations of muscle tissue in
myopathy include biopsy techniques that

PART 1 CjtNtKAL MfcUlLINt ■ (.napier ia: diseases or me mustuiusiseieiai sysien

have been described. 3,17 Needle biopsies
require a specialized Bergstrom muscle
biopsy needle, which most practitioners
do have on hand. Open biopsy is
recommended in order to obtain a strip of
muscle. Biopsy of either the semi-
membranosus or semitendinosus muscles,
at a site between the base of the tail and
the tuber ischium, provides an adequate
sample. Muscle biopsy samples can be
processed for either frozen section or
routine fonnalin-fixed, paraffin-embedded
sections. The frozen section is considered
the gold standard.

Inclusions of periodic-acid-Schiff
(PAS)-positive, amylase-resistant complex
polysaccharide are abnormal and charac-
teristic findings in muscle of equine poly-
saccharide storage myopathy. 3

Histochemical techniques can be used
on muscle biopsies of horses with muscular
disease and animals with congenital and
inherited myopathies 4

Myoglobinuria

Myoglobinuria is a common finding in
adult horses with acute paralytic myo-
globinuria but is not a common finding in
acute nutritional muscular dystrophy
in young farm animals, except perhaps in
yearling cattle with acute muscular
dystrophy. The myoglobinuria may be
clinically detectable as a red or chocolate
brown discoloration of the urine. This
discoloration can be differentiated from
that caused by hemoglobin by spectro-
graphic examination or with the use of
orthotoluidine paper strips. Urine becomes
dark when myoglobin levels exceed
40 mg/dL of urine. Discoloration of the
plasma suggests hemoglobinuria. Both
myoglobin and hemoglobin give positive
results for the presence of protein in
urine. Porphyria causes a similar dis-
coloration although this may not be
evident until the urine has been exposed
to light for some minutes. The coloration
is lighter, pink to red rather than brown,
and the urine is negative to the guaiac test
and fluoresces with ultraviolet light.
Creatinuria accompanies acute myopathy
but has not been used routinely as a
diagnostic aid.

Electromyography is a special tech-
nique for the evaluation of the degree of
neurogenic atrophy.

NECROPSY FINDINGS

Affected areas of skeletal muscle have a
white, waxy, swollen appearance like fish
flesh. Commonly only linear strips of
large muscle masses are affected and the
distribution of lesions is characteristically
bilaterally symmetrical. Histologically the
lesion varies from a hyaline degeneration
to a severe myonecrosis, with subsequently
the disappearance of large groups of
muscle fibers and replacement by con-

nective tissue. Calcification of the affected
tissue may be present to a mild degree in
these cases.

The lesions in exertional rhabdomyolysis
in the horse are of a focal distribution and
consist of hyaline degeneration with
insignificant inflammatory reaction and
slight calcification. The degenerative
changes affect primarily the fast twitch
fibers, which have a low oxidative capacity
and are used when the horse trots at very
close to its maximum speed.

DIFFERENTIAL DIAGNOSIS

Most myopathies in farm animals occur in
rapidly growing, young animals and are
characterized clinically by a sudden onset
of acute muscular weakness, and pain
often precipitated by unaccustomed
exercise. There may be evidence of a
dietary deficiency of vitamin and selenium
in the case of nutritional muscular
dystrophy. A sudden onset of recumbency
or stiffness in young farm animals that are
bright and alert should arouse suspicion of
acute muscular dystrophy. Primary
myopathies are not common in adult
cattle, sheep or pigs but myopathy
secondary to recumbency for other reasons
does occur.

Secondary myopathy due to aortic and
iliac thrombosis in calves must be
differentiated from other common causes
of hindlimb paresis including traumatic
injury to the spinal cord, spinal cord
compression due to vertebral body abscess,
nutritional muscular dystrophy, myositis
and nerve damage due to trauma of
intramuscular injections, and clostridial
myositis . 14

The exertional myopathies in the horse
in training are usually readily obvious. The
CK levels are valuable aids to diagnosis. In
special circumstances, such as neurogenic
j | myopathy, muscle biopsy and

electromyography may be useful additional
diagnostic aids. The histological and
histochemical staining characteristics of
equine muscle have been described and
serve as a standard for comparison with
abnormal muscle.

Myositis may present a similar syndrome
but is usually present as a secondary lesion
in a clinically distinguishable primary
disease or is accompanied by obvious
trauma or toxemia.

TREATMENT

Vitamin E and selenium are indicated for
the treatment of nutritional muscular
dystrophy and the details are provided
under that heading. The treatment of
exertional rhabdomyolysis in horses has
not been well defined because of the
uncertain etiology, but enforced rest and
the relief of pain, if necessary, seems
logical. Supportive therapy for any case of
myopathy, particularly severe cases in
which there is persistent recumbency,
consists of:

° Liberal quantities of thick bedding
* Removal from solid floors to softer
ground

° Frequent turning from side to side to
minimize secondary myopathy
° Provision of fluid therapy to prevent
myoglobinuric nephrosis
° A palatable, nutritious diet.

With the exception of the sporadically
occurring congenital and inherited myo-
pathies of farm animals, all the nutritional
and exertional myopathies are amenable
to treatment if it is begun early and if
adequate supportive therapy is provided.

In myopathies associated with systemic
acidosis the use of a solution of sodium
bicarbonate may be indicated. Dietary
sodium bicarbonate at the rate of 2% of
total dry matter intake has been used for
the treatment of exertional rhabdomyolysis
in a horse. 18 Horses with postanesthetic
myositis must be considered as critical
care patients for 18-24 hours. Main-
tenance of adequate renal perfusion is
vital. Large quantities of intravenous
polyionic balanced electrolyte fluids
(50-100 L) must be given over a 24-hour
period. Dantrolene sodium at 4 mg/kg
body weight (BW) given orally immediately
upon recognition of clinical signs is
efficacious.

CONTROL

The nutritional myopathies in farm animals
can be satisfactorily prevented by the pro-
vision of adequate quantities of dietary
vitamin E and selenium in the maternal
diet during pregnancy or at the strategic
times in postnatal life. The prevention of
exertional myopathy in the horse depends
i on a progressive training program and
! avoidance of sudden unaccustomed
exercise in animals that are in good body
condition and have been inactive.
Similarly, in general terms, the prevention
i of the porcine stress syndrome will
i depend on careful handling and trans-
; portation techniques combined with
genetic selection of resistant pigs.

REVIEW LITERATURE

Valentine BA. Equine polysaccharide storage myopathy.
; Equine Vet Educ 2003; 15:254-262.

REFERENCES

1. Freestone JF, Carlson GP. Equine Vet J 1991; 23:86.

2. Hosie BD et al. Vet Rec 1986; 119:444.

3. Valentine BA. Equine Vet Educ 2003; 15:254.

4. Hafner A et al. J Comp Pathol 1996; 115:23.

5. Sarli G et al. Vet Rec 1994; 135:156.

6. Serteyn D et al.Vet Rec 1988; 123:126.

7. Bloom BA et al.Vet Rec 1999; 144:73.

8. Essen-Gustavsson B, Lindholm A. Equine Vfct J
1985; 17:434.

9. Bruce V, Turek RJ. Equine Vet J 1985; 17:317.

10. Van den Hoven R et al. Am JVet Res 1985; 46:939.

11. Van den Hoven R et al. Am J Vet Res 1985;

! 46:1755.

12. Andrews FM, Spurgeon TL. Am J Vet Res 1986;
47:1843.

13. Morley PS et al. J Am Vet Med Assoc 1996;

209:130.

14. Step DL et al. J AmVetMed Assoc 1991; 198:117.

15. Valentine BA et al. Can Vet J 2002; 43:614.

16. LefebvTe HP et al. Am J Vet Res 1994; 55:487.

17. Van den Hoven R et al. Equine Vet J 1988; 20:46.

18. Robb EJ, Kronfeld DS. J Am Vet Med Assoc 1986;

188:602.

M YOSITIS

Myositis may arise from direct or indirect
trauma to muscle and occurs as part of a
syndrome in a number of specific diseases
including blackleg, foot-and-mouth
disease, bluetongue, ephemeral fever,
swine influenza, sarcosporidiosis and
trichinosis, although clinical signs of
myositis are not usually evident in the
latter. Sporadic cases of a localized infec-
tious myositis of skeletal muscles, associ-
ated with Escherichia coii, may occur in
calves. 1 An asymptomatic eosinophilic
myositis is not uncommon in beef cattle
and may cause economic loss through
carcass condemnation. The cause has not
been determined.

Acute myositis of limb muscles

This disease is accompanied by severe
lameness, swelling, heat and pain on pal-
pation. There may be accompanying
toxemia and fever. In chronic myositis
there is much wasting of the affected
muscles and this is difficult to differ-
entiate clinically from atrophy due to
other causes. Biopsy of the muscles may
be necessary to confirm the diagnosis.

Injury to the gracilis muscle can cause
acute, severe lameness in performance
Quarter Horses. 2 Horses competing in
barrel racing may be susceptible to gracilis
muscle injury because the muscle func-
tions to adduct the hind limb. The
prognosis is good for returning to athletic
use after and an adequate period of
muscle healing and mild exercise. How-
ever, fibrotic myopathy or muscle atrophy
can be a complication of the injury
resulting in persistent gait deficits.

In horses traumatic myositis of the
posterior thigh muscles may be followed
by the formation of fibrous adhesions
between the muscles (fibrotic myopathy)
and by subsequent calcification of the
adhesions (ossifying myopathy) . External
trauma can result in fibrotic myopathy but
it may also be associated with excessive
exercise or secondary to intramuscular
injections.

Occasionally similar lesions may be
seen in the foreleg. The lesions cause a
characteristic abnormality of the gait in
that the stride is short in extension and
the foot is suddenly withdrawn as it is
about to reach the ground. The affected
area is abnormal on palpation.

An inherited disease of pigs, generalized
myositis ossificans, is also characterized

Diseases of muscles

63

by deposition of bone in soft tissues. In
traumatic injuries caused by penetration
of foreign bodies into muscle masses,
ultrasonography may be used to detect
fistulous tracts and the foreign bodies.

Extensive damage to or loss of muscle
occurs in screwworm and sometimes
blowfly infestation, although the latter is
more of a cutaneous lesion, and by the
injection of necrotizing agents. For
example, massive cavities can be induced
in the cervical muscles of horses by the
intramuscular injection of escharotic iron
preparations intended only for slow
intravenous injection. Similarly, necrotic
lesions can result from the intramuscular
injection of infected or irritant substances.
Horses are particularly sensitive to tissue
injury, or are at least most commonly
affected. Some common causes are chloral
hydrate, antimicrobials suspended in
propylene glycol, and even antimicrobials
alone in some horses.

Injection site clostridial infections in
horses

Clostridial myositis, myonecrosis, cellulitis,
and malignant edema are terms used to
describe a syndrome of severe necrotizing
soft tissue infection associated with
Clostridium spp. Affected horses typically
develop peracute emphysematous soft
tissue swelling in the region of an
injection or wound within hours of the
inciting cause. It can occur following the
intramuscular or inadvertent perivascular
administration of a wide variety of
commonly administered drugs. 3 In a series
of 37 cases, the lesion occurred within
6-72 hours of a soft-tissue injection in
most cases and most were in the neck
musculature. Aggressive treatment can be
associated with a survival rate of up to 81%
for cases due to Clostridium perfringens
alone; survival rates for other Clostridium
spp. are lower. A combination of a high
dose of intravenous antibiotic therapy and
surgical fenestration and debridement is
the recommended approach to treatment.

Injection site lesions in cattle

Muscle lesions associated with injection
sites in the cattle industry are a source of
major economic loss because of the
amount of trim required at slaughter. The
presence of injection-site lesions in whole
muscle cuts, such as the top sirloin and
outside round, limits their use and value.
The occurrence of injection- site lesions in
muscle is among the top five quality
challenges for both beef and dairy market
cows and bulls. 4 Because injection-site
lesions are concealed in muscles and/or
are under subcutaneous fat, they are
seldom found during fabrication at the
packing plant and appear instead during
wholesale/retail fabrication or at the con-
sumer level. In 1998, the National Animal

Health Monitoring System found that
47% of producers and 37% of veterinarians
administered intramuscular injections in
the upper or lower rear leg of cows; the
need for further educational effort is
apparent.

Monitoring the frequency of injection-
site lesions allows educational efforts of
state and national beef quality assurance
programs to evaluate, more definitively,
management practices of producers that
can be changed to minimize occurrence
of these defects. Audits done at abattoirs
between 1998 and 2000 in the USA
indicate that the frequency of injection-
site lesions has decreased but the need
remains for educational programs and
continued improvements in beef quality
assurance practices among beef and dairy
cattle producers. 4 Historically, most intra-
muscular injections were given in the
gluteals and the biceps femoris muscles,
which are prime cuts of beef. Surveys of
injection sites in beef cattle in North
America have found lesions in a signifi-
cant percentage of prime cuts of beef. 5
Lesions consisting of clear scars and
woody calluses are mature and probably
originated in calfhood; scars with nodules
or cysts are less mature, occurring later in
the feeding period. It is now recommended
that intramuscular injections be given in
the cervical muscles. Reducing the inci-
dence of injection site lesions requires
that manufacturers of biological and
antibiotic preparations develop less
irritating formulations. Products should
be formulated for subcutaneous use
whenever possible and administered in
the neck muscles, which are not prime
cuts of beef.

The outcome of an intramuscular
injection depends on the nature of the
lesion produced. Myodegeneration fol-
lowing intramuscular injections of anti-
biotics in sheep results in full muscle
regeneration within less than 3 weeks.' 1
Necrosis following the injection results in
scar formation with encapsulated debris,
which persists for more than a month and
leaves persistent scar tissue.

An outbreak of myositis, lameness and
recumbency occurred following the injec-
tion of water-in-adjuvanted vaccines into
the muscles of the left and right hips of
near-term pregnant beef cattle. 7 Within
24 hours, some cattle were recumbent,
some had nonweightbearing lameness
and, within 10 days, 50% of the herd
developed firm swellings up to 24 cm in
vaccination sites. Histologically, granulo-
matous myositis with intralesional oil was
present. The swellings resolved over a
period of 6 months. The acute transient
lameness was attributed to the use of two
irritating biological vaccines in the hip
muscles of cows near parturition.

632

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

REFERENCES

1. Mills LL et al. J Am Vet Med Assoc 1990; 197:1487.

2. Dabareiner RM et al. J Am Vet Med Assoc 2004;
224:1630.

3. Ffeek SF et al. EquineVet J 2003; 35:86.

4. Roeber DL et al. J Dairy Sci 2002; 85:532.

5. V&n Donkersgoed J et al. Can Vet J 1998; 39:97.

6. Mikaelian I et al.Vet Res 1996; 27:97.

7. OToole D et al. JVet Diagn Invest 2005; 17:23.

Diseases of bones

OSTEODYSTROPHY

Osteodystrophy is a general term used to
describe those diseases of bones in which
there is a failure of normal bone develop-
ment, or abnormal metabolism of bone
that is already mature. The major clinical
manifestations include distortion and
enlargement of the bones, susceptibility
to fractures and interference with gait and
posture.

ETIOLOGY

The common causes of osteodystrophy in
farm animals include the following.

Nutritional causes

Calcium, phosphorus and vitamin D
Absolute deficiencies or imbalances in
calcium-phosphorus ratios in diets cause:

Rickets in young animals, e.g.,
growing lambs fed a diet rich in
wheat bran

Absolute deficiencies of calcium
Beef calves on intensive rations with
inadequate supplementation 1
Osteomalacia in adult ruminants.

Osteodystrophia fibrosa in the horse

occurs most commonly in animals
receiving a diet low in calcium and high in
phosphorus.

Osteodystrophia fibrosa in pigs

occurs as a sequel to rickets and osteo-
malacia, which may occur together in
young growing pigs that are placed on
rations deficient in calcium, phosphorus
and vitamin D following weaning.

Copper deficiency

Osteoporosis in lambs
Epiphysitis in young cattle.

Other nutritional causes

Inadequate dietary protein and
general undernutrition of cattle and
sheep can result in severe
osteoporosis and a great increase in
ease of fracture

Chronic parasitism can lead to
osteodystrophy in young growing
ruminants

Hypovitaminosis A and
hypervitaminosis A can cause
osteodystrophic changes in cattle and
pigs

Prolonged feeding of a diet high in
calcium to bulls can cause nutritional

hypercalcitoninism combined with
replacement of trabecular bone in the
vertebrae and long bones with
compact bone, and neoplasms of the
ultimobranchial gland
° Multiple vitamin and mineral

deficiencies are recorded as causing
osteodystrophy in cattle. The mineral
demands of lactation in cattle can
result in a decrease in bone mineral
content during lactation with a
subsequent increase during the dry
period.

Chemical agents

° Chronic lead poisoning is reputed to
cause osteoporosis in lambs and foals
» Chronic fluorine poisoning causes the
characteristic lesions of osteofluorosis,
including osteoporosis and exostoses
Grazing the poisonous plants Setaria
sphaceleta, Cenchrus ciliaris, and
Panicum maximum var. trichoglume
; causes osteodystrophia in horses

Enzootic calcinosis of muscles and
other tissues is caused by the
ingestion of Solarium malacoxylon,

\ Solatium torvum, Trisetum flaoescens

| (yellow oatgrass), and Cestrum

! diurnum, which exert a vitamin-D-like

! activity

j r Bowie or bentleg, a disease caused by
poisoning with Trachymene glaucifolia,
j is characterized by extreme outward

; bowing of the bones of the front

limbs.

! Inherited and congenital causes

| There are many inherited and congenital
j defects of bones of newborn farm animals,

I which are described, and discussed in
: detail in Chapter 34. In summary, these
include:

Achondroplasia and
chondrodystrophy in dwarf calves and
some cases of prolonged gestation
Osteogenesis imperfecta in lambs and
Charolais cattle. There is marked bone
fragility and characteristic changes on
radiological examination
Osteopetrosis in Hereford and Angus
calves

Chondrodystrophy in 'acorn' calves
Inherited exostoses in horses;
inherited thicklegs and inherited
rickets of pigs, which are well-
established entities.

Angular deformities of joints of long
! bones due to asymmetric growth plate
i activity are common in foals and are
j commonly repaired surgically. 2 The distal
radius and distal metacarpus are most
often affected, the distal tibia and
metatarsal less commonly. Physiologically
immature foals subjected to exercise may
develop compression-type fractures of the
central or third tarsal bones. Some of these

foals are born prematurely or are from a
twin pregnancy. Retained cartilage in the
distal radial physis of foals 3-70 days of
age presents without apparent clinical
signs.

Physitis is dysplasia of the growth
plate, characterized by an irregular border
between the cartilage and the metaphyseal
zone of ossification, an increase in the
lateromedial diameter of the physis, and
distoproximally oriented fissures at the
medial aspect of the metaphysis, which
originate at the physis. In some cases,
these may result in bilateral tibial meta-
physeal stress fractures in foals. 3

Abnormal modeling of trabecular
bone has been recognized in prenatal and
neonatal calves. 4 Abnormalities included
growth retardation lines and lattices, focal
retention of primary spongiosa and the
persistence of secondary spongiosa. Intra-
uterine infection with viruses such as
| bovine virus diarrhea (BVD) may be a
j causative factor. 4

j Physical and environmental causes

j Moderate osteodystrophy and arthropathy
may occur in rapidly growing pigs and
cattle raised indoors and fed diets that
contain adequate amounts of calcium,
phosphorus and vitamin D. Those animals
I raised on slatted floors or concrete floors
are most commonly affected and it is
thought that traumatic injury of the
epiphyses and condyles of long bones
may be predisposing factors in osteo-
chondrosis and arthrosis in the pig (leg
weakness) and epiphysitis in cattle.
Experimentally raising young calves on
metal slatted floors may result in more
. severe and more numerous lesions of the
epiphysis than occurs in calves raised on
: clay floors. Total confinement rearing of
j lambs can result in the development of
epiphysiolysis and limb deformities.
However, the importance of weight-
: bearing injury as a cause of osteodystrophy
in fanu animals is still uncertain. In most
reports of such osteodystrophy, all other
known causes have not been eliminated.

Chronic osteodystrophy and arthropathy
have been associated with undesirable
conformation in the horse.

Vertebral exostoses are not uncommon
in old bulls and usually affect the thoracic
vertebrae (T2 and T12) and the lumbar
vertebrae (L2-L3), which are subjected to
increased pressure during the bending of
, the vertebral columns while copulating,
j The exostoses occur mainly on the ventral
j aspects of the vertebrae, fusing them to
j cause immobility of the region. Fracture
i of the ossification may occur, resulting in
J partial displacement of the vertebral
I column and spinal cord compression. The
! disease is commonly referred to as
j spondylitis or vertebral osteochondrosis

Diseases of bones

and also occurs less commonly in adult
cows and in pigs. It is suggested that the
anulus fibrosus degenerates and that the
resulting malfunctioning of the disk
allows excessive mobility of the vertebral
bodies, resulting in stimulation of new
bone formation. A similar lesion occurs
commonly in horses and may affect
performance, particularly in hurdle races
and cross-country events. The initial
lesion may be a degeneration of the
intervertebral disk.

Some types of growth plate defect

occur in young growing foals and these
are considered to be traumatic in origin.
Failure of chondrogenesis of the growth
plate may be the result of crush injuries in
heavy, rapidly growing foals with inter-
ruption of the vascular supply to the
germinal cells of the growth plate.
Asymmetric pressures due to abnormal
muscle pull or joint laxity may slow
growth on the affected side and result in
limb angulation.

Femoral fractures occur in newborn
calves during the process of assisted
traction during birth. 5 Laboratory com-
pression of isolated femurs from calves
revealed that the fracture configurations
and locations are similar to those found in
clinical cases associated with forced
extraction. The breaking strength of all
femurs fell within the magnitude of forces
calculated to be created when mechanical
devices are used to assist delivery during
dystocia. It is suggested that the wedging
of the femur in the maternal pelvis and
resulting compression during forced
extraction accounts for the occurrence of
supracondylar fractures of the femur of
calves delivered in anterior presentation
using mechanical devices in a manner
commonly used by veterinarians and
farmers.

Tumors

Osteosarcomas are highly malignant
tumors of skeletoblastic mesenchyme in
which the tumor cells produce osteoid or
bone. Osteosarcomas are the most com-
mon type of primary bone tumor in
animals such as dogs and cats but are rare
in horses and cattle. Most tumors of bone
in large animals occur in the skull. A
periosteal sarcoma on the scapula has
been recorded in the horse 6 and an
osteosarcoma of the mandible in a cow. 7

PATHOGENESIS

Osteodystrophy is a general term used to
describe those diseases of bones in which
there is a failure of normal bone develop-
ment, or abnormal metabolism of bone
that is already mature. There are some
species differences in the osteodystrophies
that occur with dietary deficiencies of
calcium, phosphorus, and vitamin D.
Rickets and osteomalacia occur primarily

in ruminants, osteodystrophia fibrosa in
horses, and all three may occur in pigs.

Rickets

Rickets is a disease of young growing
animals in which there is a failure of
provisional calcification of the osteoid
plus a failure of mineralization of the
cartilaginous matrix of developing bone.
There is also failure of degeneration of
growing cartilage, formation of osteoid on
persistent cartilage with irregularity of
osteochondral junctions and overgrowth
of fibrous tissue in the osteochondral
zone. Failure of provisional calcification of
cartilage results in an increased depth and
width of the epiphyseal plates, parti-
cularly of the long bones (humerus, radius
and ulna and tibia) and the costal
cartilages of the ribs. The uncalcified, and
therefore soft, tissues of the metaphyses
and epiphyses become distorted under
the pressure of weightbearing, which also
causes medial or lateral deviation of the
shafts of long bones. There is a decreased
rate of longitudinal growth of long bones
and enlargement of the ends of long
bones due to the effects of weight causing
flaring of the diaphysis adjacent to the
epiphyseal plate. Within the thickened
and widened epiphyseal plate there may
be hemorrhages and minute fractures of
adjacent trabecular bone of the meta-
physes. and in chronic cases the hemor-
rhagic zone may be largely replaced by
fibrous tissue. These changes can be
seen radiographically as 'epiphysitis' and
clinically as enlargements of the ends of
long bones and costochondral junctions
of the ribs. These changes at the epiphyses
may result in separation of the epiphysis,
which commonly affects the femoral
head. The articular cartilages may remain
normal or there may be subarticular
collapse resulting in grooving and folding
of the articular cartilage and ultimately
degenerative arthropathy and osteo-
chondrosis. Eruption of the teeth in
rickets is irregular and dental attrition is
rapid. Growth of the mandibles is retarded
and is combined with abnormal dentition.
There may be marked malocclusion of the
teeth.

Osteomalacia

Osteomalacia is a softening of mature
bone due to extensive resorption of
mineral deposits in bone and failure of
mineralization of newly formed matrix.
There is no enlargement of the ends of
long bones or distortions of long bones
but spontaneous fractures of any bone
subjected to weightbearing is common.

Osteodystrophia fibrosa

Osteodystrophia fibrosa may be super-
imposed on rickets or osteomalacia and
occurs in secondary hyperparathyroidism.

Diets low in calcium or that contain a
relative excess of phosphorus cause
secondary hyperparathyroidism. There is
extensive resorption of bone and replace-
ment by connective tissue. The disease is
best known in the horse and results in
swelling of the mandibles, maxillae a'nd
frontal bones (the 'bighead' syndrome).
Spontaneous fracture of long bones and
ribs occurs commonly. Radiographically
there is extreme porosity of the entire
skeleton.

Osteoporosis

Osteoporosis is due to failure or inadequacy
of the formation of the organic matrix of
bone; the bone becomes porous, light and
fragile, and fractures easily. Osteoporosis
is uncommon in farm animals and is
usually associated with general under-
nutrition rather than specifically a
deficiency of calcium, phosphorus, or
vitamin D. Copper deficiency in lambs may
result in osteoporosis due to impaired
osteoblastic activity. Chronic lead poison-
ing in lambs also results in osteoporosis
due to deficient production of osteoid. In
a series of 19 lactating or recently weaned
sows with a history of lameness, weakness
or paralysis, 10 had osteoporosis and
pathological fractures while six had
lumbar vertebral osteomyelitis. Bone ash,
specific gravity of bone and the cortical to
total ratio were significantly reduced in
sows with osteoporosis and pathological
fractures.

Ovariectomized sheep that are fed a
calcium-wasting diet develop osteoporosis,
which is being used as a model to study
the disease in humans.®

Osteodystrophy of chronic fluorosis

Osteodystrophy of chronic fluorosis is
characterized by the development of
exostoses on the shafts of long bones due
to periosteal hyperostosis. The articular
surfaces remain essentially normal but
there is severe lameness because of the
involvement of the periosteum and
encroachment of the osteophytes on the
tendons and ligaments.

Congenital defects of bone

These include complete (achondroplasia)
and partial (chondrodystrophy) failure
of normal development of cartilage.
Growth of the cartilage is restricted
and disorganized and mineralization is
reduced. The affected bones fail to grow,
leading to gross deformity, particularly of
the bones of the head.

CLINICAL FINDINGS

In general terms there is weakening of the
bones due to defective mineralization and
osteoporosis, which results in the bending
of bones, which probably causes pain
and shifting lameness - one of the earliest
clinical signs of acquired osteodystrophy.

634

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

The normal weight and tension stresses
cause distortion of the normal axial
relationships of the bones, which results
in the bowing of long bones. The dis-
tortions occur most commonly in young,
growing animals. The distal ends of the
long bones are commonly enlarged at the
level of the epiphyseal plate and circum-
scribed swellings of the soft tissue around
the epiphyses may be prominent, and
painful on palpation.

The effects of osteodystrophy on
appetite and body weight will depend on
the severity of the lesions and their
distribution. In the early stages of rickets
in calves and pigs the appetite and
growth rate may not be grossly affected
until the disease is advanced and causes
considerable pain. Persistent recumbency
due to pain will indirectly affect feed
intake unless animals are hand-fed.

Spontaneous fractures occur com-
monly and usually in mature animals.
Common sites for fractures include the
long bones of the limbs, pelvic girdle,
femoral head, vertebrae, ribs, and trans-
verse processes of the vertebrae. Ordinary
hand pressure or moderate restraint of
animals with osteomalacia and osteo-
dystrophia fibrosa is often sufficient to
cause a fracture. The rib cage tends to
become flattened and in the late stages
affected animals have a slab-sided
appearance of the thorax and abdomen.
Separations of tendons from their bony
insertions also occur more frequently and
cause severe lameness. The osteoporotic
state of the bone makes such separations
easy. Any muscle group may be affected
but, in young cattle in feedlots, separations
of the gastrocnemius are the most
common. Thickening of the bones may be
detectable clinically if the deposition of
osteoid or fibrous tissue is excessive, or if
exostoses develop as in fluorosis. Com-
pression of the spinal cord or spinal nerves
may lead to paresthesia, paresis or
paralysis, which may be localized in distri-
bution. Details of the clinical findings in the
osteodystrophies caused by nutritional
deficiencies are provided in Chapter 30.

Calcinosis of cattle is characterized
clinically by chronic wasting, lameness,
ectopic calcifications of the cardiovascular
system, lungs and kidneys, ulceration of
joint cartilage and extensive calcification
of bones.

CLINICAL PATHOLOGY

The laboratory analyses that are indi-
cated include the following:

° Serum calcium and phosphorus
° Serum alkaline phosphatase
° Feed analysis for calcium,

phosphorus, vitamin D and other
minerals when indicated (such as
copper, molybdenum, and fluorine)

° Bone ash chemical analysis
° Histopathology of bone biopsy
0 Radiographic examination of the
skeleton

0 Single photon absorptiometry, a safe
and noninvasive method for the
measurement of bone mineral
content, is now available.

Radiographic examination of the affected
bones and comparative radiographs of
normal bones is indicated when osteo-
dystrophy is suspected. Radiographic
examination of slab sections of bone is a
sensitive method for detecting abnor-
malities of trabecular bone in aborted and
young calves. 4

Serum calcium and phosphorus

concentrations in nutritional osteo-
dystrophies may remain within the
normal range for long periods and not
until the lesions are well advanced will
abnormal levels be found. Several suc-
cessive samplings may be necessary to
identify an abnormal trend.

Alkaline phosphatase levels may be
increased in the presence of increased
bone resorption but this is not a reliable
indicator of osteodystrophy. Increased
serum levels of alkaline phosphatase may
originate from osseous tissues, intestine
or liver, but osseous tissue appears to be
the major source of activity.

Nutritional history and feed analysis
results will often provide the best circum-
stantial evidence of osteodystrophy.

The definitive diagnosis is best made
by a combination of chemical analysis of
bone, histopathological examination of
bone and radiography. The details for each
of the common osteodystrophies are dis-
cussed under the appropriate headings.

NECROPSY FINDINGS

The pathological findings vary with the
cause, and the details are described under
each of the osteodystrophies elsewhere in
the book. In general terms, the nutritional
osteodystrophies are characterized by
bone deformities, bones that may be cut
easily with a knife and that bend or break
easily with hand pressure and the presence
in prolonged cases of degenerative joint
disease. In young, growing animals the
ends of long bones may be enlarged and
the epiphyses may be prominent and
circumscribed by periosteal and fibrous
tissue thickening. On longitudinal cut
sections the cortices may appear thinner
than normal and the trabecular bone may
have been resorbed, leaving an enlarged
marrow cavity. The epiphyseal plate may
be increased in depth and width and
appear grossly irregular, and small frac-
tures involving the epiphyseal plate and
adjacent metaphysis may be present.
Separation of epiphyses is common, parti-
cularly of the femoral head. The calluses

DIFFERENTIAL DIAGNOSIS

In both congenital and acquired
osteodystrophy the clinical findings are
usually suggestive. There are varying
degrees of lameness, stiff gait, long
periods of recumbency and failure to
perform physical work normally,
progressive loss of body weight h some
cases and there may be obvious
contortions of long bones, ribs, head and
vertebral column. The most common cause
of osteodystrophy in young growing
animals is a dietary deficiency or imbalance
of calcium, phosphorus and vitamin D. If
the details of the nutritional history are
available and if a representative sample of
the feed given is analyzed, a clinical
diagnosis can be made on the basis of
clinical findings, nutritional history and
response to treatment. In some cases,
osteodystrophy may be due to
overfeeding, such as might occur in rapidly
growing, large foals.

However, often the nutritional history
may indicate that the animals have been
receiving adequate quantities of calcium,
phosphorus and vitamin D, which
necessitates that other less common causes
of osteodystrophy be considered. Often
the first clue is an unfavorable response to
treatment with calcium, phosphorus and
vitamin D. Examples include copper
deficiency in cattle, leg weakness in swine
of uncertain etiology - but perhaps there is
weight-bearing trauma and a relative lack
of exercise due to confinement - or
chemical poisoning such as enzootic
calcinosis or fluorosis. These will require
laboratory evaluation of serum
biochemistry, radiography of affected
bones and pathological examination. The
presence of bony deformities at birth
suggests congenital chondrodystrophy,
some cases of which appear to be
inherited while some are due to
environmental influences.

of healed fractures of long bones, ribs,
vertebrae and pelvic girdle are common in
pigs with osteodystrophy. On histological
examination there are varying degrees of
severity of rickets in young growing
animals and osteomalacia in adult
animals, and osteodystrophia fibrosa is
possible in both young and adult animals.

TREATMENT

The common nutritional osteodystrophies
due to a dietary deficiency or imbalance of
calcium, phosphorus and vitamin D will
usually respond favorably following the
oral administration of a suitable source of
calcium and phosphorus combined with
parenteral injections of vitamin D. The
oral administration of dicalcium phos-
phate, at the rate of three to four times the
daily requirement, daily for 6 days
followed by a reduction to the daily
requirement by the 10th day, combined
with one injection of vitamin D at the rate
of 10 000 IU/kg BW is recommended.

Affected animals are placed on a diet that
contains the required levels and ratios of
calcium, phosphorus, and vitamin D. The
oral administration of the calcium and
phosphorus will result in increased
absorption of the minerals, which will
restore depleted skeletal reserves. Calcium
absorption is increased in adult animals
following a period of calcium deficiency;
young animals with high growth require-
ments absorb and retain calcium in direct
relation to intake. General supportive
measures include adequate bedding for
animals that are recumbent.

The treatment of the osteodystrophies
due to causes other than calcium and
phosphorus deficiencies depends on the
cause. Copper deficiency will respond
gradually to copper supplementation.
There is no specific treatment for the
osteodystrophy associated with leg weak-
ness in pigs and slaughter for salvage is
often necessary. Overnutrition in young,
rapidly growing foals may require a
marked reduction in the total amount of
feed made available daily.

Oxytetracycline has been used for the
treatment of flexural deformities of the
distal interphalangeal joints of young
foals. 9 It is postulated that oxytetracycline
chelates calcium, rendering it unavailable
for use for striated muscle contraction. It
is considered effective for obtaining a
short-term moderate decrease in meta-
carpophalangeal joint angle in newborn
foals. Hemicircumferential periosteal
transection and elevation has gained wide
acceptance for correction of angular limb
deformities in young foals. 1

REFERENCES

1. Caldow G et al.Vet Rcc 1995; 136:80.

2. Mitten LA, Bertone AL. J Am Vet Med Assoc 1994;
204:717.

3. Frankney RL et al. J Am Vet Med Assoc 1994;
205:76.

4. O'Connor BP, Doige CE. Can JVet Res 1993; 57:25.

5. Ferguson JG. Can Vet J 1994; 35:626.

6. Zaruby JF et al. Can Vet J 1993; 34:742.

7. Plumlee KH et al. J Am Vet Med Assoc 1993;
202:95.

8. Turner AS. Vet J 2002; 165: 232.

9. Madison JB et al. J Am Vet Med Assoc 1994;
204:246.

HYPERTROPHIC PULMONARY
OSTEOARTHROPATHY (MARIE'S
DISEASE, ACHROPACHIA OSSEA)

Although hypertrophic pulmonary osteo-
arthropathy is more common in dogs
than in the other domestic animals it has
been observed in horses, 1 cattle and
sheep. The disease is characterized by
proliferation of the periosteum leading to
the formation of periosteal bone, and
bilateral symmetrical enlargement of
bones, usually the long bones of limbs.
The enlargement is quite obvious, and in

Diseases of bones

■■n

the early stages is usually painful and
often accompanied by local edema. On
radiographic examination there is a shaggy
periostitis and evidence of periosteal
exostosis. The pathogenesis is obscure but
the lesion appears to be neurogenic in
origin, unilateral vagotomy causing
regression of the bony changes. Stiffness
of gait and reluctance to move are usually
present, and there may be clinical
evidence of the pulmonary lesion with
which the disease is almost always associ-
ated. Such lesions are usually chronic,
neoplastic or suppurative processes such
as tuberculosis.

The disease is considered to be
incurable, unless the thoracic lesion can
be removed, and affected animals are
usually euthanized. At necropsy the
periostitis, exostosis and pulmonary
disease are evident. There is no involve-
ment of the joints.

REFERENCE

1. MairTS et al. Equine Vet J 1996; 28:256.

OSTEOMYELITIS

ETIOLOGY AND PATHOGENESIS

Inflammation of bone is uncommon in
farm animals except when infection is
introduced by traumatic injury or by the
hematogenous route. Bacteria can reach
bone by any of three routes:

° Hematogenously
° By extension from an adjacent

focus of infection
° By direct inoculation through

trauma or surgery.

Focal metaphyseal osteomyelitis can
occur following open fractures in the horse.
Specific diseases that may be accompanied
by osteomyelitis include actinomycosis of
cattle and brucellosis, atrophic rhinitis
and necrotic rhinitis of pigs. Nonspecific,
hematogenous infection with other
bacteria occurs sporadically and is often
associated with omphalitis, abscesses
from tail-biting in pigs or infection of
castration or docking wounds in lambs.
A series of 28 cases of osteomyelitis of the
calcaneus of adult horses has been
described. 1

Foals and calves under 1 month of age
and growing cattle 6-12 months of age
may be affected by osteomyelitis in one or
more bones. The majority of foals with
suppurative polyarthritis have a poly-
osteomyelitis of the bones adjacent to the
affected joints. In a series of cases of tarsal
osteomyelitis in foals there was usually
evidence of infectious arthritis. 2 Osteo-
myelitis of the pubic symphysis associated
with Rhodococcus equi in a 2-year-old
horse has been described. 3 The lameness
was localized to the pelvis and was associ-

ated with a fever and an inflammatory
leukogram.

The infections occur commonly in the
metaphysis, physis, and epiphysis, which
are sites of bony growth and thus
susceptible to blood-borne infections. The,
metaphyseal blood vessels loop toward
the physis and ramify into sinusoids that
spread throughout the metaphyseal region.
Blood flow through the sinusoids is
sluggish and presents an ideal environ-
ment for propagation of bacteria. Lesions
occur on both sides of the physis in both
the metaphysis and the epiphysis. Multiple
lesions are common and support the
explanation that septic emboli are released
from a central focus.

In a series of 445 cattle with bone
infection of the appendicular skeleton a
distinction was made between hemato-
genous and post-traumatic orgin (wound/
fracture). 4 Bone infection was classified
into four types according to the site of
infection; Type 1 is metaphyseal and/or
epiphyseal osteomyelitis close to the
growth plate; type 2 is primary subchondral
osteomyelitis, mostly accompanied by
septic arthritis; type 3 is infectious osteo-
arthritis with subchondral osteomyelitis,
implying that infection in the subchondral
bone originates from the infection. Type 4
includes bone infections that cannot be
categorized in the other groups. Hemato-
genous osteomyelitis was 3.2 times more
frequent than post-traumatic osteomyelitis.
Arcanobacterium (Corynebacterium) pyogenes
was the most common etiological agent.
About 55% of the affected animals with
osseous sequestration had physical evi-
dence of lacerations, contusions, abra-
sions or puncture wounds from a previous
traumatic event.

Hematogenous osteomyelitis in

cattle can be of:

° Physeal type, in which an infection
generally of metaphyseal bone
originates at or near the growth plate,
usually affecting the distal metacarpus,
metatarsus, radius or tibia 5
° Epiphyseal type, in which an infection
originates near the junction of the
subchondral bone and the immature
epiphyseal joint cartilage, most often
affecting the distal femoral condyle
epiphysis, the patellar and the distal
radius.

The epiphyseal osteomyelitises are usually
due to infection with Salmonella spp. and
are most common in calves under 12 weeks
of age. The physeal infections are usually
due to A. pyogenes and occur most com-
monly in cattle over 6 months of age.

Osseous sequestration in cattle

Osseous sequestration is a common
orthopedic abnormality in cattle and

636

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

horses. 6 In most cases, the lesions
develop in the bones of the distal portion
of the limbs. Sequestration is associated
with trauma that results in localized
cortical ischemia and bacterial invasion
secondary to loss of adjacent periosteal
and soft-tissue integrity and viability. The
soft tissues covering the bones that
comprise the distal portions of the limbs
fail to provide adequate protection and
collateral blood supply to the bone.

Osteomyelitis secondary to trauma

In horses, osteomyelitis is a frequent
sequela to wounds of the metacarpal and
metatarsal bones and the calcaneus.
These bones have limited soft tissue
covering, which may predispose them to
osteomyelitis following traumatic injury.
Similarly, a portion of the lateral aspect of
the proximal end of the radius has limited
soft-tissue covering. Penetrating and
nonpenetrating wounds in this region,
therefore, may result in serious con-
sequences even though they may initially
appear to be minor. Because lesions may
be an extension of septic arthritis, a
thorough examination of the wound area
is necessary.

Osteomyelitis of the sustentaculum
tali in horses has been described. 7

Inflammation of bone marrow

Inflammation of bone marrow in animals
has been described. 8-9 Acute inflammation
commonly accompanies bacterial sepsis,
resulting in either multifocal micro-
abscesses or perivascular infiltrates of
neutrophils, fibrin, edema, and hemorrhage.
The most common abnormality associated
with fibrinous inflammation is dis-
seminated intravascular coagulopathy.
Discrete granulomas may occur in the
marrow of animals with systemic mycotic
disease, idiopathic granulomatous disease
and serous atrophy of fat.

CLINICAL FINDINGS

The common clinical findings of osteo-
myelitis include:

° Lameness

° Generalized soft tissue swelling
and inflammation
° Pain on palpation of the affected
area

° Chronic persistent drainage
° Secondary muscle atrophy of the
affected limb 1

Erosion of bone occurs and pus dis-
charges into surrounding tissues, causing
a cellulitis or phlegmon, and to the exterior
through sinuses, which persist for long
periods. The affected bone is often
swollen and may fracture easily because
of weakening of its structure. When the
bones of the jaw are involved, the teeth
are often shed and this, together with

pain and the distortion of the jaw, interferes
with prehension and mastication. Involve-
ment of vertebral bodies may lead to the
secondary involvement of the meninges
and the development of paralysis. Lame-
ness and local swelling are the major
manifestations of involvement of the limb
bones.

Most osseous sequestra in cattle
are associated with the bones of the
extremities, most commonly the third
metacarpal or metatarsal bone. Cattle
6 months to 2 years of age are most likely
to have a sequestrum compared with
animals less than 6 months of age. 6

The lesions are typically destructive of
bone and cause severe pain and lameness.
Those associated with Salmonella spp. are
characteristic radiographically in foals and
calves. A. pyogenes, Corynebacterium spp.,
and E. coli may also be causative agents.
Affected animals are very lame and the
origin of the lameness may not be
obvious. A painful, discrete soft-tissue
swelling over the ends of the long bones
is often the first indication. The lameness
characteristically persists in spite of
medical therapy and the animal may
become lame in two or more limbs and
spend long periods recumbent.

Osteomyelitis affecting the cervical
vertebrae, usually the fourth to sixth
vertebra, causing a typical syndrome of
abnormal posture and difficulty with
ambulation. Initially there is a stumbling
gait, which then becomes stiff and
restricted and with a reluctance to bend
the neck. Soon the animal has difficulty
eating off the ground and must kneel to
graze pasture. At this stage there is
obvious atrophy of the cervical muscles
and pain can be elicited by deep, forceful
compression of the vertebrae with the
fists. There is no response to treatment
and at necropsy there is irreparable
osteomyelitis of the vertebral body and
compression of the cervical spinal cord.
Radiological examination is usually
confirmatory.

Cervicothoracic vertebral osteo-
myelitis in calves between 2 and 9 weeks
of age is characterized by difficulty in
rising with a tendency to knuckle or kneel
on the forelimbs, which are hypotonic
and hyporeflexic. Thin can be elicited on
manipulation of the neck. The lesion
usually involves one or more of the
vertebrae from C6-T1. 8 Salmonella dublin
is commonly isolated from the vertebral
lesion.

CLINICAL PATHOLOGY

Radiographic changes include:

° Necrotic sequestrum initially
c New bone formation
° Loss of bone density.

The lesions are characteristically centered
at the growth and extend into both
metaphysis and epiphysis. Culture of
the inflammatory exudate and necrotic
sequestra removed surgically is necessary
to determine the species of bacteria and
their antimicrobial sensitivity. 6 Samples of
bone obtained at surgery provide the
most accurate culture results compared to
specimens obtained from the draining
sinuses, which may yield a mixed flora.
Specimens should consist of sequestra
and soft tissues immediately adjacent to
bone thought to be infected. Special
transport media are desirable for optimum
culture results. Anaerobic bacteria are
frequently associated with osteomyelitis
and should be considered when submit-
ting samples for culture.

NECROPSY FINDINGS

At necropsy the osteomyelitis may not be
obvious unless the bones are opened
longitudinally and the cut surfaces of the
metaphysis and epiphysis are examined.

DIFFERENTIAL DIAGNOSIS

A differential diagnosis for a destructive
lesion in the end of a long bone of a foal
or calf would include: a healing fracture,
traumatic periostitis or osteitis, bone
tumor, nutritional osteodystrophy and
infection of the bone due to external
trauma, fracture, extension from adjacent
infection or hematogenous spread. The
absence of equal pathological involvement
in the comparable parts of long bones and
the young age of the animal will usually
suggest infection of bone. The pathological
features of multiple bone infection in foals
are described.

TREATMENT

Despite advances in antimicrobial therapy
and refined diagnostic techniques, the
clinical management of osteomyelitis is
difficult. Medical therapy alone is rarely
completely successful because of the poor
vascularity of the affected solid bone and
the inaccessibility of the infection. In
cases of long-term infection or those with
extensive bone necrosis, surgery is gener-
ally recommended to remove sequestra,
devitalized tissue and sinus tracts that are
harboring large numbers of bacteria. 1-6
Good results are obtained when the
affected bone is removed and the affected
area is irrigated daily through a temporary
drainage tube.

In septic physitis, the implantation of
homologous cancellous bone grafts
following debridement of necrotic bone,
and the application of a walking cast for
4-5 weeks and antimicrobial therapy
for 2 weeks was highly successful. 10
Absolute asepsis is required for successful
application of a bone graft and, after

Diseases of joints

debridement of the necrotic bone, the
cavity is flushed with saline and ampicillin.

Antimicrobials are an integral part of
the treatment and selection of the most t
appropriate drug should be based on
identification of the organism. Parenteral
antimicrobial therapy should be continued
for 4-6 weeks following surgical curettage.
However, in a series of osteomyelitis of the
calcaneus of adult horses, there was no
difference in the survival rate of animals
between those treated surgically and those
treated conservatively. 1 Prolonged
antibiotic therapy can be successful for the
treatment of osteomyelitis of the proximal
end of the radius in the horse. 11

Most anaerobic bacteria associated
with osteomyelitis are sensitive to peni-
cillin and the cephalosporins, but some
species of Bacteroides fragilis and Bacteroides
asaccharolyticus and other species of
Bacteroides are known to produce beta-
lactamases, which can inactivate penicillin
and cephalosporin. Metronidazole and
clindamycin will penetrate bone and can
be considered.

REFERENCES

1. MacDonald MH et al. J Am Vet Med Assoc 1989;

194:1317.

2. Firth EC, Goodegebuure SA.Vet Q 1988; 10:99.

3. Clark-Price SC et al. J Am Vet Med Assoc 2003;

222:969.

4. Verschooten F et al. Vet Radiol Ultrasound 2000;

41:250.

5. Firth EC et al.Vet Rec 1987; 120:148.

6. Valentino LW et al. J Am Vet Med Assoc 2000;

217:376.

7. Hand DR et al.J Am Vet Med Assoc 2001; 219:341.

8. Healy AM et al.Vet J 1997; 154:227.

9. Weiss DJ et al.Vet Clin Pathol 1992; 21:79.

10. Barneveld A. Vet Q 1994; 16(Suppl 2):S104.

11. Swinebroad EL et al. J Am Vet Med Assoc 2003;

223:486.

Diseases of joints

ARTHROPATHY
(OSTEOARTHROPATHY,
DEGENERATIVE JOINT DISEASE)

The terms osteoarthropathy and degener-
ative joint disease are used here to describe
noninflammatory lesions of the articular
surfaces of joints characterized by:

11 Degeneration and erosion of articular
cartilage

0 Eburnation of subchondral bones
0 Hypertrophy of bone surrounding the
articular cartilage resulting in lipping
and spur formation at the joint
margins.

Osteochondrosis is a degeneration of
both the deep layers of the articular carti-
lage and the epiphyseal plate - a defect in
endochondral ossification - which occurs
in pigs and horses and is similar to the
well-recognized disease in dogs.

ETIOLOGY AND EPIDEMIOLOGY

The etiology is not clear but in most of the j
commonly occurring cases the lesions
are considered to be multifactorial and I
perhaps secondary to conformational j
defects resulting in excessive joint laxity, j
acute traumatic injury of a joint, the j
normal aging process and nutritional
deficiencies. The etiological information is
primarily circumstantial and some of the
epidemiological observations that have
been associated with osteoarthritis of
farm animals are outlined here.

Nutritional causes

° Secondary to, or associated with,
rickets, osteomalacia, bowie and
osteodystrophia fibrosa
° Coxofemoral arthropathy in dairy
cattle associated with aphosphorosis
° Copper deficiency thought to be
related to enlargement of limb joints
in foals on pasture and pigs fed
experimental copper-deficient diets
j Experimental diets deficient in
manganese or magnesium causing
arthropathy and joint deformity in
some calves

° Experimental riboflavin deficiency in
pigs.

Poisonings

° Chronic zinc poisoning in pigs and
foals

° Fluorosis in cattle
° As part of the enzootic calcinosis
syndrome caused by poisoning with
Solanum malacoxylon and others.

Steroid-induced

The intra-articular injection or prolonged
parenteral administration of corticosteroids
in horses may lead to degenerative joint
disease.

Biomechanical trauma
® Acute traumatic injury, e.g. injury to
joint surfaces, menisci and ligaments,
especially the cruciate ligaments of
the stifle joints of breeding bulls, may
lead to chronic progressive
osteoarthritis. Injuries to the
femorotibial ligaments of horses can
predispose to osteoarthropathy of the
stifle joint

0 Repeated subacute trauma to joint
surfaces can lead to degenerative
arthropathy. This is common in young
racehorses in training, which may
have their joint surfaces and
surrounding tissues made susceptible
to injury because of conformational
defects and subtle deficiencies of
calcium and phosphorus. Hard
running surfaces may also contribute
to the onset

° Trauma caused by movement is

suspected of contributing to the
erosive lesions on the articular

637

surfaces of some horses affected by
enzootic incoordination, the
intervertebral joints of caudal thoracic
and cranial lumbar vertebrae of old
bulls with spondylitis, and the
condition of bulls with inherited
spasticity. Coxofemoral osteoarthritis
may occur in aged horses with joint
instability and in calves with hip
dysplasia.

Growth rate, body size, and genetic
predisposition

Degenerative coxofemoral arthropathy
occurs in young beef bulls as early as
9 months of age. A congenital shallow
acetabulum may predispose. It may be
secondary to hip dysplasia, but in some
cases there is no evidence of this. The
large, weightbearing joints subjected to
the greatest movement and concussion
appear to be most susceptible. Rapidly
growing bull calves appear to be most
susceptible and some of them have an
inherited susceptibility.

Osteochondrosis

Osteochondrosis is an important cause
of lameness in horses. It is usually seen in
young rapidly growing animals, and
affects males more commonly than
females. The predilection sites of osteo-
chondrosis in the horse and their general
order of incidence are hock, stifle, shoulder,
fetlock, and cervical spine. The stifle, hock,
and shoulder joints are more commonly
affected, but many other joints may also
be affected, including the metatarsal and
metacarpal bones and rarely the acetabula
of young foals.

The epidemiology, heritability and
body measurements and clinical findings
of osteochondrosis of hock and fetlock
joints in Standardbred trotters have been
examined. 1 The incidence of the disease is
high in the Swedish Standardbred popu-
lation and well developed by the age
of 1.5 years. The incidence of osteo-
chondrosis is higher in horses born later
in the foaling season than earlier and
the incidence was related to body size:
affected horses were taller at the withers
and had a greater circumference of the
carpus. 1 This suggests that differences in
body size at birth and the first few months
of the foal's life are of major importance
in the development of osteochondrosis.
The heritability estimates of osteo-
chondrosis in the hock and fetlock joints
of 753 Standardbred trotters 6-21 months
of age was 0.52 and 0.21, respectively. 2

Aging process

Degenerative arthropathy in aged dairy
cows and bulls may be a manifestation of
the nonnal aging process. Osteochondrosis,
degenerative joint disease and vertebral
osteophysis occur in middle-aged bulls.

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

Osteoarthrosis of the antebranchial
joint of riding horses has been described. 3
Affected animals were aged mares that
developed osteoarthrosis and ankylosis.
The cause was unknown.

Conformation and intensive animal
production

Osteoarthropathy occurs in rapidly growing
cattle and pigs raised in confinement on
hard, usually concrete, floors and with
minimal exercise. Osteochondrosis in
feedlot cattle may be associated with a
high-caloric diet and rapid growth rate. It
is thought that weight-bearing trauma in
these rapidly growing animals is sufficient
to cause degenerative lesions of certain
joints, especially in animals with a skeletal
conformation that results in abnormal
stress on certain weightbearing condyles
of long bones.

In a series of 42 cases of stifle lameness
in cattle, 18 had evidence of subchondral
bone cyst and ranged in age from
6-18 months. It is suggested that the sub-
chondral bone cyst is an indicator of osteo-
chondrosis. In a series of osteochondrosis
in cattle, male, purebred cattle of a mean
age of 21 months were affected. 4

Osteochondrosis may occur in rapidly
growing bull beef calves fed a diet lacking
adequate calcium, sodium, copper and
vitamins A, D, and E, 5 ' 6 grazing beef cattle
on improved native pasture in which a
common ancestral sire and gender (all
males) may have been contributing
factors. 7 Severe osteochondrosis of multiple
joints but with remarkable changes in the
humeral head and glenoid of both
shoulder joints in 10-month-old beef
calves has been described. 8

Osteochondrosis similar to that seen
in pigs has been recorded in purebred
Suffolk lambs raised in a system designed
to produce rapidly growing, high-value
rams. 9 The disease has been recorded in a
single pedigree Suffolk ram. 1 *

Osteochondrosis and arthrosis arc
considered to be major causes of Teg
weakness' in rapidly growing pigs. 11
Restricting the energy intake appears to
decrease the prevalence and severity of
osteochondrosis when gilts are examined
at 100 kg. The prevalence and severity of
osteochondrosis in growing pigs is prob-
ably not related to floor type. 11 Recent
work has shown a significant relationship
between body conformation and the
presence of joint lesions. Pigs with a
narrow lumbar region, broad hams and a
large relative width between the stifle
joints were highly susceptible to poor
locomotor ability due to lesions in the
elbow and stifle joints, the lumbar
intervertebral joints and the hip joint.

This excellent work represents real
progress in understanding the relation-

j ship between skeletal conformation and
1 bone and joint lesions. It is postulated
j that inherited weakness of muscle, liga-
ments, cartilage and exterior joint con-
formation results in local overloading
in the joint and the development of
osteochondrosis and arthrosis. Some
breeds, such as the Duroc, have more
problems of structure and movement in
the front legs than in the rear legs, but
osteochondrosis is not responsible for the
leg weakness. Osteochondrosis has been
recorded in wild boar-Swedish Yorkshire
crossbred pigs in which the growth rate
was low. 12

Osteoarthrosis of the distal tarsal
joints of the horse (bone spavin)

Osteoarthrosis of the distal tarsal joints
(hock), commonly known as bone spavin,
is common in Icelandic horses and
strongly related to age. 13,14 In Icelandic
horses aged 6-12 years and used for
riding, the prevalence of radiographic
signs of osteoarthrosis in the distal tarsus
increased from 18% in horses 6 years of
age up to 54% in 12-year-old horses. The
age onset of radiographic signs reflect a
predisposition to bone spavin indicating a
trait with medium-high heritability. 13
There is a high prevalence of chondro-
necrosis in young Icelandic horses,
indicating an early onset and slow
progression of disease. 14 The disease is
the most common cause of culling due to
j disease in riding horses in the age group
j 7-17 years. 15

| PATHOGENESIS

j The details of the pathogenesis of degener-
I ative joint disease have been reviewed. 16
| A brief review of the structure and
! biochemistry of the normal articular joint
j will serve as background for understanding
j the pathogenesis of osteoarthropathy. 17
; Articular cartilage is a tissue consisting
j of chondrocytes scattered in a matrix of
; collagen fibers and an amorphous inter-
j cellular substance containing proteo-
j glycans. Articular cartilage contains no
j nerves, is avascular and has a high matrix-
j to-cell ratio. The chondrocytes are the
j only living matter in cartilage, produce
the fine strands of collagen and are
engaged in protein and proteoglycan
synthesis. The matrix of the cartilage con-
sists of water-soluble proteoglycans
interspersed with collagen fibers, which
are arranged in parallel rows superficially
and crisscross rows closer to the calcified
layer. This enables the cartilage to with-
stand shearing stresses superficially and
compression more deeply.

The proteoglycans are glycos-
aminoglycan-protein complexes, bound
by a link glycoprotein to a linear
hyaluronic acid molecule. The glycos-
aminoglycans in articular cartilage are

chondroitin 4-sulfate, chondroitin 6-sulfate
and keratan sulfate. About 75% of the
proteoglycans exist on aggregates that
protect them from degradation and,
because of their high water content, form
large polyanionic complexes that have con-
siderable elastic resistance to compression.

Nutrition of the articular cartilage is
provided via the synovial fluid and is
dependent on the capillary flow to the
synovial membrane. Nutrients flow
through the synovial fluid and diffuse
through the cartilage to the chondrocytes.
Proteoglycans are synthesized by the
chondrocytes and secreted to the cell
exterior. Proteoglycans are also degraded
intracellularly by lysosomes. The normal
equilibrium between anabolism and
catabolism is maintained by several
different low-molecular-weight proteins.
V\Tien the equilibrium is disturbed and
shifts toward catabolism, degeneration
occurs.

Primary osteoarthropathy

This is due to normal aging processes and
ordinary joint usage. The initial lesions
occur in the superficial layers of the
articular cartilages where, with increasing
age, there is loss of the normal resilience
of the cartilage, a lowering of the
chondroitin sulfate content and reduction
in the permeability of the cartilaginous
matrix, which results in progressive
degeneration of the articular cartilage.
There is grooving of the articular cartilage,
eburnation of subchondral bone and
secondary hypertrophy of marginal
cartilage and bone, with the formation of
pearl-like osteophytes. In experimentally
induced arthritis in the horse the major
changes include synovitis, increased
synovial effusion and superficial fibrillation
with chondrocyte necrosis in the articular
cartilage. These are comparable to the
early changes in naturally occurring
degenerative joint disease.

Secondary osteoarthropathy

This appears to be initiated by injuries or
congenital conformational defects that
create greater shearing stresses on parti-
cular points, in contrast to the inter-
mittent compressive stresses typical of
ordinary weightbearing. These irregular
stresses result in cartilaginous erosion,
increased density of subchondral bone at
points of physical stress and proliferation
of bone and cartilage at the articular
margins.

Following acute trauma, the initial
changes are often characterized by acute
synovitis and capsulitis. As a result of
the inflammatory response, leukocytes,
prostaglandins, lysosomal enzymes and
hyaluronidase enter the synovial fluid,
which becomes less viscous and affects
the nutrition of the cartilage. There is

Diseases of joints

some evidence of immune complexes
associated with collagen-type-specific
antibodies in horses with secondary
osteoarthritis. Cytokines can be detected
in the synovial fluid after racing in horses
with degenerative joint disease. 18 The
cartilage matrix undergoes a variety of
changes, possibly because of chondrocyte
damage with lysosomal enzyme release,
or to collagen fiber injury. There is an
increase in water content and loss of orien-
tation of the collagen fibers. Proteoglycans
are lost and, while increased chondrocyte
activity synthesizes proteoglycans, they are
of lower molecular weight and altered
glycosaminoglycan composition. This
leads to loss of elasticity and surface
integrity of the cartilage, resulting in
increased friction, blistering and ulcer-
ation. There is additional lysosomal
enzyme release from the chondrocytes,
resulting in matrix destruction and further
proteoglycan destruction. The degrading
enzymes enter the altered matrix and
cause further degradation.

The first stage of matrix degradation
involves discoloration, softening and
blistering of the tangential layer of the
cartilage surface, a process known as early
fibrillation. As the fissuring extends to the
radial layer, microfractures occur, with
loss of cartilage fragments (detritus) into
the synovial fluid. As the cartilage is
destroyed the underlying bone is exposed
and becomes sclerotic. Bony proliferation
occurs in the floor of the cartilage lesions,
while at the joint margins osteophyte
formation occurs. The pathogenesis of
degenerative joint disease indicates that
the ideal treatment would be the use of a
substance that would promote synthesis
of matrix components and retard catabolic
processes.

The major proteoglycan in cartilage is
a high-molecular-weight aggrecan that
contains chondroitin sulfate and keratin
sulfate chains located on specific regions
of the core protein. These macromolecules
are continuously released into the
synovial fluid during normal cartilage
matrix metabolism. Cartilage proteoglycans
are degraded early in the course of joint
disease and released from the cartilage
into the synovial fluid, where they can be
identified. 19

In horses with degenerative joint
disease, proteoglycan fragments -
glycosaminoglycans - have been deter-
mined in equine synovial fluid as indi-
cators of cartilage metabolism in various
types of arthritides. 19 The presence of
high-molecular-weight proteoglycans
and high concentrations of hyaluronate in
horses with various arthritides - acute or
chronic traumatic arthritis, intra-articular
fracture and infectious arthritis, with and
without abnormal radiographic and/or

arthroscopic findings - compared with
control joints has been investigated. 19

The intra-articular injection of corti-
costeroids depresses chondrocyte meta-
bolism, alters the biochemical composition
and causes morphological changes in the
articular cartilage, which remains bio-
chemically and metabolically impaired for
several or more weeks.

In femoral-tibial osteoarthrosis of
bulls the secondary degenerative joint
lesions are due to rupture of the attach-
ments of the lateral meniscus resulting in
mechanical instability in the joint with
unusual mechanical stresses on the
articular cartilage leading to degeneration.
The cranial cruciate ligament becomes
progressively worn and eventually rup-
tures, resulting in loss of all joint stability
and the development of gross arthrosis. In
cattle with severe degenerative joint
disease of the coxofemoral joints, an
acetabular osseous bulla may develop at
the cranial margin of the obturator
foramen.

Osteochondrosis

Osteochondrosis (dyschondroplasia) is
characterized by disturbance of the
normal differentiation of the cells in the
growing cartilage. Both the metaphyseal
growth plate (the growth zone of the
diaphysis) and immature joint cartilage
(the growth zone of the epiphysis) are
affected. The loss of normal differen-
tiation of the cartilage cells results in
failure of provisional calcification of the
matrix and endochondral ossification
ceases. Degeneration and necrosis of
blood vessels in cartilage canals results in
ischemia of an area of growing cartilage
followed by chondrocyte degeneration
and death. The initial lesion occurs in
growing cartilage and dyschondroplasia is
a more appropriate term. The primary
lesion of osteochondrosis directly affects
the differentiation and maturation of the
cartilage cells and the surrounding matrix
that are destined to become replaced by
bone. This can occur at the two sites of
endochondral ossification in long bones -
the articular/epiphyseal cartilage complex
and the metaphyseal growth plate. In
osteochondrosis, the capillary buds fail to
penetrate the distal region of the hyper-
trophic zone, which leads to a failure of
the final stages of cartilage maturation
and modification of the surrounding
matrix. These changes lead to retention
and thickening of cartilage with sub-
sequent weakening of the articular/
epiphyseal cartilage complex.

Typical lesions in the horse involve
extensive cartilaginous and subchondral
bone degeneration with flap formation
and, ultimately, loose pieces in the joint.
This is usually referred to as osteo-

chondritis dissecans and is associated
with synovial effusion and varying degrees
of synovitis. Osteochondral fracture
associated with severe pathological
changes to the subchondral bone occurs
most commonly on the trochlear ridges
and the lateral or medial malleoli of the
hock. In some instances, cartilage damage
weakens underlying bone and causes a
bone cyst to form, usually at a site of
biomechanical stress or weightbearing. 11

It is suggested that osteochondrosis
lesions in horses develop prior to
7 months of age and that ischemic
necrosis of cartilage secondary to a defect
in vascular supply is an important factor
in the pathogenesis of the disease in
horses. 20 An osteochondrotic lesion in the
metaphyseal growth plate may disturb
growth to such a degree that the whole
shape of the bone is altered. Epiphyseolysis
may also occur. Osteochondrosis of joint
cartilage may lead to osteochondritis
dissecans and secondary osteoarthrosis.
The lesion may heal and only the
sequelae are present once the period of
growth is over.

In rapidly growing pigs raised in
confinement with minimal exercise,
osteochondrosis and arthrosis are seen
as degeneration of the deep layer of the
articular cartilage and adjacent sub-
chondral bone with degenerative lesions
of the epiphyseal plate. Lesions in the
epiphyseal plate may result in epi-
physiolysis, which occurs most commonly
in the femoral head. The typical lesions
are usually symmetrical and commonly
involve the elbow, stifle and hip joints and
the distal epiphyseal plate of the ulna.
Lesions also occur in the intervertebral
articulations. The lesions are common in
pigs when they are examined at slaughter
(90-100 kg BW) and there may have been
no evidence of clinical abnormality or a
proportion of the pigs with severe lesions
may have been affected with the leg-
weakness syndrome. Osteochondrosis
and Enjsipelothrix rhusiopathiae are the
most common causes of nonsuppurative
joint disease of pigs examined at the
abattoir. Thus not all lesions are clinical.

CLINICAL FINDINGS

The major clinical characteristic is a
chronic lameness that becomes pro-
gressively worse over a long period of
time and does not usually respond to
treatment. The disease is insidious and
generally not clinically apparent in the
early stages. A common clinical history
is that the affected animal becomes
progressively more lame over a period of
weeks and months and prefers long
periods of recumbency. The lesion may
develop slowly over a period of weeks
and months during the convalescent

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

640

stages of an acute traumatic injury to the
joint when recovery is expected but the
animal continues to be lame. Young
breeding bulls in the early stages of
coxofemoral arthropathy may be reluctant
to perform the breeding act and yet
appear to have sufficient libido. One of
the first clinical abnormalities of osteo-
chondrosis and epiphyseolysis in young
breeding boars may be inability to mount
the sow - impotentia coeundi.

There is usually difficulty in flexing
affected joints normally, which results in a
stiff and stilted gait. In cattle confined
to stanchions one of the earliest and
persistent signs is shifting of weight from
limb to limb. In daily cattle, as the lesions
become more painful, there is a decline in
appetite and milk production, prolonged
recumbency and considerable difficulty in
rising from the recumbent state. In the
early stages there may be an apparent
remission of the lameness, but relapses
are common. The bony prominences of
the joint eventually appear more pro-
minent than normal, which is due to
disuse muscle atrophy of the affected
limbs. Distension of the joint capsule is
not a characteristic, as it is in an infectious
or suppurative arthritis. The joint capsule
of palpable joints is usually not painful on
palpation. Passive flexion of affected
joints may be painful and it may be
possible to elicit crepitus due to detached
pieces of cartilage and bone and
osteophytes surrounding the articular
cartilage. However, crepitus is most com-
mon in the large movable joints, such as
the stifle, and commonly in osteo-
arthropathy secondary to acute traumatic
injury of the meniscus and cranial cruciate
ligament of the joint.

Epiphysiolysis of the head of the femur
occurs in young pigs from 5 months to
1 year of age. There is usually a history of
slight to moderate lameness, sudden in
onset and affecting one or both hind-
limbs. The onset of lameness may coincide
with some physical activity such as
breeding, farrowing or transportation. The
lameness is progressive and in about
7-10 days the animal is unable to use its
hindlegs. Crepitus may be audible on
circumduction of the affected limb and
radiography may reveal the separation.

In leg weakness associated with
osteochondrosis and arthrosis of pigs
the common clinical findings are hyper-
flexion of the carpus, limb bowing, adduc-
tion of both forelegs at the level of the
carpus, hyperextension of the fore and
hind phalanges and anterior curvature
of the tarsus. Locomotory dysfunction
involves primarily the hindlegs. There is
pronounced swaying of the hindquarters,
and crossing the hindlegs with each step,
which makes the pig appear incoordinated.

Osteochondrosis in cattle is charac-
terized by chronic long-standing lameness,
either with or without joint effusion. 4
Joint fluid analysis is usually normal or
indicates nonseptic inflammation. The
stifle joint is most commonly affected
followed by the hock joint. In osteo-
chondrosis in young growing bulls there
is reluctance to move, stiffness, enlarge-
ment of the ends of long bones and a
straightened joint. While there may be
clinical evidence of lameness in less than
40% of affected cattle, radiographically,
88% of the lesions are bilateral. 4

Osteochondrosis in the horse is
characterized by a wide range of clinical
signs and in some cases lesions are not
accompanied by clinical signs. The most
common sign of osteochondrosis is a
nonpainful distension of an affected joint.
In foals under 6 months of age, a tendency
to spend more time lying down is
common. This is accompanied by joint
swelling, stiffness and difficulty keeping
up with the other animals in the group.
An upright conformation of the limbs
may also be present. In yearlings or older
animals the common clinical signs are
stiffness of joints, flexion responses and
varying degrees of lameness.

In the horse with osteochondrosis of
the shoulder joint there is intermittent
lameness, characterized by a swinging
leg, shoulder lameness with pain elicited
by extension, flexion or abduction of the
limb. Secondary joint disease is also a
common finding. In a retrospective study
of osteochondrosis dissecans in 21 horses,
affected animals were 8 months to 5 years
of age. The usual age of onset of clinical
abnormalities was 18-24 months. The
common presenting complaints included
joint effusion and lameness of either
gradual or sudden onset. The prevalence
was higher in males than in females.

CLINICAL PATHOLOGY
Joint fluid

The changes in the synovial fluid of joints
affected with degenerative arthropathy
are usually unremarkable and can be
distinguished from the changes in infec-
tious arthritis. A summary of the laboratory
evaluation of synovial fluid in diseases of
the joints is set out in Table 13.2. The
isolation of an infectious agent from the
synovial fluid of a diseased joint suggests
the presence of an infectious arthritis but
failure to isolate an organism must not be
interpreted as the presence of a non-
infectious arthritis. In well advanced cases
of infectious arthritis the number of
organisms may be small or they have
been phagocytosed by neutrophils in the
joint fluid.

Total protein concentration and
viscosity of synovial fluid of horses can

be determined. Normal values are
available 21 and the concentration and mol-
ecular weight distribution of hyaluronate in
synovial fluid from clinically normal
horses and horses with diseased joints
have been compared. 19,22 Synovial fluid
viscosity is reduced in horses with infec-
tious and chronic arthritides and with
radiographic evidence of cartilage degener-
ation. The synovial fluid hyaluronate
concentration can be used as a diagnostic
markerfor chronic traumatic arthritis. How-
ever, high-molecular-weight proteoglycans
or other markers in the synovial fluid
cannot be used for diagnosing or monitor-
ing degenerative joint disease. 19

Hematology and serum biochemistry
should be combined with appropriate
hematology and serum biochemistry
where indicated. The concentration of
hyaluronic acid in synovial fluid can be
determined using an assay technique. The
determination of serum calcium and
phosphorus may reveal the existence of
a dietary deficiency or imbalance of
minerals.

Radiography

Radiography of the hock joints in a
craniomedial-caudolateral oblique view
and of the fetlock joints in lateromedial
view are standard techniques for the
diagnosis of osteochondrosis in the horse.
Those joints with abnormal radiographs
may be radiographed from additional
perspectives. Horses with bony fragments
or defects at the cranial edge of the
intermediate ridge of the distal aspect of
the tibia or defects at the lateral trochlea
of the talus can be classified as having
osteochondrosis. 2 The radiographic
progression of femoropatellar osteo-
chondrosis in horses under 1 year of age
at the onset of clinical signs has been
examined. 22 The full extent of the radio-
graphic lesions may take several weeks to
develop.

Arthroscopy

Arthroscopic examination and surgery of
affected joints of horses with osteo-
chondrosis can provide considerably
more information than is possible from
clinical and radiographic examination
alone. 23

NECROPSY FINDINGS

In degenerative joint disease the joint
cartilage is thin or patchily absent and
polished subchondral bone is evident. The
articular surfaces are irregular and some-
times folded. Exposed bone may be
extensively eroded and osteophytes (small
bony excrescences, like pearls) may be
present on the nonarticular parts of the
joint on the circumference of the articular
cartilage. The synovial fluid is usually only
slightly increased in volume and appears

Diseases of joints

641

fkaikif4>®i > ©«@rt&r l.bJ'I («?■ }a«n*!g ;

Synovial fluid
analysis

Normal joint

Degenerative

arthropathy

Infectious arthritis

Gross appearance

Colorless, clear

Pale yellow, may
contain flocculent
debris

Turbid, yellow

Total volume

-

Normal or slight
increase

Usually marked increase

Clot formation

No clot

No clot

May clot within minutes
after collection

Erythrocytes (piL)

< 4000

6000-12 000

4000-8000

Leukocytes (pL)

< 250

250-1000

50 000-150 000

Neutrophils (%)

7

10-15

80-90

Lymphocytes (%)

35-40

45-50

4-8

Monocytes (%)

45-50

35-40

1-3

Microbiology

May be able to culture
bacteria, mycoplasma or
virus, but not always

Total protein (g/dL)

1.2-1 .8

1.6-1 .8

3.20-4.5

Relative viscosity

-

Slightly reduced

Decreased

pH

-

-

Decreased

Other laboratory analyses of synovial fluid include: sugar content, alkaline phosphatase activity, lactic
dehydrogenase activity, aldolase activity, glumatic oxaloacetic transaminase activity, glutamic pyruvic
transaminase activity, mucinous precipitate quality

amber-colored. Menisci, intra-articular,
cartilages and ligaments may be entirely
absent and there may be areas of calcifi-
cation in the joint capsule and cartilages
free in the synovium. When the stifle is
affected, fractures of the head of the tibia
occur commonly, usually a chip of the
lateral condyle having become separated.
In such cases, fractures of the lateral
condyle of the distal end of the femur may
follow. With either of these fractures,
lameness is extreme and the animal may
often refuse to rise.

The radiographic and pathological
findings of femoral-tibial osteoarthrosis
in bulls is described. When the hip joint of
bulls is affected, the head of the femur
becomes smaller and more flattened than
normal, the acetabulum is shallower and
the round ligament is usually ruptured.
The pathology of coxofemoral arthropathy
is young bulls is described.

The pathological changes in experi-
mentally induced osteoarthritis in the
horse are similar to the early changes of
naturally occurring degenerative joint
disease.

In osteochondrosis there is splitting
and invagination of articular cartilage,
loss of articular cartilage, chip fractures of
condyles, exposed and collapsed sub-
chondral bone, osteophyte formation
around the circumference of the articular
cartilage and loose pieces of cartilage in
the joint. In the epiphyseal plates (e.g.,
the distal ulna in pigs with leg weakness)
the cartilage is uneven and thickened
with hemorrhage, fibrous tissue, collapse
of bone tissue in the metaphysis and
epiphyseal separation. Complete separation
of the epiphysis occurs most commonly at

the head of the femur. The ultrastructural
appearance of nonnal epiphyseal cartilage
of the articular-epiphyseal cartilage
complex in growing swine has been
examined and serves as a standard for
comparison with the lesions in affected
pigs.The lesions may be present in pigs at
an early age as part of the usual growth
pattern of cartilages.

In equine osteochondrosis
(dyschondroplasia), the histological
lesions can be divided into two groups. 24
In one group there are accumulations of
small rounded chondrocytes, areas of
necrosis and chondrocyte clusters. In the
second group, there are alterations in the
appearance of the mineralized matrix,
areas of necrosis, chondrocyte clusters
and an alteration in type VI collagen
immunoreactivity within the chondrocyte
clusters.

TREATMENT

The treatment of arthropathy depends
largely upon correction of the cause, but
in most cases the lesions are progressive
and irreparable and food-producing
animals should be slaughtered for sal-
vage. Tarsal degenerative joint disease in
cattle has been treated with intra-articular
injections of corticosteroids and has
provided temporary relief from pain and
discomfort. However, the corticosteroids
do not promote healing of the joint and
their use in arthropathy may actually
accelerate erosion of articular cartilage,
loss of joint sensation and the develop-
ment of'steroid arthropathy'. Large doses
of acetylsalicylic acid may be given to
reduce pain in animals that are kept for
breeding purposes.

DIFFERENTIAL DIAGNOSIS

Osteoarthropathy is characterized clinically
by a chronic lameness that becomes
progressively worse and usually does not
respond to treatment. The gait is stiff,
there is disuse muscle atrophy, the bony -
prominences of the joint are more
apparent but usually there is no marked
distension and pain of the joint capsule, as
in infectious arthritis. Examination of
synovial fluid may aid in differentiation
from infectious arthritis.

Radiographically there is erosion of
articular cartilage, sclerosis of subchondral
bone and periarticular accumulations of
osteophytes. In the early stages of the
disease in large animals, radiographic
changes may not be visible and repeated
examinations may be necessary. The
radiographic changes of osteochondrosis in
the shoulder joint of the horse consist of:

• Alteration in the contour of the
humeral head and glenoid cavity

• Periarticular osteophyte formation

• Sclerosis of the subchondral bone

• Bone cyst formation.

The literature on the medical manage-
ment of osteoarthritis in the horse has
been reviewed. 25 There are many choices
available for controlling inflammation in
osteoarthritis. Treatment is symptomatic
and largely nonspecific.

Nonsteroidal anti-inflammatory
agents

Several nonsteroidal anti-inflammatory
drugs (NSAIDs), such as phenylbutazone,
flunixin meglumine, ketoprofen,
naproxen, and carprofen, are available
treatment options. Each has associated
toxicities. They are now the most com-
monly used drugs because of their anal-
gesic, antipyretic and anti-inflammatory
properties. 25 They inhibit some component
of the enzyme system that converts
arachidonic acid into prostaglandins
and thromboxanes. All cells, including
chondrocytes and synoviocytes, possess
arachidonic acid as a fatty acid consti-
tuent of phospholipids. Once released,
arachidonic acid is oxidized by either
cyclooxygenase (COX) or 5-lipooxygenase.
COX oxidation leads to prostaglandin
production, while lipoxygenase oxidation
leads to leukotriene formation. The effect
of NSAIDs is primarily from inhibiting
COX, which blocks arachidonic acid
conversion to prostaglandin.

Intra-articular steroids

Various steroidal formulations for intra-
articular administration are available and
correct dosage, frequency of adminis-
tration, indications and toxicity are factors
to consider for each drug. They include
methylprednisolone acetate, betametasone,
and triamcinolone acetonide. 25

12

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

Chondroprotective agents

Various chondroprotective drugs such as

hyaluronic acid, polysulfated glycos-
aminoglycan, and oral glucosamine-
chondroitin sulphate are also used to
control inflammation and provide
viscosupplementation. 25

There is a notable lack of treatment
information based on randomized, blinded
placebo-controlled clinical trials in the
horse to identify the efficacy of therapeutic
agents for both symptomatic and disease-
modifying activity in degenerative joint
disease. 25 Until there are validated out-
come measures that can be used practically
in clinical trials, there will always be
uncertainty about whether these thera-
peutic agents have any real disease-
modifying action. 26

Hyaluronic acid

The changes in the synovia following the
intra-articular injection of sodium
hyaluronate into normal equine joints
and after arthrotomy and experimental
cartilage damage have been examined,
but in general the results are inconclusive.

Polysulfated glycosaminoglycans
Polysulfated glycosaminoglycans have
been reported to induce articular cartilage
matrix synthesis and to decrease matrix
degradation. 27 Experimentally, intra-
articular injections of polysulfated
glycosaminoglycan provides some
protection against chemically induced
articular cartilage damage but not against
physical defects of articular cartilage in
the horse. The polysulfated glycos-
aminoglycans inhibit lysosomal enzymes
and neutral proteases. The allo-
transplantation of synovial fluid into the
joints of horses with arthropathies has
been examined. A survey of the use of
polysulfated glycosaminoglycans by equine
practitioners for the treatment of lame-
ness in horses found that the drug is
moderately effective overall and is con-
sidered most beneficial in the treatment
of subacute degenerative joint disease. 28
Its efficacy for incipient and chronic forms
of degenerative joint disease is considered ;
comparable to that of sodium hyaluronate.

The prevention of further trauma
should be assured and possible nutritional
causes corrected. The treatment of active
disease, particularly in soft tissues, that is
contributing to articular degeneration
includes rest, immobilization, physical
therapy, intra-articular injections of
corticosteroids, NSAIDs, joint lavage and
intra-articular injection of sodium
hyaluronate, all of which have been used
with variable success. 29

Other treatments

Surgical therapy includes curettage of
articular cartilage, removal of osteophytes

and surgical arthrodesis. 29 In a retro-
spective study of stifle lameness in
42 cattle admitted to two veterinary
teaching hospitals over a period of
6 years, 18 had radiographic evidence of
subchondral bone cyst without radio-
graphic evidence of degenerative joint
disease. The prognosis in those with a
subchondral bone cyst was favorable,
75% returning to their intended function,
while in septic arthritis only 22% returned
to normal.

Chemical arthrodesis using the intra-
articular injections of monoiodoacetate
(MIA) has been described as an alter-
native to surgical arthrodesis for the
treatment of degenerative joint disease of
the distal tarsal joints. 30 MIA causes an
increase in intracellular concentration of
adenosine triphosphate resulting in
inhibition of glycolysis and cell deaths. It
causes dose-dependent cartilage degener-
ation characterized by cartilage fibrillations,
chondrocyte death and glycosaminoglycan
and proteoglycan depletion. MIA pro-
duces reliable radiographic and histo-
logical ankylosis of the distal tarsal joints.
Resolution of the lameness required
12 months and occasionally longer. Sound-
ness was achieved in 82% and 85% of
horses at 12 and 24 months, respectively.
Complications of the injections were
uncommon and were probably related to
peri-articular injection or leakage of MIA,
or to use of higher concentrations or
volumes. Postinjection pain was marked
in a small number of horses but was
transient and managed effectively with
analgesic drugs. The procedure is contro-
versial. 31 Some clinicians argue that
arthrodesis should only be used where
lameness is localized to the tarsometatarsal
and centrodistal joints with objective
means such as local analgesic techniques,
and when other more conservative treat-
ments have failed.

CONTROL AND PREVENTION

Prevention of osteoarthropathy will
depend upon recognition and elimination
of the predisposing causes: provision of
an adequate diet and the avoidance of
ovemutrition; regular exercise for confined
animals; the provision of suitable flooring to
minimize persistent concussion and the
use of breeding stock that have a body
conformation that does not predispose to
joint lesions.

REVIEW LITERATURE

Clegg P. Therapy for osteoarthritis in the horse - how
do we know that it works? Vet J 2006; 171:9-10.
Goodrich LR, Nixon AJ. Medical treatment of
osteoarthritis in the horse: a review. Ve t J 2006;
171:51-69.

REFERENCES

1. Sandgen B et al. Equine Vet J Suppl 1993; 16:31,
38, 48.

2. Grondahl AM, Dolvik NI. J Am Vet Med Assoc
1993; 203:101.

3. Magnusson LE, Ekman S. Acta Vet Scand 2001;
42:429.

4. Trostle SS et al. J Am Vet Med Assoc 1997;
211:1566.

5. Davies IH et al. Cattle Pract 1998; 4:243.

6. Davies IH, Munro R. Vet Rec 1999; 145:232.

7. Hill BD et al. AustVet J 1998; 76:171.

8. Scott PR et al. Vet Rec 2000; 147:608.

9. Scott CA et al. Vet Rec 1996; 139:165.

10. Doherty ML et al.Vet Rec 1996; 138:137.

11. RayCS et al. EquineVetJ 1996; 28:225.

12. Uhlorn H et al. Acta Vet Scand 1995; 36:41.

13. Arnason T, Bjomsdottir S. Livestock Prod Sci
2003; 79:285.

14. Bjomsdottir S et al. Equine Vet J 2004; 36:5.

15. Bjomsdottir S et al. Acta Vet Scand 2003; 44:161.

16. Clyne MJ. Equine Vet J 1987; 19:15.

17. Fhlmer JL, Bertone AL. Equine Vet ] 1994; 26:263.

18. Billinghurst RC et al. Equine Vet J 1995; 27:208.

19. Tulamo RM et al. Am J Vet Res 1996, 57:932.

20. Carlson CS et al. Vet Pathol 1995; 32:641.

21. Tulamo RM et al. Am J Vet Res 1994; 55:710.

22. Davbareiner RM et al.Vet Surg 1993; 22:515.

23. Mcllwraith CW. EquineVetJ Suppl 1993; 16:27.

24. Henson FMD et al.Vet J 1997; 154:53.

25. Goodrich LR, Nixon AJ.VetJ 2006; 171:51.

26. Clegg PD. Vet J 2006; 171:9.

27. Todhunter RJ, Lust G. J Am Vet Med Assoc 1994;
204:1245.

28. Caron JP, Kaneene JB. J Am Vet Med Assoc 1996;
209:1564.

29. Mcllwraith CW. J Am Vet Med Assoc 1982;
180:239.

30. Dowling BA et al. AustVet J 2004; 82:38.

31. Whitton C.AustVetJ 2004; 82:286.

ARTHRITIS AND SYNOVITIS

Inflammation of the synovial membrane
and articular surfaces as a result of infec-
tion occurs commonly in farm animals. It
is characterized by varying degrees of
lameness and a warm and swollen painful
joint. The synovial fluid is usually abnor-
mal, containing an increased leukocyte
count and the pathogens causing the
arthritis. The arthritis may be severe
enough to cause systemic illness, and in
some cases a draining sinus tract may
occur.

ETIOLOGY AND EPIDEMIOLOGY

Specific bacterial infections of the joints
are most common in newborn farm
animals, in which localization of infection
occurs in joints following bacteremia or
septicemia. Surveys of Thoroughbred
studs have shown that the incidence of
infectious arthritis is higher in foals with
other perinatal abnormalities and in
which the ingestion of colostrum was
delayed for more than 4 hours after birth.
Calves with hypogammaglobulinemia are
particularly susceptible to bacteremia and
meningitis, ophthalmitis and arthritis.
Some of the important infectious causes
of arthritis are as follows.

Calves

° Nonspecific joint-ill from

omphalophlebitis associated with

Diseases of joints

6 '

A. pyogenes, Fusobacterium
necrophorum, Staphylococcus sp.

o Erysipelothrix rhusiopathiae
sporadically in older calves

o Salmonella dublin, Salmonella

lyphimurium and Mycoplasma bovis.

Lambs

b E. rhusiopathiae in newborn and
recently tail-docked lambs

<> Sporadic cases associated with
F. necrophorum, Staphylococcus sp.,
Corynebacterium pseudotuberculosis,
Histophilus somni, Mannheimia
haemolytica

<• Chlamydophila spp. cause polyarthritis
extensively in feedlot lambs
In tick pyemia associated with
Staphylococcus aureus.

Foals

■ Actinobacillus equuli, Rhodococcus equi,
Salmonella abortivoequina in the
newborn

Chlamydophila sp. has caused
polyarthritis in foals.

Piglets

' Streptococci, Lancefield groups C, E,
and L

- Streptococcus suis

E. rhusiopathiae in pigs of any age. Up
to 65% of joints of pigs at slaughter
are affected and up to 80% of the
farms from which the pigs come do
not vaccinate for erysipelas. Mortality
in preweaning groups of pigs may
affect 18% of litters, 3.3% of the
piglets with a herd mortality of 1.5%

° In a 4-year period in a swine research
station, 9411 piglets were born alive
and 9.8% were treated for lameness. 1
About 75% of the cases were observed
in piglets under 3 weeks of age. The
incidence of lameness was much
higher in piglets born from sows of
parity 3 (11.4%) compared to piglets
born to sows of parity 4-7 (8%).

Cattle

Histophilus somni is a cause of
synovitis

Mycoplasma agalactia var. bovis is a
common cause of synovitis, arthritis
and pneumonia in young feedlot
cattle

Mycoplasma bovigenitalium may cause
mastitis in cows, with some animals
developing arthritis

- Mycoplasma mycoidcs may cause
arthritis in calves vaccinated with the
organism against contagious bovine
pleuropneumonia. Calves already
sensitive to the organism develop an
immediate-type allergic reaction of
the synovial membrane

,J Brucella abortus: occasional cows with
brucellosis develop an arthrodial
synovitis

p Some cases of ephemeral fever have a
sterile arthritis

° BVD virus in young bulls, rarely
° Idiopathic septic arthritis in dairy
heifers. The etiology is unknown
° Septic arthritis of the proximal
interphalangeal (pastern) joint in
cattle due to perforating wounds. 2
A. pyogenes is the most common cause
in cattle.

Sheep and goats
° As part of melioidosis

Mycoplasma sp. of serositis - arthritis
° Streptococcus dysgalactiae in dairy
goats.

Pigs

° Glasser's disease
° Mycoplasma sp. in synovitis and
arthritis of growing pigs especially in
housed pigs

° Brucella suis commonly infects bones,
especially vertebrae, and joints.

Horses

° Septic arthritis after penetrating
wounds, intra-articular injection of
corticosteroids, and surgery; young
foals under 6 months of age usually
associated with a septicemia; adult
horses without a known etiology
« In a series of 34 cases of

monoarticular infectious arthritis in
adult horses admitted to a veterinary
teaching hospital over a period of
10 years, 16 had a penetrating wound
over the joint, four had a puncture
wound of the sole and in five the
infection was iatrogenic (three had
received intra-articular corticosteroids,
one had received intra-articular
anesthesia and one had sepsis after a
purulent thrombophlebitis)."’ In nine
cases, no cause could be determined
" Spread to the joints from generalized
strangles

c Rare cases of non-erosive

polysynovitis in a horse, possibly
immunological and immune-
mediated polysynovitis in foals 4
Acedosporium prolificans, a newly
recognized opportunistic fungus, has
been associated with an incurable
arthritis and osteomyelitis in a mature
horse. 5

All species

Sporadic cases are due to:

' Traumatic perforation of the joint
capsule

« Spread from surrounding tissues, e.g.
footrot to interphalangeal joints in
cattle and pigs, interdigital abscess in
sheep

° Hematogenous spread from
suppurative lesions commonly in
udder, uterus, diaphragmatic abscess.

infected navel or tail, castration
wound.

PATHOGENESIS

In infectious arthritis that is hemato-
genous in origin there is usually a
synovitis initially, followed by changes in
the articular cartilages and sometimes
bone. With almost any systemic infection
there may be localization of the infectious
agent in the synovial membrane and joint
cavity. The synovial membrane is inflamed
and edematous, and there are varying
degrees of villous hypertrophy and
deposition of fibrin. Bacteria colonize in
synovial membranes, which makes treat-
ment difficult. The synovitis causes dis-
tension of the joint capsule with fluid and
the joint is painful and warm. Successful
treatment and elimination of infection at
this early stage of synovitis will minimize
changes in articular cartilage and bone
and healing will result. A progressive
infectious synovitis commonly results in
pannus formation between articular
surfaces with erosion of articular carti-
lage, infection of subchondral bone and
osteomyelitis. In the chronic stages there
is extensive granulation tissue formation,
chronic synovitis and degenerative joint
disease with osteophyte formation, and
ankylosis is possible. Depending on the
organism, the arthritis may be suppurative
or serofibrinous. Suppurative arthritis is
particularly destructive of cartilage and
bone and commonly there is rupture of
the joint capsule. In foals with septic
arthritis there may be a concurrent poly-
osteomyelitis, usually in either the epi-
physis and/or the metaphysis of the long
bones.

Experimental infectious arthritis in
calves

Septic arthritis induced by E. coli is a
reliable and reproducible model of
infectious arthritis in laboratory animals,
horses and calves. 6 The inoculation of
E. coli into the tarsal joint of newborn
colostrum-fed calves resulted in septic
arthritis in all calves. Clinical signs of
septic arthritis appeared on day 2 after
infection and persisted until day for all
calves. E. coli was cultured from synovial
fluid on day 2 for one calf and until day 4
for five other calves. Polymerase chain
reaction (PCR) for E. coli was positive in
the synovial fluid of all calves. Synovial
fluid neutrophil and white blood cell
counts were increased on days 2-4. All
bacterial cultures were negative on day 8,
although clinicopathological signs of
inflammation persisted until day 20.
Rapid recovery occurred within 1 week
when an appropriate treatment was
begun early in the course of the disease.

644

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

Foals with septicemia

Septicemic foals may develop infectious
arthritis and a concurrent polyosteomyelitis
because of the patency of transphyseal
vessels in the newborn foal; this allows
spread of infection across the physes with
the development of lesions in the rneta-
physis, epiphysis and adjacent to the arti-
cular cartilage. The syndrome is classified
according to the location of the lesions:

0 A foal with S-type septic

arthritis-osteomyelitis has synovitis
without macroscopic evidence of
osteomyelitis

3 Foals with E-type osteomyelitis have
osteomyelitis of the epiphysis at the
subchondral bone -cartilage junction
° Those with P-type have osteomyelitis
directly adjacent to the physis
° The same joint may have a single type
or any combination of types but most
foals with the S-type have concurrent
bone lesions.

Horses

Septic arthritis has been reproduced
experimentally in horses and the sequential
synovial fluid changes monitored. Follow-
ing intra-articular inoculation of S. aureus,
clinical signs are evident as early as 8 hours
after infection. A high and persistent
neutrophilia is one of the earliest and
most accurate diagnostic abnormalities.
The total white blood cell count rises
within 12-24 hours to a mean value of
100 x 10 9 /L. Total protein also increases.
Synovial fluid acidosis also occurs in
infectious arthritis, which may interfere
with the antibacterial activity of some
antimicrobials. In experimental arthritis,
the synovial pH declined from a mean
value of 7.43 to 7.12. Bacteria could be
detected in 40% of the smears of infected
synovial fluid samples and primary cultures
of the fluid were positive in 70%. The intra-
articular inoculation of E. coli into horses
induces a reliable, reproducible and
controlled model of infectious arthritis
consistent with the naturally occurring
disease and has been used to evaluate the
efficacy of gentamicin for treatment. The
injection of E. coli lipopolysaccharide into
various joints of horses can cause clinical
signs of endotoxemia, and the synovial
fluid total nucleated cell count and total
protein are linearly responsive in increases
in endotoxin. 7

Endothelin (ET)-l, a 21-amino-acid
polypeptide, is locally synthesized in the
joints of horses with various forms types
of joint disease. 8 It induces a potent and
sustained vasoconstriction. Synovial fluid
concentrations of ET-1 varies among
horses with joint disease, with higher
concentrations in animals with joint
sepsis suggesting a pathogenetic role in
septic arthritis.

Synovial fluid in infectious arthritis in
the horse may contain the proteolytic
enzymes collagenase and caseinase
which may derive from both synovial cells
and neutrophils. 5 These enzymes are
involved in the degradation of connective
tissue and loss of cartilage matrix. Lavage
of affective joints is intended to remove
these enzymes.

Infectious arthritis may occur follow-
ing traumatic injury to a joint but the
pathogenesis is obscure. Traumatic injury
of the joint capsule resulting in edema
and inflammation may allow latent
organisms to localize, proliferate and
initiate an arthritis.

CLINICAL FINDINGS

Inflammation of the synovial membrane
causes pain and lameness in the affected
limb, sometimes to the point that the
animal will not put it to the ground. Pain
and heat are usually detectable on pal-
pation and passive movement of the joint
is resented. The joint may be swollen but
the degree will depend on the type of
infection. Pyogenic bacteria cause the
greatest degree of swelling and may result
in rupture of the joint capsule. Some
enlargement of the epiphysis is usual and
this may be the only enlargement in
nonpyogenic infections, particularly that
associated with E. insidiosa.

Fever, inappetence to anorexia, endo-
toxemia, loss of body weight and dis-
comfort may occur in animals with only
one severely affected joint or when
several joints are less severely affected.

In many of the neonatal infections
there will also be an accompanying
omphalophlebitis and evidence of lesions
in other organs, particularly the liver,
endocardium and meninges. Arthritis in
older animals may also be accompanied
by signs of inflammation of the serous
membranes and endocardium when the
infection is the result of hematogenous
localization.

The joints most commonly involved
are the hock, stifle and knee but infection
' of the fetlock, interphalangeal and inter-
vertebral joints is not uncommon. In
chronic cases there may by physical
impairment of joint movement because of
fibrous thickening of the joint capsule,
periarticular ossification and rarely
ankylosis of the joints. Crepitus may be
detectable in joints where much erosion
has occurred.

In newborn and young animals,
involvement of several joints is common.
The joints may become inflamed simul-
taneously or serially. Lameness is often so
severe that affected foals lie down in
lateral recumbency most of the time and
may have to be assisted to rise. Decubitus
ulcerations due to prolonged recumbency

are common. The gait may be so impaired
as to suggest ata>ia of central origin.

The prognosis in cases of advanced
septic arthritis is poor. Neglected animals
may die or have to be destroyed because
of open joints or pressure sores. The sub-
sequent development of chronic arthritis
and ankylosis may greatly impede loco-
motion and interfere with the usefulness
of the animal.

CLINICAL PATHOLOGY
Arthrocentesis

Aspiration of joint fluid for culture and
analysis is necessary for a definitive
diagnosis. Careful disinfection of the skin
and the use of sterile equipment is
essential to avoid the introduction of
further infection.

Analysis of joint fluid

Total and differential cell count, total
protein concentration and specific gravity
are determined.

In infectious arthritis the volume of
joint fluid is increased and the total
leukocyte count is increased, with a high
percentage (80-90%) of neutrophils. The
severity of infectious arthritis may be
manifested systemically by a leukocytosis
with a marked regenerative left shift. In
degenerative joint disease, the volume
may be normal or only slightly increased
and the total and differential leukocyte
count may be manifested within the
normal range. In traumatic arthritis there
may be a marked increase in the number
of erythrocytes. Special biochemical
examinations of joint fluid are available
that measure for viscosity, strength of the
mucin clot and concentrations of certain
enzymes. The laboratory findings in
examination of the joint fluid are sum-
marized in Table 13.2. The synovial fluid
analysis of 130 cases in cattle compared
the characteristics of animals with infec-
tious and noninfectious arthritis. 10

Culture of joint fluid

Joint fluid must be cultured for aerobic
and anaerobic bacteria and on specific
media when Mycoplasma sp. is suspected.
It is often difficult to isolate bacteria from
purulent synovial fluid. The rates of
recovery of organisms vary from 40-75%.
In one study of suspected infectious
arthritis in 64 horses admitted to a
veterinary teaching hospital over a period
of 8.5 years, positive cultures were
obtained from 55% of the joints sampled. 11
The most common organisms were
S. aureus, E. coli and Pseudomonas aeruginosa,
accounting for more than half the isolates
obtained.

There is no single test that is reliable
for the diagnosis of septic arthritis. Failure
to isolate organisms on culture does
not exclude the a bacterial cause, and

Diseases of joints

645

organisms are often not observed in
synovial fluid smears. Poor collection,
storage and laboratory techniques, prior
administration of antibiotics or partial
success of the immune system in contain-
ing the infection may explain the failure
to detect organisms. Arthrocentesis should
be done before antibiotics are given and a
blood culture bottle should be inoculated
immediately, a Gram stain made and
culture for anaerobes included. 12 Positive
cultures from synovial fluid can be
expected in only about 65% of cases.

A biopsy sample of synovial mem-
brane may be more reliable than synovial
fluid for culture but there is little evidence
based on comparative evaluations to
support such a claim. PCR has been
examined in in-vitro studies to detect
selected bacterial species in joint fluid
compared with microbial culture. 13 The
benefits would include rapid and accurate
diagnosis infectious arthritis, ability to
detect bacteria in synovial fluid in the
presence of antimicrobial drugs and diag-
nosis of infectious arthritis when culture
results are inconclusive. However, initial
studies found no difference between
microbial culture and PCR analyses.

Serology of joint fluid

Serological tests may be of value in
determining the presence of specific
infections with Mycobacterium mycoides, i
Salmonella spp., Brucella spp., and
E. insidiosa. Radiographic examination
may aid in the detection of joint lesions
and can be used to differentiate between
inflammatory and degenerative changes.

In foals with arthritis and suspected
osteomyelitis there may be radiographic
evidence of osteolysis of the metaphysis
or epiphysis.

Radiography

Radiography of the affected joint will
often reveal the nature and severity of the
lesions. Typical radiographic findings of
septic arthritis include osteolytic lesions
of the articular cartilage, increased width
of intra-articular joint space, and soft
tissue swelling. Osteomyelitic changes are
seen in some cases. Because radiographic
changes usually appear after 2-3 weeks
when destruction of subchondral bone
has become extensive, it may be necess-
ary to take a series of radiographs several
days apart before lesions are detectable.

Ultrasonography

Arthrosonography is an effective, fast
and noninvasive complement to traditional
diagnostic techniques for comprehensive
evaluation of the pathology of joints of
cattle. 14 Distension of the joint cavities
can be imaged; assessing echogenicity,
acoustic enhancement and ultra-
sonographic character of the exudate cor-

relates well with findings by arthrocentesis,
arthrotomy or at necropsy. Joint effusion,
which is the earliest indication of septic
arthritis, can usually be detected with
ultrasound by an experienced operator in
the early stages. The synovial membrane,
synovial fluid, ligaments, tendons and
periarticular soft tissue, only inadequately
imaged by radiography, can be imaged
with ultrasonography. In advanced septic
arthritis, ultrasonography provides
accurate information on the location of
the soft-tissue swelling, the extent and
character of the joint effusion and involve-
ment of concurrent periarticular synovial
cavities.

Arthroscopy

Endoscopy is now used widely to define
joint abnormalities more clearly and to
gain access to the joint cavity as an aid in
the treatment of septic arthritis. 15

NECROPSY FINDINGS

The nature of the lesions varies with the
causative organism. The synovial mem-
brane is thickened and roughened and
there is inflammation and erosion of the
articular cartilage. There is usually an
increase in the amount of synovial fluid
present, varying from a thin, clear, serous,
brownish fluid through a thicker, sero-
fibrinous fluid to pus. There may be some
inflammation of the periarticular tissues
in acute cases and proliferation of the
synovial membrane in chronic cases. In
the latter, plaques of inspissated necrotic
material and fibrin may be floating free in
j the synovial fluid. Infectious arthritis due
| to A. pyogenes is characterized by extensive
i erosion and destruction of articular carti-
j lage and extensive suppuration. There
j may be a primary omphalophlebitis in
| newborn animals and metastatic abscesses
j may be present in other organs.

j Infectious arthritis is characterized
\ clinically by swollen joints which are painful
! and warm to touch, and lameness of
j varying degrees of severity. The volume of
! joint fluid is usually markedly increased and
j the leukocyte count is increased with a
| high percentage of neutrophils. In the early
stages of synovitis and in chronic
! nonsuppurative arthritis, the joint may not
I be visibly enlarged and careful examination
by palpation may be necessary to reveal
j abnormalities of the joint capsule.

| Lameness is common, however, even
I though only slight in some cases, and
should arouse suspicion of the possibility of
arthritis.

• The diseases of the musculoskeletal
system that cause lameness and
stiffness of gait include;

• Degenerative joint disease

• Osteodystrophy and epiphysitis

• Osteomyelitis

• Degenerative myopathy

• Myositis

• Traumatic injuries of tendons and
ligaments

• Diseases of the nervous system,
especially the peripheral nerves and
spinal cord, may be confused with
arthritis unless the joints are examined
carefully

• Some severe cases of polyarthritis may
cause recumbency that may be
erroneously attributed to the nervous
system.

Degenerative joint disease is

characterized by an insidious onset of
moderate lameness and stiffness of gait
that becomes progressively worse over
several weeks. The joint capsule is usually
not grossly enlarged and not painful, and
there is usually no systemic reaction. The
total leukocyte count in the joint fluid is
only slightly increased and the differential
count may be normal. Chronic arthritis is
often difficult to differentiate clinically from
degenerative joint disease. Chronic arthritis
is more common in young animals than in
older animals such as rapidly growing
yearling bulls, adult bulls, aged dairy cows
and horses, in which degenerative
arthropathy is most common. A sudden
onset of acute lameness and marked
swelling of a joint with severe pain
suggests an infectious arthritis or traumatic
injury to the joint. Marked swelling of
several joints suggests infectious
polyarthritis.

Osteodystrophy is characterized by:

• Lameness and stiffness of gait

• Usually an absence of joint capsule
abnormalities

• Enlargements and deformities of the
long bones in growing animals

• A number of animals may be affected
at about the same time.

Radiography may reveal the abnormal
bones and the nutritional history may
explain the cause.

Degenerative myopathy causes acute
lameness, a stiff and trembling gait, often
leading to recumbency and absence of
joint or bone involvement.

Traumatic sprains of tendons or
ligaments and fractures of the epiphyses
may cause lameness and local pain and,
when they involve periarticular tissues, may
be difficult to differentiate from arthritis.

Arthritis is never present at birth and
apparent fixation of the joints should
arouse suspicion of a congenital anomaly.
The differentiation between arthritis and
diseases of the peripheral nerves or spinal
cord, both of which can cause lameness
and/or recumbency, may be difficult if the
arthritis is not clinically obvious. Diseases of
the peripheral nerves cause lameness due
to flaccid paralysis and neurogenic atrophy.
Lesions of the spinal cord usually result in
weakness of the hindlimbs, weak or absent
withdrawal reflexes and loss of skin
sensation.

16

PART 1 GENERAL MEDICINE ■ Chapter 13: Diseases of the musculoskeletal system

TREATMENT

Parenteral antimicrobials

Acute septic arthritis should be treated as
art emergency to avoid irreversible changes
in the joint. The conservative approach is
the use of antimicrobials given parenterally
daily for several days and up to a few
weeks in some cases. The selection of the
drug of choice will depend on the sus-
pected cause of the arthritis. The anti-
microbial sensitivities of bacterial isolates
from horses with septic arthritis/synovitis
or osteomyelitis after fracture repair vary
widely. A combination of cephalosporin
and amikacin is recommended before
culture and sensitivity results are
available.

The antimicrobials that perfuse into
the joint in therapeutic concentrations
include the natural and synthetic
penicillins, tetracycline, trimethoprim-
potentiated sulfonamides, neomycin,
gentamicin, and kanamycin.

Cloxacillin, methicillin, or penicillin
have been used successfully for the treat-
ment of staphylococcal septic arthritis in the
horse.

Amphotericin B given intravenously
daily for up to 30 days combined with
joint drainage has been used for the
treatment of Candida sp. arthritis in the
horse. 16

The relative efficacies of antimicrobials
administered parenterally versus by intra-
articular injections has been uncertain.
Trimethoprim-sulfadiazine, given to
calves parenterally, results in therapeutic
concentrations of the drug in the synovial
fluid of calves and penetrability was not
enhanced nor restricted by experimental
joint inflammation. Oxytetracycline and
penicillin given parenterally readily
penetrate the synovial membrane of both
normal neonatal calves and those with
experimental arthritis. Since peak synovial
joint fluid levels of oxytetracycline and
penicillin exceeded the minimum inhi-
bitory concentrations for organisms such
as A. pyogenes, the use of parenteral
antimicrobials for the treatment of infec-
tious arthritis in calves is appropriate.
Ceftiofur at 1 mg/kg BW intravenously
every 12 hours for 20 days, along with
joint lavage, was successful in treating
experimental septic arthritis associated
with E. coli. ( ' The duration of antibiotic
therapy is empirical; 3 weeks is rec-
ommended. Cephapirin administered
parenterally to normal calves or those
with arthritis resulted in synovial fluid
levels approximately 30% of serum levels.
The use of ampicillin trihydrate in calves
with suppurative arthritis, at a dose of
10 mg/kg BW intramuscularly, resulted in
a peak serum concentration of 2.5 pg/mL,
2 hours after injection; the highest
concentration in normal synovial fluid

was 3.5 pg/mL at 4 hours and the highest
concentration in suppurative synovial
fluid was 2.7 pg/mL at 2 hours.

Marbofloxacin at 4 mg/kg BW intra-
muscularly daily for 10 days was effective
for the treatment of infectious arthritis in
calves. 17 Amoxicillin at 40 mg/kg BW
intravenously is effective for the treatment
of infectious joint disease in horses. 18

The administration of trimethoprim-
sulfadiazine at 30 mg/kg BW orally once
daily to horses with experimentally
induced S. aureus arthritis was ineffective
in maintaining adequate levels of both
drugs in infected synovial fluid. The use of
the same drug at 30 mg/kg BW orally
given every 12 hours was effective in
maintaining therapeutic concentrations
of both drugs in the serum and in the
joint fluid.

In piglets at 2 weeks of age,
streptococcal arthritis is most likely and
it will respond quickly to penicillin given
parenterally. Likewise, acute arthritis
associated with erysipelas in pigs will
respond beneficially if treated early before
there is pannus formation.

Synovitis due to Histophilus somni
infection responds quickly to systemic
treatment. However, in other specific
types of infectious arthritis the response is
poor and recovery, if it does occur, requires
several days or a week. Mycoplasmal
arthritis in cattle is relatively non-
responsive to treatment and affected
cattle may be lame for up to several
weeks before improvement occurs and
complete recoveiy may not occur. Chronic
arthritis due to infection of pigs with
E. insidiosa will commonly develop into a
rheumatoid- like arthritis and be refrac-
tory to treatment.

Failure to respond to conservative
therapy has been attributed to:

° Inadequate concentrations of
antimicrobials achieved in the joint
cavity

° Presence of excessive amounts of
exudate and fibrin in the joint making
the infectious agent inaccessible to
the antimicrobial
° Drug-resistant infections
° The development of rheumatoid-like
arthritis, which is chronic and
progressive.

It is often not possible to determine
which situation is responsible.

If conservative treatment is not provid-
ing sufficient improvement and the value
of the animal warrants extended therapy, a
joint sample should be obtained for culture
and sensitivity. The most suitable anti-
microbial may then be given parenterally
and/or by intra-articular injection. Strict
asepsis is necessary to avoid introduction
of further infection.

Intra-articular antimicrobials

The combined intra-articular and intra-
venous administration of gentamicin to
normal horses can result in concen-
trations 10-100 times greater than after
intravenous administration alone. In
addition, gentamicin concentration in
synovial fluid remained above the mini-
mum inhibitory concentration for many
common equine bacterial pathogens for
at least 24 hours after treatment. The
intra-articular administration of gentamicin
is advantageous for the treatment of
infectious arthritis in animals in which the
systemic administration of the drug may
be contraindicated, especially in the
presence of impaired renal function or
endotoxemia. Continuous infusion of
gentamicin into the tarsocrural joint of
horses for 5 days is an acceptable method
of treating septic arthritis. 19

An timicrobial-impregnated
polymethylmethacrylate beads have
been used for the treatment of orthopedic
infections involving bone, synovial struc-
tures and other soft tissues. 20-22 The anti-
microbials diffuse from the beads in a
bimodal fashion. There is a rapid release
of 5-45% of the total amount of anti-
microbial within the first 24 hours after
implantation and then a sustained elution
that persists for weeks to months, depend-
ing on the antimicrobial used. For effective
diffusion, the antimicrobials must be
water-soluble, heat-stable and available
in powder form. Aminoglycosides and the
cephalosporins have been incorporated
most commonly into the beads.

Regional limb perfusion with anti-
microbials has been used for the treat-
ment of experimentally induced septic
arthritis. The antimicrobial is infused
under pressure to a selected region of the
limbs through the venous system. The
concentration of the antimicrobial in the
septic synovial fluid will usually exceed
those obtained by intravenous adminis-
tration. However, there are insufficient
data available to evaluate the procedure in
naturally occurring cases. Therapeutic
concentrations of cefazolin are achieved
in the synovial fluid of clinically normal
cows when injected intravenously distal
to a tourniquet and the technique could
be used as an alternative to systemic
administration of antimicrobials to pro-
vide adequate concentrations in a joint
cavity.

Lavage of joint

Drainage of the affected joint and
through-and-through lavage of the joint
is also desirable along with the systemic
administration of antimicrobials. Aspiration
and distension-irrigation of the joint
cavity using polyionic electrolyte solutions
buffered to 7.4 is recommended. 6 The

Diseases of joints

irrigation removes exudates and lysozymes
that destroy articular cartilage. A through -
and-through lavage system may also be
used with drainage tubes. General or local
anesthesia should be provided. The
distended joint is identified by palpation,
the hair is clipped short and the skin is
prepared with appropriate surgical dis-
infection. A 2 cm 16-gauge needle is
inserted into the joint cavity, avoiding
direct contact with the bones of the joint.
A second needle is inserted into the joint
as far as possible from the first needle to
cause any fluid perfused into the joint to
pass through as much of the joint cavity
as possible. 0.5-1 L of Ringer's solution
warmed to 37°C is flushed through the
joint using a hand-pumped pressure bag
to keep a steady fluid flow into the joint. 6

Arthroscopy

Arthroscopy provides excellent visualization
of most parts of an affected joint and can
be used to access the joint for the
treatment of septic arthritis. 15 The endo-
scope can be used to explore and debride
the affected joint during the same inter-
vention. Purulent exudate can be removed
and necrotic areas within the synovial
membrane can be debrided.

Surgical drainage and arthrotomy

Failure to respond to parenteral and intra-
articular medication may require surgical
opening of the joint capsule, careful
debridement and excision of synovium
and infected cartilage and bone. This may
be followed by daily irrigation of the joint
cavity with antimicrobials and saline. A
lavage system can be established and the
joint cavity infused with an antimicrobial
and saline daily for several days. 23
Arthrotomy with lavage was more effec-
tive in eliminating joint infections by
providing better drainage than arthroscopy,
synovectomy and lavage. However, with
arthrotomy the risk of ascending bacterial
contamination is greater and the major
difficulty is to eliminate the infection from
the joint and incision site. 24 Infected
sequestra and osteomyelitis of subchondral
bone will prevent proper healing. Curettage
of septic physeal lesions in foals may be
necessary.

Open drainage and intra-articular and
parenteral antimicrobials has been used
to treat persistent or severe septic
arthritis/tenosynovitis. While joint lavage
through needles is still effective in many
horses with acute infectious arthritis or
tenosynovitis, in those with chronic or
recurring septic arthritis, open drainage is
indicated to remove the inflammatory
exudate from the synovial space. Infected
synovial structures are drained through a
small (3 cm) arthrotomy incision left open
and protected by a sterile bandage. Joint
lavage using antimicrobials is done daily

and parenteral antimicrobials are given
intensively.

Septic pedal arthritis in cattle may

be treated successfully by the creation of a
drainage tract to promote adequate drain-
age. In cattle with septic arthritis of the
digit, placement of a wooden block under
the unaffected digit decreases weight-
bearing on the affected digit and provides
for earlier, less painful ambulation. 23

Arthrodesis or artificial ankylosis

Surgical arthrodesis can be used for the
treatment of chronic septic arthritis in
horses and calves. 26,27

Septic arthritis of the distal inter-
phalangeal joint is a common complication
of diseases of the feet of cattle. Facilitated
ankylosis of the joint is a satisfactory
alternative to amputation of the affected
digit in valuable breeding animals. 28 In a
series of 12 cases of septic arthritis of the
distal interphalangeal joint treated by use
of facilitated ankylosis, the success rate
was 100%.

Physical therapy

The local application of heat, by hot
fomentations or other physical means, is
laborious but, if practiced frequently and
vigorously, will reduce the pain and local
swelling. Analgesics are recommended if
there is prolonged recumbency. Persistent
recumbency is one of the problems in the
treatment of arthritis, particularly in foals.
The animal spends little time feeding or
sucking and loses much condition. Com-
pression necrosis over bony prominences
is a common complication and requires
vigorous preventive measures.

Anti-inflammatory agents

NSAIDs are used parenterally to decrease
the inflammatory response and to provide
analgesia. In experimental synovitis in the
horse, similar to septic arthritis, phenyl-
butazone was more effective than
j ketoprofen in reducing lameness, joint
j temperature, synovial fluid volume and
j synovial fluid prostaglandin. 29

I Prognosis for survival and athletic
j use in horses with septic arthritis

j The factors affecting the prognosis for
j survival and athletic use in 93 foals treated
j for septic arthritis have been examined. 12
; The femoropatellar and tarsocrural joints
j were most commonly affected. Osteo-
‘ myelitis or degenerative joint disease
were detected in 59% of the foals. Failure
of transfer of passive immunity, pneu-
; monia and enteritis were common. Treat-
ment consisted of lavage, lavage and
- arthroscopic debridement with or without
i partial synovectomy, or lavage and
j arthrotomy to debride infected bone and
parenteral antibiotics. Seventy-five foals
; survived and were discharged from
i hospital, and approximately one-third

raced. Isolation of Salmonella from synovial
fluid was associated with an unfavorable
prognosis for survival, and multisystemic
disease was associated with an unfavorable
prognosis for survival and ability to race.
The key to successful outcome for septic
arthritis is rapid diagnosis and initiation
of treatment.

In a series of 507 horses treated for
joint disease at one equine hospital
during a period of 7 years, the risk factors
affecting discharge from the hospital, of
ever being sound, or of being alive after a
3-month followup were examined; 30 5 8%
of foals, 78% of yearlings and 94% of
racing adults were discharged. Foals with
a less severe lameness, duration of less
than 1 day and infectious arthritis had
increased odds of discharge.

CONTROL

The control of infectious arthritis is of
major importance in newborn farm
animals. The early ingestion of adequate
quantities of good-quality colostrum and
a clean environment for the neonate are
necessary. The prophylactic use of anti-
microbials may be considered to reduce
incidence. Some of the infectious arthritides
associated with specific diseases can be
controlled through immunization pro-
grams. For example, vaccination of piglets
at 6-8 weeks of age will provide pro-
tection against both the septicemic and
arthritic forms of erysipelas.

REVIEW LITERATURE

Streppa HK, Singer MJ,Budsberg SC. Applications of
local antimicrobial delivery systems in veterinary
medicine. J Am Vet Med Assoc 2001; 219:40-48.
Sayeh AI, Moore RM. Polymethylmethacrylate beads
for treating orthopedic infections. Compend
Contin Educ Pract Vet 2003; 25:788-793.

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I 11. Madison JB et al. J Am Vet Med Assoc 1991;
| 198:1655.

\ 12. Steel CM et al. J Am Vet Med Assoc 1999; 215:973.
| 13. Crabill MR et al.Vet Surg 1996; 25:195.

: 14. Kofler J. BrVet J 1996; 152:683.

; 15. Munroe GA, Cauvin ER. BrVet J 1994; 150:439.

1 16. Madison JB et al. J Am Vet Med Assoc 1995;
I 206:328.

17. Grandemange E et al. IrVet J 2002; 55:237.

| 18. Errecalde JO et al. J Vbt Pharmacol Ther 2001;
| 24:1.

' 19. LescumTB et al. Am JVet Res 2002; 63:683.

20. Streppa HK et al. J Am Vet Med Assoc 2001;
219:40.

■ 21. Sayegh AI. Compend Contin Educ PractVet 2003;

25:788.

rHni i oci>icr\ML ivicumv-iimc

vnapier 13; Lmeabeb ui me mubcuiubKeieicJi bybiem

22. Trostle SS et al. J Am Vet Med Assoc 1996;
208:404.

23. McClure SR et al. J Am Vet Med Assoc 1993;
202:973.

24. Bertone AL et al. Am J Vet Res 1992; 53:585.

25. Guard C. Proc Am Assoc Bovine Pract 2000; 35:21.

26. Riley CB, Farrow CS. Can Vet J 1998; 39:438.

27. Groom LJ et al. Can Vet J 2000; 41:117.

28. Desrochers A et al. J Am Vet Med Assoc 1995;
206:1923.

29. Owens JG et al. Am J Vet Res 1996; 57:866.

30. Fubini SL et al. Can J Vet Res 1999; 63:253.

Congenital defects of
muscles, bones, and joints

Defects of the musculoskeletal system are
among the most common congenital
abnormalities in farm animals. In cattle
476 such defects are listed. Many of them
are lethal, and most of the remainder are
life-threatening because of interference
with grazing or the prehension of food.
Many of them occur in combinations so
that single defects are uncommon. For
example, most axial skeletal defects and
cleft palates occur in calves that already
have arthrogryposis.

Because of the very large volume of
literature involved it is not possible to
deal with all the recorded defects here,
and the text is limited to those defects
that are thought to be of general import-
ance. Whether or not they are inherited or
have an environmental cause is often not
known so that an etiological classification
is not very effective. Nor is an anatomical
or pathological classification, so we are
reduced to a classification based on
abnormal function.

FIXATIO N OF JOINTS

Because arthrogryposis, which has been
used to convey the description of joint
fixation, strictly means fixation in flexion,
the term congenital articular rigidity has
been introduced. The immobilization of
the joint may be due to lack of extensibility
of muscles, tendons, ligaments or other
tissues around the joint, or to deformity of
articular surfaces, or theoretically to
fusion between the bones at the articular
surface. Muscle contracture, which is the
principal cause of joint fixation, has been
produced experimentally, and occurs
naturally, as a result of primary muscle
atrophy or of atrophy resulting from
denervation. Articular surface deformity is
usually associated with gross deformity of
the limb bones and is usually identifiable
but the principal problem in the diagnosis
of congenital articular rigidity is to deter-
mine what the pathogenesis might have
been and, beyond that, what was the
specific cause.

Congenital fixation of joints can be
caused by some well known entities, as
follows.

Cattle

0 Hereditary congenital articular rigidity
(HCAR) with cleft palate in Charolais
0 HCAR with normal palates in
Friesians, Danish Reds, Swedish,
Shorthorns

0 Inherited arthrogryposis
° Inherited multiple tendon contracture
0 Inherited multiple ankylosis of
Holstein-Friesian cattle.

Environmentally induced congenital
articular rigidity caused by:

° Intrauterine infection with Akabane
virus

° Ingestion of lupins
• Ingestion of Astragalus and Oxytropis
spp. (locoweeds)

0 Sorghum, Johnson grass, Sudan grass
0 Dietary deficiency of manganese.

Sheep and goats

0 Inherited congenital articular rigidity
in Merino sheep
0 Infection with Akabane virus
0 Poisonous plants as for cattle
Poisoning with parbendazole and
cambendazole .

Piglets

° Inherited congenital articular rigidity
0 Nutritional deficiency of vitamin A
■' Poisonous plants, hemlock ( Conium
maculatum), Prunus serotina, Jimson
weed ( Datura stramonium), tobacco
wastes.

Foals

0 'Contracted' foals having congenital
axial and appendicular contractures of
joints in the us, cause unknown, not
thought to be inherited. Deformities
include torticollis, scoliosis, thinning
of ventral abdominal wall, sometimes
accompanied by eventration,
asymmetry of the skull, flexion
contracture in distal limb joints
Congenital articular rigidity also
occurs in foals from mares fed on
hybrid Sudan grass pastures
Sporadic cases of congenital joint
deformity occur in foals and calves.
They are manifested usually by
excessive flexion of the
metacarpophalangeal joints causing
affected animals to'knuckle'at the
fetlocks and sometimes walk on the
anterior aspect of the pastern. A
similar defect occurs in the hindlegs.
Many mild cases recover
spontaneously but surgical treatment
may be required in badly affected
animals. The cause in these sporadic
cases in unknown and necropsy
examination fails to reveal lesions

other than excessive flexion of the
joints caused by shortening of the
flexor tendons. Rarely such fixations
are associated with spina bifida or
absence of ventral horn cells of the
spinal cord.

HYPERMOBILITY OF JOINTS

This is recorded as an inherited defect in
Jersey cattle. Affected animals are unable
to rise or stand because of the lack of
fixation of limb joints. The joints and
limbs are usually all affected simultaneously
and are so flexible that the limbs can be
tied in knots. Causes include:

° Inherited joint hypermobility in Jersey
cattle

0 Heredity in Holstein-Friesian cattle,
which also have pink teeth due to
absence of enamel
0 In inherited congenital defects of
collagen formation including
dermatosparaxis, hyperelastosis cutis
and Ehlers-Danlos syndrome in cattle
° Sporadically in newborn animals.

WEAKNESS OF SKELETAL
MUSCLES

A number of sporadic myopathies are
recorded in cattle and sheep. Causes have
not been determined in most of them.
Splayleg in pigs has been well described
and occurs in most countries.

CONGENITAL HYPERPLASIA OF
M YOFIBE R

There is only one identified state; it is the
inherited form of doppelender, double
muscling or culard of cattle, described in
Chapter 35. The principal cause of the
bulging muscles is an increase in the num-
ber of myofibers in the muscle.

OBVIOUS ABSENCE OR
DEFORMITY OF SPECIFIC PARTS
OF THE MUSCULOSKELETAL
SYSTEM

A number of these defects are known to
be inherited and are dealt with in Chapter
34. They include:

° Achondroplastic dwarfism, inherited
miniature calves, bulldog calves
° Umbilical, scrotal hernia,
cryptorchidism

Tail deformity (kinking), taillessness
° Reduced phalanges, including

hemimelia (individual bones missing),
amputates (entire limbs missing),
vestigial limbs (all parts present but
limbs miniaturized). Amputates in
outbreak form are recorded in cattle
and produced experimentally by
irradiation injury of sows, cows and
ewes during early pregnancy.

Congenital defects of muscles, bones and joints

Inherited arachnomyelia (spidery
limbs) of calves
Congenital thickleg of pigs,
osteopetrosis of calves, muscular
hypertrophy of calves

° Cyclopian deformity. Inherited form
associated with prolonged gestation.
Toxic form associated with ingestion
of Veratrum californicum

° Displaced molar teeth, mandibular
prognathism. Agnathia in lambs takes
a variety of forms, including complete
absence of lower jaw and tongue.

PART 1 GENERAL MEDICINE

Diseases of the skin, conjunctiva, and
external ear

INTRODUCTION 651

PRINCIPLES OF TREATMENT OF
DISEASES OF THE SKIN 653

Primary treatment 653
Supportive treatment 653

DISEASES OF THE EPIDERMIS AND
DERMIS 654

Pityriasis 654
Hyperkeratosis 654
Parakeratosis 654
Pachyderma 654
Impetigo 655
Urticaria 655

Dermatitis and dermatosis 656
Photosensitization 659

DISEASES OF THE HAIR, WOOL,
FOLLICLES, SKIN GLANDS, HORNS
AND HOOVES 661

Alopecia and hypotrichosis 661
Achromotrichia 662
Leukoderma and leukotrichia 662
Vitiligo 662

Seborrhea 662
Folliculitis 663

Diseases of hooves and horns 663

DISEASES OF THE SUBCUTIS 664

Subcutaneous edema (anasarca) 664
Angioedema (angioneurotic
edema) 664

Subcutaneous emphysema 665
Lymphangitis 665
Panniculitis 665
Hemorrhage 666
Necrosis and gangrene 666
Subcutaneous abscess 666
Cutaneous cysts 667

GRANULOMATOUS LESIONS OF THE
SKIN 667

CUTANEOUS NEOPLASMS 667

Papilloma and sarcoid 667
Squamous-cell carcinoma 668
Melanoma 668
Cutaneous angiomatosis 668
Lymphomatosis 668

Mast cell tumors 668

Neurofibromatosis 668

Histiocytoma 668

Hemangioma and
hemangiosarcoma 669

Lipoma 669

CONGENITAL DEFECTS OF THE
SKIN 669

CONGENITAL SKIN NEOPLASMS 669

DISEASES OF THE
CONJUNCTIVA 670

Conjunctivitis and
keratoconjunctivitis 670

CONGENITAL DEFECTS OF THE
EYELIDS AND CORNEA 670

Dermoid cysts 670

DISEASES OF THE EXTERNAL
EAR 670

Otitis externa 670

Otitis media 671

Introduction

The major functions of the skin are:

0 To maintain a normal body temperature
0 To maintain a normal fluid and
electrolyte balance within the animal
° To act as a sensory organ perceiving
those features of the environment
which are important to the subject's
survival.

In general these functions are not greatly
impeded by most diseases of the skin of
large animals, with the exceptions of
failure of the sweating mechanism, which
does seriously interfere with body tem-
perature regulation, and severe burns or
other skin trauma, which may cause fatal
fluid and electrolyte loss.

The major effects of skin diseases in
large animals are esthetic and economic.
The unsightly appearance of the animal
distresses the owner. Discomfort and
scratching interfere with normal rest and
feeding and when the lips are affected
there may be interference with prehension.
There is loss of the economic coat and the
sales value and acceptability of animals
for transport and appearance in exhi-
bitions, especially in other sovereign states,
is greatly reduced.

Primary/secondary lesions

Diseases of the skin may be primary or
secondary in origin. In primary skin

disease the lesions are restricted initially
to the skin although they may sub-
sequently spread from the skin to involve
other organs. On the other hand, cutaneous
lesions may be secondary to disease
originating in other organs. Differentiation
between primary and secondary skin
diseases should be attempted by seeking
evidence that organs other than the skin
are affected. If there is no such evidence
produced during a complete clinical
examination of the patient, it is reason-
able to assume that the disease is primary.
Even if involvement of other organs is
diagnosed it is still necessary to determine
whether the involvement constitutes the
primary state or whether it has developed
secondarily to the skin disease. This
decision can be based on the chronology
of the signs, elicited by careful history-
taking, and a detailed knowledge of the
individual diseases likely to be encountered.

When a careful clinical examination has
been made and an accurate history taken it
is then necessary to make a careful exam-
ination of the skin itself, using the proper
technique of examination, especially (and
essentially) histopathological examination
of a biopsy specimen. It is then possible
to determine the basic defect, whether it
be inflammatory, degenerative or dys-
functional, and thus to define the type of
lesion present.

The purpose of this chapter is to
describe the basic skin lesions so that the

differential diagnosis, up to the point of
defining the type and nature of the lesion,
the pathoanatomical diagnosis, can be
accomplished. A definitive etiological
diagnosis requires further examination
and is included in the discussion of the
specific diseases in Part Two of this book.

Clinical signs and special
examination

A general clinical examination is followed
by a special examination of the skin and
must include inspection and, in most
cases, palpation. Additional information
can be obtained by taking swabs for bac-
teriological examinations, scrapings for
examination for dermatophytes and
metazoan parasites, and biopsy for histo-
pathological examination.

Biopsy material should include abnor-
mal, marginal, and normal skin. Artifacts
are common in biopsy specimens, includ-
ing nonrepresentative sampling, crushing
the specimen by forceps or hemostat, and
inadequate fixation.

Wood's lamp finds a special use in the
examination of the skin for dermatophytes.

Descriptions of lesions should include
size, depth to which they penetrate,
geographical distribution on the body and
size of the area covered. Abnormalities of
sebaceous and sweat secretion, changes
in the hair or wool coat and alterations in
color of the skin should be noted, as
should the presence or absence of pain or

652

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

pruritus and the manifestations of skin
disease and the common lesions defined
below.

Lesions

An accurate definition of the lesions,
summarized in Table 14.1, is an essential
part of a skin patient's clinical record. The
table makes a primary differentiation into
discrete and diffuse lesions and these
categories need to be further categorized
in terms of size, e.g. they may be limited
diffuse lesions or extensive localized ones.

Abnormal coloration

This parameter includes jaundice, pallor
and erythema, and these are best seen in
the oral or vaginal mucosa or in the
conjunctiva. In animals they are rarely
visible in light-colored skins. Red-purple ]
discoloration of the skin of septicemic, j

white pigs may be dramatic but no diag-
nostic significance can be attached to its
degree. Early erythema is a common
finding where more definite skin lesions
are to develop, as in early photo-
sensitization. The blue coloration of early
gangrene (e.g. of the udder and teat skin
in the early stages of peracute bovine
mastitis associated with Staphylococcus
aureus) is characterized by coldness and
loss of elasticity.

Hypopigmentation of the skin may
be general, as in albino, pseudoalbino and
lethal white animals. Local patches of
hypopigmentation are characteristic of
vitiligo and leukoderma.

Pruritus

® Pruritus or itching is the sensation

that gives rise to scratching

° Hyperesthesia is increased sensitivity
to normal stimuli

p Paresthesia is perverted sensation, a
subjective sensation, and not
diagnosed in animals.

Ail sensations that give rise to rubbing
or scratching are therefore included
with pruritus, more properly defined as
scratching. Pruritus can arise from
peripheral or central stimulation. When
it is peripheral in origin it is a primary
cutaneous sensation like heat, cold, pain
and touch; it differs from pain because it
is purely epidermal, whereas pain can still
be felt in areas of skin denuded of
epidermis. Thus itching does not occur in
the center of deep ulcerations nor in very
superficial lesions, such as those of
ringworm, where only the hair fibers

'!.£!«) te i Y *. Mi 1 feTflhnig iyj3&o| 11®

Vofehliilif.y feji@Ws .

Name of lesion

Nature of lesion

Relation to skin surface

Skin surface

Scales

Dry, flaky exfoliations

On surface only, no penetration of

Unbroken

Excoriations

Traumatic abrasions and scratches

skin

Penetration below surface

Variable skin surface damage - depends

Fissures

Deep cracks

Penetrate into subcutis

on severity
Disrupted

Dry gangrene

Dry, horny, black, avascular, shield-like

Above skin, usually all layers

Removed

Early, moist gangrene

Blue-black, cold, oozing serum

affected

In plane of skin or below

Complete depth of subcutis

Keratosis

Overgrowth of dry, horny, keratinized

Above skin

Undamaged stratum corneum is

Acanthosis

epithelium

Like keratosis but moist, soft

Above skin

retained

Prickle cell layer swollen; is really part of

Hyperkeratosis

Excessive overgrowth of keratinized,

Above skin

skin

Skin surface unbroken

Parakeratosis

epithelium-like scab
Adherent to skin

Above skin

Cells of stratum corneum nucleated and

Eczema

Erythematous, itching dermatitis

Superficial layer of epidermis

retained; really part of skin
Weeping, scabby disruption of surface

Hypermelanosis

Increased deposits of melanin, e.g.

affected

In epidermis or dermis

Unbroken

Hypomelanosis

melanosis, meloderma
Decreased deposits of melanin

In epidermis or dermis

Unbroken

Discrete lesions

Vesicle, bleb, bulla, blister

Fluid (serum or lymph)-filled blister

Above skin surface, superficial

Unbroken but will slough

Pustule

1 -2 cm diameter
Pus-filled blister, 1-5 mm

Above, superficial

Will rupture

Wheal

Edematous, erythematous, swellings,

Above, all layers affected

Undamaged

Papules (pimples)

transitory

Elevated, inflamed, necrotic center, up to

Above surface, all layers affected

Points and ruptures

Nodules, nodes

1 cm diameter

Elevated, solid, up to 1 cm diameter.

Above surface, all layers

Surface unbroken

Plaque

Acute or chronic inflammation.

No necrotic center

A larger nodule, up to 3-4 cm diameter

All layers affected; raised above

Surface unbroken

Acne

Used synonymously with pimple but

surface

Above surface of skin; all layers

May point and rupture

Comedo

strict meaning is infection of sebaceous
gland

Plugged (sebum, keratin) hair follicle

affected

Raised above skin

May rupture

Impetigo

Flaccid vesicle, then pustule, then scab,

Raised above skin; very superficial

Upper layers destroyed

Scab (or crust)

up to 1 cm diameter

Crust of coagulated, blood, pus and

Raised above skin

Disrupted, depth varying with original

Macule (patch)

skin debris

Small area of color change; patch is larger

Within superficial layers

lesion

Unbroken

'Above skin, usually all

2 Pyoderma is any infection of skin; includes impetigo, acne, pustule, pimple

Principles of treatment of diseases of the skin

653

and keratinized epithelium are involved.
Itching can be elicited over the entire
skin surface but is most severe at the
mucocutaneous junctions. Common
causes include the following.

Cattle

o Sarcoptic and chorioptic mange
9 Aujeszky's disease
• Nervous acetonemia
= Lice infestation.

Sheep

o Lice, mange, ked, blowfly and itch-
mite infestations
° Scrapie.

Pigs

° Sarcoptic and chorioptic mange
o Lice infestation.

Horses

9 Chorioptic mange on the legs
o Queensland (sweet) itch along the
dorsum of the body
" Lice infestation

o Pterianal pruritus due to Oxyuris equi
infestation.

All species

9 The early stages of photosensitive
dermatitis

» Urticarial wheals in an allergic
reaction

® 'Licking syndromes' such as occur in
cattle on copper-deficient diets are
accompanied by pica and the licking
of others as well as themselves. They
are examples of depraved appetites
developed in response to nutritional
deficiency and are not a response to
pruritus

0 Itching of central origin derives in
the main from the scratch center
below the acoustic nucleus in the
medulla. It may have a structural
basis, as in scrapie and pseudorabies,
or it may be functional in origin, as in
the nervous form of acetonemia. The
only lesions observed are those of a
traumatic dermatitis with removal of
the superficial layers to a variable
depth, breakage or removal of the
hairs and a distribution of lesions in
places where the animal can bite or
rub easily.

Secretion abnormalities of skin
glands

The activity of the sweat glands is
controlled by the sympathetic nervous
system and is for the most part a
reflection of body temperature. Excite-
ment and pain may cause sweating due to
cerebral cortical activity. A generalized
form of hyperhidrosis, apparently
inherited, has been recorded in Shorthorn
calves. Local areas of increased or
decreased sweating may arise from
peripheral nerve lesions or obstruction of

sweat gland ducts. A generalized anhidrosis
is recorded in horses and occasionally in
cattle.

Excess secretion of sebum by sebaceous
glands causes oiliness of the skin or
seborrhea but its pathogenesis is poorly
understood.

Abnormalities of wool and hair
fibers

Deficiency of hair or wool in comparison
to the normal pilosity of the skin area is
alopecia or hypotrichosis.

Hirsutism, abnormal hairiness, mani-
fested by a long, shaggy, usually curly,
coat is most common in aged ponies with
adenomas of the pars intermedia of the
pituitary gland.

The character of the fiber may also vary
with variations in the internal environ-
ment. For example, in copper deficiency
the crimp of fine wool fibers is lost and
the wool becomes straight and 'steely'.
Alternation in coat color, achromotrichia,
may be generalized or segmental along
the fiber.

Principles of treatment of
diseases of the skin

PRIMARY TREAT M ENT

Primary treatment commences with
removal of hair coat and debris to enable
topical applications to come into contact
with the causative agent. Accurate diag-
nosis of the cause must precede the
selection of any topical or systemic treat-
ment. In bacterial diseases sensitivity tests
on cultures of the organism are advisable.
Specific skin diseases due to bacteria,
fungi and metazoan parasites are reason-
ably amenable to treatment with the
appropriate specific remedy.

Bacterial resistance to antimicrobials
used in veterinary dermatological practice
is a concern . 1 The broad application of
antimicrobials for various therapeutic and
nontherapeutic purposes has accelerated
the spread of pre-existing resistance
genes and led to the apparent develop-
ment of mechanisms by which resistance
genes are spread, not only within a
bacterial species, but also between
bacterial species. Every veterinarian must
strive to practice prudent use of anti-
microbials in order to minimize the
resistance problem.

Removal of the causative agent in
allergic diseases and photosensitization
may be impossible and symptomatic
treatment may be the only practicable
solution. In many cases, too, the primary
disease may be confounded by the pre-
sence of a secondary agent, which can

lead to confusion in diagnosis. Treatment
may be unsuccessful if both agents are
not treated.

SUPPORTIV E TREATMENT

Supportive treatment includes prevention
of secondary infection by the use of
bacteriostatic ointments or dressings and
the prevention of further damage from
scratching.

° Effective treatment of pruritus

depends upon the reduction of central
perception of itch sensations by the
use of ataractic, sedative or narcotic
drugs administered systemically or on
successful restraint of the mediator
between the lesion and the sensory
end organ. In the absence of accurate
knowledge of the pathogenesis of
pain it is usual to resort to local
anesthetic agents, which are
shortlived in their activity, and
corticosteroids, which are longer-
acting and effective, provided that
vascular engorgement is part of the
pruritus-stimulating mechanism
When large areas of skin are involved
it is important to prevent the
absorption of toxic products by
continuous irrigation or the
application of absorptive dressings.
Losses of fluid and electrolytes should
be made good by the parenteral
administration of isotonic fluids
containing the necessary electrolytes
° Ensure an adequate dietary intake of
protein, particularly sulfur-containing
amino acids to facilitate the repair of
skin tissues

Boredom contributes significantly to
an animal's response to itch stimuli,
and close confinement of affected
animals is best avoided.

REVIEW LITERATURE

Pascoe RR. Equine dermatoses. University of Sydney
Postgraduate Communications in Veterinary
Science Review 22. Sydney: University of Sydney,
1974.

Montes LF, Vaughan JT. Atlas of skin diseases of the
horse. Philadelphia: WB Saunders, 1983.
Mullowney PC. Symposium on large animal
dermatology. Vet Clin North Am Large Anim Pract
1984; 6:1-226.

Mullowney PC, Fadok VA Dermatologic diseases of
the horse. Compend Contin Educ Pract Vet 1984;
6:S16-S20, S22-S26.

Scott DW. Large animal dermatology. Philadelphia:
WB Saunders, 1988.

Schwarz S, Noble WC. Aspects of bacterial resistance
to antimicrobials used in veterinary
dermatological practice. Vet Dermatol 1999;
10:163-176.

Matousek JL, Campbell KL. A comparative review of
cutaneous pH. Vet Dermatol 2002; 13:293-300.

REFERENCE

1. Schwarz S, Noble WC. Vet Dermatol 1999;
10:163-176.

654

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

Diseases of the epidermis
and dermis

PITYRIASIS

Primary pityriasis, excessive bran-like
scales on the skin, characterized by over-
production of keratinized epithelial cells,
can be caused by:

■ Hypovitaminosis A

Nutritional deficiency of B vitamins,
especially of riboflavin and nicotinic
acid, in pigs, or linolenic acid, and
probably other essential unsaturated
fatty acids

« Poisoning by iodine

Pityriasis rosea occurs in humans and
pigs and the etiology is unknown. The
literature for and against an infectious
etiology has been reviewed . 1

Secondary pityriasis, characterized by
excessive desquamation of epithelial cells
is usually associated with:

Scratching in flea, louse and mange
infestations

<* Keratolytic infection, e.g. with
ringworm fungus.

Pityriasis scales are accumulations of
keratinized epithelial cells, sometimes
softened and made greasy by the exudation
of serum or sebum. Overproduction, when
it occurs, begins around the orifices of the
hair follicles and spreads to the surround-
ing stratum corneum.

Primary pityriasis scales are superficial,
accumulate where the coat is long, and
are usually associated with a dry, luster-
less coat. Itching or other skin lesions
are not features. Secondary pityriasis is
usually accompanied by the lesions of the
primary disease.

Pityriasis is identified by the absence of
parasites and fungi from skin scrapings.

i DIFFERENTIAL DIAGNOSIS

r

• Hyperkeratosis (see below)

• Parakeratosis (see below)

TREATMENT

Primary treatment requires correction of
the primary cause.

Supportive treatment commences
with a thorough washing, followed by
alternating applications of a bland, emol-
lient ointment and an alcoholic lotion.
Salicylic acid is frequently incorporated
into a lotion or ointment with a lanolin
base.

HYPERKERATOSIS

Epithelial cells accumulate on the skin
as a result of excessive keratinization of

epithelial cells and intercellular bridges,
interference with normal cell division in
the granular layer of the epidermis and
hypertrophy of the stratum corneum.

Lesions may be local at pressure
points, e.g. elbows, when animals lie
habitually on hard surfaces. Generalized
hyperkeratosis may be caused by:

» Poisoning with highly chlorinated
naphthalene compounds
° Chronic arsenic poisoning
° Inherited congenital ichthyosis
-- Inherited dyserythropoiesis-
dyskeratosis.

The skin is dry, scaly, thicker than normal,
usually corrugated, hairless and fissured
in a gridlike pattern. Secondary infection
of deep fissures may occur if the area is
continually wet. However, the lesion is
usually dry and the plugs of hyperkeratotic
material can be removed, leaving the
underlying skin intact.

Confirmation of the diagnosis is by the
demonstration of the characteristically
thickened stratum corneum in a biopsy
section, which also serves to differentiate
the condition from parakeratosis (see
below) and inherited ichthyosis.

Primary treatment depends on correc-
tion of the cause. Supportive treatment is
by the application of a keratolytic agent
(e.g. salicylic acid ointment).

PARAKERATOSjS

Fkrakeratosis, a skin condition characterized
by incomplete keratinization of epithelial
cells, can be:

Caused by nonspecific chronic
ii flammation of cellular epidermis
Associated with dietary deficiency of
zinc

Part of an inherited disease listed
below.

The initial lesion comprises edema of the
prickle cell layer, dilatation of the inter-
cellular lymphatics, and leukocyte infil-
tration. Imperfect keratinization of
epithelial cells at the granular layer of the
epidermis follows, and the horn cells
produced are sticky and soft, retain their
nuclei and stick together to form large
masses, which stay fixed to the under-
lying tissues or are shed as thick scales.

The lesions may be extensive and
diffuse but are often confined to the flexor
aspects of joints (referred to historically in
horses as mallenders and sallenders).
Initially the skin is reddened, followed by
thickening and gray discoloration. Large,
soft scales accumulate, are often held in
place by hairs and usually crack and
fissure, and their removal leaves a raw, red
surface. Hyperkeratosis scales are thin, dry
and accompany an intact, normal skin.

Confirmation of a diagnosis of para-
keratosis is by the identification of imperfect
keratinization in a histopathological
examination of a biopsy or a skin section
at necropsy.

•

Hyperkeratosis (see above)

•

Pachyderma (see below)

•

Ringworm

•

Inherited ichthyosis

•

Inherited Adema disease in cattle

•

Inherited dermatosis vegetans

in pigs

•

Inherited epidermal dysplasia

TREATMENT

Primary treatment requires correction of
any nutritional deficiency.

Supportive treatment includes removal
of the crusts by the use of keratolytic
agent (e.g. salicylic acid ointment) or by
vigorous scrubbing with soapy water,
followed by application of an astringent
(e.g. white lotion paste), which must be
applied frequently and for some time
after the lesions have disappeared.

PACHYDERMA

Pachyderma, including scleroderma, is
thickening of the skin affecting all layers,
often including subcutaneous tissue, and
usually localized but often extensive as in
lymphangitis and greasy heel in horses.
There are no specific causes, most cases
being due to nonspecific chronic or
recurrent inflammation.

In affected areas the hair coat is thin or
absent and the skin is thicker and tougher
than usual. It appears tight and, because
of its thickness and reduced volume of
subcutaneous tissue, cannot be picked
into folds or moved easily over underlying
tissue. The skin surface is unbroken and
there are no lesions and no crusts or scabs
as in parakeratosis and hyperkeratosis
(see above).

Confinnation of the diagnosis depends
on histopathological examination of a
biopsy. The cells in all layers are usually
normal but the individual layers are
increased in thickness. There is hyper-
trophy of the prickle cell layer of the
epidermis and enlargement of the inter-
papillary processes.

DIFFERENTIAL DIAGNOSIS

• Parakeratosis (see above)

• Cutaneous neoplasia

• Papillomatosis

TREATMENT

Primary treatment requires removal of
the causal irritation but in well-established

Diseases of the epidermis and dermis

cases little improvement can be anticipated,
and surgical removal may be a practical
solution when the area is small. In early
cases local or systemic corticosteroids
may effect a recovery.

IMPETIGO

A superficial eruption of thin -walled,
small vesicles, surrounded by a zone of
erythema, that develop into pustules,
then rupture to form scabs.

In humans, impetigo is specifically a
streptococcal infection but lesions are
often invaded secondarily by staphylococci.
In animals the main organism found is
usually a staphylococcus. The causative
organism appears to gain entry through
minor abrasions, with spread resulting
from rupture of lesions causing contami-
nation of surrounding skin and the
development of secondary lesions. Spread
from animal to animal occurs readily.

The only specific examples of impetigo
in large animals are:

° Udder impetigo of cows
° Infectious dermatitis or'contagious
pyoderma' of baby pigs associated
with unspecified streptococci and
staphylococci.

Small (3-6 mm) vesicles appear chiefly on
the relatively hairless parts of the body
and do not become confluent. In the early
stages each vesicle is surrounded by a
narrow zone of erythema. No irritation is
evident. Vesicle rupture occurs readily but
some persist as yellow scabs. Involvement
of hair follicles is common and leads to
the development of acne and deeper,
more extensive lesions. Individual lesions
heal rapidly in about a week but successive
crops of vesicles may prolong the duration
of the disease.

Confirmation of the diagnosis is by
culture of vesicular fluid and identification
of the causative bacterium and its
sensitivity.

DIFFERENTIAL DIAGNOSIS

• Cowpox, in which the lesions occur
almost exclusively on the teats and pass
through the characteristic stages of pox

• Pseudocowpox, in which lesions are
characteristic and also restricted in
occurrence to the teats.

TREATMENT

Primary treatment with antibiotic
topically is usually all that is required
because individual lesions heal so rapidly.

Supportive treatment is aimed at
preventing the occurrence of secondary
lesions and spread of the disease to other
animals. Twice daily bathing with an

efficient germicidal skin wash is usually
adequate.

URTICAR IA

An allergic condition characterized by
cutaneous wheals. It is most common in
horses. 2

ETIOLOGY

Primary urticaria results directly from
the effect of the pathogen, e.g.:

° Insect stings

0 Contact with stinging plants
° Ingestion of unusual food, with the
allergen, usually a protein
° Occasionally an unusual feed item,
e.g. garlic to a horse 3
° After a recent change of diet
° Administration of a particular drug,
e.g. penicillin; possibly guaifenesin or
other anesthetic agent 4
° Allergic reaction in cattle 8 days
following vaccination for foot-and-
mouth disease 5

° Death of warble fly larvae in tissue
0 Milk allergy when Jersey cows are
dried off

° Transfusion reaction.

Secondary urticaria occurs as part of a
syndrome, e.g.:

° Respiratory tract infections in horses,
including strangles and the upper
respiratory tract viral infections
° Erysipelas in pigs.

PATHOGENESIS

The lesions are characteristic of an allergic
reaction. There is degranulation of mast
cells followed by liberation of chemical
mediators inflammation, resulting in the
subsequent development of dermal edema.
A primary dilatation of capillaries causes
cutaneous erythema. Exudation from the
damaged capillary walls causes local
edema in the dermis and a wheal develops.
Only the dermis, and sometimes the
epidermis, is involved. In extreme cases
the wheals may expand to become
seromas, when they may ulcerate and
discharge. The lesions of urticaria usually
resolve in 12-24 hours but in recurrent
urticaria an affected horse may have
persistent and chronic eruption of lesions
over a period of days or months. 6

CLINICAL FINDINGS

Wheals, mostly circular, well delineated,
steep-sided, easily visible elevations in
the skin, appear very rapidly and often in
large numbers, commencing usually on
the neck but being most numerous on the
body. They vary from 0.5-5 cm in diameter,
with a flat top, and are tense to the touch.
There is often no itching, except with
plant or insect stings, nor discontinuity
of the epithelial surface, exudation or

weeping. Pallor of the skin in wheals can
be observed only in unpigmented skin.
Other allergic phenomena, including
diarrhea and slight fever, may accompany
the eruption. The onset of the lesions
is acute to peracute with the wheals
developing within minutes to hours after
exposure to the triggering agent. When
associated with severe adverse systemic
responses, including apnea, respiratory
arrest, atrial fibrillation, cardiac arrest or
sudden death, the case qualifies as one of
anaphylaxis.

Subsidence of the wheals within
24-48 hours is usual but they may persist
for 3-4 days because of the appearance
of fresh lesions. In some very sensitive
horses, dermatographism, the production
of a continuous wheal following the pat-
tern of a blunt-pointed instrument drawn
across the skin, can be demonstrated
about 30 minutes later. 7

Urticaria lasting 8 weeks or longer is
classified as chronic or recurrent urticaria,
which may require testing for atopic
disease using intradermal skin testing and
serum testing for antigen-specific IgE.

Adverse reactions in dairy cattle
following annual vaccination for foot-
and-mouth disease are characterized by
wheals (3-20 mm in diameter) covering
most of the body, followed by exudative
and necrotic dermatitis. 5 The affected
areas become hairless and the wheals
exude serum and become scabbed over.
Edema of the legs is common and vesicles
occur on the teats. The lesions appear
8-12 weeks postvaccination and may
persist for 3-5 weeks. Loss of body weight
and lymphadenopathy also occur. Pruritus,
depression and a drop in milk yield are
common.

CLINICAL PATHOLOGY

Intradennal skin tests to detect the presence
of hypersensitivity are of little value because
many normal horses, as well as those with
urticaria, will respond positively to injected
or topically applied allergens. Also,
reactions usually occur within the first
24 hours after the injection, but the interval
is very erratic. The duration of the reaction
also varies a great deal. 8 Intradermal tests in
horses without atopy and horses with
atopic dennatitis or recurrent urticaria using
environmental allergens indicate a greater
number of positive reactions for intradennal
tests in horses with atopic dennatitis or
recurrent urticaria, compared with horses
without atopy. This provides evidence of
type-1 IgE-mediated hypersensitivity for
these diseases. 6

Biopsies show that tissue histamine
levels are increased and there is a local
accumulation of eosinophils. Blood hista-
mine levels and eosinophil counts may
also show transient elevation.

I

656

PARTI GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

1

DIFFERENTIAL DIAGNOSIS

Urticaria is manifested by a sudden
appearance of a crop of cutaneous wheals,
sometimes accompanied by restlessness,
mostly in horses, occasionally in cattle.
Identification of the etiology is also helpful
in diagnosis but is often difficult,
depending on a carefully taken history and
examination of the environment.

The differential diagnosis list is
limited to angioedema, but in urticaria the
lesions can be palpated in the skin itself.
Angioedema involves the subcutaneous
tissue rather than the skin and the lesions
are much larger and more diffuse. The two
conditions may appear in the one animal
at the one time.

TREATMENT

Primary treatment
A change of diet and environment, j
especially exposure to the causal insects
or plants, is standard practice. Spontaneous
recovery is common.

Supportive treatment
Corticosteroids, antihistamines, or epi-
nephrine by parenteral injection provide the
best and most rational treatment, especially
in the relief of the pruritus, which can be
annoying in some cases. One treatment is
usually sufficient but lesions may recur. The
local application of cooling astringent
lotions such as calamine or white lotion or a
dilute solution of sodium bicarbonate is
favored. In large animal practice parenteral
injections of calcium salts are used with
apparently good results.

Long-term medical management of
persistent urticaria involves the adminis-
tration of corticosteroids and or anti-
histamines. Oral administration or
prednisone or prednisolone at the lowest
possible dose on alternate days is the
method of choice. 2 The antihistamine of
choice is oral hydroxyzine hydrochloride
initially at 600 mg three times daily,
followed by gradual reduction to a mini-
mum maintenance dose required to keep
the horse free of lesions.

REVIEW LITERATURE

Evans AG. Urticaria in horses. Compend Contin Educ
PractVet 1997; 15:626-632.

Stannard AA. Immunologic diseases. Vet Dermatol
2000; 11:163-178.

Chuh A, Chan H, Zawar V. Pityriasis rosea-evidencc
for and against an infectious etiology.
Epidemiology 2004; 132:381-390.

REFERENCES

1. Chuh A et al. Epidemiology 2004; 132:381.

2. Stannard AA. Vet Dermatol 2000; 11:163.

3. Miyazawa K et al. JVet Med Sci 1991; 53:747.

4. Matthews NS et al. Equine Vet J 1993; 25:555.

5. Yerhuam I et al. Vet Dermatol 2001; 12:197.

6. Lorch G et al. Am J Vet Res 2001; 62:1051.

7. Cornick JL, Brumbaugh GW. Cornell Vet 1989;
79:109.

8. Evans AG et al. Am JVet Res 1992; 53:203.

DERMATITIS AND DERMATOSIS

Synopsis _ ,

Etiology Any disease of skin, including
those characterized by inflammation. All
pathogens, infectious, chemical, physical,
allergic, autoimmune
Epidemiology Sporadic or outbreak,
acute or chronic course, cosmetic to lethal,
but of most importance as constraints on
movement, sale or exhibition
Clinical signs Primarily localized to skin,
including lesions varying from parakeratosis
and pachyderma to weeping, through
necrosis, vesicles and edema. Secondarily
signs of shock, toxemia, anaphylaxis
Clinical pathology Positive findings in
the area of skin swabs or scrapings
Necropsy lesions Inflammatory,
degenerative a vascular lesions in skin
biopsy

Diagnostic confirmation Positive
finding in skin biopsy
Treatment primary is removal of the
pathogen; supportive includes treatment
for shock, toxemia or fluid and electrolyte
loss

ETIOLOGY

Some of the identifiable occurrences of
dermatitis in food animals and horses are
as follows.

All species

° Mycotic dermatitis due to

Dermatophihis ccngolensis, in horses,
cattle, sheep

- Staphylococcus aureus is a common
finding in cases in all species, either
as a sole pathogen or combined with
other agents

° Ringworm

Ci Photosensitive dermatitis
° Chemical irritation (contact
dermatitis) topically
° Arsenic - systemic poisoning
' Mange mite infestation - sarcoptic,
psoroptic, chorioptic, demodectic
mange

- Trombidiiform mite infestation
(tyroglyphosis)

° Biting flies especially Culicoides spp.
Observed most commonly in horses,
but also in other species 1
° Stephanofilaria sp. dermatitis
° Strongyloides (Pelodera) sp. dermatitis
■ Infection with the protozoon Besnoitia
spp.

Cattle

" Udder impetigo - S. aureus
° Cutaneous botryomycosis of the
udder caused by a combination of
trauma and infection by Pseudomonas
aeruginosa
0 Cowpox

° Ulcerative mammillitis - udder and
teats only

° Lumpy skin disease - Allerton and
Neethling'strains'

° Foot-and-mouth disease - vesicles
around natural orifices; vesicular
stomatitis with lesions on teats and
coronet

c Rinderpest, bovine virus diarrhea,
bovine malignant catarrh, bluetongue
- erosive lesions around natural
orifices, eyes, coronets
Sweating sickness
0 Perianal vesicular and necrotic

dermatitis associated with mushroom
poisoning

° Dermatitis on legs - potato poisoning
topical application of irritants or
defatting agents, e.g. diesoline
° Dermatitis due to the ingestion of
Vicia villosa and Vicia dasycaiya
0 Plaque-like and cracked skin lesions
on the udder, hindquarters, lips and
muzzle of cattle bedded on straw
heavily contaminated with Fusarium
sporotrichioides 2
° Flexural seborrhea
° Bovine exfoliative dermatitis (see below)
° Slurry heel (see below).

Sheep and goats

0 Strawberry footrot - Dermatophihis
pedis

° Sheep pox
0 Contagious ecthyma
’> Ulcerative dermatosis
° Rinderpest, peste de petits ruminants,
bluetongue - as for cattle
0 Foot-and-mouth disease and
vesicular stomatitis
° Fleece rot - constant wetting and
associated with P. aeruginosa 3
° Lumpy wool - D. congolensis
a Itch-mite ( Psorergates ovis) infestation
° Blowfly infestation (cutaneous
myiasis)

° 'Cockle' (probably related to louse
infestation) 4

° Elaeophoriasis (E laeophora sp.
infestation)

0 Ovine atopic dermatitis
° Caprine idiopathic dermatitis
° Postdipping necrotic dermatitis (see
below).

Pigs

° Ulcerative granuloma - Borrelia suilla
° Exudative epidermitis - Staphylococcus
hyicus (greasy pig disease)

• Pig pox

° Swine vesicular disease, vesicular
exanthema of swine, foot-and-mouth
disease - vesicles around natural
orifices

0 Contact with fresh parsnip tops,
celery
° Sunburn

° Porcine necrotic ear syndrome
° Nonspecific nutritional dermatitis -
experimental nutritional deficiency of

Diseases of the epidermis and dermis

nicotinic acid, riboflavin, pantothenic
acid, biotin

o Pityriasis rosea - cause unknown
t Idiopathic chronic recurrent
dermatoses.

Horses

o Staphylococcus hyicus in a syndrome
reminiscent of greasy heel
« Actinomyces viscosum
o Horsepox
s Canadian horsepox
e Viral papular dermatitis
e Vesicular stomatitis - vesicles around
natural orifices

o Vesicular dermatitis around nasal
area, eyes, ears in horses stabled on
shavings of a tree of the Quassia spp. 5
o Spongiotic vesicular dermatitis of
unknown etiology 6
= Sporotrichosis

° Dermatophytes, including ringworm,
follicular dermatitis, hyphomycosis
(pythiosis), tinea versicolor dermatitis
• Scald - constant wetting
o Queensland (sweet) itch - sensitivity
to Culicoides spp. sandflies 7
e Atopic dermatitis (IgE-mediated
hypersensitivity) 8

o Chronic eosinophilic dermatitis (see
below)

® Pemphigus, lupus erythematosus,
erythema multiforme, eosinophilic
dermatitis and stomatitis, described
separately below

° Molluscum contagiosum (see below)

0 Linear hyperkeratosis (see below)
r ' Nodular necrobiosis (see below)

° Ear plaque (see below)

° Uasin gishu disease
° Cutaneous habronemiasis
° Tropical lichen (see below)

0 Midline, ventral dermatitis due to
infestation with Hydrotaea irritans
(horn fly and buffalo fly)

0 Trombidiiform mites, e.g. Pyemotes
tritici and Acarus (Tyroglyphus) farinae
IJ Ulcerative dermatitis,

thrombocytopenia and neutropenia in
neonatal foals (see Alloimmune
hemolytic anemia of the newborn
(Neonatal isoerythrolysis, isoimmune
hemolytic anemia of the newborn),
Ch.33).

Special local dermatitides

These include dermatitis of the teats and
udder, the bovine muzzle and coronet,
and flexural seborrhea, and are dealt with
under their respective headings.

PATHOGENESIS

Dermatitis is basically an inflammation of
the deeper layers of the skin involving the
blood vessels and lymphatics. The purely
cellular layers of the epidermis are involved
only secondarily. The noxious agent
causes cellular damage, often to the point

of necrosis, and, depending on the type of
agent responsible, the resulting dermatitis
varies in its manifestations. It may be
acute or chronic, suppurative, weeping,
seborrheic, ulcerative or gangrenous. In
all cases there is increased thickness and
increased temperature of the part. Pain or
itching is present and erythema is evident
in unpigmented skin. Histologically there
is vasodilatation and infiltration with
leukocytes and cellular necrosis. These
changes are much less marked in chronic
dermatitis.

CLINICAL FINDINGS

Affected skin areas first show erythema
and increased warmth. The subsequent
stages vary according to the type and
severity of the causative agent. There may
be development of discrete vesicular
lesions or diffuse weeping. Edema of the
skin and subcutaneous tissues may occur
in severe cases. The next stage may be
the healing stage of scab formation or, if
the injury is more severe, there may be
necrosis or even gangrene of the affected
skin area. Spread of infection to sub-
cutaneous tissues may result in a diffuse
cellulitis or phlegmonous lesion. A
distinctive suppurative lesion is usually
classified as pyoderma. Deep lesions which
cause damage to dermal collagen may
cause focal scarring and idiopathic
fibrosing dermatitis (see below).

A systemic reaction is likely to occur
when the affected skin area is extensive.
Shock, with peripheral circulatory failure,
may be present in the early stages. Toxemia,
due to absorption of tissue breakdown
products, or septicemia due to invasion
via unprotected tissues, may occur in the
later stages.

Individual dermatitides are as follows:

® Bovine exfoliative dermatitis in

calves associated with the excretion of
an unidentified agent in the dam's
milk. The calves show a widespread
dermatitis, including vesicles on the
muzzle, scaling and hair loss, at a few
days of age but recover spontaneously
before 3 months of age. The dam has
the same disease in a mild but chronic
form 9

° Slurry heel 10 is erosion and deep
fissuring of the epithelium and horn
of the heel of cattle housed indoors
and standing continuously in slurry.
The affected claws are destabilized by
the disappearance of support so that
the pedal bone projects downwards
and through the dorsal surface of the
sole; the heel sinks and the toe
overgrows. Sole ulceration is a
common sequel. The condition can be
confused with interdigital dermatitis
° Ovine postdipping necrotic
dermatitis is associated with

P. aeruginosa and related to dipping in
solutions containing no bacteriostatic
agent. 11 Necrotic lesions (1-3 cm in
diameter), with cellulitis down to the
underlying muscle, occur only along
the backline and may be related to
trauma during dipping. It may be
accompanied by an outbreak of fatal
otitis media with P. aeruginosa present
in the lesion

° Ovine atopic dermatitis: Only the
wool-less parts of the skin are
affected by symmetrical erythema,
alopecia, lichenification and
excoriation. Only occasional sheep in
the flock are affected and these are
affected each summer, with remission
during the winter months 12

« Caprine idiopathic dermatitis:
Alopecic, exudative dermatitis of all
ages and both sexes of pygmy goats 13
is characterized by hair loss, scaling
and crusting around eyes, lips and
chin, ears, poll, perineum and ventral
abdomen. Histologically the lesions
have a psoriasis-like form

° Porcine dermatitis-nephropathy
syndrome, an idiopathic low
morbidity but highly fatal disease of
feeder pigs, 14-16 is characterized by
papular, vascular dermatopathy,
systemic necrotizing vasculitis and
exudative, proliferative
glomerulonephritis. Skin lesions are
full-depth necrosis appearing as
multiple, flat, red-blue papules up to
2 cm in diameter (which may coalesce
to form large plaques) on any part of
the body. Some pigs die of
glomerulonephritis without skin
lesions having been apparent. Many
cases that show only skin lesions
recover spontaneously in several
weeks. The disease may disappear if
the commercial grain ration used is
ground more coarsely

° Porcine necrotic ear syndrome is an
extensive necrosis of the edges of the
ears. The cause is unknown but the
possibility that a combination of
S. hyicus infection and trauma by
biting by pen mates is the cause
seems high

° Porcine idiopathic chronic,

recurrent dermatitis is recorded in
sows in specific farrowing houses. 17
Boars and piglets were not affected
and lesions disappeared as soon as
the sows left the houses. Annular
macules 11 cm diameter and patches
of erythema 11 cm diameter occur
only on white skin. There are no
systemic signs

° Equine staphylococcal dermatitis is

a serious disease because the lesions
are intractable to treatment and are so
painful to touch that the horse is hard

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

to handle, and the presence of the
lesions under harness, where they
commonly are, prevents the horse
from working kindly. Harness horses
are at a particular disadvantage.
Individual lesions are raised nodules,
3-5 mm diameter, covered by a small,
easily removed scab. When these lift
they take a tuft of hair with them and
a small crater is left. A little pus
exudes and only a red serous fluid can
be expressed. Individual lesions last a
long time, at least several weeks, and
fresh crops occur, causing the disease
to spread slowly on the animal
Chronic equine eosinophilic
dermatitis is characterized by marked
acanthosis and hyperkeratosis, and
eosinophilic granulomas in pancreas,
salivary glands and other epithelial
organs. The systemic involvement is
accompanied by severe weight loss.
The disease is chronic, and the cause
unknown

Spongiotic vesicular dermatitis has

been described in horses. 6 Lesions are
characterized by a multifocal,
exudative, oozing dermatitis
characterized histologically by
epidermal spongiotic vesicles and
perivascular eosinophilic, neutrophilic
and mixed mononuclear
inflammation. Some horses are
pruritic

Equine nodular necrobiosis: Firm,
small (up to 1 cm diameter) nodules,
usually a number of them, occur on
the sides of the trunk and neck. The
cause is unknown. The lesions consist
largely of an accumulation of
eosinophils

Molluscum contagiosum is a

chronic, progressive dermatitis 18
characterized by raised, hairless
lesions 0.5-2 cm in diameter, covered
by soft keratin, that bleed profusely
when the horse is groomed. The
lesions are on the face, shoulders,
trunk, lateral aspects of limbs, fetlocks
and pasterns. Histological
examination identifies the disease
because of the presence of
characteristic inclusions in cells. These
are thought to be pox virus virions,
but the virus cannot be cultivated
from the lesions. There is no specific
treatment

Systemic lupus erythematosus

(SLE) is an extensive dermatitis,
manifested as a scaly, crusty
dermatitis of the face, neck and trunk,
with loss of hair over the lesions,
edema of the limbs and a mild to
moderate lymph node
enlargement. 7,19 Multiple ulcers 11 cm
in diameter are present on the oral
mucosa, especially the

mucocutaneous junctions of the lips
and nares, and on the tongue. There is
a severe systemic reaction, including a
marked loss of body weight, a
temperature up to 39.5°C, heart rate
80/min, respiratory rate up to 60/min,
painful swollen joints containing
sterile serous fluid, stiff gait,
reluctance to move, and persistent
lateral recumbency. SLE is an
immune-mediated disease with a
characteristic histopathology
including a necrotizing, lymphocytic
dermatitis and focal accumulations of
lymphocytes in the liver, membranous
glomerulonephritis and synoviocyte
hyperplasia. An antinuclear antibody
test is diagnostic. No treatment is
effective and the disease runs a
chronic progressive course marked by
remissions and exacerbations

o Discoid lupus erythematosus is an
uncommon, benign variant of the
systemic disease, with cutaneous
lesions similar to those in the major
disease but with no involvement of
other tissues

' Erythema multiforme is a self-
limiting skin disease of horses and
cattle characterized by macular,
papular, urticarial or bullous skin
lesions but without any abnormality
of the epidermis or loss of hair, and
with no apparent itching or pain. The
lesions occur symmetrically on most
parts of the body, persist for long
periods and increase in size up to
4-5 cm to form annular or crescent-
shaped wheals. Spontaneous
disappearance of the lesions after
about 3 months is usual. Symptomatic
treatment may be effective but is not
usually necessary

Equine ear plaque: Multiple white
plaques, resembling papilloma and
about 1 cm in diameter, develop on
the inner surface of the ear pinna of
horses

Equine tropical lichen is an

intensely irritating, papular eruption
in the skin on the side of the neck,
under the mane, the shoulders and at
the tail head, occurring in summer
and recurring annually. The disease
closely resembles the cutaneous
sensitivity to Culicoidcs spp. but
responds dramatically to treatment
with ivermectin. Microfilariae, thought
to be Onchocerca spp., can be found in
histological sections
Linear keratosis is most common in
horses, especially Quarter horses. One
case has been recorded in cattle. 20
Lesions appear spontaneously in
horses 1-5 years old and persist,
usually for life. They appear first as
isolated scaly lumps, which then

coalesce to form a ridge, usually
vertical, 3-4 cm wide and up to 70 cm
long, of hyperkeratotic, hairless skin.
There may be one or more lesions,
commonly on the sides of the neck
and chest. Symptomatic treatment
appears to have no effect on the
lesions

* Idiopathic fibrosing dermatitis: The

end stage of several severe
dermatoses, this causes damage to
dermal collagen. 21 Manifested by
multiple fibrous plaques in the skin
caused by sclerosis of the skin or
subcutis, it resembles human
morphea and the skin granulomas of
animals.

Pemphigus

This is an autoimmune disease of the
skin, sometimes affecting mucosae and
characterized by the presence of vesicles
or bullae, which are usually very difficult
to find, and subsequent erosions and ulcer-
ations. There are a number of manifes-
tations, including pemphigus vulgaris,
bullous pemphigoid and pemphigus
foliaceus. 7 It is a chronic autoimmune
disease often accompanied by severe
weight loss.

Pemphigus foliaceus is the most com-
mon autoimmune disease of the horse.'
The majority of cases occur in mature
horses, usually 5 years of age or older; a
small number occur in horses 1 year of
age or younger. The classic, but rarely
seen, primary lesion is a vesicle or pustule.
Usually, the earliest lesions visible are
crusted papules best seen in lightly or
nonhaired skin adjacent to muco-
cutaneous junctions - the nostrils, eyelids
or lips. Lesions rapidly coalesce to form
multifocal or diffuse areas of crusting. It
occurs as a generalized scabby, weeping
dermatitis 22 but it may be localized as
circumscribed, circular lesions in the
mouth and vulva and on the skin at
mucocutaneous junctions. The lesions are
subepidermal bullae from which the top
layer can be pulled away, and are sore to
the touch. In some cases the lesions are
around the coronary bands on all limbs.
Edema of the extremities, especially the
hindlimbs, and the ventral abdominal
region are commonly present.

The differential diagnoses include all
skin diseases caused by scaling and
crusting. These include dermatophytosis,
dermatophilosis, systemic granulomatous
disease and primary or idiopathic abnor-
malities of keratinization.

A direct immunofluorescence examin-
ation, consisting of a fluorescein-
antihorse IgG applied to the lesion, can
confirm the diagnosis. Corticosteroid or
gold (aurothioglucose) therapy has been
reported to effect improvement but an

Diseases of the epidermis and dermis

inexorable deterioration is usual. Pemphi-
gus foliaceus is recorded in goats as a
widespread disease characterized by the
presence of scales, sometimes in heavy
crusts, and involvement of the coronets.

CLINICAL PATHOLOGY

Examination of skin scrapings or swabs
for parasitic, bacterial or other agents is
essential. Culture and sensitivity tests for
bacteria are advisable to enable the best
treatment to be selected. Skin biopsy may
be of value in determining the causal
agent. In allergic or parasitic states there
is usually an accumulation of eosinophils
in the inflamed area. In mycotic dermatitis
organisms are usually detectable in the
deep skin layers although they may not be
cultivable from superficial specimens.

DIAGNOSIS

The clinical features of dermatitis are
apparent. The characteristic features of
the etiological types of dermatitis are
described under each specific disease.
Diagnostic confirmation is by histo-
pathological demonstration in a biopsy
specimen.

DIFFERENTIAL DIAGNOSIS

• Hyperhidrosis and anhidrosis

are dysfunctions of sweating and have
no cutaneous lesion

• Cutaneous neoplasm is differentiable
on histopathological examination

• Epitheliogenesis imperfecta

is a congenital absence of all layers of
skin

• Vascular nevus is a congenital lesion
commonly referred to as 'birth mark'

TREATMENT

Primary treatment must be to remove
the noxious physical or chemical agent
from the environment or to supplement
the diet to repair a nutritional deficiency.
The choice of a suitable treatment for
infectious skin disease will depend upon
the accurate identification of the etiological
agent.

Supportive treatment includes both
local and systemic therapy. Local appli-
cations may need to be astringent either
as powders or lotions in the weeping
stage or as greasy salves in the scabby
stage. The inclusion of corticosteroids or
antihistamine preparation is recommended
in allergic states and it is desirable to
prescribe sedative or anesthetic agents
when pain or itching is severe.

If shock is present, parenteral fluids
should be administered. If the lesions are
extensive or secondary bacterial invasion
is likely to occur, parenterally administered
antibiotics or antifungal agents may be
preferred to topical applications. To facili-

tate skin repair, a high protein diet or the
administration of protein hydrolysates or
amino acid combinations may find a place
in the treatment of valuable animals. Non-
specific remedies such as gold-containing
remedies (e.g. aurothioglucose) are com-
monly used in autoimmune diseases such
as pemphigus.

The use of vaccines as prophylaxis in
viral and bacterial dermatitides must not
be neglected. Autogenous vaccines may
be most satisfactory in bacterial infec-
tions. An autogenous vaccine is parti-
cularly recommended in the treatment of
staphylococcal dermatitis in horses and
bovine udder impetigo in which long and
repeated courses of treatment with peni-
cillin produce only temporary remission.
An autogenous vaccine produces a cure in
many cases.

REFERENCES

1. Yeruham I et al.AustVet] 1993, 70:348.

2. Wu W et al. Vet Rec 1997; 140:399.

3. El-Sukhon SN. Vet Dermatol 2002; 13:247.

4. Heath ACG et al. Vet Rirasitol 1996; 67:259.

5. Campagnolo ER. et al. J Am Vet Med Assoc 1995;
207:211.

6. Hargis AM ct al.Vct Dermatol 2001; 12:291.

7. Stannard AA. Vet Dermatol 2000; 11:163.

8. Lorch G ct al. Am J Vet Res 2001; 62:1051.

9. Bassett H. IrVet J 1985; 39:106.

10. Blowey RW, Done SH. Vet Rec 1995; 137:379.

11. Davies IH, Done SH.VbtRec 1993; 93:460.

12. Scott DW, Campbell SG. Agri-practice 1987; 8:46.

13. Jefferies AR ct al. Vet Rec 1997; 121:576.

14. Helic P et al. Can Vet J 1995; 36:150.

15. Vinhalderen A. J S AfrVet Assoc 1995; 66; 108.

16. Smith WJ ct al.Vct Rec 1993; 132:47.

17. Scott DW et al. Agri-practice 1989; 10:43.

18. Van Rensburg 1BJ. J S AfrVet Assoc 1991; 62:72.

19. Scott DW, Gcor RJ. J Am Vet Med Assoc 1990;
197:1489.

20. DeprezP et al.Vct Dermatol 1995; 6:45.

21. Littlcwood JD et al. Equine Vet Educ 1995; 7:295.

22. Laing JA et al. Equine Vet J 1992; 24:490.

PHOTOSENSITIZATION

Etiology Caused by the sensitization of
dorsally situated, lightly pigmented skin,
mucosa and cornea to light. Dermatitis
develops when the sensitized skin is
exposed to sunlight

• Intake of primary photodynamic agents
(PDAs)

• Faulty excretion of phylloerythrin
(metabolic product of chlorophyll and a
PDA) due to liver damage

• Inherited defects of porphyrin
metabolism, producing PDAs

• Many unexplained cases and outbreaks
in pastured or housed animals

Epidemiology Exposure to
photosensitizing substances and sunlight.
Similar incidence of sporadic cases and
outbreaks. Always life-threatening unless
exposure to sunlight can be avoided

Clinical signs Primary cases have
cutaneous signs only (erythema, edema,
necrosis, gangrene of light colored skin or
mucosae exposed to sunlight). Secondary
cases have also signs of hepatic
dysfunction (jaundice, prostration, short
course, death), or porphyrin metabolism
Clinical pathology Nil for evidence of
photosensitivity. In secondary cases there is
evidence of the primary disease
Necropsy lesions Only skin lesions in
primary cases. Secondary cases show liver
lesions or evidence of porphyrin
accumulation

Differential diagnosis Clinical
evidence of restriction of damage to white,
wool-less skin on body dorsum and lateral
aspects of limbs, teats, corneas and tongue
and lips

Treatment Primary: remove from
exposure to sunlight and PDA. Supportive:
treat for infection, shock, toxemia

ETIOLOGY AND EPIDEMIOLOGY

If photosensitizing substances (photo-
dynamic agents) are present in sufficient
concentration in the skin, dermatitis
occurs when the skin is exposed to light.
Photodynamic agents are substances that
are activated by light and may be ingested
preformed (and cause primary photo-
sensitization) or be products of abnormal
metabolism (and cause photosensitization
due to aberrant synthesis of pigment)
or be normal metabolic products that
accumulate in tissues because of faulty
excretion through the liver (and cause
hepatogenous photosensitization) . Faulty
excretion through the liver may be due to
hepatitis, caused in most instances by
poisonous plants, or to biliary obstruction
caused by crystal-associated cholangio-
hepatopathy, or rarely by cholangio-
hepatitis or biliary calculus.

Primary photosensitization

Photosensitization due to the ingestion of
exogenous photodynamic agents usually
occurs when the plant is in the lush green
stage and is growing rapidly. Livestock
are affected within 4-5 days of going on
to pasture and new cases cease soon after
the animals are removed. In most cases
the plant responsible must be eaten in
large amounts and will therefore usually
be found to be a dominant inhabitant of
the pasture. All species of animals are
affected by photodynamic agents, although
susceptibility may vary between species
and between animals of the same species.
Photosensitizing substances that occur
naturally in plants include:

9 Dianthrone derivatives - hypericin in
Hypericum perforatum (St John's wort)
and other Hypericum spp. and
fagopyrin in seeds and dried plants of
Fagopyrum esculentum (buckwheat)

E

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

® Furocounrarins in Cymopterus spp.
(wild carrot), Ammi majus and
Thamnosma texana
° Perloline from perennial ryegrass
(Lolium perenne )

’> Cocoa shells in feedlot rations causing
photosensitization in feedlot calves 1
;i Gluten metabolites in dairy cattle
concentrates being fed to horses 2
c; Erodium moschatum, an exotic weed in
South Africa, causing
photosensitization in sheep 3
° Unidentified photodynamic agents in
Medicago denticulata (burr trefoil) and
the aphids that infest it, and in
Brassica spp., Erodium spp., and
Trifolium spp.

° Miscellaneous chemicals including
phenothiazine (its metabolic end-
product phenothiazine sulfoxide is
photosensitizing to calves), rose
Bengal and acridine dyes
o Cows treated with corticosteroids to
induce calving may develop a
photosensitive dermatitis of the teats,
escutcheon and udder. Its occurrence
is sporadic and does not appear to be
related to a particular drug.

Photosensitization due to aberrant
pigment synthesis

The only known example in domestic
animals is inherited congenital porphyria,
in which there is an excessive production
in the body of porphyrins, which are
photodynamic.

Hepatogenous photosensitization

The photosensitizing substance is in all
instances phylloerythrin, a normal end-
product of chlorophyll metabolism excreted
in the bile. When biliary secretion is
obstructed by hepatitis or biliary duct
obstruction, phylloerythrin accumulates
in the body and may reach levels in the
skin that make it sensitive to light.
Although hepatogenous photosensitization
is more common in animals grazing green
pasture, it can occur in animals fed
entirely on hay or other stored feeds
and in animals exposed to hepatotoxic
chemicals e.g. carbon tetrachloride. There
appears to be sufficient chlorophyll, or
breakdown products of it, in stored
feed to produce critical tissue levels
of phylloerythrin in affected animals.
The following list includes those sub-
stances or plants that are common causes
of hepatogenous photosensitization.
The individual plants are discussed in
more detail in the section on poisonous
plants.

Plants containing hepatotoxins

° Pithomyces chartarum fungus on
perennial ryegrass - causing facial
eczema

0 Periconia sp. fungus on Bermuda grass

® Cyanobacteria associated with blue-
green algae (water bloom) on
drinking water in ponds, dams and
dugouts - Microcystis flosaquae
® Lupins - Lupinus angustifolius plus the
accompanying fungus, Phomopsis
leptostromiformis

° Signal grass (. Brachiaria decumbens and
Brachiaria brizantha), a common
component of established pastures in
Brazil 4

° Alligator weed ( Alternanthera
philoxeroides), a South American
aquatic plant causing
photosensitization in dairy cattle in
Australia and New Zealand 5
° Weeds including lantana ( Lantana
camara ), Lippia rehmanni, sacahuiste
(. Nolina texana), coal oil bush
( Tetradymia spp.), alecrim ( Holocalyx
glaziovii), ngaio ( Myopormn laetum ),
Crotalaria retusa, ragwort ( Senecio
jacobea), Sphenosciadium spp.

Plants containing steroidal saponins

These cause crystal-related cholangio-
hepatopathy.

° Agave lecheguilla, Narthecium
ossifragmn, Panicum spp. (panic and
millet grasses), Tribulus terrestris
(caltrop, geeldikkop), plants being
grazed particularly by sheep
0 Alveld, a hepatogenous

photosensitivity disease of sheep
(lambs) grazing on pastures
containing Narthecium ossifragum
(bog asphodel) on the west coast of
Norway and in Scotland, northern
England, Ireland, and the Faroe
Islands. 6 The disease is known as
alveld (literally 'elf fire') in Norway,
plochteach, saut or yellowses in the
British Isles and ormajuka ('worm
disease') in the Faroe Islands.
Narthecium ossi fragum-containing
pastures in these countries are
commonly used for grazing sheep.
Photosensitization of sheep grazing
this plant usually occurs in
2-6- month-old lambs and is rarely
seen in adult sheep. It produces
similar clinical signs to those due to
facial eczema, a disease most
commonly seen in New Zealand and
associated with the fungal toxin
sporidesmin.

Congenitally defective hepatic
function

Inherited congenital photosensitivity in
Corriedale and Southdown lambs is an
inherited defect in the excretion of bile
pigment.

Photosensitization of uncertain
etiology

In the following diseases it has not been
possible to ascertain whether the photo-

sensitization is primary or due to hepatic
insufficiency:

® Feeding on rape or canola ( Brassica
rapa), kale, lucerne or alfalfa
( Medicago sativa), burr medic or burr
trefoil ( Medicago denticulata), Medicago
minima, Trifolium hybridum (alsike or
Swedish clover), Erodium cicutarium
and Erodium moschatum (lamb's
tongue, plantain)

° Cattle feeding on water-damaged or
moldy alfalfa hay or alfalfa silage;
extensive outbreaks usually with no
signs suggestive of hepatic disease
® Cattle, sheep and horses grazing lush
pasture; many clinical cases occur
sporadically

° Corticosteroids used systemically to
terminate parturition in cows
° Phenanthridium used in the
treatment of trypanosomiases.

PATHOGENESIS

Penetration of light rays to sensitized
tissues causes local cell death and tissue
edema. Irritation is intense because of the
edema of the lower skin level, and loss of
skin by necrosis or gangrene and sloughing
is common in the terminal stages. Nervous
signs may occur and are caused either by
the photodynamic agent, as in buckwheat
poisoning, or by liver dysfunction.

Hepatogenous photosensitization
involves production of a toxin, by a higher
plant, fungus or cyanobacterium (algae),
that causes liver damage or dysfunction,
resulting in the retention of the photo-
sensitizing agent phylloerythrin.

CLINICAL FINDINGS
General signs

These commence with intense irritation
and the animal rubs the affected parts,
often lacerating the face by rubbing it in
bushes. When the teats are affected the
cow may kick at them and walk into
ponds to immerse the teats in water, some-
times rocking backwards and forwards as
if to cool the affected parts. In nursing
ewes there may be resentment towards
the lambs sucking, and heavy lamb
mortalities due to starvation may result.

Local edema is often severe and may
cause drooping of the ears, closure of the
eyelids and nostrils, causing dyspnea, and
dysphagia due to swelling of the lips. Air
early sign is increased lacrimation, with the
initially wateiy discharge developing into a
thicker, serous discharge accompanied by
blepharospasm and swelling of the eyelids.
Initial erythema of the muzzle is followed
by fissuring, then sloughing of the thick
skin.

Skin lesions

Skin lesions are initially erythema, followed
by edema and subsequently weeping
with matting then shedding of clumps of

Diseases of the hair, wool, follicles, skin glands, horns and hooves

61

hair, and finally gangrene. They have a
characteristic distribution, restricted to the
unpigmented areas of the skin and to those
parts which are exposed to solar rays. They
are most pronounced on the dorsum of the
body, diminishing in degree down the sides
and are absent from the ventral surface. The
demarcation between lesions and normal
skin is very clear-cut, particularly in animals
with broken-colored coats.

Predilection sites for lesions are the
ears, conjunctiva, causing opacity of the
lateral aspect of the cornea, eyelids, muzzle,
face, the lateral aspects of the teats and, to
a lesser extent, the vulva and perineum. In
solid black cattle dermatitis will be seen at
the lips of the vulva and on the edges of
the eyelids, and on the cornea. Linear
erosions often occur on the tip and sides
of the tongue in animals with unpigmented
oral mucosa. In severe cases the exudation
and matting of the hair and local edema
causes closure of the eyelids and nostrils.
In the late stages necrosis or dry gangrene
of affected areas leads to sloughing of
large areas of skin.

Systemic signs

These include shock in the early stages,
due to extensive tissue damage. There is
an increase in the pulse rate with ataxia
and weakness. Subsequently a considerable
elevation of temperature (41-42°C,
106-107°F) may occur.

Nervous signs

These including ataxia, posterior paralysis
and blindness; depression or excitement
are often observed. A peculiar sensitivity
to water is sometimes seen in sheep with
facial eczema: when driven through water
they may lie down in it and have a
convulsion.

Liver insufficiency

Signs are described elsewhere and may
accompany photosensitive dermatitis
when it is secondary to liver damage.

CLINICAL PATHOLOGY

There are no suitable field tests to deter-
mine whether or not photosensitivity is
present.

Hepatogenous photosensitization can
be diagnosed by analysis of plasma
phylloerythrin concentration using a
spectroscopic method. Plasma or serum
fluorescence can be used to measure the
elevation of phylloerythrin above normal
levels prior to hepatogenous photo-
sensitization.'^ 9 Hie levels of phylloerythrin
in plasma of lambs grazing Narthecium
ossifragum are increased from a normal
of less than 0.05pg/mL to more than
0.3 pg/mL when clinical signs of photo-
sensitization are observed. 9 Levels in skin
are also increased.

In lambs in which facial eczema was
experimentally induced by dosing with

the mycotoxin sporidesmin, the plasma
concentrations of phylloerythrin were
increased from a normal of less than
0.1 pmol/L to 0.3 pmol/L when clinical
signs were evident. 8 The concentration
of phylloerythrin in the skin began
increasing 2-3 days later than that in the
blood.

NECROPSY FINDINGS

In primary photosensitization, lesions are
restricted to white-haired or pale-skinned
areas of skin or mucosa that have been
exposed to sunlight, and vary from
necrosis to gangrene. Lesions charac-
teristic of hepatic injury or metabolic
defects of porphyrin metabolism are
described elsewhere.

Diffuse hepatocellular hydropic degener-
ation and hyperplasia of the smooth
endoplasmic reticulum associated with
marked multifocal cholangitis in the
portal triads with bile duct proliferation
are characteristic of the hepatic lesions of
sheep grazing Brachiaria decumbens . 4
Foam cells are present in the liver and
mesenteric and hepatic lymph nodes of
cattle grazing Brachiaria spp. 10 Hepato-
cellular degeneration is the primary event
in alveld photosensitization in sheep. 6
High concentrations of conjugated epi-
sapogenins are present in both liver and
bile in alveld-affected lambs.

DIFFERENTIAL DIAGNOSIS

The diagnosis of photosensitivity depends
almost entirely on the distribution of the
lesions. It can be readily confused with
other dermatitides if this restriction to
unpigmented and hairless parts is not kept
in mind.

• Mycotic dermatitis is often mistaken for
photosensitization because of its
tendency to commence along the back
line and over the rump, but it occurs on
colored and white parts alike

• Frequent wetting, as in periods of
heavy rainfall, along the back in horses
or cattle with a dense hair coat

• Bighead of rams associated with
Clostridium novyi infection may also be
confused with photosensitization but
the local swelling is an acute
inflammatory edema and many
Clostridia are present in the lesion

• The eye lesions in photosensitization
have been confused with those of pink-
eye but that disease is not accompanied
by extensive dermatitis.

Treatment

Primary treatment includes immediate
removal from direct sunlight, prevention
of ingestion of further toxic material and
the administration of laxatives to eliminate
toxic materials already eaten. In areas
where the disease is enzootic the use of

dark-skinned breeds may make it poss-
ible to utilize pastures that would otherwise
be too dangerous.

Local treatment will be governed by
the stage of the lesions. Nonsteroidal
anti-inflammatory drugs (NSAIDs), corti-
costeroids or antihistamines can be admin-
istered parenterally and adequate doses
maintained. To avoid septicemia the pro-
phylactic administration of antibiotics
may be worthwhile in some instances.

REVIEW LITERATURE

Rowe LD. Photosensitization problems in livestock.
Vet Clin North Am Large Anim Pract 1989;
5:301-323.

Plumlee KH. Photosensitization in ruminants. Vet
Med 1995; 90:605-612

House JK et al. Primary photosensitization in cattle
ingesting silage. J Am Vet Med Assoc 1996;
209:1604.

REFERENCES

1. Yeruham I et al. Vet Hum Toxicol 2003; 45:249.

2. Yeruham 1 et al. Vet Hum Toxicol 1999; 41:386.

3. Stroebel JC. J S AfrVet Assoc 2002; 73:57.

4. DriemeierD et al.Toxicon 2002; 40:1027.

5. Bourke CA. Rayward D. AustVet J 2003; 81:361.

6. Wisloff H et al. Vet Res Commun 2002; 26:381.

7. SchieEetal. NZ Vet J 2003; 51:99.

8. Schie E et al. N Z Vet J 2003; 51:104.

9. Schie E et al. N Z V?t J 2002; 50:104.

10. Gomar MS et al. J Vet Med A 2005; 52:18.

Diseases of the hair, wool,
follicles, skin glands, horns,
and hooves

ALOPECIA AND HYPOTRICHOSIS
ETIOLOGY

Alopecia is complete absence of the hair
or wool coat; hypotrichosis is less than
the normal amount of hair or wool. Both
may be caused by the following conditions.

Failure of follicles to develop

° Congenital hypotrichosis.

Loss of follicles

° Cicatricial alopecia due to scarring
after deep skin wounds that destroy
follicles. Cicatricial alopecia occurs
following permanent destruction of
the hair follicles, and regrowth of hair
will not occur. Examples include
physical, chemical or thermal injury,
severe furunculosis, neoplasia and
certain infections such as cutaneous
onchocerciasis. 1

Failure of the follicle to produce a
fiber

° Inherited symmetrical alopecia
0 Congenital hypotrichosis
° Hair-coat-color-linked follicle
dysplasia

° Inherited dyserythropoiesis and
dyskeratosis
In baldy calves and
adenohypophyseal hypoplasia

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external' ear

~ Congenital hypothyroidism (goiter)
due to iodine deficiency in the dam
° After viral infection of the dam,
alopecia congenitally in the newborn,
e.g. after bovine virus diarrhea in
cattle and infection by a similar virus
in sheep (Border disease)

» Neurogenic alopecia due to peripheral
nerve damage
3 Infection in the follicle
« Alopecia areata of horses and, less
commonly, cows 2 characterized by
one or more round lesions of
spontaneously disappearing,
nonscarring alopecia over the face,
neck, shoulders and brisket. At
histopathological examination normal
skin contains accumulations of
lymphocytes around the hair follicles.

Loss of preformed fibers

° Dermatomycoses - ringworm
o Mycotic dermatitis in all species due
to D. cmgolensis

- Metabolic alopecia subsequent to a
period of malnutrition or severe
illness -'a break in the wool', e.g.
excessive whale, palm or soya oil in
milk replacers to calves; the fibers
grown during the period of nutritional
or metabolic stress have a zone of
weakness and are easily broken
^ Traumatic alopecia due to excessive
scratching or rubbing associated with
louse, tick or itch-mite infestations;
rubbing against narrow doors, feed
troughs or tethers in confined
housing, against harness in working
animals

Poisoning by thallium, selenium,
arsenic, mercury or the tree Leucaena
leucocephala

■> Idiopathic hair loss from the tail-
switch of well-fed beef bulls
-- In sterile eosinophilic folliculitis of
cattle

° Wool slip

-■ In many primary skin diseases,
e.g. parakeratosis, hyperkeratosis,
dermatitis, cutaneous neoplasia,
sarcoid; pythiosis hair is lost at the
site of local lesions.

PATHOGENESIS

Normal shedding of hair fibers is a
constant but largely unexplained process,
especially during significant changes in
environmental temperature. The long
winter coat is shed in response to warmer
spring temperatures and increased hours
of sunlight, and rapidly regrows as environ-
mental temperatures fall in the autumn.
In inherited hair defects there may be a
reduction in follicle numbers or a reduced
capacity of each follicle to produce fibers.
Chemical depilation produced by cytotoxic
agents, such as cyclophosphamide, occurs
as a result of induced cytoplasmic degener-

ation in some of the germinative cells of j
the bulb of the wool follicle. The alteration j
in cell function is temporary, so that
regrowth of the fiber should follow.

CLINICAL FINDINGS

When alopecia is due to breakage of the
fiber, the stumps of old fibers or develop-
ing new ones may be seen. When fibers
fail to grow the skin is shiny and in most
cases is thinner than normal. In cases of
congenital follicular aplasia, the ordinary
covering hairs are absent but the coarser
tactile hairs about the eyes, lips and
extremities are often present. Absence of
the hair coat makes the animal more
susceptible to sudden changes of environ-
mental temperature. There may be mani-
festations of a primary disease and
evidence of scratching or rubbing.

Congenital hypotrichosis results in
alopecia which is apparent at birth or
develops within the neonatal period.

CLINICAL PATHOLOGY

If the cause of the alopecia is not apparent
after the examination of skin scrapings or
swabs, a skin biopsy will reveal the status
of the follicular epithelium.

DIFFERENTIAL DIAGNOSIS

Diagnostic confirmation of alopecia is by
visual recognition, the diagnostic problem
being to determine the primary cause of
the hair or fiber loss.

Hypotrichosis is a reduction in numbers
of fibers instead of a complete absence.
Inherited diseases of the skin are presented
in Chapter 34.

TREATMENT

Primary treatment consists of removing
the causes of trauma or other damage
to fibers. In cases of faulty follicle or fiber
development treatment is not usually
attempted.

REVIEW LITERATURE

Fciscoe RR. Alopecia, diagnosis and treatment. Equine
Pract 1993; 15:8-16.

REFERENCES

1. Stannard AA.Vet Dermatol 2000; 11:191.

2. Scott DW, Guard CL. Agri-practice 1988; 9(4):16.

ACHROMOTRICHIA

Deficient pigmentation in hair or wool
fiber as follows:

° Bands of depigmentation in an
otherwise black wool fleece are the
result of a transitory deficiency of
copper in the diet

° Cattle on diets containing excess
molybdenum and deficient copper
show a peculiar speckling of the coat
caused by an absence of pigment in a
proportion of hair fibers. The

speckling is often most marked
around the eyes, giving the animal the
appearance of wearing spectacles
° General loss of density of

pigmentation in all coat colors, e.g.
Hereford cattle shade off from their
normal deep red to a washed-out
orange.

LEUKODERMA AND
LEUKOTRICH IA

Several skin diseases of the horse are
characterized by an acquired loss of
melanin pigment in the epidermis of
hair . 1 Melanocytes in the epidermis and
those in the hair bulbs are frequently
affected independently. Leukotrichia
occurs when the melanocytes in the
hair bulbs lose their normal amount of
melanin pigment. When the melanocytes
in the epidermis are affected and the skin
loses normal pigmentation, the abnor-
mality is leukoderma. The etiology and
pathogenesis of leukoderma are unknown.
Reticulated leukotrichia, spotted leuko-
trichia and juvenile Arabian leukoderma
have been described . 1

VITILIGO

Patchy depigmentation of the skin with
premature graying of the local hair is not
uncommon in cattle and horses. The
usual manifestation is the appearance of
patches of gray or white hair -'snowflakes'-
in an otherwise pigmented coat. The
defect is esthetic only. Histopathological
examination reveals a complete absence
of melanocytes from affected areas but
the cause is unknown in most cases. A
genetic etiology is suspected in Arabian
horses and Holstein-Friesian cattle. It can
also be caused by:

0 Application of'supercooled'

instruments that selectively destroy
melanocytes, the basis for freeze
branding

3 Prolonged pressure, e.g. by poorly
fitting harness
° X-irradiation

° An idiopathic state in horses, usually
during a debilitating disease, with
patchy depigmentation of skin
appearing on the prepuce, perineum,
underneath the tail, and on the face.
There is no discontinuity of the skin.

SEBORRH EA

ETIOLOGY

Seborrhea is an excessive secretion of
sebum on to the skin surface. In large
animals it is always secondary to dermatitis
or other skin irritation, e.g.:

n Exudative epidermitis of pigs
associated with S. hyicus

Diseases of the hair, wool, follicles, skin glands, horns and hooves

Greasy heel of horses, including ;

infection with S. hyicus
Greasy heel of cattle j

Flexural seborrhea of cattle.

PATHOGENESIS

Increased blood supply to the skin and j
increased hair growth appear to stimulate ;
the production of sebum, but why sebor- j
rhea is provoked in some individuals and
not in others is unknown. j

CLINICAL FINDINGS j

In primary seborrhea there are no lesions, j
only excessive greasiness of the skin. The j
sebum may be spread over the body j
surface like a film of oil or be dried into j
crusts, which can be removed easily.
Sebaceous glands may be hypertrophied. |

I

Flexural seborrhea I

Flexural seborrhea is most common in I
young, periparturient dairy cows. Severe j
inflammation and a profuse outpouring i
of sebum appear in the groin between the |
udder and the medial surface of the thigh, j
or in the median fissure between the two j
halves of the udder. Extensive skin necrosis ;
follows, causing a pronounced odor of :
decay, which may be the first sign observed j
by the owner. Irritation may cause lame- i
ness and the cow may attempt to lick the j
part. Shedding of the oily, malodorous I
skin leaves a raw surface beneath; healing j
follows in 3-4 weeks.

Greasy heel of cows

Cows grazing constantly irrigated, wet
pastures, or in very muddy conditions in
tropical areas may develop local swelling,
with deep fissuring of the skin and an
outpouring of evil-smelling exudate, on the
back of the pastern of all four feet but most
severely in the hind limbs. Affected animals
are badly lame and their milk yield declines
sharply. Removing the cows to dry land
and treating systemically with a broad-
spectrum antibiotic effects a rapid recovery.

Greasy heel of horses (scratches)

Greasy heel occurs mostly on the hind
pasterns of horses that stand continuously
in wet, insanitary stables. 2 Some cases do
occur in well managed stables. It has been
suggested that secondary infections
associated with either S. aureus and
D. congolensis may be causative factors. 2
Derma tophytosis, chorioptic mange and
photosensitization arc also possible
causative factors.

Lameness and soreness to touch are
due to excoriations called 'scratches' on
the back of the pastern that extend down
to the coronary band. The skin is thick
and greasy and, if neglected, the con-
dition spreads around to the front and up
the back of the leg; this involvement can
be severe enough to interfere with normal
movement of the limb.

CLINICAL PATHOLOGY

The primary cause of the seborrhea may
be diagnosed by a suitable examination
for the presence of parasitic or bacterial
pathogens.

DIFFERENTIAL DIAGNOSIS

The lesion is characteristic and diagnostic
confirmation is by histopathological
examination of a biopsy specimen; the
principal difficulty is to determine the
primary cause. All the types listed may be
mistaken for:

• Injury, commonly wire cuts or rope burn

• Flexural seborrhea for injury, usually due
to straddling a gate or wire fence

• Greasy heel of horses for chorioptic
mange.

TREATMENT

The skin must be kept clean and dry.
Affected areas should be defatted with
hot soap and water washes, then properly
dried, and an astringent lotion, e.g. white
lotion, should be applied daily. In acute
cases of greasy heel the application at
5-day intervals of an ointment made up of
five parts salicylic acid, three parts boric
acid, two parts phenol, two parts mineral
oil and two parts petroleum jelly is
recommended. Long-standing cases profit
from the twice-daily washing of the part
and covering with an ointment contain-
ing an antibiotic, a fungistat and a
corticosteroid, e.g. gentamicin, clotrimazole,
betametasone.

FOLLIC ULITIS

ETIOLOGY

Infection and inflammation of hair
follicles associated with suppurative organ-
isms, including staphylococci. Identifiable
forms of folliculitis as individual diseases
include:

° Staphylococcal dermatitis of horses
1 Contagious acne of horses
n Benign facial folliculitis of sucking
lambs

° Demodectic mange

° Bovine sterile eosinophilic
folliculitis.

PATHOGENESIS

Sebaceous gland ducts blocked by
inspissated secretion and epithelial debris
or by pressure become infected. Folliculitis
is also a sequel to seborrhea, with hyper-
trophy of sebaceous glands and dilatation
of their ducts.

CLINICAL FINDINGS

The sequence of lesion development is:
nodules around the base of the hair, then
pustules, then crusts, finally hair fiber
loss. Itching may occur, but pain and rup-
ture of pustules under pressure are more

j common. Pustule rupture leads to con-
j tamination of the surrounding skin and
i development of further lesions.

In bovine sterile, eosinophilic follicu-
litis, the multiple lesions are crusted,

; alopecic, 3-5 cm diameter nodules on all
! parts of the body except the limbs. They
j are composed largely of eosinophils and
I are negative on culture.

! CLINICAL PATHOLOGY

{

j Swabs should be taken for bacteriological
j and parasitological examination.

Diagnostic confirmation is by
demonstration of infection of hair follicles
in a biopsy specimen.

! • Udder impetigo of cattle; lesions

j are superficial and confined to the

i udder

I • Infectious dermatitis (contagious
pyoderma) of baby pigs associated
with streptococci and staphylococci;
lesions are limited to face and caused
by bites from needle teeth

• Exudative epidermitis of pigs due to
5. hyicus, with extensive seborrheic
dermatitis

• Ulcerative dermatitis of face in
adult sheep

• Leg dermatitis down to coronet of
sheep

• Chronic pectoral and ventral midline
abscesses in horses due to

Corynebacterium pseudo tuberculosis ;
not a skin lesion but it resembles
furunculosis.

TREATMENT

Primary treatment commences with
cleaning the skin by washing followed by
a disinfectant rinse. Affected areas should
be treated with antibacterial ointments or
lotions. If the lesions are extensive the
parenteral administration of antibiotics is
recommended. The course of treatment
should last 1 week; in chronic cases
this may need to be at least 1 month; a
broad-spectrum preparation such as
trimethoprim-sulfadiazine is rec-
ommended. In stubborn cases an auto-
genous vaccine may be helpful.

Supportive treatment - infected
animals should be isolated and grooming
tools and blankets disinfected.

REFERENCES

1. Stannard AA.Vet Dermatol 2000; 11:205

2. Stannard AA.Vet Dermatol 2000; 11:217.

DISEASES OF HOOVES AND
HORN S

Diseases of the hooves are presented in
textbooks on large animal surgery and
lameness in horses and cattle.

Horn cancer is covered in the section
on squamous-cell carcinoma of the skin,

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

and hoof diseases that cause lameness are
listed in Table 13.1,

Skin diseases of the bovine digit
associated with lameness

Diseases of the skin of bovine digit
include digital dermatitis (hairy heel
warts), interdigital necrobacillosis (foot
rot), dermatitis verrucosa and interdigital
hyperplasia. 1 These are presented in
Chapters 16-20.

Sloughing of the hooves and
dewclaws (chestnuts)

Separation of the hooves from the sen-
sitive laminae and, in severe cases,
sloughing of the horn occur in:

D Severe edema of the legs, due to limb
lymphangitis or from severe trauma,
causing capillary dilatation and fluid
effusion into the laminar tissues
0 Burns in grass fires where only the
undersurface of the body is burned
0 Coronitis occurring as part of
pemphigus in horses
0 Horses poisoned by eating
mushrooms

0 Terminally in laminitis.

There is no treatment once the hooves
have sloughed and all attempts should be
made to avoid it if separation is already
evident at the coronet. Reduction of the
swelling in the limb is critical, requiring
enhancement of lymphatic and vascular
drainage from the area.

REVIEW LITERATURE

Demirkan I, Murray RD, Carter SD. Skin diseases of
the bovine digit associated with lameness. Vet Bull
2000; 70:149-171.

REFERENCE

1. Demirkan I et al.Vet Bull 2000; 70:149-171 .

Diseases of the subcutis

SUBCUTANEOUS EDEMA
(ANAS ARCA)

ETIOLOGY

Extensive accumulation of edema fluid in
the subcutaneous tissue is part of general
edema and caused by the same diseases,
as follows.

Increased hydrostatic pressure

<! Congestive heart failure
r ’ Viscular compression by tumor, e.g.
anterior mediastinal lymphosarcoma,
udder engorgement in heifer about to
calve.

Hypoproteinemic edema

° In liver damage with reduced albumin
production due to liver insufficiency,
especially fascioliasis
0 Renal damage with protein loss into
urine occurs rarely in animals.

DIFFERENTIAL DIAGNOSIS

Diagnostic confirmation is by clinical
detection of serous fluid in a subcutaneous
site.

• In cattle, extravasation of urine as a

result of urethral obstruction and
perforation

• Subcutaneous hemorrhage,
hematoma or seroma, which is not
necessarily dependent, nor bilaterally
symmetrical

• Ventral hernia, usually unilateral and
does not pit on pressure

• Cellulitis, usually asymmetric, hot,
often painful, does not pit on pressure
and can be sampled by needle
puncture

Renal amyloidosis

0 Protein-losing enteropathy, e.g. in
intestinal lymphosarcoma
‘ 5 Intestinal nematodiasis
° Protein starvation

Vascular damage

° In purpura hemorrhagica
° Anasarca in hypovitaminosis A
0 Subcutaneous plaques of equine
infectious anemia and dourine
0 Subcutaneous plaques in dourine
° Horses standing in black walnut
shavings as bedding.

Inflammatory edema

Many bacteria cause local edema due to
infection:

° Clostridium spp. are the most noted
° Anthrax in swine and horses
° Sporadic lymphangitis of horses
° Insect, especially bee, stings.

Fetal anasarca

° Some pigs with congenital goiter also
have myxedema, especially of the neck
° Sporadic cases due to unknown
causes are sometimes associated with
deformities, e.g. in Awassi sheep 1
° Congenital absence of lymph nodes
and some lymph channels causes
edema to be present at birth.

PATHOGENESIS

Alteration to the balance between the
hydrostatic pressure of intravascular fluids,
the blood and lymph, to the osmotic
pressure of those fluids or to the integrity
of the filtering mechanism of the capillary
endothelium leads to a positive advant-
age by the hydrostatic pressure of the
system and causes a flow of fluid out of
the vessels into the tissues. This results in
anasarca and, coincidentally, in fluid
accumulations in the body cavities.

CLINICAL FINDINGS

There is visible swelling, either local or
diffuse. The skin is puffy and pits on

pressure; there is no pain unless inflam-
mation is also present. In large animals
the edema is usually confined to the ven-
tral aspects of the head, neck and trunk
and is seldom seen on the limbs.

CLINICAL PATHOLOGY

Anasarca is a clinical diagnosis but many
estimates, for example of arterial blood
pressure, serum and urine protein levels,
provide contributory evidence. Differen-
tiation between obstructive and inflam-
matory edema can be made by cytological
and bacteriological examination of the
fluid.

TREATMENT

Primary treatment requires correction of
the causal abnormality. Supportive treat-
ment includes removal of the fluid by
drainage methods such as intubation or
multiple incision, both likely to result in
damaging infection in animals in the
average farmyard situation, or by the use
of a diuretic.

REFERENCE

1. Hailat N et al. AustVet J 1997; 75:257.

ANGIOEDEMA (ANGIONEUROTIC
EDEMA)

ETIOLOGY

Transient, localized subcutaneous edema
due to an allergic reaction and caused by
endogenous and exogenous allergens
provokes either local or diffuse lesions.
Angioedema occurs most frequently in
cattle and horses on pasture, especially
during the period when the pasture is in
flower. This suggests that the allergen is a
plant protein. Fish meal may also provoke
an attack. Recurrence in individual animals
is common.

PATHOGENESIS

After an initial erythema, local vascular
dilatation is followed by leakage of plasma
through damaged vessels.

CLINICAL FINDINGS

Local lesions most commonly affect the
head with diffuse edema of the muzzle,
eyelids, conjunctiva and cheeks. Occasion-
ally only the conjunctiva is affected, so
that the eyelids are puffy, the nictitating
membrane swollen and protruding, and
lacrimation is profuse. Affected parts are
not painful to touch but shaking the head
and rubbing against objects suggest
irritation. Salivation and nasal discharge
may be accompanying signs.

Perineal involvement includes vulvar
swelling, often asymmetrical, and the
perianal skin, and sometimes the skin of
the udder, is swollen and edematous.
When the udder is affected, the teats and
base of the udder are edematous and
cows may paddle with the hind limbs,
suggesting irritation in the teats. Edema

of the lower limbs, usually from the knees
or hocks down to the coronets, is a rare
sign.

Systemic signs are absent, except in
those rare cases where angioedema is
part of a wider allergic response, when
bloat, diarrhea and dyspnea may occur,
often with sufficient severity to require
urgent treatment.

CLINICAL PATHOLOGY

The blood eosinophil count is often with-
in the normal range, but may be elevated
from a normal level of 4-5% up to
12-15%.

DIFFERENTIAL DIAGNOSIS

Diagnostic confirmation is found with
sudden onset and disappearance of edema
at the typical sites.

• Subcutaneous edema (above) due
to vascular pressure occurs mostly in
dependent parts and is not irritating

• In horses, and rarely in cattle,
angioedema may be simulated by
purpura hemorrhagica, but
hemorrhages are usually visible in the
mucosae in purpura.

TREATMENT

Primary treatment to remove the specific
cause is usually impossible but affected
animals should be removed from the
suspected source of allergens. Cattle run-
ning at pasture should be confined and
fed on dry feed for at least a week.

Supportive treatment to relieve the
vascular lesion is always administered even
though spontaneous recovery is the rule. In
acute cases with severe dyspnea epineph-
rine can be administered parenterally,
but cautious intravenous injection is
recommended. For subacute cases corti-
costeroids or other anti-inflammatories are
preferred over antihistamines or epineph-
rine; usually only one injection is required.

SUBCUTANEOUS EMPHYSEMA

ETIOLOGY

Emphysema, free gas in the subcutaneous
tissue, occurs when air or gas accumulates
in the subcutaneous tissue as a result of:

' Air entering through a cutaneous
wound made surgically or accidentally
; Air entering tissues through a
discontinuity in the respiratory tract
lining, e.g. in fracture of nasal bones;
trauma to pharyngeal, laryngeal,
tracheal mucosa caused by external or
internal trauma as in lung puncture
by a fractured rib; a foreign body, as in
traumatic reticulitis
s Rumen gases migrating from a
rumenotomy or ruminal
trocharization

Diseases of the subcutis

6

° Extension from a pulmonary
emphysema

° Gas gangrene infection.

PATHOGENESIS

Air moves very quickly through fascial
planes, especially when there is local
muscular movement. For example when a
lung is punctured, or in cases of severe
interstitial pulmonary edema, air escapes
under the visceral pleura and passes to
the hilus of the lung, hence to beneath
the parietal pleura, between the muscles
and into the subcutis.

CLINICAL FINDINGS

Visible subcutaneous swellings are soft,
painless, fluctuating and grossly crepitant
to the touch, but there is no external skin
lesion. In gas gangrene, discoloration,
coldness and oozing of serum may be
evident. Emphysema may be sufficiently
severe and widespread to cause stiffness
of the gait and interference with feeding
and respiration.

CLINICAL PATHOLOGY

None is necessary except in cases of gas
gangrene, when a bacteriological examin-
ation of fluid from the swelling should be
carried out to identify the organism present.

DIFFERENTIAL DIAGNOSIS

Diagnostic confirmation is based on the
observation of crepitus and the extreme
mobility of the swelling; these distinguish
emphysema from other superficial
swellings.

• Anasarca, dependent and pits on
pressure (see above)

• Hematoma, seroma at injury sites,

confirmed by needle puncture (see
below)

• Cellulitis is accompanied by toxemia,
confirmed by needle puncture.

TREATMENT

Primary treatment is to close the entry
point for the gas but this is usually
impossible to locate or to close. Supportive
treatment is only necessary when the
emphysema is extensive and incapacitating,
when multiple skin incisions may be
necessary. Gas gangrene requires immedi-
ate and drastic treatment with antibiotics.

LYMPHANGITIS

This is characterized by inflammation and
enlargement of the lymph vessels and is
usually associated with lymphadenitis.

ETIOLOGY

Lymphangitis is due in most cases to local
skin infection with subsequent spread to
the lymphatic system. Common causes
are as follows.

Horse

° Glanders, epizootic lymphangitis,
sporadic lymphangitis, ulcerative
lymphangitis due to
C. pseudotuberculosis
■-> Strangles in cases where bizarre
location sites occur
° In foals ulcerative lymphangitis
associated with Streptococcus
zooepidemicus.

Cattle

° Skin farcy associated with Nocardia
farcinica, Rhodococcus equi
° Cutaneous tuberculosis associated
with atypical mycobacteria, rarely
Mycobacterium bovis.

PATHOGENESIS

Spread of infection along the lymphatic
vessels causes chronic inflammation and
thickening of the vessel walls. Abscesses
often develop, with discharge to the skin
surface through sinuses.

CLINICAL FINDINGS

An indolent ulcer usually exists at the
original site of infection. The lymph
vessels leaving this ulcer are enlarged,
thickened and tortuous and often have
secondary ulcers or sinuses along their
course. Local edema may result from
lymphatic obstruction. In chronic cases
much fibrous tissue may be laid down in
the subcutis and chronic thickening of the
skin may follow. The medial surface of the
hindlimb is the most frequent site,
particularly in horses.

CLINICAL PATHOLOGY

Bacteriological examination of discharges
for the presence of the specific bacteria or
fungi is common practice.

TREATMENT

Primary treatment requires vigorous,
early surgical excision or specific antibiotic
therapy.

Supportive treatment is directed
toward removal of fluid and inflammatory
exudate and relief of pain.

PANNICULITIS

Panniculitis is diffuse, sterile inflam-
mation of subcutaneous fat. Deep-seated,
firm and painful nodules up to 5 cm in
diameter develop, often in large numbers,
anywhere over the body but especially on
the neck and sides, most commonly in
young horses and rarely in cattle. 1 The
lesions may fluctuate greatly in size and
number, or even disappear spontaneously.
In a few cases there is transient fever,
reduced feed intake and weight loss.
Lameness may be evident in horses with
extensive lesions. 2

Diagnosis is by histological examination
of a biopsy specimen. At necropsy exam-
ination there are no other lesions. The

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

lesions reduce in size and number after
the administration of dexametasone, but
recur when treatment stops. J

REFERENCES

1. Scott PR et al.Vet Rec 1996; 139:262.

2. Bassage EJ et al. J Am Vet Med Assoc 1996;
209:1242.

3. Karcher LF et al. J Am Vet Med Assoc 1990;
196:1823.

HEMORRHAGE

This is extravasation of whole blood into
the subcutaneous tissues.

ETIOLOGY

Accumulation of blood in the sub-
cutaneous tissues beyond the limit of that
normally caused by trauma may be due to
defects in the coagulation mechanism or to
increased permeability of the vessel wall.
Common causes include:

" Dicoumarol poisoning from moldy
sweet clover hay
Purpura hemorrhagica in horses
o Bracken poisoning in cattle, and other
granulocytopenic disease. These
diseases are manifested principally by
petechiation and the lesions are
observed only in mucosae
Hemangiosarcoma in subcutaneous
sites

Inherited hemophilia.

PATHOGENESIS

Leakage of blood from the vascular
system can cause local swellings, which
interfere with normal bodily functions but
are rarely sufficiently extensive to cause
signs of anemia.

CLINICAL FINDINGS

Subcutaneous swellings resulting from
hemorrhage are diffuse and soft with no
visible effect on the skin surface. There
may be no evidence of trauma. Specific
locations of subcutaneous hemorrhages
include the frontal aspect of the chest -
due to fracture of the first rib in collisions
at full gallop and often fatal through
internal hemorrhage - and perivaginal at
foaling, causing massive swelling of the
perineum and medial aspect of the thigh.

CLINICAL PATHOLOGY

Visual examination of a needle aspirate
confirms the existence of subcutaneous
hemorrhage. Diagnosis of the primary
cause is greatly assisted by platelet counts
and prothrombin, clotting and bleeding
times.

TREATMENT

Primary treatment targets removal or
correction of the cause.

Supportive treatment: The hemor-
rhages should not be opened until clotting
is completed, except in the case of a

DIFFERENTIAL DIAGNOSIS

Subcutaneous hemorrhages are usually
associated with hemorrhages into other
tissues, both manifestations being due to
defects in clotting or capillary wall
| | continuity.

Diagnostic confirmation is by opening
the swelling, preferably by needle puncture
to avoid massive blood loss and difficulty in
locating the bleeding point.

massive hemorrhage that is interfering
with respiration, defecation or urination.
If blood loss is severe, blood transfusions
may be required. Parenteral injection of
coagulants can be justified if the hemor-
rhages are recent and severe.

NECROSIS AND GANGRENE

Necrosis is tissue death; gangrene is
sloughing of dead tissue. When either
change occurs in the skin it involves the
dermis, epidermis and subcutaneous
tissue.

ETIOLOGY

Severe damage to the skin in the follow-
ing categories causes gangrene:

“ Severe or continued trauma, e.g.
pressure sores, saddle and harness
galls, carpal or tarsal necrosis in
recumbent animals
Strong caustic chemicals, e.g. creosote
Severe cold or heat, bushfires and
stable fires being the worst offenders.
Frostbite is an unusual occurrence in
animals unless the patient has a
circulatory deficit, e.g. in the neonate,
in severe shock or toxemia
Beta-irradiation.

Infections, especially:

Erysipelas and salmonellosis in pigs
Clostridial infections in cattle affecting
subcutis and muscle
Staphylococcal mastitis in cattle,
pasteurella mastitis in sheep
Bovine ulcerative mammillitis of the
udder and teats.

Local vascular obstruction - obstruction
by thrombi or arterial spasm causes skin
gangrene, but includes deeper structures
also from poisoning by:

Claviceps purpurea

Festuca arundinacea (probably due to
an accompanying fungus)

Aspergillus terreus
Mushrooms.

Similar cutaneous and deeper structure
involvement occurs in systemic infections
in which bacterial emboli block local
vessels, e.g. in salmonellosis in calves,

and after tail vaccination of calves with
Mycoplasma mycoides.

Other causes

Final stages of photosensitive
dermatitis and flexural seborrhea
Screw-worm infestation.

PATHOGENESIS

The basic cause of gangrene is inter-
ference with local blood supply by exter-
nal pressure, by severe swelling of the
skin, as in photosensitization, or by
arteriolar spasm or damage to vessels
by bacterial toxins.

CLINICAL FINDINGS

If the arterial and venous systems are

closed the initial lesions will be moist and
the area is swollen, raised, discolored and
cold. Separation occurs at the margin and
the affected skin may slough before it
dries; the underlying surface is raw and
weeping.

If the veins and lymphatics remain
patent, the lesion is dry from the begin-
ning and the area is cold, discolored and
sunken. Sloughing may take a long time
and the underlying surface usually con-
sists of granulation tissue.

DIFFERENTIAL DIAGNOSIS 1

..... A: ■ ; :4$*j

Confirmation of the diagnosis is by visual
recognition.

• Gangrenous mastitis in cows or ewes

• Photosensitive dermatitis

• Claviceps purpurea poisoning.

TREATMENT

Primary treatment requires removal of
the etiological insult.

Supportive treatment comprises the
application of astringent and antibacterial
ointments to facilitate separation of the
gangrenous tissue and to prevent bacterial
infection.

SUBCUTANEOUS ABSCESS

Most subcutaneous abscesses are matters
of purely local and esthetic concern but
if sufficiently extensive and active
localized infections, they may cause
mild toxemia. Their origins include the
following.

Trauma

Most subcutaneous abscesses are the
result of traumatic skin penetration with
resulting infection, ^or example facial
subcutaneous abscesses are common in
cattle eating roughage containing foxtail
grass ( Hordeum jubatum). Several animals
in a herd may be affected at one time. The
awns of these plants migrate into the

cheek mucosa, causing subcutaneous
abscesses containing Arcanobacterium
(formerly Actinomyces) pyogenes and
Actinobacillus spp. The abscesses contain
purulent material, are well encapsulated
and must be surgically drained and
treated as an open wound. Medical
therapy with parenteral antimicrobials
and iodine is ineffective.

Hematogenous

Rarely the infection reaches the site via
the bloodstream, e.g. chronic pectoral
abscesses of horses, infections in foals
with R. equi, infections in all species with
Pasteurella pseudotuber culosis, infections
in lambs with Histophilus somni (formerly
Histophilus ovis) or Pseudomonas
pseudomallei.

Extension

Abscesses may originate by extension
from lesions of furunculosis, pyoderma or
impetigo, or by contiguous spread by
contact from an internal organ, e.g. from
traumatic reticuloperitonitis.

CUTANEOUS CYSTS

Cysts contained by an epithelial wall
enclosing amorphous contents or living
tissue may be congenital, inherited defects
or acquired as a result of inappropriate
healing of accidental wounds. They are
smooth, painless, about 1. 5-2.5 cm in
diameter, round and usually fluctuating,
although inspissated contents may make
them feel quite hard. The skin and hair
coat over them is usually nonnal, although
some may leak mucoid contents on to the
skin. Epidermoid cysts are lined with skin;
denmoid cysts usually contain differentiated
tissue such as sebaceous glands and hair
follicles; dentigerous cysts contain teeth
or parts of them. Acquired cysts include
apocrine, sebaceous and keratin varieties.

Developmental cysts, which are present
from birth, are usually located at specific
anatomical sites, and include:

Branchial cysts in the neck, formed

from an incompletely closed branchial

cleft

False nostril cysts in horses

Wattle cysts in goats.

Cysts may occur anywhere on the body,
but most commonly they are found near
the dorsal midline. 1 In horses a common
site is the base of the ear.

Other diseases that cause cutaneous
nodules in horses include collagenolytic
granuloma, mastocytosis, amyloidosis,
lymphoma, sarcoid and infestation with
Hypoderma spp.

Surgical excision for cosmetic reasons
is common practice. 2

Cutaneous neoplasms

667

REFERENCES

1. Abraham CG, Genetzky RM. Vet Med 1995; 90:72.

2. Misk NA et al. Equine Pract: 1994; 16:31.

Granulomatous lesions of
the skin

Granulomatous lesions are chronic inflam-
matory nodules, plaques and ulcers; they
are cold, hard, progress slowly and are
often accompanied by lymphangitis and
lymphadenitis. In many cases there is no
cutaneous discontinuity, nor alopecia.
Some of the common causes in animals
are as follows.

Cattle

Mycobacterium spp. especially
Mycobacterium farcinogenes
c Nocardia farcinica
° A. lignieresi

° Infestation with Onchocerca sp.

0 Hypoderma sp. larvae

° Mucor sp. fungi in thick-walled
nodules in the skin on the
posteroventral aspect of the udder
Lechiguana, a disease of cattle in
Brazil in which very large
granulomata consisting of fibrous
tissue and containing Pasteurella
granulomatis develop in subcutaneous
sites in any part of the body. 1

Sheep

Strawberry footrot - D. congolensis
; Ecthyma

Ulcerative lesions of lower jaw and
dewlap associated with A. lignieresi.

Pigs

: Actinomyces spp. and B. suilla cause
lesions on the udder.

Horses

1 Tumorous calcinosis causes hard,
painless, spherical granulomata, up to
12 cm in diameter, near joints and
tendon sheaths, especially the stifle
joint. Surgical removal is
recommended

Cutaneous amyloidosis
Collagenolytic granuloma (nodular
necrobiosis) - the most common
nodular skin disease of the horse. 2
The etiology is unknown. There are
multiple firm nodules located in the
dermis ranging in size from 0.5-5 cm
in diameter. The overlying skin surface
and hair are usually normal. Biopsy
reveals collagenolysis. Treatment
consists of surgical removal and
consideration of corticosteroids
Botryomycosis, or bacterial
pseudomycosis, results from bacterial
infection at many sites, often
accompanied by a foreign body.
Lesions on the limbs, brisket, ventral

abdomen and scrotum vary in size
from nodules to enormous fungating
growths composed of firm
inflammatory tissue riddled by
necrotic tracts, leading to discharging
sinuses, often containing small,
yellow-white granules or 'grain s'.
Surgical excision is the only
\ practicable solution

Equine eosinophilic granuloma -
non-alopecic, painless, nonpruritic,
firm nodules, 2-10 cm in diameter
and covered by normal skin develop
on the neck, withers and back of
horses, especially in the summer. The
cause is unknown and palliative
treatment, surgical excision or
corticosteroid administration is
usually provided
Systemic granulomatous disease
(equine sarcoidosis) 3 - a rare disease
of horses characterized by skin lesions
and widespread involvement of the
lungs, lymph nodes, liver,
gastrointestinal tract, spleen, kidney,
bones, and central nervous system

° Actinobacillus mallei - cutaneous farcy
or glanders

° Actinomadura spp. and Nocardia
brasiliensis - painless mycetomas

a Histoplasma fardminosum - epizootic
lymphangitis

0 C. pseudotuberculosis - ulcerative
lymphangitis

« Habronema megastoma, Hyphomyces
destruens as causes of swamp cancer,
bursattee, Florida horse leech and
blackgrain mycetoma

“ Infestation with Onchocerca sp.

Chronic urticaria. 4

REFERENCES

1. Riet-Corrca P et al.Vet Pathol 1992; 29:93.

; 2. Stannard A A. Vet Dermatol 2000; 11:179.

j 3. Stannard AA. Vet Dermatol 2000; 11:163.

4. Evans AG. Compcnd Contin Educ Pract Vet 1993;
15:626.

Cutaneous neoplasms

Many cutaneous neoplasms have been
recorded in large animals but at a very
low incidence. A brief description of only
the more common types is given here.

PAPILLOMA AND SARCOID

Sarcoid of horses and cutaneous papil-
lomatosis of horses, goats, and cattle are
specific diseased. The lesions are charac-
teristically nodular growths of viable
tissue and, if there is no traumatic injury,
with no discontinuity of the covering
epidermis.

Aural flat warts (aural plaques)

occur commonly in the horse and are

i8

PART 1 GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

caused by the papilloma virus. 1 Blackflies
may serve as a vector. Lesions consist of
one to several gray or white plaques
involving the inner surface of the pinna.
Similar lesions may occur around the
anus, vulva and inguinal regions. The
lesions are usually asymptomatic, may
persist indefinitely, may regress spon-
taneously and are refractory to treatment.

SQUAMOUS-CELL CARCINOMA

This neoplasm can occur anywhere on the
skin, and also in the mouth and maxillary
sinus.

0 Cancer-eye is the commonest lesion,
on the eyelids and the eyeball in
horses and cattle

• Genital squamous-cell carcinomas

affecting the glans penis and prepuce
of aged horses can cause fatal
metastases unless amputation is
performed in the early stages. Grossly
similar lesions are caused by epithelial
hyperplasia, habronemiasis, and
squamous papillomata. Squamous-
cell carcinomas also occur on the
vulva of cattle and a greater incidence
has been observed on unpigmented
than on pigmented vulvas
° Vulvar squamous-cell carcinoma
appears frequently in Merino ewes as a
result of excessive exposure of vulvar
skin to sunlight after radical perineal
surgery to help control blowfly strike 2
0 Cancer of the horn core in cattle and
rarely in sheep 3 is a squamous-cell
carcinoma arising from the mucosa of
the frontal sinus and invading the
horn core; it is most prevalent in
aged, white, Indian breeds of cattle. In
the early stages affected animals may
rub the horns against a fixed object, or
shake the head frequently. A bloody
discharge begins from the nostril on
the affected side, or from the base of
the horn, and the animal holds its
head down and toward one side. The
horn becomes loosened and falls off,
leaving the tumor exposed to
infection and fly infestation.

Secondary metastases are not
uncommon. The high prevalence of
metastases in regional lymph nodes
and internal organs discourage
treatment but a phenol extract of horn
core tissue is immunogenic and
immunotherapy may be a successful
treatment technique. 4 Other forms of
therapy are also practiced for
squamous-cell carcinoma generally,
including surgical excision, preferably
by cryotherapy, and radiofrequency
hyperthermia

Ear cancer in sheep is in most cases a
squamous-cell carcinoma. The lesion
commences around the free edge of

the ear and then invades the entire ear,
which becomes a large, cauliflower-
shaped mass. A high incidence may
occur in some flocks but the cause is
not known; the presence of papilloma
virus in many aural precancerous
lesions suggests that the virus may
participate in the etiology
0 Ovine skin cancer: a high incidence
of epitheliomas has been recorded in
some families of merino sheep in
Australia. The lesions occurred on the
woolled skin and were accompanied
by many cutaneous cysts. It has been
suggested that predisposition to the
neoplasm is inherited. Metastasis is
common with both epitheliomas and
squamous-cell carcinomas
° 'Brand cancer', which occurs as a
granulomatous mass at the site of a
skin fire or freeze brand, is usually
considered to be of chronic
inflammatory rather than neoplastic
origin, but squamous cell carcinomas
are recorded at branding sites in
sheep and cattle 5

° In goats, the perineum is a common
site for squamous-cell carcinoma. The
udder, ears, and base of the horns
may also be affected. Ulceration, fly
strike and matting of hair are
unattractive sequels. A bilaterally
symmetrical vulvar swelling due to
ectopic mammary tissue that enlarges
at parturition is likely to be confused
with squamous-cell carcinoma. Milk
can be aspirated from the swellings.

MELANOMA

Superficially situated melanomas occur
most commonly at the tail root in aged,
gray horses and rarely in dark-skinned
cattle, sheep and goats. Equine lesions are
not usually malignant and rarely meta-
stasize widely. The skin is intact but
ulcerates in rapidly growing tumors.
Bovine melanomas are usually benign. A
high rate of occurrence of malignant
melanomas has been observed in
neonatal pigs of the Duroc-Jersey breed.
Inherited melanomas and kindred
neoplasms occur commonly in Sinclair
miniature and NIH miniature swine but

j they frequently regress spontaneously.

i

I

| CUTANEOUS ANGIOMATOSIS

This condition is manifested clinically by
recurrent profuse hemorrhage from small
(1-1.5 cm diameter), single, inconspicuous,
cutaneous lesions situated most com-
monly along the dorsum of the back in
adult dairy' cows. The lesions consist of
what appears to be protruding granulation
tissue and are benign. Surgical excision is
effective.

A juvenile version of angiomatosis in
calves 6 is characterized by similar lesions,
but in many organs, sometimes including
the skin.

LYMPHOMATOSIS

In cattle and horses skin lesions occur as
nodules in the subcutaneous tissue, most
commonly in the paralumbar fossae and
the perineum. In cattle the lesions are
associated with the virus of epizootic
bovine leukosis, and are only one mani-
festation of the disease, usually being
accompanied by lesions in other organs.
In horses there are no leukemic lesions in
lymph nodes or visceral organs.

MAST CELL TU MORS

Cattle

Cutaneous mastocytoma appears as a
rapidly growing intradennal nodule, which
may become widely disseminated if excised
or, less commonly, there may be multiple
tumors in the first instance. The nodules
show no tendency to metastasize internally
and are compatible with life provided they
do not ulcerate and become repulsive.

Horses

Cutaneous mastocytomas (mastocytosis)
is a neoplasm recorded in horses of all
ages. The neonatal form is manifested by
multiple cutaneous nodules up to 3 an in
diameter; in adults there are usually only
single lesions. The skin surface is intact
except for larger lesions, which are some-
times ulcerated. Lesions occur all over
the body, but especially on the flanks. Each
nodule appears, enlarges and then
regresses during a period of about
30 days. Fresh lesions may appear for up to
about a year. Histologically the lesions
contain aggregations of mast cells. Surgical
excision is recommended, few cases
showing any recurrence at the surgery site.

NEUROFIBROMATOSIS

This common lesion of nerves in cattle
usually attracts attention only in abattoir
specimens but can occur in a cutaneous
form resembling a similar disease of
humans; 7 a particularly high prevalence of
this benign disease is recorded in breeds
of European pied cattle. Clinical cases are
usually recorded in calves, in which there
are cutaneous lesions that appear as
tumor-like lumps between the eyes and
on the cheeks. They are flat, round tumors
up to 8 cm in diameter and of a lumpy,
elastic consistency.

HISTIOCYTOMA

This is a very rare benign neoplasm in
farm animals but is recorded as cutaneous
nodules or plaques, which bleed easily, in

Congenital skin neoplasms

61

goats and cattle. The lesions regress
spontaneously.

HEMANGIOMA AND
H EM ANGIOSARCOMA

Benign cutaneous hemangiomas occur
rarely in most species, including a rare
occurrence in cattle 8 and relatively
commonly on distal parts of limbs in
young horses, sometimes in neonates. 9
The lesions are small (1-3 cm diameter),
round, blue to black lumps that bleed
easily and are morphologically the same
as bovine cutaneous angiomatosis lesions.
Vascular nevi in newborn foals have a very
similar appearance.

Hemangiosarcomas (hemangio-
epithelioma) are malignant tumors
recorded relatively frequently in older
horses. They are large, highly vascular,
subcutaneous masses, usually associated
with one or more internal lesions. The
primary lesion may be internal,

commonly in the spleen, or cutaneous.
Recurrence after excision, extensive local
infiltration and death due to anemia are
common sequelae. 10

LIP OMA

External lipomas are not cutaneous
neoplasms but they do occur as large
subcutaneous masses and invade fascia
and muscle , n They are generally susceptible
to surgical removal.

REVIEW LITERATURE

Daniels PW, Johnson RH. Ovine squamous-cell
carcinoma. Vet Bull 1987; 57:153-167.

MacFadden KE et al. Squamous-cell carcinoma of
horses. Compend Contin Educ Pract Vet 1991;
13:669-677.

Somvanshi R. Horn cancer in Indian cattle. Vet Bull
1991; 61:901-911.

Malikides N et al. Mast cell tumors in the horse.
Equine Pract 1996; 18:12-17.

REFERENCES

1. Stannard AA.Vct Dermatol 2000; 11:217.

2. Howarth S et al. Equine Vet J 1991; 23:53.

3. Salyari M et al. Indian Vet 1994; J 71:1233

4. Batra UK et al. Indian ) Anim Sci 1988; 58:14. .

5. Yeruham I et al. J Comp Pathol 1996; 114:101. j

6. Watson TDG, Thompson H. Vet Rec 1990; 127:279. 1

7. Sartin EA et al. Am J Pathol 1994; 145:168.

8. Munro R et al. Vet Rec 1994; 135:333. |

9. Johnson GC et al.Vet Pathol 1996; 33:142.

10. Collins MB et al. AustVet J 1994; 71:296.

11. Dunkcrley SAC et al. J Am Vet Med Assoc 1997; 1

210:332. j

i

I

” ~ ' I

Congenital defects of the
skin |

The common diseases are inherited, i

Examples are: j

I

Inherited parakeratosis (lethal trait
A46, Adema disease, inherited
nutritional zinc deficiency) of cattle

° Dermatosis vegetans of pigs
° Inherited congenital ichthyosis (fish-
scale disease) of calves
3 Inherited hypotrichoses and alopecias
in cattle

3 Congenital absence of skin

(epitheliogenesis imperfecta) in all
species

3 Epitheliogenesis imperfecta, a rare
congenital defect in foals inherited as
a single autosomal recessive trait. 1
There are sharply demarcated areas in
which there is absence of epidermis.
The lesions bleed easily and
secondary bacterial infection is
common; death usually due to
septicemia

° Epidermolysis bullosa of foals, which
occurs especially the Belgian breed
and may occur in American
Saddlebred, is inherited as autosomal
recessive. 1 The defect is present at
birth but it may be several months
before the disease is clinically
apparent. 2 Lesions involve the
skin, mucocutaneous junctions
and oral mucosa and are
characterized by separation of the
dermal-epidermal junction beneath
the basal epithelium
° Hyperelastosis cutis of newborn
foals 1 is a group of inherited
connective tissue diseases, also
known as cutaneous asthenia,
Ehlers-Danlos syndrome and
dermatopraxis, that is seen only in
Quarter horses. The condition is
characterized by sharply demarcated
areas of loose skin, which is
hyperfragile, tears easily and exhibits
impaired healing

Epitheliogenesis imperfecta in piglets
due to ingestion of Fusarium spp.
toxin

Dyserythropoiesis and dyskeratosis of
cattle

3 Hair-coat-color-linked follicular
dysplasia

3 Familial acantholysis and

dermatosparaxis - in familial bovine
acantholysis the skin is normal at
birth, but is shed later at the carpus
and the coronet

Hereditary junctional mechanobullous
disease of foals, calves, lambs
" Inherited epidermolysis bullosa
and inherited redfoot, both of sheep
3 Dermatosparaxis, hyperelastosis cutis
and the Ehlers-Danlos syndrome,
all in cattle. A mild form of
dermatosparaxis is recorded in
sheep

Vascular nevus: irregularly shaped,
cutaneous masses, present at birth
and originally covered with hair, but
subsequently hairless. Individual
lesions in foals are 3-4 cm in

diameter, bright pink, ulcerated and
inflamed. The lesions consist of
densely packed convoluted blood
vessels, which bleed easily. Most
lesions are on the lower limbs,
especially at the coronet. Surgical
excision is usually attempted

° Dermoid cysts.

REFERENCES

1. Stannard AA. Vet Dermatol 2000; 11:211

2. Brounts SH et al.Vet Dermatol 2001; 12:219.

Congenital skin neoplasms

Congenital tumors are defined as those
existing at birth. A broader definition is
that congenital tumours can be detected
in fetuses, and newborns until 2 months
of age. 1 Embryonic tumours are those that
arise during embryonic, fetal or early
postnatal development from a particular
organ rudiment or tissue while it is still
immature. Hamartomas are benign,
tumor-like nodules composed of over-
growth of mature cells, which normally
occur in the affected part but often with
one element predominating. Hamartomas
include hemangiomas, ameloblastomas
and rhabdomyomas. Teratomas are true
neoplasms consisting of different types of
tissue not native to the area in which they
occur.

Cattle

Congenital skin neoplasms of cattle
described include mast cell tumors,
lymphosarcoma, myxoma and vascular
hamartoma. 2 Benign melanomas,
mastocytomas 1,3 hemangiomas and
lymphangiomas, fibrosarcomas, neuro-
fibromatosis, subcutaneous lipomas, mul-
tiple lipomas and retroperitoneal lipomas
have also been recorded in calves. 1 The
comparative aspects of tumors in calves
have been described. 4

Pigs

The literature on congenital and
i hereditary tumors in piglets has been
j reviewed. 0 Spindle cell sarcoma, malig-
i nant melanoma and papillomatosis are
• common congenital tumors of the skin of
| piglets. Congenital cutaneous papillo-
i matosis of the head and neck of a
j newborn piglet has been described from a
j pig-breeding farm where sporadic cuta-
i neous papillomatosis of the prepuce and
j scrotum had previously occurred in
j several boars. 4

j Foals

j Congenital tumors in foals are rare.
! Congenital skin tumors are of the
| papillomatous, vascular and melanocytic
j types. 6 The vascular tumors are capillary
j hemangiomas, cavernous hemangiomas,
and hemangiosarcomas.

PARTI GENERAL MEDICINE ■ Chapter 14: Diseases of the skin, conjunctiva, and external ear

•670 -

REFERENCES

1 . Misdorp W. Vet Q 2002; 24:1.

2. Yeruham I et al.Vet Dermatol 1999; 10:149.

3. Smith BI, Phillips LA. Can Vet J 2001; 42:635.

4. Misdorp W. J Comp Pathol 2002; 127:96.

5. Misdorp W. Vet Q 2003; 25:17.

6. Misdorp W. Vet Q 2003; 25:61.

Diseases of the conjunctiva

Some of the common diseases of the
conjunctiva are listed here because they
are often treated medically as they are
often secondary to the presence of some
other disease, and also because an exam-
ination of the conjunctiva often provides
additional information on which to base a
diagnosis. General practitioners need to
know something of the common diseases
of the eye for these reasons.

The following notes are intended only
to provide guidelines to the relevant
sections of Fhrt Two, where specific forms
of conjunctivitis have been described in
detail.

CONJUNCTIVITIS AND
KE R ATOCONJUNCTIVITI S

This is inflammation of the covering
membrane of the eye, including the orbit
and the inner surface of the eyelids.
The inflammation commonly extends to
layers below the conjunctiva, hence
keratoconjunctivitis.

ETIOLOGY

Specific conjunctivitis

Cattle

Infectious bovine keratoconjunctivitis is
associated with:

Moraxella bovis, the only significant
cause

M. bovis with infectious bovine
rhinotracheitis virus
Neisseria catarrhalis
Mycoplasma spp.

Chlamydophila spp.

Sheep

Rickettsia conjunctivae is the important
infection

N. catarrhalis
Mycoplasma conjunctivae
Acholeplasma oculi is also listed
Chlamydophila spp.

Goats

R. conjunctivae.

Pigs

Rickettsia spp.

Horses

There is no well-identified specific
conjunctivitis in this species but Moraxella
equi has been recorded as a cause on several
occasions . 1 There is also infestation with
Thelazia spp. and Habronema spp.

Specific keratitis lesions

Thelazia spp. in cattle and horses
Onchocerca spp. in cattle
Elaeophora schneideri in sheep and
goats

; Habronema spp. in horses

Fungal keratomycosis in foals 1 and
adult horses; Aspergillus flavus has
been identified in some cases.

: Aspergillus fumigatus is listed amongst the
causes of mycotic keratitis in animals . 2
Most cases begin as traumatic injuries
with secondary infections or begin in eyes
treated for long periods with broad-
: spectrum antibiotics.

i Secondary diseases in which
, conjunctivitis is a significant but
| secondary part of the syndrome

j Cattle

: Bovine viral diarrhea

■ Bovine malignant catarrh
c Rinderpest

< Infectious bovine rhinotracheitis
* Viral pneumonia due to various
viruses.

Sheep

c- Bluetongue.

Pigs

r Swine influenza

Inclusion body rhinitis.

j Horses

| Equine viral arteritis

! Equine viral rhinopneumonitis.

i Nonspecific conjunctivitis

: ■ Inflammation caused by foreign

bodies or chemicals, or secondarily as
exposure keratitis, and conjunctivitis/
keratitis in paralysis of eyelids as in
listeriosis. Ant-bite conjunctivitis
occurs in similar circumstances.

CLINICAL FINDINGS

Blepharospasm and weeping from the
affected eye are tire initial signs. Watery
tears are followed by mucopurulent, then
purulent ocular discharge if the lesion
extends below the conjunctiva. Varying
degrees of opacity of the conjunctiva may
develop, depending on the severity of the
inflammation. In the severest lesions
there is underrunning of the conjunctiva
with pus accompanied by vascularization
of the cornea. During the recovery stage
there is often long-lasting, diffuse opacity
of the eye and terminally a chronic white
scar in some cases.

CLINICAL PATHOLOGY

In herd or flock outbreaks conjunctival
swabs and/or scrapings should be taken
for culture and examination of cells using
special stains and histological techniques.

REFERENCES

1. Huntington PJ et al. AustVet J 1987; 64:110.

2. Grahn B et al. Prog Vet Comp Ophthalmol 1993;
3:2.

Congenital defects of the
eyelids and cornea

DERMOID CYSTS

Ocular dermoid cysts are solid, skin-like
; masses of tissue, adherent usually to the
anterior surface of the eye, causing
irritation and interfering with vision. The
eyelid, the third eyelid and the canthus
: may also be involved, and the lesions may
: be unilateral or bilateral. When they occur
; at a high frequency in a population, it is
| likely they are inherited, as they can be in
\ Hereford cattle. It is also recorded in foals.

; The defect is sometimes associated with
| microphthalmos. Surgical ablation is
| recommended.

Diseases of the external ear

Ear cancer is discussed in the section on
squamous cell carcinoma.

OTITIS EXTERNA

Otitis externa, inflammation of the skin
and external auditory canal, can affect
cattle of all ages, in isolated cases, an entire
herd or in entire regions . 1 The literature on
the causes of otitis in cattle has been
reviewed . 1

Arthropod parasites, foreign bodies
and sporadic miscellaneous infections may
cause irritation in the ear, accompanied by
rubbing of the head against objects and
frequent head-shaking.

In tropical and subtropical regions,
parasitic otitis is more important than
in other more temperate regions . 1,2 The
mites Raillietia auris and Dermanyssus
avium, the tick Otobius magnini, larvae
(. Stephanofilaria zahaeeri), free-living
nematodes ( Rhabditis bovis) and the blue
fly ( Chrysomia bezziano) are of importance
in Europe, Africa, India and America.
Malassezia spp., Candida spp., Rhodotorula
mucilaginosa, Aspergillus spp. and Micelia
sterilia are common causes of otitis
externa in cattle in Brazil . 3,4

When the syndrome occurs in a large
number of a herd, as it does in tropical
countries, it is necessary to look for a
specific causative agent. Rhabditis bovis is
the common cause. Affected animals are
depressed, eat little and appear to experi-
ence pain when they swallow, and they
shake their heads frequently. Both ears
are affected in most cases and there is a
stinking, blood-stained discharge that
creates a patch of alopecia below the ear.
The area is painful when touched, the
external meatus of the aural canal is

obviously inflamed and the parotid lymph
nodes are enlarged. Extension to the
middle ear is an unusual sequel. Topical
treatment with ivermectin and a broad-
spectrum antibiotic is effective.

OTITIS MEDIA

Otitis media (middle ear infection) occurs
in milk-fed calves from a few days of age

up to 10 weeks and in weaned calves
from 4-8 months and from 12-18 months
of age. 1 The major bacteria that cause
otitis media in calves include Actinomyces
spp., C. pseudotuberculosis, Escherichia coli,
Histophilus somni (formerly Haemophilus
somnus), Pasteurella multocida, Mannheimia
(formerly Pasteurella) haemolytica, Pseu-
domonas spp.. Streptococcus spp. and
M. bovis.

Diseases of the external ear

REVIEW LITERATURE

Duarte ER, Hamdan JS. Otitis in cattle, an aetiological
review. J Vet Med B 2004; 51:1-7.

REFERENCES

1. Duarte ER, Hamdan JS. J Vet Med B 2004; 51:1-7.

2. Duarte HR et al. Vet Parasitol 2001; 101:45.

3. Duarte ER et al. Med Mycol 2003; 41:137.

4. Duarte ER et al. J Vet Med B 2001; 48:631.

PART 1 GENERAL MEDICINE

Diseases of the mammary gland

INTRODUCTION 673

BOVINE MASTITIS 673

MASTITIS PATHOGENS OF
CATTLE 697

MASTITIS OF CATTLE ASSOCIATED
WITH COMMON CONTAGIOUS
PATHOGENS 697

Staphylococcus aureus 697

Streptococcus agalactiae 703

Mycoplasma bovis and other
Mycoplasma species 705

Corynebacterium bovis 708

MASTITIS OF CATTLE ASSOCIATED
WITH TEAT SKIN OPPORTUNISTIC
PATHOGENS 708

Coagulase-negative staphylococci 708

MASTITIS OF CATTLE ASSOCIATED
WITH COMMON ENVIRONMENTAL
PATHOGENS 709

Coliform mastitis associated with
Escherichia coli, Klebsiella species and
Enterobacter aerogenes 709

Environmental streptococci 719

Arcanobacterium pyogenes 722

MASTITIS OF CATTLE ASSOCIATED
WITH LESS COMMON
PATHOGENS 724

Pseudomonas aeruginosa 724
Pasteurella species 725
Nocardia species 725

MISCELLANEOUS CAUSES OF
BOVINE MASTITIS 726

Bacillus species 726
Campylobacter jejuni 726
Clostridium perfringens type A 726
Fusobacterium necrophorum 727
Histophilus somni 727
Listeria monocytogenes 727
Mycobacterium species 727
Serratia species 727
Fungi and yeasts 727
Algae 728

Traumatic mastitis 728

CONTROL OF BOVINE MASTITIS 728

Options in the control of mastitis 729
Principles of controlling bovine
mastitis 730

Mastitis control programs 730

The ten-point mastitis control
program 731

Assessment of the cost-effectiveness of
mastitis control 748

MISCELLANEOUS ABNORMALITIES
OF THE TEATS AND UDDER 749

Lesions of the teat and udder skin 749
Lesions of the bovine teat 750
Lesions of the bovine teat and
udder 751

Lesions of the bovine udder other than
mastitis 751
Udder edema 752

Rupture of the suspensory ligaments of
the udder 752
Agalactia 752

Neoplasms of the udder 753

Teat and udder congenital defects 753

MASTITIS-METRITIS-AGALACTIA
SYNDROME IN SOWS 754

MASTITIS OF SHEEP 759

MASTITIS OF GOATS 761

MASTITIS OF MARES 762

Introduction

Mastitis is inflammation of the paren-
chyma of the mammary gland regardless of
the cause. Mastitis is therefore characterized
by a range of physical and chemical changes
in the milk and pathological changes in the
glandular tissue. The most important
changes in the milk include discoloration,
the presence of clots and the presence of
large numbers of leukocytes. There is
swelling, heat, pain and edema in the
mammary gland in many clinical cases.
However, a large proportion of mastitic
glands are not readily detectable by manual
palpation nor by visual examination of the
milk using a strip cup; these quarters
represent subclinical infections. Because of
the large numbers of subclinical cases, the
diagnosis of mastitis depends largely on
indirect tests, which depend, in turn, on the
somatic cell concentration (SCC) or
electrolyte (sodium or chloride) concen-
tration of milk. It seems practicable and
reasonable to define mastitis as a disease
characterized by the presence of a
significantly increased SCC in milk from
affected glands. The increased SCC is, in
almost all cases, due to an increased
neutrophil concentration, represents a
reaction of glandular tissue to injury and is

preceded by changes in the milk that are the
direct result of damage to glandular tissue.
However, the exact clinical and laboratory
changes that occur in the udder as a result
of infection can also be caused by other
factors in the absence of infection. 1 Until
such time as it becomes common usage to
define mastitis in tenns of the sodium or
chloride concentration of the milk (as
measured by electrical conductivity) or
increased permeability of the blood-milk
barrier (as measured by albumin concen-
tration) there appears to be no point in
changing the current definition of mastitis
based on an abnormal looking secretion
or an increased SCC. Characterization of
mastitis depends on the identification of
the causative agent whether it be infec-
tious or physical.

Most of the information presented
here deals almost entirely with bovine
mastitis because of its economic import-
ance, but small sections on ovine, caprine,
porcine and equine mastitis are included
at the end of the chapter.

Bovine mastitis

GENERAL FEATURES

A total of about 140 microbial species,
subspecies and serovars have been

Synbpsfc

Etiology

• Contagious pathogens:

Staphylococcus aureus, Streptococcus
agalactiae, Mycoplasma bovis and
Corynebacterium bovis

• Teat skin opportunistic pathogens:
coagulase-negative staphylococci

• Environmental pathogens:
environmental Streptococcus spp.
including Streptococcus uberis and
Streptococcus dysgalactiae, which are
the most prevalent; less prevalent is
Streptococcus equinus (formerly
referred to as Streptococcus bovis).
Environmental coliforms include the
Gram-negative bacteria Escherichia coli,
Klebsiella spp. and Enterobacter spp.,
and Arcanobacterium (formerly
Actinomyces) pyogenes

• Uncommon pathogens: many,
including Nocardia spp., Pasteurella
spp., Mycobacterium bovis, Bacillus
cereus, Pseudomonas spp., Serratia
marcescens, Citrobacter spp., anaerobic
bacterial species, fungi and yeasts

Epidemiology

• Incidence of clinical mastitis ranges
from 1 0-1 2% per 1 00 cows at risk per
year. Prevalence of intra mammary
infection is about 50% of cows and
10-25% of quarters. Case fatality rate
depends on cause of mastitis

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

• Contagious pathogens are transmitted
at time of milking; teat skin
opportunistic pathogens take any
opportunity to induce mastitis;
environmental pathogens are from the
environment and induce mastitis
between milkings

• Environmental pathogens are the most
common cause of clinical mastitis in
herds that have controlled contagious
pathogens

• Prevalence of infection with contagious
pathogens ranges from 7-40% of cows
and 6-35% of quarters

• Prevalence of infection with
environmental pathogens: coliforms
1-2% of quarters; streptococci less
than 5%

Risk factors

• Animal risk factors: prevalence of
infection increases with age. Most new
infections occur in dry period and in
early lactation. Highest rate of clinical
disease occurs in herds with low
somatic cell counts (SCCs). Morphology
and physical condition of teat are risk
factors. Selenium and vitamin E status
influence incidence of clinical mastitis.
High-producing cows are more
susceptible

• Environmental risk factors: poor
quality management of housing and
bedding increases infection rate and
incidence of clinical mastitis due to
environmental pathogens

• Pathogen risk factors: ability to
survive in environment, virulence factors
(colonizing ability, toxin production),
susceptibility to antimicrobial agents

• Economics: subclinical mastitis is a
major cause of economic loss due to
loss of milk production, costs of
treatment and early culling

Clinical signs

• Gross abnormalities in milk

(discoloration, clots, flakes, pus)

• Physical abnormalities of udder:
acute - diffuse swelling, warmth, pain,
gangrene in severe cases; chronic -
local fibrosis and atrophy

• Systemic response, may be normal or
mild, moderate, acute, peracute with
varying degrees of anorexia, toxemia,
dehydration, fever, tachycardia, ruminal
stasis, and recumbency and death

Clinical pathology

• Detection at the herd level: bulk
tank milk SCCs. Culture of bulk tank
milk

• Detection at the individual cow
level: abnormal looking milk, culture of
composite or quarter milk samples.
Indirect tests include SCCs of composite
or quarter milk samples, California
Mastitis Test (CMT) of quarter milk
samples, inline milk conductivity tests of
quarter milk samples

• Use of selective media to
differentiate Gram-positive and
Gram-negative pathogens in cases of
clinical mastitis

• Differential diagnosis list: other
mammary abnormalities: Peri parturient
udder edema, rupture of suspensory
ligament, and hematomas. Blood in the
milk of recently calved cows

Treatment

• Clinical mastitis in lactating cow:

mild cases of clinical mastitis (abnormal
secretion only) may not require
treatment; however, all clinical mastitis
episodes accompanied by an abnormal
gland or systemic signs of illness should
be treated with antimicrobial agents
given by intramammary infusion (all
cases) and parenterally (selected cases).
Acute and peracute mastitis cases
require also require supportive therapy
(fluid and electrolytes) and nonsteroidal
anti-inflammatory agents (NSAIDs).
Culture milk of representative clinical
cases but antimicrobial susceptibility
testing has not been validated

• Dry cow therapy: intramammary
infusion of long-acting antimicrobial
agents at drying off provides the best
treatment for subclinical mastitis due to
contagious pathogens. Must adhere to
milk withholding times after treatment
with antimicrobial agents to prevent
milk drug residues, which is major
public health issue. Currently available
cowside antimicrobial residue tests are
not reliable

Control

• Principles of control:

A. Eliminate existing infections

B. Prevent new infections

C. Monitor udder health status

• Components of Mastitis Control
Program:

1. Use proper milking management
methods

2. Proper installation, function, and
maintenance of milking equipment

3. Dry cow management

4. Appropriate therapy of mastitis
during lactation

5. Culling chronically infected cows

6. Maintenance of an appropriate
environment

7. Good record keeping

8. Monitoring udder health status

9. Periodic review of the udder health
management program

10. Setting goals for udder health
status

isolated from the bovine mammary gland.
Microbiological techniques have enabled
precise determination of the identity of
many of the mastitis pathogens. Based on
their epidemiology and pathophysiology,
these pathogens have been further
classified as causes of contagious, teat
skin opportunistic or environmental
mastitis.

Contagious mastitis pathogens

There are many contagious mastitis patho-
gens. The most common are Staphylococcus
aureus and Streptococcus agalactiae. The
usual source of contagious pathogens is
the infected glands of other cows in the
herd; however, the hands of milkers can
act as a source of S. aureus. The pre-
dominant method of transmission is from
cow to cow by contaminated common

udder wash cloths, residual milk in teat
cups and inadequate milking equipment.
Programs for the control of contagious
mastitis involve improvements in hygiene
and disinfection aimed at disrupting the
■ cow-to-cow mode of transmission. In
' addition, methods to eliminate infected
| cows involve antimicrobial therapy and
the culling of chronically infected cows.

In general, a conscientious mastitis
: control program will eradicate S. agalactiae
from most dairy herds. It is much more
difficult to deal with a herd that has a
high prevalence of S. aureus, but S. aureus
can be eradicated from low-prevalence
herds.

Mycoplasma bovis is a less common
cause of contagious mastitis; it causes
: outbreaks of clinical mastitis that do not
respond to therapy and are difficult to
control. Most outbreaks of M. bovis are
’ associated with recent introductions of
new animals into the herd. Character-
istically, clinical mastitis occurs in more
than one quarter, there is a marked drop
in milk production and there is little
evidence of systemic disease. The laboratory
• diagnosis of mycoplasmal mastitis requires
specialized media and culture conditions.
Antimicrobial therapy is relatively in-
: effective and culling is the predominant
: strategy.

Teat skin opportunistic mastitis
pathogens

The incidence of mild clinical mastitis
! associated with bacterial pathogens that
normally reside on the teat skin is
increasing, particularly in herds that have
controlled major contagious mastitis
pathogens. Teat skin opportunistic patho-
gens have the ability to create an intra-
mammary infection via ascending infection
through the streak canal. Accordingly,
their epidemiology of infections differs
from those of contagious and environ-
mental pathogens, and it is useful to con-
sider them in a separate category.
Coagulase-negative staphylococci are
the most common teat skin opportunistic
mastitis pathogens.

Environmental mastitis pathogens

Environmental mastitis is associated with
three main groups of pathogens, the
coliforms (particularly E. coli and Klebsiella
spp.), environmental Streptococcus spp.
and Arcanobacterium pyogenes. The source
of these pathogens is the environment
of the cow. The major method of trans-
mission is from the environment to
the cow by inadequate management of
the environment. Examples include wet
bedding, dirty lots, milking wet udders,
inadequate premilking udder and teat
preparation, housing systems that allow
teat injuries, and poor fly control. Control
strategies for environmental mastitis

Bovine mastitis

include improved sanitation in the barn
and yard areas, good premilking udder
preparation so that teats are clean and dry
at milking time, and fly control. Special
attention is necessary during the late dry
period and in early lactation.

Coliform organisms are a common
cause of clinical mastitis, occasionally in a
severe peracute form. Clinical cases of
coliform infection are generally found in
low levels in most herds and do not
routinely result in chronic infections.
There is increasing evidence that, as the
contagious pathogens are progressively
controlled in a herd, the incidence of
clinical cases associated with coliform
organisms increases. The pathogenesis,
epidemiology, predisposing risk factors,
diagnostic problems, therapy and control
methods have been the subject of exten-
sive, worldwide research efforts.

Environmental streptococci have
become a major cause of mastitis in dairy
cattle. Streptococcal infections are associ-
ated with many different species, however
the most prevalent species are Streptococcus
uberis and Streptococcus dysgalactiae. Infec-
tions with these organisms can cause
clinical mastitis that is commonly mild to
moderate in nature. More frequently,
these organisms cause a chronic subclinical
infection with an increased milk SCC.
Many herds that have implemented the
five-point program for mastitis control
have found that environmental streptococci
represent their most common mastitis
problem.

A. pyogenes is an important seasonal
cause of mastitis in dry cows and late
pregnant heifers in some parts of the
world. Intramammary infections with
A. pyogenes are severe and the gland is
almost always lost to milk production.

Several other pathogens are included
in the environmental class of infections.
These pathogens invade the mammary
gland when defense mechanisms are
compromised or when they are inadver-
tently delivered into the gland at the time
of intramammary therapy. This group of
opportunistic organisms includes Pseu-
domonas spp., yeast agents. Prototheca
spp., Serratia marcescens and Nocardia spp.
Each of these agents has unique micro-
biological culture characteristics, mechan-
isms of pathogenesis and clinical outcomes.
These infections usually occur sporadically.
However, outbreaks can occur in herds or
in an entire region and are usually the
result of problems with specific manage-
ment of hygiene or therapy. For example,
mastitis associated with Pseudomonas
aeruginosa has occurred in outbreaks
associated with contaminated wash hoses
in milking parlors. Iodide germicides used
in wash lines are often at too low a con-
centration to eliminate Pseudomonas spp.

Outbreaks of clinical mastitis associated
with Nocardia spp. have been associated
with the use of blanket dry cow therapy
and the use of a specific neomycin-
containing dry cow preparation.

The mastitis pathogens, and their rela-
tive importance, continue to evolve as
new management methods and control
practices are developed. Thus, there is an
ongoing need for epidemiological studies
to characterize the pathogens and describe
their association with the animals and
their environment. Improved control
methods can develop only from investi-
gations into the distribution and pathogenic
nature of the microorganisms isolated.

ETIOLOGY

Bovine mastitis is associated with many
different infectious agents, commonly
divided into those causing contagious
mastitis, which are spread from infected
quarters to other quarters and cows, those
that are normal teat skin inhabitants and
cause opportunistic mastitis, and those
causing environmental mastitis, which
are usually present in the cow's environ-
ment and reach the teat from that source.
Rithogens causing mastitis in cattle are
further divided into major pathogens
(those that cause clinical mastitis) and
minor pathogens (those that normally
cause subclinical mastitis and less fre-
quently cause clinical mastitis).

Major pathogens

Contagious pathogens
n S. agalactiae
c ■ S. aureus
-• M. bovis.

Environmental pathogens
Environmental Streptococcus species
include S. uberis and S. dysgalactiae, which
are the most prevalent; less prevalent is
S.equinus (formerly referred to as S. bovis).
The environmental coliforms include the
Gram- negative bacteria E. coli, Klebsiella
spp. and Enterobacter spp. A. pyogenes
mastitis can be an important problem in
some herds.

Minor pathogens

Several other species of bacteria are often
found colonizing the teat streak canal
and mammary gland. They rarely cause
clinical mastitis and are known as minor
pathogens. They include the coagulase-
negative Staphylococcus spp. such as
Staphylococcus hyicus and Staphylococcus
chromogenes, which are commonly isolated
from milk samples and the teat canal.
Staphylococcus xylosus and Staphylococcus
sciuri are found free-living in the environ-
ment; Staphylococcus warneri, Staphylococcus
simulans and Staphylococcus epidermidis
are part of the normal flora of the teat
skin (and therefore are teat skin oppor-
tunistic pathogens). The prevalence of

i coagulase-negative Staphylococcus spp. is
| higher in first-lactation heifers than cows,

| and higher immediately after calving than
| in the remainder of lactation. In recent
studies, they have been found as teat
canal and intramammary infections in
nulliparous heifers.

C. bovis is also a minor pathogen; it is
mildly pathogenic and the main reservoir
is the infected gland or teat duct. How-
ever, in some herds, C. bovis appears to be
a common cause of mild clinical mastitis.
C. bovis spreads rapidly from cow to cow
in the absence of adequate teat dipping.
The prevalence of C. bovis is low in herds
using an effective germicidal teat dip,
good milking hygiene and dry cow
therapy. The presence of C. bovis in a gland
will reduce the likelihood of subsequent
infection with S. aureus.

Uncommon mastitis pathogens

Many other bacteria can cause severe
mastitis, which is usually sporadic and
usually affects only one cow or a few cows
in the herd. These include Nocardia
asteroides, Nocardia brasilimsis and Nocardia
farcinica, Histophilus somni, Pasteurella
multocida, Mannheimia (formerly Pasteurella)
haemolytica, Campylobacter jejuni, B. cereus
and other Gram-negative bacteria
including Citrobacter spp., Enterococcus
faecalis, Enterococcus faecium, Proteus spp.,
P. aeruginosa, and Serratia spp. Anaerobic
bacteria have been isolated from cases of
mastitis, usually in association with other
facultative bacteria, e.g. Peptostreptococcus
indolicus, Prevotella melaninogenica (fonnerly
Bacteroide s melaninogenicus), Eubacterium
combesii, Clostridium sporogenes and
Fusobacterium necrophorum.

Fungal infections include Trichosporon
spp., Aspergillus fumigatus, Aspergillus
nidulans and Pichia spp.; yeast infec-
tions include Candida spp., Cryptococcus
neoformans, Saccharomyces spp. and
Torulopsis spp. Algal infections include
Prototheca trispora and Prototheca zopfii.

Leptospiras, including- Leptospira
interrogans serovar. pomona, and especially
Leptospira interrogans hardjo, cause damage
to blood vessels in the mammary gland
and gross abnormality of the milk. They
are more correctly classified as systemic
diseases with mammary gland manifes-
tations, and are described under those
headings in the book.

Some viruses may also cause mastitis
in cattle, but they are of little importance.

EPIDEMIOLOGY

This section deals with the general aspects
of epidemiology of bovine mastitis. For
information about the epidemiology of
mastitis in the other animal species see
the appropriate sections at the end of this
chapter.

676

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

Occurrence and prevalence of
infection

Occurrence refers to the location of the
disease and the kinds of animals affected.
Prevalence is the percentage of the
population affected with a specific disease
in a given population at a certain point in
time. The incidence is a rate, such as
the total number of new cases of clinical
mastitis as a percentage of the animals at
risk that occur during a certain period
of time. Prevalence is a function of the
incidence and the duration of infection.

Prevalence

In most countries, surveys in dairy herds
indicate that the prevalence of infection

of mastitis pathogens is approximately
50% of cows and 10-25% of quarters. The
prevalence of infection in dairy heifers of
breeding age and in pregnant dairy
heifers varies widely 1 from 30-50% of
heifers and 18% of quarters 2 to as high as
97% of heifers and 75% of quarters. 3

Incidence

The average annual incidence of clinical
mastitis, calculated as the number of clini-
cal quarter cases per 100 cows at risk per
year, including the dry period, in individual
herds ranges from 10-12% in most herds 4
but higher incidences, ranging from
16-65%, occur in some herds. 5,6 The
greatest risk of first acquiring mastitis
occurs early in lactation, usually in the first
50 days. 7 The risk of clinical mastitis also
increases with increasing parity. 7 In beef
herds, 32-37% of cows and 18% of quarters
may have intramammary infection, which
has a significant negative effect on calf
weaning weights. 8

Case fatality rates vary widely depend-
ing largely on the identity of the causative
organism. For example, S. agalactiae
mastitis is not a fatal disease but peracute
staphylococcal mastitis in a recently
calved cow often may be fatal. Details of
the occurrence of the different types of
mastitis are presented in their individual
sections in this chapter.

Relative prevalence of infection with
intramammary pathogens

The prevalence of infection with intra-
mammary pathogens in cattle is remarkably
similar in different countries. The bacterio-
logical identification of mastitis pathogens
is important because control and eradi-
cation procedures depend on the kind of
infection prevalent in the herd. In addition,
the validity of epidemiological investi-
gations aiming at detenxiining transmission
patterns or the impact of environmental
and managemental factors to a large extent
depends on exact bacteriological diagnosis.

Contagious pathogens

The prevalence of infection with S. aureus

in cows ranges widely, usually from

7^0%, but higher in some herds. 9 A
survey of Danish dairy herds found that
21-70% of all cows and 6-35% of all
quarters were infected. 10 S. aureus was
isolated from 10% of quarter samples and
was the most common species isolated. 10
The prevalence of streptococci, including
S. agalactiae, ranges from 1-8% of cows. A
relative incidence of S. agalactiae, other
streptococci and S. aureus of 1:1:2 is a
common finding. S. aureus may still
assume some importance as a cause of
subclinical mastitis but its prevalence has
been reduced by modern mastitis control
programs, leading to a higher proportion
of culture-negative mastitic quarters and
a corresponding, and perhaps consequent,
increase in infections by £. coli and
Klebsiella spp.The prevalence of infection
due to Mycoplasma spp. varies widely’
The prevalence of infection due to an
individual pathogen, and therefore the
ratio between its incidence and that of
other pathogens, depends on several risk
factors such as size of herd and quality of
management, especially milking parlor
hygiene and cleanliness of accommodation,
and parity of animal (heifer or cow). For
example, large, zero-grazed herds kept in
drylot conditions are likely to encounter
more hygiene problems than conven-
tionally housed herds mainly because of
constant soiling of the udder by in-
adequate or improper bedding in larger
units. In those circumstances there is
likely to be a much higher prevalence
than usual of mastitis associated with
E. coli and S. uberis.

Teat skin opportunistic pathogens
Coagulase-negative staphylococcal species
were found in 4.1% of samples; the
most frequently isolated were S. epidermidis
(1.3%), S. chromogenes (1.0%) and S. simulans
(0.7%).

Environmental pathogens
'Hie prevalence of intramammary coliform
infections in a dairy herd seldom exceeds
1-2%; the prevalence of intramammary
environmental streptococci is less than
5% in well managed herds but may
exceed 10% in some problem herds. 11 A
characteristic of intramammary coliform
infections is the short duration: 40-50%
persist less than 7 days. The majority of
environmental streptococci infections last
less than 30 days. In a survey of Danish
dairy herds, S. dysgalactiae (1.6%) and
S. uberis (1.4%) were the second and third
most common species isolated.

Heifers

Surveys of intramammary infection of
heifers in regions such as Louisiana
indicate variability in prevalence and
duration of intramammary infection
according to species of bacteria present

around the time of parturition. About
20% of heifers were infected with S. aureus
and 70% with coagulase-negative staphy-
lococci, the minor pathogens that are part
of the normal teat skin flora of heifers. 12
S. chromogenes was isolated from 15% of
all quarters of heifers before parturition
but decreased shortly after parturition to
1%. 13 Up to 97% of breeding age and
pregnant dairy heifers and 75% of their
quarters may be infected with S. aureus,
S. hyicus and S. chromogenes ? Infections with
S. simulans and S. epidermidis occurred in
1-3% of quarters both before and after
parturition. S. dysgalactiae was isolated
from 4-6% of quarters before and immedi-
ately after parturition. Intramammary
infections with S. aureus rarely occurred
before parturition but increased during
the first week after parturition. There was
no association between the prevalence of
S. aureus in heifers before parturition and
the prevalence in lactating cows.

Distribution of pathogens in clinical
mastitis

The distribution of pathogens isolated
from cases of clinical mastitis has changed
with the adoption of control programs
from a high frequency of isolation of
S. aureus and S. agalactiae to a higher
isolation rate of other pathogens, parti-
cularly environmental pathogens. For
example, in 171 randomly selected dairy
herds, the average annual incidence of
clinical mastitis was 12.7 quarter cases per
100 cows per year. The most frequent
isolates from clinical cases were E. coli
(16%), S. aureus (14%), S. uberis (11%),
and S. dysgalactiae (8%) 4 In another
survey, the most common isolates from
clinical cases were coagulase-negative
staphylococci and E. coli, each at 15% of
samples taken. In a 2-year observational
study of 65 dairy herds in Canada, there
was considerable variation in the inci-
dence of clinical mastitis among farms. 7
Overall, 20% of cows experienced one or
more cases of clinical mastitis during
lactation. The pathogens isolated were
coliforms (17%), other Streptococcus spp.
(14%), S. aureus (7%), Gram-positive
bacilli (6%), C. bovis (2%), S. agalactiae
(1 %), and other Staphylococcus spp. (29%).
There was no growth in 18% of samples
and 8% were contaminated. Clearly the
main difference is that the rate of S. aureus
in clinical cases is higher in continental
Europe 4 and lower in England and North
America.

Source of infection

Contagious pathogens
S. agalactiae and S. aureus reside primarily
in the udder of infected cows; the source
of infection is other infected cows and
exposure to uninfected quarters is limited
to the milking process.

Bovine mastitis

Teat skin opportunistic pathogens
A number of species of coagulase-
negative staphylococcus reside primarily
on the teat skin of cattle.

Environmental pathogens
S. uberis, S. dysgalactiae, and coliforms are
common inhabitants of the cow's environ-
ment such as bedding. The exposure of
uninfected quarters to environmental
pathogens can occur at any time during
the life of the cow, including milking time,
between milkings, during the dry period
and prior to first calving in heifers.

Methods of transmission

Infection of each mammary gland occurs
via the teat canal, the infection originating
from either an infected udder or the
environment; in dairy cattle the infection
originating from infected udders is trans-
mitted to the teat skin of other cows by
milking machine liners, milkers' hands,
wash cloths and any other material that
can act as an inert carrier.

Risk factors

Risk factors that influence the prevalence
of infection and the incidence of clinical
mastitis are outlined here. Individual
factors that are of particular importance
in the individual types of mastitis are
described under those headings.

Animal risk factors
Age and parity

The prevalence of infected quarters
increases with age, peaking at 7 years.
Surveys of the prevalence of intramammary
infection in dairy heifers a few days before
their first parturition reveals that 45% are
infected, and the quarter infection rate
may be 18%. 2 Some studies found intra-
mammary infections in 97% of heifers
and 74% of quarters. 3

Stage of lactation

Most new infections occur during the
early part of the dry period and in the
first 2 months of lactation, especially
with the environmental pathogens. In
heifers, the prevalence of infection is
often high in the last trimester of preg-
nancy and several days before parturition,
followed by a marked decline after
parturition. 13 In dairy heifers, most of
these prepartum infections are associated
with the minor pathogens but some
surveys have found evidence of infection
by the major pathogens. 2,3 The mean
prevalence of S. aureus intramammary
infection in primiparous cows at first
parturition in high prevalence herds can
be as high as 30%, ranging from 13-65%,
and in low prevalence herds it may as low
as 2%, ranging from 0-5%. H The overall
prevalence of infection of S. aureus intra-
mammary infection in primiparous cows
at parturition was 8%, ranging from

0-27%. Of those cows with S. aureus
intramammary infection at parturition,
43% had S. aureus intramammary infec-
tion at least 2 months after parturition.
Primiparous cows with these infections
may represent significant reservoirs of
infection to uninfected animals in the
herd.

Some of these differences may be
related to changes in the milk as a medium
for bacterial growth. For example, bacteria
such as C. bovis grow best in milk secreted
in the middle of lactation, whereas dry
period secretion inhibits its growth. 15
Duringthe dry period the quarter's capacity
to provide phagocytic and bactericidal
activities diminishes. 16

Somatic cell count

The highest average incidence of clinical
mastitis due to environmental bacteria
may occur in herds with the lowest bulk
tank milk SCC (< 150 000 cells/mL) and a
low prevalence of subclinical infection. 17

Breed

Generally the incidence of mastitis is
greater in Holstein-Friesians than in
Jerseys, but this may reflect differences in
management rather than a true genetic
difference. Valid comparisons between
breeds have not been reported.

Milking characteristics and morphology
of udder and teat

High milking rate and large teat canal
diameter have been associated with
increased SCC or risk of intramammary
infection. 18 Milk leaking in cows in herds
with a low bulk tank milk SCC has also
been associated with an increased rate of
clinical mastitis. Decreasing teat-end-to-
floor distance is also a risk factor for
clinical mastitis and may be associated
with an increased incidence of teat
lesions. Heritability estimates of teat-
end-to-floor distance or udder height
range from 0.2-0.7, which may be a con-
sideration in the selection indices of bulls.
Periparturient udder edema may also be a
risk factor for clinical mastitis.

Physical condition of teat
The teat end is the first barrier against
invading pathogens, and the efficiency of
teat defense mechanisms depends on the
integrity of teat tissue; its impairment
leads to an increase in the risk of intra-
mammary infection. Teat thickness is an
aid to evaluating teat tissue status. Milking
machine characteristics can induce a
decrease or increase in teat thickness after
milking compared with premilking values.
Increases in teat thickness of more than
5% are significantly associated with infec-
tion and new infection, but the associ-
ation was not significant when teat
thickness decreased by more than 5%. 19
Coagulase-negative staphylococcal infec-

tions are significantly associated with
both increases and decreases in teat
thickness numerically greater than 5%,
but there is no association between teat
thickness and S. aureus infections.

Hyperkeratosis of the teat orifice is a
commonly observed condition in the
dairy cow because of machine milking;
the degree of hyperkeratosis may be
increased by a poor milking system. 20
There is wide variation in the degree of
hyperkeratosis between herds; the score
increases with lactational age and peaks,
for any lactation, at 3-4 months after
parturition, declining as the cows dry
off. There is no significant relationship
between mean SCC and the degree of
hyperkeratosis at the herd level.

Udder hygiene

Dirty udders are associated with increased
SCC and an increased prevalence of intra-
mammary infection due to contagious
pathogens, but surprisingly are not
associated with intramammary infections
due to environmental pathogens. 21 This
suggests that udder hygiene is a proxy for
general mastitis management skills, in
that good mastitis control programs result
in low prevalence of infection with con-
tagious pathogens.

Nutritional status

Vitamins E and A and selenium may be
involved in resistance to certain types of
mastitis 22 Early reports found that supple-
mentation with antioxidants such as
selenium and vitamin E had a beneficial
effect on udder health in dairy cattle by
decreasing the incidence and duration of
clinical mastitis. An increase in selenium
concentration in whole blood was associ-
ated with a decrease in all infections,
including S. aureus, A. pyogenes, and
C. bovis. 23 There was no association
between different infections or SCC and
concentrations of vitamin E, vitamin A, or
beta-carotene, but an association existed
between vitamin A concentration and
SCC. The lower selenium concentration
in whole blood did not increase the
incidence of clinical mastitis.

Genetic resistance to mastitis
A variety of morphological, physiological
and immunological factors contribute to a
cow's resistance or susceptibility to
mastitis, and each of these factors is
influenced to some extent by heredity.
Differences in udder depth, teat length,
teat shape, and teat orifice morphology
are thought to be associated with differ-
ences in mastitis. The production of
keratin in the streak canal and the
physical and biochemical characteristics
of keratin are important contributors to
mastitis resistance. Many of the defense
mechanisms of the udder, including

678

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

lysozyme, lactoferrin, immunoglobulins
and leukocytes, are direct products of
genes and have a genetic basis. For dairy
cattle, heritability estimates for clinical
mastitis average about 0.05. These low
heritability estimates indicate that there is
very little genetic influence on clinical
mastitis but a very strong environmental
influence. 24

Somatic cell count Differences in heri-
tability between herds with high and low
SCCs are not significant. However, differ-
ences among bulls' daughter groups for
both clinical mastitis and SCC are reason-
ably large, suggesting that selection of
sires can be important in mastitis
control. 25 An analysis of the disease and
breeding records of a large number of
Swedish bulls siring daughters whose
milk had a low SCC count found genetic
correlations from 0.71-0.79 between SCC
and clinical mastitis. It was concluded
that it is possible to improve resistance
to clinical mastitis by selecting for a
low SCC.

The strong phenotypic and genetic
association between SCC and mastitis
indicates that breeding programs based
on SCC may be effective as an indirect
means of improving mastitis resistance.
However, greater emphasis on SCC may
decrease genetic gain in yield traits, which
are economically more important. 25

Milk yield

The genetic correlation between milk
yield and mastitis is about 0. 2-0.3, which
suggests that animals genetically above
average for milk yield are more susceptible
to mastitis and that low-yielding cows
tend to be more resistant. However, the
low correlation value suggests that this
relationship is not a strong tendency. The
positive correlation implies that genetic
improvement for milk yield is accompanied
by a slow decline in genetic resistance to
mastitis. Examination of the association
between milk yield and disease in a large
number of dairy cows found that higher
milk yield was not a factor for any disease
except mastitis. 27 However, the associ-
ation between milk yield and mastitis
does not imply causation. At least two
biological explanations are plausible:
increased injury and leaking of milk
between milkings. Improved mastitis
control efforts have offset the genetic
trend for increased susceptibility to
mastitis. The low heritability for mastitis
indicates the great importance of environ-
mental factors in causing differences in
the prevalence of infection and the
incidence of clinical mastitis.

In summary, selection for milk yield
alone results in increased incidence of
mastitis. The positive genetic correlation
between milk yield and mastitis suggests

that genes that increase milk yield tend to
increase susceptibility to mastitis. Selection
indices that maximize genetic improve-
ment for net economic benefit will not
decrease the incidence of mastitis, but
indices that include SCC, udder depth or
clinical mastitis will diminish the rate of
increase in mastitis by 20-25%. Using
predicted transmitting ability (PTA), an
estimate of genetic merit, it has been
found on average that daughters of bulls
with high PTAs for SCC have a higher
incidence of mastitis; sires with low PTA
for somatic cell scores should therefore be
selected. All of the economically import-
ant traits are weighted into a selection
index for the selection of bulls which
will improve net income over cost of
production.

Other concurrent diseases
These may be important risk factors for
mastitis. Retained placentas, teat injuries
and teat sores may be associated with a
higher incidence of mastitis. Sole ulcer-
ation of any severity occurring in more
than one digit has been associated with
an approximately threefold higher risk of
S. aureus infections in the first lactation. 28
It is suggested that sore feet could
increase the risk of teat lesions, presumably
as a result of difficulty in standing.

Immunological function of mammary
gland

The immune function of the mammary
gland is impaired during the periparturient
period; it is susceptible to mastitis during
transition periods, such as drying off and
colostrogenesis. As a result, the incidence
of new intramammary infections is
highest during the early nonlactating
period and the periparturient period.

The most important components of the
defense against common bacterial patho-
gens are blood-derived neutrophils and
opsonizing antibodies. An inadequate
rate of neutrophil recruitment to combat a
new intramammary infection has a
profound effect on the outcome of infec-
tion, in that cows with a rapid and
massive recruitment of neutrophils to an
infected gland clear an intramammary
infection within 12-18 hours postinfection.

It is also important that an early
inflammatory response in the infected
mammary gland enables leakage of IgG 2
(opsonizing antibodies) as this facilitates
neutrophil phagocytosis of bacteria. The
staggered one-two punch of peak IgG 2
concentrations within 4 hours of infec-
tion and peak neutrophil response within
6-12 hours of infection greatly facilitates
clearance of new intramammary infections.

Blood- derived neutrophils must under-
go margination, adherence and mi-
gration in order to arrive in the mammary'
gland, where they perform phagocytosis,

respiratory burst and degranulation.

Margination is via expression of three
adhesion molecules from the selectin
family, specifically L -selectin (also called
CD62L) on neutrophils, E-selectin (also
called CD62E), and P-selectin (also called
CD62P) on vascular endothelial cells.
Neutrophil L-selectin makes the initial
contact between 'streaming' neutrophils
in the blood stream and the vascular wall;
this contact slows neutrophil movement
and allows them to 'roll' along the endo-
thelium while surveying for the presence
of proinflammatory mediators at the sites
of tissue infection. When the rolling
neutrophils detect the presence of one
or more proinflammatory mediators they
immediately shed surface L-selectin
(CD62L) adhesion molecules and up-
regulate and activate Mac-1 (CDllb/CD18)
adhesion molecules, thereby stopping
neutrophil rolling and permitting tight
adherence of the neutrophil to the
endothelium. Once adhered, neutrophils
commence diapedesis by migrating
between endothelial cells to the site of
infection. Neutrophil migration therefore
has three components; hyperadherence
(cessation of rolling), diapedesis and
chemotaxis. Any delay or inhibition in this
process can lead to peracute mastitis and
severe clinical disease. This is best illus-
trated by bovine leukocyte adhesion
deficiency (BEAD) in Holstein-Friesian
cattle; affected calves cannot produce
Mac-1 molecules and have a prominent
neutrophilia because streaming neutrophils
cannot migrate to the site of infection.
Migration of neutrophils is slow during
the first few weeks of lactation and this
delay in neutrophil migration is believed
to be responsible for the increased
incidence and severity of intramammary
infections during early lactation.

Previous mastitis

Cows with a history of mastitis in the
preceding lactation may be almost twice
as susceptible to clinical mastitis in the
current lactation as those without mastitis
in the preceding lactation. 29

Pre-existing intramammary infections
Natural infection with minor pathogens
has a protective effect against infections
with major pathogens. 30 The lowest rate
of infection with major pathogens has
been observed in quarters infected with
C. bovis. Elimination of these minor
pathogens with postmilking teat dis-
infection may result in an increase in the
incidence of clinical mastitis. Discontinu-
ation of the teat dipping may be
associated with an increase in the preva-
lence of minor pathogens, increase in the
incidence of S. aureus infections, and
decrease in the incidence of E. coli infec-
tions. Thus quarters already infected with

Bovine mastitis

a minor or major infection are less likely
to acquire a new infection than uninfected
quarters.

Use of recombinant bovine somatotropin
Because the risk of clinical mastitis
increases as milk production increases
there has been considerable scientific and
public controversy over the potential
effects that the use of recombinant bovine
somatotropin (bST) might have on the
incidence of clinical mastitis and the
subsequent use of antimicrobials from
therapy. In some field trials, the use of
bST did not result in an increase in the
incidence of clinical mastitis compared to
controls. In other trials, a significant
increase in the incidence of clinical mastitis
occurred in treated cows compared to
controls. However, the incidence of clinical
mastitis was greater in treated cows
compared to controls before bST was
used. In trials done on well managed
farms which had controlled contagious
mastitis and had low rates of clinical
mastitis due to environmental pathogens,
the use of bST was not associated with an
increase in clinical mastitis, discarded
milk because of therapy or culling for
mastitis. 31 Interpretation of a direct effect
of bST on mastitis incidence is confounded
by the higher incidence of mastitis in
cows of higher milk production.

Environmental and management risk
factors

Quality and management of housing
Factors such as climate, housing system,
type of bedding and rainfall interact to
influence the degree of exposure of teat
ends to mastitis pathogens. Because dairy
cattle spend 40-65% of their time lying
down, the quality and management of
housing for dairy cattle has a major
influence on the types of mastitis patho-
gen that infect the mammary gland, as
well as the degree of infection pressure.

The major sources of environmental
pathogens arc the cow's environment,
including bedding, soil, feedstuffs and
water supplies. Environmental pathogens
multiply in bedding materials, with which
the cow's teats are in close and prolonged
contact. Bacterial growth in bedding
depends on temperature, amount of
moisture and nutrients available, and the
pH. Fresh bedding can be a source of
contamination even before it is used:
Klebsiella pneumoniae can be present in
green, hardwood sawdust in higher
numbers than in other types of bedding
and major outbreaks of environmental
mastitis due to K. pneumoniae have occurred
following the use of contaminated wood
products bedding, described in detail in
that section. Dry, unused bedding contains
few pathogens but after being used it
becomes contaminated and provides a

source in which pathogens multiply to
high numbers in 24 hours. Organic
bedding materials such as straw, sawdust,
wood shavings and paper support the
growth of pathogens. Inorganic materials
such as sand retain less moisture and do
not provide a supply of nutrients for the
pathogens; bacterial counts in these
materials are usually lower than in
organic materials. Housing lactating cattle
on sawdust leads to six times more
Klebsiella bacteria and twice as much
coliform bacteria on the teat ends compared
to housing cattle on sand. In contrast,
there were 10 times more environmental
streptococci bacteria on teat ends when
cows were housed on sand, compared to
housing on sawdust. 32 Surveys indicate
that herds using wood chips or sawdust
as bedding material have higher rates of
clinical mastitis compared to those using
straw bedding. 33

High humidity and high ambient
temperatures favor growth of pathogens.
Cows in confinement housing with organic
bedding materials have the highest
incidence of environmental mastitis in the
want), humid months of the year. Pasturing
herds during the summer months usually
reduces the incidence of coliform mastitis,
although rates of environmental strepto-
cocci may remain high. In drylot systems
the incidence of coliform mastitis may be
associated with periods of high rainfall.
Herds with more months on pasture may
have a higher incidence of clinical
mastitis, 33 which may be associated with
factors such as sanitation and the stress of
transition between pasture and confine-
ment housing.

The management and design of
housing systems influence the preva-
lence of intramammary infection and the
incidence of clinical mastitis. Any housing
factor or management system that allows
cows to become dirty or damage teats or
that causes overcrowding will result in an
increase in clinical mastitis. This includes
the size and comfort of free stalls, the size
of the alleyways, ease of movement of
cattle and the cleaning system. Failure to
keep alleyways, cow stalls and bedding
clean and dry will increase the level of
contamination of the teats. Overcrowding,
poor ventilation, access to dirty ponds of
water and muddy areas where cows
congregate are major risk factors.

The size of the milking cow herd
may be positively associated with an
increased incidence of clinical mastitis
because it can be more difficult to control
contagious mastitis in a herd with a
greater prevalence of infection and a
larger number of cow-to-cow contacts. As
herd size increases, manure disposal and
sanitation problems may increase
exposure to environmental pathogens.

However, regional and management dif-
ferences may confound the association of
size with infection status. Some recent
data suggest lower SCC in large herds.
The use of designated maternity areas
providing an isolated and clean environ-
ment for parturition 33 may be associated
with a lower incidence of clinical mastitis.

If hygiene and bedding maintenance
are neglected in the housing accommo-
dation the prevalence of environmental
forms of mastitis may increase markedly.
Periodic inspection of dry cows is an
essential part of mastitis control.

Milking practices

The failure to employ established and
reliable methods of mastitis control is
an important risk factor. This is a major
subject, which includes efficiency of
milking personnel, milking machines,
high milking speed and especially hygiene
in the milking parlor. Wet teats and
udders are a risk factor for increased SCC,
especially in the presence of teat impacts
from liner slippage. 33 The use of a
separate drying cloth for each cow is
associated with a lower SCC. Effective use
of a postmilking germicidal teat dip is
critical for the control of contagious
mastitis. Increasing person-hours spent
milking per cow may be associated with a
higher rate of clinical mastitis. 33 Contami-
nated milking equipment - including
milk hoses, udder wash towels and teat
dip products - has been associated with
outbreaks of environmental mastitis from
S. marcescens and P. aeruginosa. Drying off
procedures at the end of lactation and an
active policy on drying off treatment are
equally important.

The absence of milk quality regu-
lations that place emphasis on SCC is
also a risk factor. Conversely, the presence
of strict regulations with penalties for
high SCC is an important incentive to
institute mastitis control programs that
improve the quality of milk. The absence
of a health management program consist-
ing of regular farm visits by the veterinarian
may also be a risk factor for mastitis,
which may be associated with a relative
lack of awareness by the producer of the
importance of the principles of mastitis
control.

Season of year

The relationship between the incidence of
mastitis and season of the year is variable,
depending on geographical and climatic
conditions. In subtropical and tropical
areas the incidence may be higher during
winter or spring calvings from the increase
in infection pressure associated with
increased humidity. In temperate climates,
the incidence of mastitis is higher in
autumn and winter, when calving occurs
along with an extended period of housing. 34

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

Under conditions of housing for long
winter periods, infectious agents are most
likely to be found in higher numbers in
the bedding. In the UK there is an in-
creased frequency of mastitis when cows
are housed for the winter.

Pathogen risk factors
Viability of pathogens
The ability of the pathogen to survive
in the cow's immediate environment
(resistance to environmental influences
including cleaning and disinfection pro-
cedures) is a characteristic of each patho-
gen. The causes of contagious mastitis are
more susceptible to disinfection than the
causes of environmental mastitis.

Virulence factors

There is a wide variety of virulence factors
among the mastitis pathogens. These are
described under specific mastitides. The
influence of many bacterial virulence
factors depends on the stage of lactation
and severity of the intramammary infec-
tion and the effects elicited by the
virulence factors on bovine mammary
tissue. A few examples of the common
virulence factors are noted here.

Colonizing ability

The ability of the pathogens to colonize
the teat duct, then to adhere to mammary
epithelium and to initiate mastitis is a
major characteristic of the major bacterial
causes of mastitis. S. aureus strains that
cause mastitis can bind to ductular udder
epithelial cells and to explant cultures of
bovine mammary glands. There are differ-
ences in the adhesion characteristics among
strains of the organism, which may explain
the different epidemiological characteristics
of the organisms in some herds. Com-
parison of strains isolated from different
S. aureus mastitis cases between herds
reveals that only a limited number of
genotypes of S. aureus are most prevalent. 34

Toxins

E. coli isolates that cause mastitis produce
lipopolysaccharide endotoxin, which is
responsible for many of the inflammatory
and systemic changes observed during
acute coliform mastitis. S. aureus isolated
from intramammary infections produces
many potential virulence factors, including
enterotojins, coagulase and alpha, beta,
delta toxins, hemolysin, hyaluronidase
and leukocidins, which are considered to
be involved in the varying degrees of
inflammation characteristic of staphy-
lococcal mastitis from subclinical to
peracute gangrenous mastitis. Virulence
factors of S. uberis include hyaluronidase
and the hyaluronic capsule.

Production and economic losses

Although mastitis occurs sporadically in
all species, it assumes major economic

importance in dairy cattle and may be one
of the most costly diseases in dairy herds.
Mastitis results in economic loss for
producers by increasing the costs of
production and by decreasing productivity.
The premature culling of potentially
profitable cows because of chronic mas-
titis is also a significant loss. Because of
the large economic losses, there is a
potential for high returns on investment
in an effective control program. The com-
ponent economic losses can be divided
into:

o Loss of milk production
o Discarded milk from cows with
clinical mastitis and treated cows
° Replacement cost of culled cows
o Extra labor required for treatment and
monitoring

» Veterinary service for treatment and
control

° Cost of first trimester abortions due to
clinical mastitis 36
o Cost of control measures.

There are additional costs such as anti-
microbial residues in milk from treated
cows, milk quality control, dairy food
manufacturing, nutritional quality of milk,
degrading of milk supplies due to high
bacteria or SCC, and interference with the
genetic potential of some cows from early
involuntary culling because of chronic
mastitis. The total annual cost of mastitis
in the dairy cattle population is estimated
to be 10% of the total value of farm milk
sales, and about two-thirds of this loss is
due to reduced milk production in sub-
clinically affected cows.

The production and economic losses
are commonly divided into those associ-
ated with subclinical and clinical mastitis.

Subclinical mastitis

Total milk losses from quarters affected
with subclinical mastitis have been esti-
mated to range trom 10-26%. 37 Lower
SCCs are associated with higher milk
production, and rolling herd average milk
production has been estimated to decrease
by 190 kg per unit increase of linear somatic
cell score. Most estimates indicate that on
average an affected quarter results in a
30% reduction in productivity, and an
affected cow is estimated to lose 15% of
its production for the lactation. This loss is
sometimes expressed as a loss of about
340 kg of saleable milk, due to loss of
production and the value of milk that has
to be withheld from sale. The loss in
production by an infected quarter may be
largely compensated by increased pro-
duction in the other quarters so that the
net loss from the cow may be less than
expected. In addition to these losses,
there is an added loss of about 1% of total
solids by changes in composition (fat,

casein, and lactose are reduced and
glycogen, whey proteins, pH, and chlorides
are increased), which interferes with
manufacturing processes, and other losses
include increased culling rates and costs
of treatment. Comparisons between low-
and high-prevalence herds always show a
financial advantage of about 20% to the
low-prevalence herds, the gain varying
with the local price of milk or butter fat. In
beef herds the losses are in the form of
rare deaths of cows and failure of the
calves to gain weight.

Approximately 75% of the economic
loss from subclinical mastitis is attributable
to loss of milk production. Other costs
include discarding milk from treated
cows, drug costs, veterinary costs, labor
and loss of genetic potential of culled
cows.

Clinical mastitis

Clinical mastitis results in marked decreases
in milk production, which are much larger
in early than late lactation. Milk pro-
duction losses are also greater in cows with
multiple lactations than first-lactation
cows, and clinical mastitis also decreases
the duration of lactation and increases the
likelihood of culling. Clinical cases of brief
duration that occur after the peak of
lactation affect milk production very little
but can induce abortion during the first
45 days of gestation. 36 Clinically affected
quarters may not completely recover milk
production in subsequent lactations but
these carry-over losses are not as large as
the losses from acute mastitis. In the
National Animal Health Monitoring
System of dairy herds in the US, clinical
mastitis alone was the most costly disease
identified, at a loss to the producer of
$27-50 per cow per year 37

The costs of clinical mastitis and
mastitis prevention in dairy herds have
been estimated, based on monitoring
50 dairy herds over 1 year. 38 Mean inci-
dence of clinical mastitis was 39 cases/100
cow-years; each clinical case cost $38/
cow-year, with a mean cost per clinical
episode of US$107. Prevention of mastitis
cost $14. 50/cow-year. 39 Lost milk pro-
duction was estimated at $14. 85/cow-
year, which does include the losses associ-
ated with subclinical mastitis.

The component causes of economic
loss associated with mastitis outlined above
vary according to the causative pathogen
and are described under specific mastitides.
In general terms S. aureus and E. coli
may cause death from peracute mastitis;
A. pyogenes causes complete loss of
quarters; staphylococci and streptococci
cause acute clinical mastitis, but their
principal role is in causing subclinical
mastitis, resulting in a reduction of milk
produced and a downgrading of its

Bovine mastitis

681

quality. Of these, S. agalactiae causes the
greatest production loss, whereas S. aureus
has the higher infection rate, greater
resistance to treatment and longer
duration of infection. At one time S. aureus
represented the impassable barrier to
mastitis control programs.

Other factors that affect the magnitude
of the loss associated with mastitis
include age (the loss is greatest in mature
cows), and when the attack occurs in the
first 150 days of lactation.

Zoonotic potential

With mastitis there is the danger that the
bacterial contamination of milk from
affected cows may render it unsuitable for
human consumption by causing food
poisoning, or interfere with manufacturing
processes or, in rare cases, provide a
mechanism of spread of disease to
humans. Tuberculosis, streptococcal sore
throat and brucellosis may be spread in
this way. Raw (unpasteurized) milk can be
a source of food-borne pathogens, and
consumption of raw milk can result in
sporadic disease outbreaks. For instance,
sampling bulk tank raw milk in Ontario
revealed the presence of Listeria mono-
cytogenes, Salmonella spp., Campylobacter
spp. or verocytoxigenic E. coli in 2.7%,
0.2%, 0.5% and 0.9% of milk samples,
respectively. 40 These findings emphasize
the importance of continued diligence in
the application of hygiene programs
within dairies and the separation of raw
from pasteurized milk and milk products.

PATHOGENESIS

Infection of the mammary gland always
occurs via the teat canal and on first
impression the development of inflam-
mation after infection seems a natural
sequence. However, the development of
mastitis is more complex than this and
can be most satisfactorily explained in
terms of three stages: invasion, infec-
tion, inflammation. Of the three phases,
prevention of the invasion phase offers
the greatest potential for reducing the
incidence of mastitis by good manage-
ment, notably in the use of good hygienic
procedures.

Invasion is the stage at which patho-
gens move from the teat end to the milk
inside the teat canal.

Infection is the stage in which the
pathogens multiply rapidly and invade
the mammary tissue. After invasion the
pathogen population may be established
in the teat canal and, with this as a base,
a series of multiplications and extensions
into mammary tissue may occur, with
infection of mammary tissue occurring
frequently or occasionally depending on
its susceptibility. Multiplication of certain
organisms may result in the release of
endotoxins, as in coliform mastitis, which

causes profound systemic effects with
minimal inflammatory effects.

Inflammation follows infection and
represents the stage at which clinical
mastitis occurs with varying degrees of
clinical abnormalities of the udder and
variable systemic effects from mild to
peracute; gross and subclinical abnor-
malities of the milk appear. Abnormalities
of the udder include marked swelling,
increased warmth and, in acute and
peracute stages, gangrene in some cases
and abscess formation and atrophy of
glands in chronic stages. The systemic
effects are due to the mediators of inflam-
mation. Gross abnormalities of the milk
include a decrease in milk yield, the
presence of the products of inflammation
and marked changes in the composition
of the milk.

The most significant subclinical abnor-
mality of the milk is the increase in the
somatic cell count, the most common
measurement of milk quality and udder
health. Milk somatic cells in a healthy
gland consist of several cell types, includ-
ing neutrophils (< 11 %), macrophages
(66-88%), lymphocytes (10-27%), and a
smaller percentage of epithelial cells
(0-7%). 41 Neutrophils are the predominant
cell type found in mammary tissues and
secretions during inflammation, in mastitis
they constitute more than 90% of total
mammary gland leukocytes. Once at the
site of infection, neutrophils phagocytose
and kill pathogens. Neutrophils exert
their bactericidal effect through a respir-
atory burst that produces hydroxyl and
oxygen radicals, important components of
the oxygen-dependent killing mechanism.

In the healthy lactating mammary
gland, the SCC isless than 100 000 cells/mL
of milk. During intramammary infection,
the glandular SCC can increase to more
than 1 000 000 cells/mL of milk within a
few hours because of the combined effect
of an increased number of neutrophils
(numerator) and a decreased glandular
secretion volume (denominator). The
severity and duration of mastitis are
critically related to the promptness of
the neutrophil migratory response and
their bactericidal activity at the site of
infection. As they colonize and multiply
in the mammary gland, some bacteria
release metabolic byproducts or cell-wall
components (endotoxin if a Gram-negative
bacteria) that serve as chemoattractants
for leukocytes. If neutrophils move
rapidly from the blood stream and are
able to eliminate the inflammatory stimuli
(bacteria), then recruitment of neutrophils
ceases and the SCC returns to normal
levels. If bacteria are able to survive this
immediate host response, then the
inflammation continues, resulting in
neutrophil migration between adjacent

mammary secretory cells toward the
alveolar lumen. Prolonged diapedesis of
neutrophils damages mammary tissue,
resulting in decreased milk production.
The duration and severity of the inflam-
matory response therefore has a major
impact on the quantity and quality of milk
produced.

The major factor affecting the SCC at
the herd and individual cow level is the
prevalence of intramammary infection at
a glandular level. Because marked increases
in SCC are a result of cells being attracted
to the mammary tissue because of the
mediators produced during a local infec-
tion, events that do not affect udder
health are unlikely to have a direct or
dramatic effect on SCC. Little evidence
exists that any factor other than normal
diurnal variation has a major influence on
SCC in the absence of intramammary
infections.

The effects of mastitis on milk yield are
highly variable and depend on the severity
of the inflammation, the causative agents
and the lesions produced, the efficiency of
treatment, the production level and the
stage of lactation. 42 Mastitis in early
lactation causes a larger decrease in milk
yield with long-term effects than mastitis
in late lactation. Mastitis due to S. aureus
generally evolves into persistent but
moderate infections, unlike those associ-
ated with coliforms. Mastitis associated
with A. pyogenes results in suppurative
lesions, poor response to treatment and
culling. M. bovis causes chronic induration
and almost complete loss of milk pro-
duction without recovery.

CLINICAL FINDINGS

Details of the clinical findings are pro-
vided under each specific type of mastitis.
The clinical findings should be used only
as a guide because different pathogens
can cause chronic, subclinical, subacute,
acute and peracute forms of the disease,
and clinical differentiation of the different
causes of mastitis is difficult. The greatest
clinical accuracy achievable, even in a
specialist hospital environment and after
adaptation to suit local conditions, is
about 70%, 43 which is not sufficiently
accurate to be clinically useful. In other
words, bacteriological culture of milk
from an affected gland is required before
specific pathogen -directed treatment can
be implemented.

Clinical mastitis is detected using only
the results of the physical examination,
and a useful definition of clinical mastitis
is a negative answer to the question
'would you drink this?' In other words,
'undrinkable' is a simple and generalizable
concept for defining clinical mastitis, in
that milk from cows with clinical mastitis
is not suitable for drinking. New cases of

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

clinical mastitis are defined as being j
separated by at least 14 days.

The clinical findings in mastitis include i
abnormalities of secretion, abnormalities
of the size,- consistency and temperature
of the mammary glands and, frequently, a
systemic reaction. In other words, there
are three categories of clinical mastitis,
abnormal milk, abnormal gland and an
abnormal cow (systemic disease). Abnor-
mal milk is visibly abnormal (i.e. is not
'drinkable'). An abnormal gland is larger
and firmer than other quarters. An
abnormal cow is pyrexic, depressed or has
decreased appetite or milk production.
This three-part categorization scheme
has excellent clinical utility, is readily
understood by everyone and provides a
sound pathophysiological basis for treat-
ment. In particular, it is likely that optimal
treatment protocols can be developed
for the three levels of clinical mastitis.
Other categorization systems have been
developed, but they lack the simplicity
and generalizability of the secretion,
gland and cow system.

Clinical mastitis episodes are also
categorized according to their severity
and duration.

Severity is characterized as:

° Peracute: severe inflammation, with
swelling, heat and pain of the quarter,
with a marked systemic reaction,
which may be fatal

° Acute: severe inflammation without a
marked systemic reaction
° Subacute: mild inflammation with
persistent abnormality of the milk.

Duration is characterized as:

° Short-term (as in E. coli and Klebsiella
spp.)

0 Recurrent (as in S. aureus and
S. dysgalactiae)

° Persistent (as in S. agalactiae and
M. bovis).

Abnormal milk

Proper examination of the milk requires
the use of a strip cup, preferably one that
has a shiny, black plate, permitting the
detection of discoloration as well as clots,
flakes and purulent material. Milk is
drawn on to the black plate in pools and
comparisons are made between the milk
of different quarters. Because the herds-
man frequently has little time to examine
milk for evidence of mastitis it is customary
to milk the first few streams on to the
floor; in some parlors black plates are set .
in the floor. The practice does not appear
to be harmful if the floor is kept washed
down.

Discoloration may be in the form of
blood-staining or wateriness, the latter
usually indicating chronic mastitis when
the quarter is lactating. Little significance

is attached to barely discernible wateriness
in the first few streams but, if this persists
for 2-3 streams or more, it is an abnor-
mality. One of the major unresolved
issues in bovine mastitis is how to treat a
cow with abnormal secretion on the first
1-2 streams that subsequently has
normal-looking milk. Clots or flakes are
usually accompanied by discoloration and
they are always significant, indicating a
severe degree of inflammation, even
when small and present only in the first
few streams. Blood clots are of little
significance in a mastitis case, neither are
the small plugs of wax that are often
present in the milk during the first few
days after calving, especially in heifers.
Flakes at the end of milking may be
indicative of mammary tuberculosis in
cattle.

During the dry period in normal
cows, the secretion changes from normal
milk to a clear watery fluid, then to a
secretion the color and consistency of
honey, and finally to colostrum in the last
few days before parturition. Some variation
may occur between individual quarters in
the one cow; if this is marked, it should
arouse suspicion of infection.

The strip cup provides a valuable tool
to detect clinical mastitis and constitutes
part of the routine physical examination
of the lactating cow. The most sensitive
use of the strip cup is to observe the
ability of milk from one quarter to mix
with milk from another quarter; incomplete
mixing (evidence of'streaming') indicates
that secretions from the two quarters
differ and suggests the presence of an
intramammary infection in one of the
quarters. However, it should be remem-
bered that the strip cup can only detect
clinical mastitis, and detection of sub-
clinical mastitis requires use of indirect
tests such as SCC of composite milk
samples from individual cows, or appli-
cation of the California Mastitis Test to
quarter samples or measuring the electrical
conductivity of quarter samples.

Abnormal gland

Abnormalities of size and consistency of
the quarters may be seen and felt.
Palpation is of greatest value when the
udder has been recently milked, whereas
visual examination of both the full and
empty udder may be useful. The udder
should be viewed from behind and the
two hind quarters should be examined for
symmetry. By lifting up the hind quarters,
the fore quarters can be viewed. A
decision on which quarter of a pair is
abnormal may depend on palpation,
which should be carried out simul-
taneously on the opposite quarter of the
pair. Although in most forms of mastitis
the observed abnormalities are mainly in

the region of the milk cistern, the whole
of the quarter must be palpated, parti-
cularly if tuberculosis is suspected. The
teats should be inspected and palpated
for skin lesions, especially around the teat
end. The supramammary lymph nodes
should also be palpated for evidence of
enlargement.

Palpation and inspection of the udder
are directed at the detection of fibrosis,
inflammatory swelling and atrophy of
mammary tissue. Fibrosis occurs in
various forms. There may be a diffuse
increase in connective tissue, giving the
quarter a firmer feel than its opposite
number and usually a more nodular
surface on light palpation. Local areas of
fibrosis may also occur in a quarter; these
may vary in size from pealike lesions to
masses as large as a fist. Acute inflam-
matory swelling is always diffuse and
is accompanied by heat and pain and
marked abnormality of the secretion. In
severe cases there may be areas of
gangrene, or abscesses may develop in
the glandular tissue. The terminal stage of
chronic mastitis is atrophy of the gland.
On casual examination an atrophied
quarter may be classed as normal because
of its small size, while the normal quarter
is judged to be hypertrophic. Careful
palpation may reveal that, in the atrophic
quarter, little functioning mammary tissue
remains.

Abnormal cow (systemic response)

A systemic response including toxemia,
fever, tachycardia, ruminal stasis, de-
pression, recumbency and anorexia may
or may not be present, depending on the
type and severity of the infection. A
systemic response is usually associated
with severe mastitis associated with
E. coli, Klebsiella spp. or A. pyogenes and
occasionally with Streptococcus spp. or
Staphylococcus spp. Clinical mastitis epi
sodes due to A. pyogenes produces the
greatest decrease in milk production. In
contrast, clinical mastitis due to environ-
mental streptococci and coagulase-
negative staphylococci is associated with
the smallest decrease in milk production. 44
Clinical mastitis episodes due to S. aureus
are associated with the highest risk of
culling. 45

DIAGNOSIS

Detection of clinical mastitis

The initial diagnosis of clinical mastitis is
made during the routine physical
examination. Laboratory culturing of milk
samples for bacteria and Mycoplasma spp.,
and for detennining the antimicrobial sus-
ceptibility of S. aureus (specifically whether
it produces beta-lactamase), is very useful
for instituting optimal treatment protocols
for cows with clinical mastitis and for
instituting appropriate control measures.

Bovine mastitis

However, because subclinical mastitis has
the greatest influence on the cost of mas-
titis to the producer, it is advantageous to
also diagnose subclinical mastitis, on a cow
and quarter level.

Detection of subclinical mastitis

Culturing large numbers of milk samples,
although the gold standard for intra-
mammary infection and subclinical mas-
titis, is expensive and impractical for
routine use. Much attention has therefore
been given to the development of indirect
tests to predict the presence of an intra-
mammary infection. Currently available
indirect tests detect only the presence of
inflammation but are of value as screen-
ing tests; milk from quarters or cows with
a positive screening test are then sub-
mitted to bacteriological culture. Sub-
clinical mastitis can only be detected
by laboratory examination and cannot,
by definition, be detected during the
routine physical examination. In other
words, the secretion from a quarter with
subclinical mastitis appears drinkable.

Detection at the herd level

The prevalence of subclinical mastitis or
intramammary infection is monitored by
determining the bulk tank milk SCC and
the most likely mastitis pathogens are
identified by culturing bulk tank milk.
These two methods are recommended to
diagnose the presence and prevalence of
mastitis pathogens on a herd basis.

Bulk tank milk somatic cell counts
The SCC of bulk tank milk is an indirect
measure of the prevalence of mastitis
within a dairy herd. The SCC is increased
primarily, but not exclusively, because
of subclinical mastitis associated with
Gram-positive bacterial intramammary
infections. There is a good correlation
between the number of streptococci
(S. agalactiae, S. dysgalactiae, and S. uberis)
colony-forming units found in bulk tank
milk and its SCC. The number of colony
forming units (cfu) of S. aureus is moder-
ately correlated to the bulk tank milk
SCC. 46 As contagious mastitis has become
more effectively controlled, environmental
mastitis pathogens have become a relatively
more important cause of high SCC in
bulk tank milk, especially in herds with
moderate (<400 000 cells/mL) to low
(< 150 000 cells/mL) bulk tank milk SCC.

The association between management
practices, dairy herd characteristics and
SCC of bulk tank milk has been examined
in about 60 000 cows in 843 herds over a
2-year period , 47 Results indicated that the
prevalence of S. agalactiae and S. aureus
intramammary infections was associated
with bulk tank SCC. 47 In herds free of
S. agalactiae mastitis, the prevalence of
S. aureus and C. bovis intramammary

; infections were correlated with bulk tank
, SCC. For herds without S. agalactiae, use
| of sawdust bedding was associated with a
j decrease in SCC in bulk tank milk, while
. a dirty loose housing area was associated
: with an increase in SCC in bulk tank milk.

I Increased milk production, repeated mas-
titis control visits and use of particular
predip compounds were significantly
; associated with decreased SCC in bulk
! tank milk in all herds, regardless of
: whether any cows in the herd had
! S. agalactiae mastitis. In herds with
i S. agalactiae mastitis, use of iodine,

: chlorhexidine, peroxide or sodium
; chlorite-lactic acid as a predip was associ-
i ated with a decrease in SCC of bulk tank
I milk. 47

The SCC of bulk tank milk has

i become a widely used test because it
j provides a sensitive and specific indicator
j of udder health and milk quality. The
! sample for analysis is obtained by agitat-
i ing the milk for 5-10 minutes and collect-
1 ing a sample from the top of the bulk tank
milk using a clean dipper. The sample
i should not be collected near the outlet
: valve because this varies from that in the
rest of the tank. The SCC of bulk tank
: milk is widely used to regulate whether
milk may be legally sold and to determine
the price paid for raw milk. Premium and
: penalty payments are calculated on the
i basis of 3-month geometric mean of
j weekly bulk milk tank SCC measure-
I ments. Milk processing plants in most
I developed countries use automatic elec-
tronic somatic cell counters routinely in
order to provide a monthly report of the
bulk tank milk SCC. The test requires only
that the sample for examination be taken
randomly and not frozen, that it be
prepared with the correct reagent, that
the laboratory counter be set at the right
calibration and that the sample be
examined quickly or preserved with
formalin to prevent cell losses during
storage. The bulk tank milk SCC is
extremely useful in creating awareness of
the existence of a mastitis problem, so
that when the SCC of bulk tank milk
exceeds permissible limits further investi-
gation of the herd is indicated. In a
seasonal herd in which all cows are at the
same stage of lactation the bulk milk cell
count will normally be high in early
I lactation and just before drying off. To
I overcome these and other factors that are
j likely to transiently influence bulk tank
| milk SCC, it is recommended that
j correction factors be introduced into the
j estimation or that a rolling SCC, in which
monthly data are averaged for the
j preceding 3 months, be used. Consider-
j ation of this figure will avoid too hasty
j conclusions on one high count caused by
j an extraneous factor.

: -J. : ■ ' ■

Bulk tank milk
somatic cell
count (cells/mL)

Infected
quarters
in herd (%)

hi;.? 'c/

Production
loss (%)

200 000

6

0

500 000

16

6

1 000 000

32

18

1 500 000

48

29

It is not possible to use the bulk tank
; milk SCC to determine the number of
| cows in a herd affected by mastitis but it
■ is possible to estimate fairly accurately the
number of infected quarters. In general,

; as the bulk tank milk SCC increases, the
; prevalence of infection increases and
j losses in production increase. Production
} losses calculated as a percentage of
production expected with a count of
: 200 000 cells/mL are shown in Table 15.1.

! A bulk tank milk SCC of more than
300 000 cells/mL is considered to indicate
| a level of mastitis in the herd that war-
rants examination of individual cows.

i

j Herds with a high bulk tank milk SCC
j have significantly lower production levels
I and are less likely to use a postmilking
; teat dip or to have a regular program of
I milking machine maintenance or auto-
! matic cluster removal. 46

! Culture of bulk tank milk
| Bacteria present in bulk tank milk may
| originate from infected udders, from teat
and udder surfaces or from a variety of
other environmental sources; however,
despite the large number of potential
sources for bacteria, culture of bulk tank
milk is a useful technique for screening
for major mastitis pathogens. 48 The
culture of S. aureus and S. agalactiae from
bulk tank milk is a reliable indicator of
infection by those pathogens in the herd.
The number of those pathogens found on
culture is determined by the number of
bacteria shed, the number of infected
cows, the milk production level of infected
cows relative to herd mates, and the
severity of infection. A single culture of
bulk tank milk has low sensitivity but
high specificity for determining the
presence of S. agalactiae or S. aureus in the
herd. Thus many infected herds will be
called negative but few uninfected herds
will be called positive. Pathogens such as
Nocardia spp. and Mycoplasma spp. have
also been identified by culture of bulk
tank milk. In general, the sensitivity of a
single bulk tank milk culture to detect the
presence of intramammary infections due
to S. agalactiae ranges from 21-77%, for
S. aureus it ranges from 9-58% and for
M. bovis it is 33%.

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

Environmental bacteria such as S. uberis,
S. dysgalactiae, and coliforms may enter
milk from intramammary infections, but
also from nonspecific contamination. The
presence of these organisms in bulk tank
milk may relate to the general level of
environmental contamination and milking
hygiene in the herd. Udder infections with
these environmental pathogens are pre-
dominantly of short duration and charac-
terized by clinical disease, which makes
their inadvertent introduction to the bulk
tank less likely.

String sampling or milk line sampling
from the positive pressure side of the
milking system is the collection of milk
samples from a group of cattle instead of
the entire herd, as in bulk tank milk
sampling. String sampling may have
some merit in identifying subgroups of
cattle with the highest prevalence of
infection. String sampling is thought to be
more sensitive in monitoring herds for
contagious pathogens than bulk tank
milk sampling. If a production group tests
positive on a string culture, then indivi-
dual composite milk cultures can be
performed to identify individual animals.
Information of the culture results from
string sampling should assist development
of control programs; however, milk samples
left in the pipeline from one string can
confound the culture results of subsequent
strings.

Numerous bacteriological techniques
have been used to isolate and identify
pathogens in bulk tank milk but none has
been established as the gold standard
method for the culture of milk from bulk
tanks. The most suitable laboratory
medium for growth and classification of
the pathogens from bulk tank milk needs
to be assessed. Sampling strategies have
included weekly and monthly samples,
but it remains to be determined which
strategy is optimal relative to herd size
and management, disease characteristics
and practicality.

Culture of bulk tank milk has been
compared to bulk tank SCC, herd
summaries of SCC of individual cows and
herd summaries of cultures of individual
cows. 48 A significant correlation was found
between bulk tank SCC and the frequency
of isolating S. agalactiae from monthly
samples of bulk tank milk. The correlations
between S. aureus from bulk tank milk
and SCC are lower.

Detection at the individual cow level
Abnormalities of the udder and gross
abnormalities of milk in cattle with
clinical mastitis have been described
above under clinical findings. In indivi-
dual cows with clinical mastitis, culture of
the secretion from an infected quarter can
be done. In animals without clinical mas-

titis, culture of the secretion represents a
direct test for subclinical mastitis. The
objective is to identify cows with contagious
mastitis so that they can be treated or
culled, or to identify the nature and source
of environmental mastitis pathogens.
Fulfillment of these requirements requires
bacteriological culture of milk samples
so that the pathogens can be named;
identification of mastitis pathogens is
central to the development of effective
treatment and control programs. Detec-
tion of infected cows requires an indivi-
dual cow examination and application of
an indirect (screening) test for infection,
such as the SCC of a composite milk
sample, followed by culture of a represen-
tative subset of cows in order to deter-
mine the most prevalent pathogen.
Indirect tests estimate the prevalence
of infection and microbiological exam-
ination identifies the mastitis pathogens;
from this information an appropriate
control plan can be formulated.

Culture of individual cow milk
Individual cow milk can be cultured as
part of a herd examination for mastitis, or
on individual quarter samples, or on
composite samples including milk from
all four quarters. An intramammaxy infec-
tion is defined as the presence of the same
pathogen in duplicate samples collected
immediately after each other, or the
presence of the same pathogen in two of
three consecutive cultures obtained on
different sampling dates. Individual
quarter samples are preferred because
the costs of treatment dictate that the
least possible number of quarters be
treated. With this technique only affected
quarters are treated; if the quarter infec-
tion rate is low the saving in treatment
costs is relatively large.

Milk sampling for culture must be
carried out with due attention to cleanli-
ness since samples contaminated during
collection are worthless. The technique of
cleaning the teat is of considerable
importance. If the teats are dirty, they
must be washed and then properly dried
or water will run down the teat to the teat
end and infect the milk sample. The end
of the teat is cleaned with a swab dipped
in 70% alcohol, extruding the external
sphincter by pressure to insure that dirt
and wax are removed from the orifice.
Brisk rubbing is advisable, especially of
teats with inverted ends. The first two or
three streams are rejected because their
cell and bacterial counts are likely to be a
reflection of the disease situation within
the teat rather than within the udder as a
whole. The next few streams, the premilking
sample, is the approved one because of its
greater accuracy. For complete accuracy a
premilking and a postmilking sample are

taken. If tuberculosis is suspected, the last
few streams are the critical ones. Indirect
and chemical tests for mastitis can be
carried out as accurately on foremilk as on
later milk.

If individual quarter samples are
collected, screw-cap vials are most satis-
factory. During collection the vial is held
at an angle to the ground in order to avoid
as far as possible the entrance of dust,
skin scales and hair. If there is delay
between the collection of samples and
laboratory examinations, the specimens
should be refrigerated or frozen. Freezing
of milk samples appears to have variable
effects on bacterial counts, depending on
the bacteria. A. pyogenes and E. coli counts
are decreased by freezing, coagulase-
negative Staphylococcus spp. counts are
increased, and Streptococcus and S. aureus
counts are either unaffected or increased
by about 200%. 49

The laboratory techniques used vary
widely and depend to a large extent on
the facilities available. Incubation on
blood agar is most satisfactory, selective
media for S. agalactiae having the dis-
advantage that other pathogens may go
undetected. Smears of incubated milk are
generally unsatisfactory as not all bacteria
grow equally well in milk. An augmented
system of culturing milk samples, which
has given superior results in terms of the
number of infected quarters detected,
includes preculture incubation, then
freezing of the milk sample, then inocu-
lation of the medium with a larger than
normal inoculum of milk. 50 The concern
with augmented culture systems is that
they may amplify contaminants obtained
during sampling and therefore decrease
the specificity of milk culture. Laboratory
culturing techniques can be very time-
consuming and expensive unless modern,
prepackaged identification systems are
used. They also provide the speed needed
to make the examination a worthwhile one.

A milk sample is considered contami-
nated when more than three species of
bacteria are isolated. A quarter is con-
sidered to be infected when the same
bacteria is isolated in at least two out of
three milk samples. A quarter is considered
to be cured when bacteria, isolated at
drying off, are not present in any samples
28 days after calving. An uninfected
quarter at drying off that is infected at
calving is considered to indicate a new
intramammary infection. A quarter that is
infected at drying off but infected with
another bacteria at calving also indicates a
new intramammary infection.

Selective culture plates, such as biplates
(MacConkey agar and blood agar with
1% esculin), triplates (MacConkey agar,
blood agar and TKT agar (thallium, crystal
violet and staphylococcal toxin in 5%

blood agar with 1% esculin)), Petrifilm®
plates, which are selective culture media
products, 51 the MASTiK® diagnostic kit
or the ColiMast® test can be used to
differentiate between Gram-positive
and Gram- negative pathogens and no
growth, 52 and may aid in the rational and
targeted use of antimicrobial agents for
clinical cases of mastitis. A commercially
available cowside test for endotoxin
(Limast-test®) is available in Scandinavia.
The test takes 15 minutes to run on milk
samples and is able to detect the presence
of endotoxin using the Limulus amebocyte
lysate assay. The test therefore can detect
the presence or absence of Gram-nega-
tive bacteria but does not differentiate
between E. coli and K. pneumoniae . 53 At
least 10 4 -10 5 cfu of Gram-negative bacteria
are necessary for a positive test result; this
does not decrease the clinical utility of the
test, because low bacterial counts in the
milk from infected quarters usually
indicates that antimicrobial agents are not
required in order to clear the infection.

There is interest in developing other
cowside tests to determine whether the
causative pathogen is Gram- negative or
Gram-positive. One such approach uses
dilution of the milk sample, filtration
through a membrane with a pore size that
retains bacteria, and staining of the
bacteria with specific stains. 54 The filtration
procedure reportedly takes 5 minutes, but
the need for microscopic examination de-
creases the utility of this as a cowside test.

A common diagnostic problem is a
bacteriologically negative culture in cows
with clinical mastitis. Even when milk
samples are collected appropriately and
bacteriological culture is done using
routine laboratory methods, 15-40% of
samples from clinical mastitis episodes
are bacteriologically negative (yield no
growth) . Failure of these samples to yield
a mastitis pathogen may be the result of
spontaneous elimination of infection, a
low concentration of pathogens in the
milk, intermittent shedding of the patho-
gen, intracellular location of the pathogens
or the presence of inhibitory substances
in the milk. Augmented culture techniques
may reduce, but do not eliminate negative
culture results and may facilitate growth
of contaminant organisms. Dairy producers
and veterinarians therefore face a dilemma
when no bacteria or bacteria commonly
regarded to be of minor pathogenicity,
such as C. bovis or coagulase-negative
Staphylococcus spp., are cultured from the
milk of cows with clinical mastitis,
particularly if clinical signs persist. 55 Most
bacteriologically negative cases of clinical
mastitis appear to be caused by low-grade
infections with Gram-negative bacteria. 55
When no bacterial pathogen can be isolated
from cases of clinical mastitis using

Bovine mastitis

6

standard culture . techniques, enzyme-
linked immunosorbent assays (ELISAs)
may be used to detect antigens against
S. aureus, E. coli, S. dysgalactiae, and
S. agalactiae. 56 Antigens to these pathogens
may be detectable using an ELISA in up
to 50% of quarter samples from cows with
clinical mastitis in which no pathogens
were isolated but in which the SCC was
more than 500 000 cells/mL. Despite these
promising findings, ELISAs are not widely
used in the identification of mastitis
pathogens.

Indirect tests for subdinical mastitis

Indirect tests include SCCs using auto-
mated electronic counters, the California
Mastitis Test, increases in electrical
conductivity of milk, and increases in the
activity of cell associated enzymes (such as
NAGase) in milk. ELISA tests to detect
neutrophil components have been
developed but are not commercially
available 57 Of these indirect tests, only the
CMT and electrical conductivity can
be used cowside, with CMT providing a
more accurate screening test than electrical
conductivity.

The somatic cell count of composite or
quarter samples

There is a strong relationship between the
SCC of quarter samples of milk and the
milk yield, with SCC increasing slightly as
milk production decreases but increasing
markedly with intramammary infection of
the quarter. The distribution of SCC in a
herd therefore reflects the distribution
of intramammary infections. The most
important factor affecting SCC in an
individual cow is the number of quarters
infected with a major or minor pathogen.
In most herds, the prevalence of infection
will increase through a lactation and will
also increase with the age of the cow. Cell
counts in the first few days of the lactation
are often exceptionally high and unreliable
as indicators of intramammary infection,
and in uninfected cows the counts will
drop to a low level within 2 weeks of
calving and remain low throughout the
lactation unless an intramammary infec-
tion occurs. The SCC of a cow that remains
free of infection throughout her life will
remain very low. However, older cows
may have higher counts because the
prevalence of infection is higher with age
and older cows are more likely to have
had previous infections with residual
lesions and leaking of somatic cells into
the milk. There are also consistent and
significant differences in actual SCC
between cows, individual cows tending
to maintain the same class of count
throughout their lives. Cows that have
consistently low SCC do not seem to be
more susceptible to mastitis than others.
Attempts to base a breeding program to

reduce the prevalence of mastitis on the
selection of cows with an innately low
composite SCC have been discarded
because of fluctuations in numbers within
cows.

Healthy quarters have a SCC below
100 000 cells/mL, and this cutpoint should
be used to indicate the absence or pre-
sence of intramammary infection on a
gland basis. This cutpoint looks very solid
for a gland, because many milk components
differ from normal \®lues whenever the
SCC exceeds 100 000 cells/mL. Moreover,
mean SCC counts for bacteriologically
negative quarters, quarters infected with
minor pathogens and quarters infected
with major pathogens were 68 000,
130 000, and more than 350 000 cells/mL,
respectively. 58

Because of the time and labor saved it
is now customary to do automated
electronic cell counts on composite milk
samples that have already been collected
for butterfat testing. Regular reports of
individual cow SCCs are therefore widely
available in herds that routinely test
production parameters of their cattle. An
exciting new development in mastitis
control is the portable somatic cell
counter, which was designed for on farm
use, thereby providing targeted and
immediate SCC information for quarter
or composite milk samples. Using the
composite sample technique does distort
the SCC; for example, the dilution of
high-SCC milk from a bad quarter by
low-SCC milk from three normal quarters
could mean that a cow with one infected
quarter might not be detected. Composite
SCCs of less than 200 000 cells/mL are
considered to be below the limit indi-
cative of inflammation, even though
uninfected quarters have a SCC of less
than 100 000 cells/mL. Factors that affect
the composite milk SCC include the
number. of infected quarters infected, the
kind of infection (S. agalactiae is a more
potent stimulator of cellular reaction than
S. aureus), the strictness with which milk
from cows with clinical mastitis is kept
out of the bulk tank, the age of the cows
(older cows have higher counts), the stage
of lactation (counts are highest in the first
days after calving and toward the end of
lactation) and the herd's average pro-
duction, the cell count reducing as milk
yield increases. 59

A SCC scoring system that divides the
SCC of composite milk into 10 categories
from 0-9, known as linear score, is
becoming more widely used. The linear
score is a base 2 logarithm of the SCC
(in cells/mL), whereby linear score =
log 2 (SCC/100 000) + 3. Likewise, to
calculate SCC (in cells/mL) from the
linear score (LS), the following formula is
used: SCC = 100 000 x 2 (LS ' 3) . A SCC of

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

100 000 cells/mL therefore converts to a
score of 3. Each 1-unit increase (or
decrease) in linear score is associated with
a doubling (or halving) of the SCC. For
example, score 2 is equivalent to a SCC of
50 000 cells/mL, and scores of 4 and 5
correspond to 200 000 and 400 000 cells/
mL. Conversion of SCC to linear score
values is performed as shown in Tables
15.3 and 15.4. The principal reason for
using the linear score is to achieve
properties that are required in order to
use conventional statistical methods:
mean equal to median, normal distribution
and uniform variance amongst samples
within lactation, amongst cows within
herd or among daughters within sire.

The proportion of neutrophils in
the SCC is very low (< 11 %) in healthy
quarters but is markedly increased in
quarters with intramammary infection (to
> 90%) . Accordingly, the percentage of
neutrophils in the SCC may provide a
useful indication of intramammary infec-
tion, but is not currently performed 08

Somatic cell counts can also be deter-
mined for colostrum, where they are
useful in indicating the presence of intra-
mammary infection (Table 15.2). 60

The California Mastitis Test of quarter
samples

The CMT is the most reliable and
inexpensive cowside test for detecting
subclinical mastitis. The CMT is also
known as the Rapid Mastitis test, Schalm
test or Mastitis-N-K test, was developed
in 1957 and constituted a modification of

Example: SCC = 200 000 cells/mL

a. Divide the SCC by 100 000 cells/mL
(200 000/100 000 = 2 )

b. Determine the natural log (In) of the
results of step 1 (In 2 = 0.693)

c. Divide this value by 0.693
(i.e. 0.693/0.693 = 1)

d. Add 3 to the result of step c = 1 + 3 =
4 linear score

the Whiteside test. The CMT reagent con-
tains a detergent that reacts with DNA of
cell nuclei, and a pH indicator (bromcresol
purple) that changes color when the milk
pH is increased above its normal value of
approximately 6.6 (mastitis increases pH to
6.8 or above). The CMT is mixed with
quarter milk samples that have been
previously collected into a white con- j
tainer and the sample is gently swirled; j
the result is read within 15 seconds as a ;
negative, trace, 1, 2, or 3 reaction depend- |
ing on the amount of gel fonnation in the ;
sample. Maximum gel formation actually !
occurs from 1-2.5 minutes, depending on j
the quarter SCC and continued swirling |
of the mixture after the time of peak i
viscosity produces an irreversible de-
crease in viscosity. 61 Cows in the first
week after calving or in the last stages of I
lactation may give a strong positive :
reaction.

The close relationship between the
CMT reaction and the SCC of milk and

the reduced productivity of affected cows
is shown in Table 15.4. If the CMT is used
to minimize the false negative rate
(produce the highest sensitivity), then the
test should be read as negative (CMT =
negative) or positive (CMT = trace, 1, 2 or
3). If the CMT is used to minimize the
false-positive rate (produce the highest
specificity) for culling decisions, then the
test should be read as negative (CMT =
negative or trace) or positive (CMT = 1, 2
or 3).

CMT scores can also be determined for
colostrum, where the score is useful in
indicating the presence of intramammary
infection (Table 15.2). The equivalent SCC
for CMT scores of negative or trace are
different for colostrum and milk, but the
SCC for CMT scores of 1, 2 and 3 are
similar for colostrum and milk. 62

The NAGase test of composite or
quarter samples

The NAGase test is based on the
measurement of a cell-associated enzyme
(N-acetyl-(3-D-glucosaminidase) in the
milk, a high enzyme activity indicating a
high cell count. NAGase is an intracellular
lysosomal enzyme derived primarily from
neutrophils but also from damaged
epithelial cells. The test is suited to the
rapid handlingof large numbersof samples
because of the ease of its automation, and
the test can be done on fresh milk and
read on the same day. 63 However, because
most of the NAGase activity is intracellular,
samples should be frozen and thawed
before analysis to induce maximal

1 1 . ■

Test result

Reaction observed

Equivalent milk SCC

Equivalent linear score

Colostrum geometric mean SCC

Negative

The mixture remains fluid
without thickening or gel
formation

0-200 000 cells/mL

0-4

500 000 cells/mL

Trace

A slight slime formation is
observed. This reaction is most
noticeable when the paddle is
rocked from side to side

150 000-500 000 cells/mL

5

670 000 cells/mL

1 +

Distinct slime formation occurs
immediately after mixing solutions.
This slime may dissipate over time.
When the paddle is swirled, fluid
neitherforms a peripheral mass nor
does the surface of solution become
convex or 'domed up'

400 000-1 500 000 cells/mL

6

890 000 cells/mL

2+

Distinct slime formation occurs
immediately after mixing solutions.
When the paddle is swirled the fluid
forms a peripheral mass and the
bottom of the cup is exposed

800 000-5 000 000 cells/mL

7-8

3 400 000 cells/mL

3+

Distinct slime formation occurs
immediately after mixing solutions.
This slime may dissipate over time.
When the paddle is swirled the
surface of the solution becomes
convex or 'domed up'

> 5 000 000 cells/mL

■ f '

9

6 260 000 cells/mL

1 Ibil/E .Oil : ;r"f5 r '*

Linear score

Somatic cell count
midpoint (cells/mL)

Pounds of milk lost per lactation
First Second

0

12 500

0

0

1

25 000

0

0

2

50 000

0

0

3

100 000

200

400

4

200 000

400

800

5

400 000

600

1200

6

800 000

800

1600

7

1 600 000

1000

2000

8

3 200 000

1200

2400

9

6 400 000

1400

2800

NAGase activity. 58 The NAGase test is
reputed to be the most accurate of the
indirect tests and as good as SCC in
predicting the infected status of a quarter.
The NAGase test uses a less sophisticated
reading instrument than the average
automatic cell counter. If all tests are
available it is best to consider the NAGase
test and SCC as complementary tests and
carry out both of them. Milk NAGase
levels are high at the beginning and the
end of lactation, as with cell counts. The
test has also been validated for use with
goat milk.

Electrical conductivity tests of quarter
samples

A test that has received a lot of attention
because it can be used in robotic milking
systems is based on the increase in
concentration of sodium and chloride
ions, and the consequent increase in
electrical conductivity, in mastitic milk. 64
The electrolyte changes in milk are the
first to occur in mastitis and the test has
attractions for this reason. A number of
factors affect these characteristics, how-
ever, and to derive much benefit from the
test it is necessary to examine all quarters
and use differences between the quarters
to indicate affected quarters. For greater
accuracy all quarters need to be monitored
each day. An experimental unit that takes
all these factors into consideration has
been fitted to a milking machine and, by a
computer-prepared analysis, monitors
variations in electrical conductivity in
each quarter every day. 65 Electrical con-
ductivity is attractive as a test because it
measures actual injury to the udder rather
than the cow's response to the damage, as
SCC and NAGase activity do. 66 However,
a meta-analysis indicated that using an
absolute threshold for conductance did
not provide a suitable screening test, as
both sensitivity and specificity were
unacceptably low. 67 The use of differential
conductivity (within cow quarter com-
parison) results in improvement in test
sensitivity and specificity, and is currently

the only recommended application of this
indirect test. 58,68

The most commonly promoted method
for measuring electrical conductivity is a
hand-held device with a built-in cup into
which milk is squirted (foremilk is pre-
ferred). Experimentally induced clinical
mastitis due to S. aureus and S. uberis was
detectable by changes in electrical con-
ductivity of foremilk: 90% of cases were
detectable when clots first appeared and
55% of cases were detectable up to two
milkings prior to the appearance of clots. 64
This suggests that clinical mastitis associ-
ated with these two major pathogens may
be able to be detected earlier by electrical
conductivity than by waiting for milkers
to detect visible changes in the milk.

Comparison of indirect methods
The effects of subclinical intra mammary
infection on several parameters in foremilk
from individual quarter milk samples
have been compared. 62 Somatic cell count,
electrical conductivity, pH, NAGase activity
and the concentrations of sodium, pot-
assium, lactose and alpha-l-antitrypsin
were measured from individual quarters.
Somatic cell count, NAGase activity,
electrical conductivity and concentrations
of sodium, alpha-l-antitrypsin and lactose
were all useful indirect indicators of infec-
tion. The SCC was better able to discri-
minate between infected and uninfected
quarters and cows than were the electrical
conductivity, pH and NAGase activity.

Hematology and serum biochemistry

In severe clinical mastitis there may be
marked changes in the leukocyte count,
packed cell volume and serum creatinine
and urea nitrogen concentration because
of the effects of severe infection and
toxemia. 69 In particular, clinical mastitis
episodes associated with Gram-negative
bacteria frequently cause a profound
leukopenia, neutropenia, lymphopenia
and monocytopenia as a result of the
endotoxemia. as well an increased packed
cell volume. 70 In contrast, the leukogram
in cattle with clinical mastitis associated

Bovine mastitis

: with Gram- positive bacteria is normal or
mildly increased.

Ultrasonography of the mammary
gland

Two-dimensional ultrasonographic images
of the gland cistern, parenchymal tissue
and teat are easily obtained using a 5, 7.5/
: or 8.5 MHz linear array transducer, and
; ultrasonography is becoming more widely
used to guide treatment of teat and gland
cistern abnormalities. However, there are
; few reports of the use of ultrasonography
; to diagnose or prognose clinical mastitis
: episodes, although this is likely to be a
; fruitful area for investigation.

The best two-dimensional images of
I the udder parenchyma are obtained by
\ clipping the hair on the udder and apply-
ing a coupling gel. This minimizes air
between the transducer face and skin.
Imaging the normal adjacent quarter is
very helpful in identifying abnormalities,
j Imaging should be performed in two
planes, sagittal to the teat (and therefore
perpendicular to the ground), and trans-
verse to the teat (and therefore horizontal
to the ground). The injection of sterile
0.9% NaCl through a teat cannula into
the gland provides a practical contrast
agent that can help further define the
extent of any abnormalities. The superficial
superinammary lymph nodes can be
ultrasounded using a 7.5 MHz linear
transducer, with the lymph node being
j well demarcated from the surrounding
j tissues. Mean lymph node length was
| 7.4 cm (range 3.5-15.0 cm) and mean
j depth was 2.5 cm (range, 1.2-5. 7 cm),
j Lymph node size increased with age but
j was not correlated with SCC. 71
j Mastitis produces an increased hetero-
j geneous echogenicity to the milk in the
gland cistern, compared to an uninfected
quarter. It is important to make this
visual comparison without altering the con-
trast and brightness setting on the ultra-
sonographic unit. 72

Three-dimensional ultrasonography of
the bovine mammary gland and teat has
recently been evaluated 73 and has many
promising applications.

Biopsy of mammary tissue

A biopsy of mammary tissue can be used
for histological and biochemical evaluation
in research studies. The use of a rotating
stainless steel cannula with a retractable
blade at the cutting edge has been
: described for obtaining biopsy material
from cows. 74 Despite some postoperative
bleeding, milk yield and composition
in the biopsied gland were affected only
transiently.

NECROPSY FINDINGS

Necropsy findings are not of major interest
in the diagnosis of mastitis and are

688

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

omitted here but included in the descrip-
tion of specific infections.

DIFFERENTIAL DIAGNOSIS

The diagnosis of clinical mastitis is not
difficult if a careful clinical examination of
the udder is carried out as part of the
complete examination of a cow with
systemic clinical findings. Examination of
the udder is sometimes omitted in a
recumbent animal only for severe mastitis
to be discovered later. The diagnosis of
mastitis depends largely upon the
detection of clinical abnormalities of the
udder and gross abnormalities of the milk
or the use of an indirect test like the CMT
to detect subclinical mastitis.

Other mammary abnormalities that must
be differentiated from clinical mastitis
include periparturient edema, rupture
of the suspensory ligament, and
hematoma. These are not accompanied
by abnormalities of the milk unless there is
hemorrhage into the udder. The presence
of stray voltage in the milking plant should
not be overlooked in herds where the
sudden lowering of production arouses an
unfounded suspicion of mastitis.
Differentiation of the different causes of
mastitis is difficult on the basis of clinical
findings alone but must be attempted,
especially in peracute cases where specific
treatment must be given before results of
laboratory examinations are available. A
pretreatment sample of milk from the
affected glands for culture and
antimicrobial sensitivity may provide useful
information about the health record of the
cow and the need to consider alternative
therapies, and could provide information
on new infections in the herd.

TREATMENT

The treatment of the different causes of
clinical and subclinical mastitis may require
specific protocols, which are described
under specific mastitis pathogens later in
the chapter. The general principles of
mastitis treatment are outlined here.

Historical aspects of antimicrobial
therapy for clinical and subclinical
mastitis

Between about 1950 and 1990, on a world-
wide basis, all forms of both clinical and
subclinical bovine mastitis were treated
with a wide variety of antimicrobial
agents either by intramammary infusions
or parenterally, and commonly by both ■
routes in acute and peracute cases. Most
veterinarians treated clinical mastitis and
evaluated the response on the basis of
clinical outcome. In general, it was believed
that antimicrobial agents were effective
for the treatment of clinical and sub-
clinical mastitis in lactating cows. How-
ever, there are very few scientific
publications based on randomized clinical
trials in which the efficacy of intra-
mammary antimicrobial agents for treat-

ment of clinical mastitis was compared to
untreated controls. If antimicrobial agents
were used and the animal recovered, it
was assumed that treatment was effica-
cious. If the cow did not respond favorably,
several reasons were usually enumerated
for the treatment failure. However, most
of these reasons, while biologically attract-
ive, are hypothetical and have not been
substantiated scientifically. Gradually,
over the years, veterinarians began to
doubt the efficacy of antimicrobial agents
for the treatment of all cases of clinical
mastitis. In addition, and of major import-
ance, milk from treated cows had to be
discarded for up to several days after the
last day of treatment because of anti-
microbial residues; this was a major
expense. Currently, optimized treatment
strategies focus on efficacy, economics,
animal welfare aspects and the milk
withhold time of antimicrobial treatment.

Efficacy is assessed on the basis of
clinical cure or bacteriological cure.
Most producers are interested in the
return to normal milk (clinical cure) and
are much less interested in the return to a
sterile quarter (bacteriological cure).
Because clinical mastitis is defined as
abnormal milk, the return to normal
('drinkable') milk represents a clinical
cure. Bacteriological cure represents the
inability to isolate the initial pathogen
14-28 days after the start of treatment.
Other important indicators of efficacy are
milk production, dry matter intake, the
amount of saleable milk and mortality or
culling rates after treatment.

Some examples of the efficacy or
inefficacy of antimicrobial agents illustrate
the controversy. It is well accepted that
the cure rate following intramammary
treatment of clinical or subclinical mastitis
due to S. agalactiae in the lactating cow is
high (80-90%). In contrast, the cure rate
of clinical and subclinical mastitis due to
S. aureus in the lactating cow is con-
siderably lower (40-50%), but certainly
not 0%. In herds with a low prevalence of
contagious mastitis, most cases of mild
clinical mastitis (abnormal secretion only)
in lactating cows are due to environmental
streptococci and coliforms and may
recover without antimicrobial therapy,
although antimicrobial administration
increases the clinical and bacteriological
cure rate. Antimicrobial agents may be
ineffective for the treatment of clinical mas-
titis associated with M. bovis, A. pyogenes,

\ Nocardia spp., and P. aeruginosa.

In the 1970s dairy processing plants,

| veterinarians, consumer advocates, public
: health authorities and milk-quality
| regulating agencies began to express
i concern about antimicrobial residues in
! milk from cows treated for mastitis. The
public health and milk industry concerns

about residues combined with the contro-
versy about the efficacy of antimicrobial
agents for clinical mastitis has also pro-
vided a stimulus to evaluate the efficacy
and consequences of using antimicrobial
agents. Since the early 1990s much
emphasis has been placed on alternative
methods of treating clinical mastitis,
leading to a reduction in the use of
antimicrobial agents during the lactating
period. 75 Such strategies have been
defended based on a lack of information
concerning the efficacy and economics of
antimicrobial therapy associated with
pathogens other than S. agalactiae, and
by the need to reduce the risk of residue
violation. However, a recent study con-
cluded that not administering antibiotics
to cows with clinical mastitis was imprud-
ent and unethical. 76

There is a need for randomized con-
trolled field trials to evaluate the use of
antimicrobial agents for the treatment of
clinical mastitis; the design for such trials
and the statistical analysis required have
been reviewed 77 Well conducted clinical
mastitis treatment trials represent an
invaluable, although difficult and expen-
sive, effort to evaluate efficacy of anti-
microbial agents under field conditions.
The use of intramammaiy antimicrobial
agents for the treatment of clinical mastitis
in lactating cows in 40 dairy herds over
4 years found an economic benefit com-
pared to nonmedicated controls. 78 In the
antimicrobial-treated group, the number of
pathogens in the milk following treatment
was reduced, the number of quarters
returning to normal milk was increased,
and the number of cured quarters was
increased. In should be noted that the use
of antimicrobial agents for the treatment of
subclinical mastitis at the end of
lactation, known as dry cow therapy, is
accepted worldwide and is based on
scientific evidence using randomized
clinical trials. Dry cow therapy is one of the
principles applied in the effective control of
bovine mastitis, in which much progress
has been made since the early 1970s.

Treatment strategy

The treatment strategy will depend on
whether the mastitis is clinical or sub-
clinical, and the health status of the herd,
including its mastitis history. Clinical
mastitis is further categorized as abnormal
milk, abnormal gland or abnormal cow,
as described under Diagnosis. If treat-
ment is indicated, the major decision is
whether to administer antimicrobial agents
parenterally or by intramammaiy infusion.

An important aspect of treatment is
the accurate positive identification of the
animal(s) to be treated, the recording
of the relevant clinical and laboratory
information, and the treatments being

Bovine mastitis

used, and monitoring the response. Use-
ful information would include:

o Cow identification
o Quarters affected
o Date of mastitis event
0 Lactation number
c Date of calving
<j Identification of pathogen(s)
o Treatment used, including dose, route
and duration

» Milk withholding time and time when
returned to the milking string
o Most recent level of milk production.

Options for treating cows with clinical
mastitis include treating all cows with
antimicrobial agents, treating none of the
cows with antimicrobial agents or treating
only specific cows with antimicrobial
agents. 79 Treating all cows results in
increased costs for those cows with
clinical mastitis associated with patho-
gens not susceptible to the antimicrobial
agent used, especially if the signs are
likely to resolve before the milk with-
holding period has expired. Treatment of
all cows is also associated with increased
risk of violative residues in the bulk milk.
Treating none of the cows with anti-
microbial agents has animal welfare
implications, in that an effective treat-
ment is not administered to some cattle
with clinical mastitis, and nontreatment
allows Gram-positive pathogens to persist,
increasing the probability of a recurrence
of clinical mastitis or causing a herd
epidemic of mastitis. Accordingly, non-
treatment of all cases of mastitis is not a
viable option. Treating only specific cows
with antimicrobial agents requires an
accurate method of determining which
animals should be treated. However, clinical
judgment and predictive models are too
inaccurate to distinguish between clinical
mastitis associated with Gram-negative
and Gram-positive pathogens. 79 To select
cows for antimicrobial therapy on the basis
of bacteriological culture is costly and delays
treatment; clinical judgment would still be
necessary because bacteria are not isolated
from 15-40% of milk samples from cows
with clinical mastitis.

Veterinarians should always ask and
answer four questions related to anti-
microbial therapy in bovine mastitis:

Is antimicrobial therapy indicated?

' Which route of administration
(intramammary, parenteral or both)
should be used?

Which antimicrobial agent should be
administered?

J What should be the frequency and
duration of treatment?

Is antimicrobial therapy indicated?

The first decision is whether to treat a
particular case with antimicrobial agents

and whether supportive therapy is
required. Therapy decisions should be
made in context with the overall objec-
tives of the lactating cow treatment
protocol. The availability of approved,
effective treatment products is an essen-
tial component of the program. A number
of factors are important in determining
which cases of mastitis should be treated
during lactation. These factors include the
type of pathogen involved, the type and
severity of the inflammatory response, the
duration of infection, the stage of lacta-
tion, and the age and pregnancy status of
the cow.

Type of pathogen involved
There are marked differences in the
bacteriological cure rates of the various
major mastitis pathogens after therapy
during lactation. The outcome of treat-
ment during lactation is poor for cases of
S. aureus mastitis. On the other hand,

S. agalactiae responds extremely well to
lactating cow therapy and all infected
cows should be treated. Cases of mastitis
associated with environmental organ-
isms have reasonable, but variable, cure
rates.

Type and severity of the inflammatory
response

The predominant type of inflammatory
process involved influences the objectives
of the therapy program. Herds with
clinical mastitis problems will aim at
reducing clinical signs, returning the milk
to saleable quality and avoiding residue
violations. Herds with a predominance of
subclinical mastitis are concerned with
avoiding the spread of infection and
reducing the prevalence of the major
pathogens involved. Both types of herd
have the primary objective of restoring
the production potential.

The severity of the inflammatory
response is also important in the selection
of cases for mastitis therapy during
lactation. Heat, pain and swelling of the
quarter (abnormal gland) are clinical
signs that indicate the need for anti- j
microbial therapy. Many producers, how- j
ever, will treat any cow that shows clots in j
the milk (abnormal milk). There are no j
reports to verify that treatment of cows j
exhibiting abnonnal milk only is efficacious j
and economically justifiable, although it is
probable that treatment of clinical
mastitis episodes of abnormal milk but
normal gland due to S. agalactiae
is efficacious and economic. Treatment
success is lower in cows with high
NAGase concentrations in milk compared
to low NAGase concentrations. 80

Duration of infection

For the contagious organisms, especially
S. aureus, the duration of infection is an

important determinant of its susceptibility
to therapy during lactation. In chronic S.
aureus mastitis, the organism survives
intracellularly in leukocytes, becomes
walled-off in small abscesses of mam-
mary ducts, and has the ability to exist in
the L-form state. At this point S. aureus is
virtually incurable during lactation. With
new methods of automated detection of
subclinical intramammary infection such
as in-line electrical conductivity measure-
ment, new infections may be detected
much earlier. The cure rate of S. aureus
during lactation needs to be re-evaluated
when treatment is administered early in
the course of infection.

Stage of lactation

The stage of lactation is an important
determinant of the benefit:cost ratio of
mastitis therapy during lactation. It may
be uneconomical to treat even cases with
a high probability of cure during late
lactation.

Age and pregnancy status of cow
The probability of a cure is greater in
young cows, and age should be con-
sidered in selecting cases for mastitis
therapy during lactation. 80 The economic
aspects of treatment for late-lactation,
nonpregnant cows are obviously different
from those for midlactation pregnant
cows.

A mastitis therapy program for
lactating cows should be based on a
complete understanding of the mastitis
status of the herd, and individual cow
treatment decisions should be consistent
with the overall herd mastitis therapy
program. A record system for treatment
should be established so that it is possible
to monitor the efficacy of the mastitis
treatment program.

The udder health status in a particular
herd will determine whether the lactating
cow mastitis therapy strategy should be
targeted at the individual cow level or at
the herd level. The level of emphasis
should clearly reflect the objectives of the
therapy program. For example, a herd
with low bulk tank milk SCC and sporadic
cases of environmental mastitis should
target the lactating cow therapy strategy
at the cow level. The primary objectives
would be to alleviate clinical signs, to
achieve a bacteriological cure and to
restore the cow's production. On the
other hand, a herd with moderate to high
bulk tank milk SCCs and a significant
prevalence of contagious organisms
| should aim the program at the herd level,
j In this case, the objective would be to
j limit the spread of infection, markedly
1 reduce or eradicate a specific pathogen
j and increase herd production. A clear state-
] ment of treatment philosophy (individual
j cow level or herd level) in a particular

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

herd is needed to direct establishment of ;
well defined treatment protocols for j
mastitis in lactating cows.

Intramammary infection (mastitis) is :
identified by the presence of clinical signs i
or the results of a direct test (culture of :
milk) or indirect tests such as SCC, CMT
or electrical conductivity. The detection of !
clinical or subclinical mastitis does not
necessarily indicate that therapy should
be administered, although animal welfare ,
issues dictate that treatment must be
administered to cattle with an abnormal
gland or systemic signs (abnormal cow) I
because these animals are undergoing pain
and discomfort. A decision to use treatment
during lactation should be based on the I
likelihood of achieving the objectives of j
the therapy program. Several factors are j
important in the selection of cows for i
treatment. These factors can significantly !
influence the cure rate achieved with j
therapy, or the economic benefit realized. j

The herd history of udder health will j
indicate the probable cause of clinical (
mastitis. Cows with mild cases of clinical
mastitis (abnormal milk only) in herds
with a low prevalence of contagious
mastitis pathogens are likely to be affected
with environmental pathogens 17 and
commonly return to clinically normal
milk in four to six milkings. 81 This has led
to the development of treatment algorithms
based on the results of culturing clinical i
cases using selective media. Using this ;
approach, milk cultures are obtained from j
all cattle with clinical mastitis and plated
using biplates or triplates. All cattle with
abnormal glands or signs of systemic
illness (abnormal cow) are immediately j
treated with antimicrobial agents and ;
appropriate ancillary treatment, with sub-
sequent antimicrobial treatment based
on the preliminary culture results at
18-24 hours or the final culture results at
48 hours. In contrast, treatment is initially
witheld from all cattle demonstrating I
abnormal secretion only; antimicrobial
treatment is instituted based on the
culture results. One such scheme rec-
ommends using intramammary antibiotics
to treat affected quarters with S. aureus,
coagulase-negative staphylococci and
environmental streptococci, infusing
intramammary antibiotics into all quarters
of cows with one or more quarters infected
with S. agalactiae and not administering
antibiotics to cows with coliform bacteria
or no growth. 82 When using this delayed
approach to antimicrobial treatment, it is
important that cattle with abnormal milk
only are closely monitored and that
antimicrobial treatment is immediately
instituted when signs of an abnormal
gland or abnormal cow are present. The j
major difficulty with implementing the
delayed approach is the difficulty in trans-

porting the milk sample to and receiving
the results from the diagnostic laboratory
in a time effective manner.

Which route of administration
(intramammary, parenteral or both?)

The second decision is the route of
administration. The goal of antimicrobial
treatment is to attain and maintain an
effective concentration at the site of infec-
tion. Three pharmacological compart-
ments are recognized for infection by
mastitis pathogens:

Milk and epithelial lining of the ducts

and alveoli

Parenchyma of the mammary gland

The cow 83 (Table 15.5).

In general, infections confined primarily
to the milk and ducts (such as C. bovis,
coagulase-negative staphylococci) are
easily treated with intramammary anti-
biotics. In contrast, infections due to
mastitis pathogens with potential for
systemic infection (such as E. coli,
K. pneumoniae, M. bovis) are best treated
with parenteral antibiotics. Mastitis
pathogens that are the most difficult to
treat are those that are principally
infections of parenchymal tissue (such as
S. aureus, A. pyogenes); this is because it is
more difficult to attain and maintain an
effective antibiotic concentration at this
anatomical site when administering
antibiotics by the intramammary or
parenteral routes.

Which antimicrobial agent should be
administered?

The third decision is the antimicrobial
agent. The selection of the antimicrobial

: class for the particular mastitis pathogen
: has traditionally been based on culture
and susceptibility testing and, although
! some in vivo data are now available, the
; choice is still largely dependent on case
studies rather than on controlled experi-
; ments. Culture and antimicrobial suscep-
tibility testing of the pathogen is not
i necessarily a justifiable basis for selecting
; the antimicrobial agent to be used in
I individual cows, and the response to
treatment of clinical mastitis in two recent
: studies 84,83 was unrelated to the results cf
i in vitro susceptibility tests.

; Antimicrobial agents are usually
j selected based on availability of labeled
; drugs, clinical signs in the cow, milk
| culture results for previous mastitis epi-
i sodes in the herd, experience of treatment
j outcome in the herd, treatment cost and
j withdrawal times for milk and slaughter,
i Many veterinarians and researchers have
| also recommended the use of susceptibility
1 testing to guide treatment decisions. Tire
; validity of agar diffusion susceptibility
i breakpoints derived from humans in the
treatment of bovine mastitis has not been
established and is extremely questionable
because bovine mastitic milk pH, electro-
lyte, fat, protein and neutrophil concen-
trations, growth factor composition and
I pharmacokinetic profiles differ markedly
j from those of human plasma. 86 Moreover,
j antibiotics are distributed unevenly in an
j inflamed gland, and high antibiotic con-
! centrations can alter neutrophil function
in vitro and therefore have the potential
j to inhibit bacterial clearance in vivo.

: Adequate databases of in vitro mini-

i mum inhibitory concentration (MIC)

Mastitis pathogen

Pharmacological compartment

Milk and ducts
(abnormal milk)

Parenchyma
(abnormal gland)

Systemic
(abnormal cow)

Contagious pathogens

Staphylococcus aureus

+

++

-

Streptococcus agalactiae

+ +

+

-

Mycoplasma bovis

+

+

++

Corynebacterium bovis

Teat skin opportunistic pathogens

+ +

“

Coagulase-negative staphylococci
Environmental pathogens

+ +

-

E. coli

+

-

++

Klebsiella pneumoniae

+

-

++

Environmental streptococci

++

+

-

Arcanobacterium pyogenes
Antimicrobial therapy

+

++

-

Intramammary

Good to excellent

Moderate

Poor

Parenteral

Poor to moderate

Moderate to
excellent

Good to excellent

Antimicrobial therapy is categorized on the basis of route of administra tion and likely efficacy when
treating a susceptible infection

++, extensive infection; + - moderate infection; - minimal or no infection

Source: adapted from Erskine Rl et at. Vet Clin North Am Food Anim Pract 2003; 19:1 09.

Bovine mastitis

values for clinical mastitis pathogens are
currently unavailable, although adequate
databases are available for subclinical
mastitis isolates. Although we have a
good knowledge of the pharmacokinetics
of many parenteral antibiotics used to
treat clinical mastitis, most pharma-
cokinetic data have been obtained in
healthy cattle and it has not been
determined whether pharmacokinetic
values in healthy cows are the same as
those in cows with clinical mastitis. In
addition, pharmacokinetic values for
many of the intramammary antibiotics
used to treat clinical mastitis are unknown,
and we have a limited understanding of
the pharmacodynamics of antibiotics in
treating mastitis. More importantly, the
breakpoints currently recommended for
all parenterally and almost all intra-
mammarily administered antibiotics are
based on achievable serum and interstitial
fluid concentrations in humans after oral
or intravenous antibiotic administration.
The relevance of these breakpoints to
achievable milk concentrations in lactating
dairy cows after intramammary, sub-
cutaneous, intramuscular or intravenous
administration is dubious at best. 86

Results from field studies are available
to evaluate the validity of susceptibility
breakpoints in guiding treatment of cows
with clinical or subclinical mastitis. The
results from these field studies suggest
that the following antibiotics may have
valid (but not necessarily optimal) break-
points for treating clinical or subclinical
mastitis associated with specific bacteria:
parenteral penicillin G for subclinical
S. aureus infections, intramammary
cephapirin for clinical Streptococcus spp.
infections, and parenteral trimethoprim-
sulfadiazine for clinical E. coli infections.
Of these three antibiotics, the breakpoints
for penicillin G and cephapirin have only
been validated for bacteriological cure,
whereas the breakpoint for trimethoprim-
sulfadiazine is validated for clinical cure. 84
Because duration of infection before
treatment, antibiotic dosage, dosage
interval and duration of treatment influence
treatment outcome, many more field
studies must be completed to validate the
currently assigned antibiotic breakpoints
for pathogens causing clinical mastitis.

To properly utilize the known pharma-
cokinetics of parenterally and intra-
mammarily administered drugs, it is
necessary to know something about their
diffusion into mammary tissue, the
degree of binding of a drug to mammary
tissues and secretions, the ability to pass
through the lipid phase of milk and the
degree of ionization. All of these factors
influence the level of the antibiotic in the
mammary gland. For lactating cows the
preferred treatment is one that maintains

a MIC for 72 hours without the need for
multiple infusions and without pro-
longation of the withdrawal time. The
most successful antimicrobial agents for
dry period treatment are those that persist
longest in the udder, preferably as long as
8 weeks. These characteristics depend on
the release time from the transport agent
in the formulation, and the particle size
and diffusion capabilities of the antibiotic.

The formulation of the preparation will
affect the duration of the maintenance of
the MIC. The third-generation cepha-
losporins (such as ceftiofur) and fluoro-
quinolones are the drugs of choice for use
in cases in which the infection may be
associated with either a Gram-positive or
Gram-negative organism; however, these
antimicrobial agents may not be able to j
be used to treat mastitis in some countries.
Mixtures of penicillin and an amino-
glycoside are also in common use for this
purpose. Penicillin G and penethamate
are favored for Gram-positive infections.

Of special importance are the beta-
lactamase-producing strains of S. aureus,
against which beta-lactam penicillins are
ineffective; cloxacillin is a commonly used
and effective intramammary formulation j
for these strains of S. aureus. The drugs
that have the best record of diffusion
through the udder after intramammary
infusion are penethamate, ampicillin,
amoxicillin, erythromycin and tylosin.
Those of medium performance are
penicillin G, cloxacillin and tetracyclines.
Poor diffusers, which have a longer half-
life in the udder because they bind
to protein, include streptomycin and
neomycin. Streptomycin is not much used
now because of the high level of resist-
ance to it, especially by S. uberis and
E. faecahs.

What should be the frequency and
duration of treatment?

The fourth decision is the frequency and
duration of treatment. The frequency of
administration for parenterally adminis-
tered antimicrobial agents is dependent
primarily on their pharmacokinetics and
pharmacodynamics. Fluoroquinolones
and aminoglycosides are concentration-
dependent antimicrobial agents where
increasing concentrations at the site of
infection increase the bacterial kill rate.
Macrolides, beta-lactams, and lincosamides
are time-dependent antimicrobial agents
where exceeding the minimum inhibitory
concentration at the site of infection for a
prolonged percentage of the interdosing
interval correlates with improved efficacy. 87
In contrast, the frequency of adminis-
tration for intramammary formulations
is dependent primarily on the milking
schedule, in that these agents are pri-
marily cleared by milk removal. For

example, the clearance of pirlimycin is
strongly and positively correlated (r = 0.97)
to 24-hour milk production at the time of
dosing. 88 With all intramammary formu-
lations being licensed based on the results
of studies of twice-daily milking, the
recent industry trend in some parts of the
world towards thrice-daily milking has
created uncertainty as to whether intra-
mammary treatment should be repeated
after every milking, or even whether
once-a-day intramammary administration
is as efficacious as twice- or thrice-daily
administration.

Recent studies have confirmed long
held beliefs that appropriate anti-
microbial therapy (commonly called
extended or aggressive antimicrobial
therapy) for 5-8 days is much more
effective in treating intramammary infec-
tions than label intramammary therapy
(2-3 d). In other words, increasing the
duration of antimicrobial administration
increases treatment efficacy. 89 " 92 Extended
antimicrobial therapy is opposed by
producers because such treatment may be
off-label and results in a longer milk
withhold time, and consequently the
amount of milk that has to be discarded.
Extended therapy is opposed by dairying
administrators because of the inevitable
increase in the number of infringements
of health regulations relating to antibiotic
residues in milk. The inappropriately
short treatment duration for most intra-
mammary products has been a major
hindrance to developing effective anti-
microbial treatment protocols.

Intramammary antimicrobial therapy

For reasons of convenience and efficiency,
antimicrobial udder infusions are in
common use for the treatment of certain
causes of mastitis in lactating cows, and
for dry cow therapy. For example, the cure
rate of S. agalactiae using intramammary
infusions in lactating cows exceeds 95%.
Disposable tubes containing suitable
antimicrobials in a water-soluble oint-
ment base are ideal for dispensing and for
the treatment of individual cows. Multiple-
dose bottles containing aqueous infusions
are adequate, and much cheaper per dose
when large numbers of quarters are to be
treated, but repeated use of the same
container increases the risk of contami-
nation. The degree of diffusion into
glandular tissue is the same when either
water or ointment is used as a vehicle for
infusion; the duration of retention within
the gland depends on the vehicle.

Most antimicrobial agents currently
available in the USA in commercial
intramammary infusion products are
active against the staphylococci and
streptococci, 93 with cephapirin (a first-
generation cephalosporin) having good

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

activity against coliform bacteria, and
ceftiofur (a third-generation cephalosporin)
having excellent activity against coliform
bacteria. 94 Until recentyears the emphasis
was on the elimination of Gram-positive
cocci from the udder, but Gram-negative
infections, especially E. coli, have increased
in prevalence to the point where a broad-
spectrum preparation is almost essen-
tial for both lactation and dry period
treatments.

The choice of antimicrobial agents
for intramammary infusion should be
based on:

0 Spectrum of bacteria controlled
° Diffusibility through mammary tissue
° Cost.

Strict hygiene is necessary during treat-
ment to avoid the introduction of
bacteria, yeasts and fungi into the treated
quarters; the use of a short cannula that
just penetrates the external sphincter is
preferred as it is less likely to introduce
bacteria and leaves more of the keratin
plugin place in the streak canal; the keratin
plug has antimicrobial properties itself.
Care must be taken to insure that bulk
containers of mastitis infusions are not
contaminated by frequent withdrawals and
that individual, sterilized teat cannulas,
usually part of commercial, single-dose
ointment tubes, are used for each quarter.
Bulk treatments are best avoided because
of the high risk of spread of pathogens.

Infusion procedure

The teats must be cleaned and sanitized
before infusing the quarter in order to
avoid introduction of infection. The follow-
ing steps are recommended:

° Clean and dry the teats

Dip teats in an effective germicidal
product. Allow 30 seconds contact
time before wiping teats with an
individual disposable towel (one
towel/cow, use one corner of the
towel for each teat)

■ Thoroughly clean and disinfect each
teat end with cotton soaked in 70%
alcohol. Use a separate piece of cotton
for each teat

■ Prepare teats on the far side of the
udder first, followed by teats on the
near side

Treat quarters in reverse order; near
side first, far side last
o Insert only the tip of the cannula into
the teat end (partial insertion). Do
not allow the sterile cannula to touch
anything prior to infusion. Most
approved dry cow infusion products
(and lactating tubes, too) are
marketed with a dual cover that can
be used for partial or full insertion
° Dip teats in a germicidal product after
treatment

° Identify treated cows and remove
them from the milking herd to
prevent antimicrobials from entering
the milk supply.

Diffusion of infused intramammary drugs
is often impeded by the blockage of
lactiferous ducts and alveoli with inflam-
matory debris. Complete emptying of the
quarter by the parenteral injection of
oxytocin (10-20 IU intramuscularly)
followed by hand-stripping of affected
quarters before infusion has been rec-
ommended in cases of clinical mastitis,
but efficacy studies are lacking, the volume
stripped is usually small and the pro-
cedure is painful to the cow. If stripping is
performed, the intramammary infusion is
given after the last stripping of the day
has been done, avoiding any further
milking of the gland until the next
milking. Our current knowledge can be
summarized by the following: 'To strip or
not to strip, that is the question.'

Parenteral antimicrobial therapy

This should be considered in all cases of
mastitis in which there is an abnormal
gland or abnormal cow (fever, decreased
appetite, or inappetence). The systemic
reaction can usually be brought under
control by standard doses of antimicrobial
agents but a bacteriological cure of the
affected glands is seldom achieved
because of the relatively poor diffusion of
the antimicrobial from the blood into the
milk. However, the rate of diffusion is
greater in affected than in normal quarters.
Fbrenteral treatment is also recommended
when the gland is markedly swollen and
intramammary infusions are unlikely to
diffuse to all parts of the glandular tissue.
To achieve adequate therapeutic levels of
an antimicrobial in the mammary gland
by parenteral treatment it is necessary, for
the above reasons, to use higher than
normal dose rates daily for 3-5 days. Milk
from treated cows must be withheld from
the bulk tank for the stated period of time
of that antimicrobial following the date of
last treatment.

Treatment of lactating quarters

There are three situations to consider: the
emergency single case of clinical mastitis
requiring immediate treatment, the herd
with a problem of too many clinical cases
or intractable cases, but where the identity
of the pathogen is known, and the cow
with subclinical mastitis.

Emergency treatment when the type of
infection is unknown
Cases of acute and peracute mastitis
(abnormal cow) in lactating cows, and in
dry cows close to calving, are serious
problems for the field veterinarian. The
need for treatment is urgent; it is not
possible to wait for the results of labor-

atory tests to guide the selection of the
most appropriate antibiotic. Clinical
findings, season of the year and manage-
ment practices may give a broad hint as to
the specific bacterial cause, but in most
such circumstances it is necessary to use a
broad-spectrum approach to treatment. 95
Parenteral therapy with oxytetracycline
(administered intravenously to increase
bioavailability and therefore plasma and
milk concentrations), a potentiated
sulfonamide or similar broad-spectrum
antimicrobial agent should be supple-
mented with intramammary infusion with
a beta-lactamase -resistant antimicrobial
such as a first-generation cephalosporin
(cephapirin), a third-generation cepha-
losporin (e.g. ceftiofur), penicillin
G-neomycin combination or other
approved broad-spectrum intramammary
infusion. 96 Parenteral ceftiofur is not
effective in clinical mastitis episodes that
have abnormal secretion or abnormal
gland and secretion. 97

Field studies show that, in herds in
which clinical mastitis is often caused by
environmental pathogens, intravenous
administration of oxytetracycline, intra-
mammary infusion of cephapirin and
supportive therapy (including intravenous
administration of flunixin meglumine or
fluids) produces a higher rate of clinical
and bacteriologic cure than supportive
treatment alone. 96 In addition, anti-
microbial treatment is more effective than
supportive treatment alone. 86 In cows
with clinical mastitis caused by E. coli the
use of procaine penicillin G IM was no
more effective than not using anti-
microbial agents; 98 this result is expected
based on penicillin's Gram-positive
spectrum of activity. Knowledge of the
likely causative agent is therefore helpful
when making decisions about therapy of
clinical mastitis episodes during lactation.

Provision of other supportive therapy
such as fluids and electrolytes is also
crucial to the survival of the cow and
minimization of the severity of the mastitis
and extent of permanent injury to the
udder. The efficacy of frequent stripping,
with or without intramammary infusion,
is uncertain. NSAIDs decrease pain associ-
ated with an abnormal gland; in addition,
they enhance recovery and reduce fever in
severe cases.

Treatment when the infecting organism
is known

A common situation encountered by a
bovine practitioner is the dairy herd that
has had an outbreak of clinical mastitis or
has received a warning notice from the
milk processor that the bulk milk SCC or
bacterial count is above acceptable limits.
The situation calls for a complete mastitis
control program, including conducting an

Bovine mastitis

investigation to determine the causative
bacteria present, the source of the infec-
tion, hygiene in the milking parlor and
the importance of risk factors such as
milking machine management, plus rec-
ommended antimicrobial preparations
selected on the basis of the causative
agent. Treatment of a number of identified
subclinical cases at the commencement of
the program, and of individual cases
subsequently, can be based on the known
common infection in the herd. Among
Gram-positive cocci, the response to anti-
microbial agents is excellent for strepto-
cocci. For staphylococci a cure rate of 65%
is about the best that can be expected,
and unless there are good reasons for
doing otherwise it is recommended that
treatment be postponed until the cow is
dry. Standard treatments for lactating cows
include penicillin alone (100 000 units) or in
combination with streptomycin (1 g) or
neomycin (500 mg), and a combination of
ampicillin (75 mg) and sodium cloxacillin
(200 mg). Acid-resistant penicillins, e.g.
phenoxymethylpenicillin, are probably
best not used as mammary infusions
because of their ability to pass through
the human stomach, thus presenting a
more serious potential threat to humans
drinking contaminated milk. Because of
the widespread and often indiscriminate
use of penicillin, a large part of the mastitis
that occurs is associated with penicillin-
resistant bacteria, especially S. aureus.
Treatment programs need to take this into
account when recommendations are
made about the antibiotic to be used.

Intramammary infections associated
with environmental streptococci that
manifest signs of clinical mastitis are
usually acute but only moderately severe.
In most of these cases the streptococci are
sensitive to antimicrobial agents, and they
often recover spontaneously with good
management and nursing care. If not,
they usually respond well to therapy.
Bacteriological cure rates of 60-65% can
be expected following a single intra-
mammary infusion of a cephalosporin
product. In one randomized controlled
field trial of clinical mastitis associated
with Streptococcus spp. or colifonn bacteria,
the clinical cure rate by the tenth milking
was significantly higher when intra-
mammary cephapirin, intravenous oxyte-
tracycline, or both, were used along with
supportive therapy (oxytocin and stripping
of affected glands and, in severely affected
cows, the use of flunixin meglumine and
fluids) compared to supportive treatment
alone." These results indicate that, in
herds in which clinical mastitis is often
associated with environmental pathogens,
antimicrobial therapy and supportive
therapy may result in a better outcome
than supportive therapy alone.

Treatment of subclinical mastitis
It is generally considered not advisable to
treat subclinical mastitis during lactation.
However, it is important to consider the
causative organism and the udder health
status of the herd. There are several
situations in which lactational therapy of
subclinical mastitis is indicated; for
example, herds with S. agalactiae infections
should consider several approaches to
therapy during lactation. S. agalactiae
infections respond well to therapy during
lactation, with cure rates of 80-100%
expected. 59 All approved intramammary
therapy preparations are efficacious,
including penicillin, cephalosporins,
cloxacillin and erythromycin. In herds
with a high prevalence of S. agalactiae
mastitis, blitz therapy can be used for
eradication of the pathogen, increased
milk production and reduced penalties for
high SCCs. There is, however, a risk of
residue violation, problems with disposal
of milk from treated cows and consider-
able costs involved. It is also important to
insure that standard mastitis control
procedures, such as postmilking teat
disinfection and blanket dry cow therapy,
have been implemented. The benefit:cost
ratios for various approaches to blitz
therapy of S. agalactiae infected herds
have been studied. 59 The prevalence of
infected cows, and their stage of lactation,
are important determinants of the type of
program selected.

Therapy of cows with subclinical mas-
titis due to S. aureus during lactation is
much less rewarding. Under field con-
ditions, cases of S. aureus are difficult to
cure during lactation. Reported cure rates
following intramammary therapy are
between 15% and 60%. Lactational therapy
of subclinical S. aureus mastitis using intra-
muscular penicillin along with intra-
mammary amoxicillin infusion, compared
with the intramammary infusion alone,
increased the cure rate to 40%, which
represented a doubling of the cure rate
with intramammary therapy alone. 40 If
treatment by this method is used in
combination with data on the age of cow,
stage of lactation, duration of infection
and level of SCC, the economic benefit of
treating some cases of S. aureus mastitis
during lactation may be attractive.

Subclinical infections associated with
environmental streptococci, and occasion-
ally by coliform organisms, can be found
in moderate numbers in some herds. 56
Although spontaneous cure rates are higher
with these environmental infections, indivi-
dual cows may merit treatment during lac-
tation. In these cases, the previously listed
factors should be used, and are important
in the selection of cases to be treated.

Prepartum antibiotic treatment of
heifers is of benefit in herds experiencing

a high incidence of clinical mastitis in
recently calved heifers. Coagulase-negative
staphylococci are frequently isolated from
late-gestation heifers, and intramammary
treatment with sodium cloxacillin (200 mg)
or cephapirin sodium (200 mg) 7 days
before expected parturition is highly
effective and economically beneficial. 100

Anti-inflammatory agents

NSAIDs have been evaluated for the
treatment of field and experimental cases
of acute and peracute mastitis. NSAIDs
have beneficial effects on decreasing the
severity of clinical signs based on changes
in rectal temperature, heart rate, rumen
motility and pain associated with the
mastitis, and are routinely administered
as part of the initial treatment of cattle
with severe clinical mastitis and marked
systemic signs. On the basis of one
comparative study, NSAIDs appear to
ameliorate systemic abnormalities to a
greater degree than corticosteroids. 101 The
strongest evidence available to support
the administration of NSAIDs is available
for ketoprofen and phenylbutazone.

Ketoprofen at 2 g intramuscularly once
daily combined with sulfadiazine and
trimethoprim intramuscularly given daily
to cows with acute clinical mastitis, and
complete milking of affected quarters
several times daily, significantly improved
survival and milk production compared to
cows not receiving the NSAID. 102 A re-
analysis of the published results indicated
that phenylbutazone at 4 g intramuscularly
once daily combined with sulfadiazine
and trimethoprim intramuscularly given
daily to cows with acute clinical mastitis
significantly improved the percentage of
cows with milk production returning to
more than 75% of previous levels com-
pared to cows not receiving the NSAID. 103
However, intramuscular administration of
phenylbutazone is not currently rec-
ommended because of the potential for
myonecrosis. Dipyrone at 20 g intra-
muscularly once daily in the same study
was not effective. 103

There is no evidence that treatment of
clinical cases with NSAIDs alters the
inflammatory response in the udder, 101
although pretreatment of cattle with
experimentally induced mastitis does
alter the local (glandular) inflammatory
response to infection. Flunixin meglumine
concentrations are low in milk, which is
consistent with its properties as a weak
acid, which has difficulty crossing the
blood-milk barrier. 104 Flunixin meglumine
(2 mg/kg, intravenously, twice 24 h apart)
did not alter the survival rate of dairy
cows with severe E. coli or S. uberis mas-
titis compared to intravenous adminis-
tration of 45 L of isotonic crystalloid
fluids. 105 The one-time administration of

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

1 g of flunixin meglumine intravenously
or 4 g of phenylbutazone intravenously,
along with intramammary infusion of
gentamicin (150 mg) at 12-hour intervals
for four treatments, had no significant
beneficial effect in cows with acute toxic
mastitis associated with E. coli and
Klebsiella spp. 1 ' 6 However, the results of
this study do not indicate a lack of effec-
tiveness of flunixin meglumine or
phenylbutazone because it is difficult for
one dose of any NSAID to have a detect-
able effect on clinical signs in naturally
occurring mastitis cases.

Supportive therapy

Supportive treatment, including the intra-
venous administration of large quantities
of isotonic crystalloid fluids, is indicated
in cattle with severe systemic illness.
Large volumes of isotonic crystalloid
fluids can be rapidly administered under
pressure at 0.5 L/min through a 12-gauge
catheter in the jugular vein, using a 7.5 L
garden weed killer spray pump. 105 Tire
administration of hypertonic saline
followed by immediate access to drinking
water is a practical method of providing
fluid therapy to cows with severe mastitis,
especially peracute coliform mastitis. 1 ' 7 A
dose of 4-5 mL/kg body weight (BW) of
7.5% saline is given intravenously over
4-5 minutes. 1,8 This is usually followed by
the animal consuming large quantities of
water. Circulating blood volume is
increased and there is mild strong ion
(metabolic) acidosis, improved renal
function and changes in calcium and
phosphorus homeostasis when compared
to cows given a similar volume of 0.9%
NaCl. Fluid therapy is covered extensively
in Chapter 2.

Adjunctive therapy

Cytokines may be useful as adjunctive
therapy with existing antimicrobials to
improve therapeutic efficacy, particularly
in lactating cows." 9 Cytokines are natural
regulators of the host defense system in
response to infectious diseases. The com-
bination of a commercial formulation of
cephapirin with recombinant interleukin-

2 consistently improved the cure rate of
treating S. aureus mastitis by 20-30%
compared to use of the antimicrobial
alone. 1 ' 9

Magnitude of response to therapy

The treatment of some causes of mastitis
can be highly effective in removing
infection from the quarter and returning
the milk to normal composition. How-
ever, the yield of milk, although it can be
improved by the removal of congestion in
the gland and inflammatory debris from
the duct system, is unlikely to be returned
to normal in severe clinical cases, at least
until the next lactation. Tire degree of

j response obtained depends particularly j
j on the causative agent, the speed with
| which treatment is commenced, and
j other factors described above. A'cure' may
j mean disappearance of clinical signs,
j elimination of the infectious cause, or i
j both of those plus return to normal func-
! tion and productivity. Which of these is :
j the objective in any particular case or herd j
I will influence the decisions to be made j
; about treatment in an individual case of I
; the disease. ;

Failure to respond to therapy of the :
j lactating cow may be due to:

The presence of microabscesses and :

j inaccessibility of the drug to the :

; pathogen j

j Ineffective drug diffusion

j Inactivation of the antimicrobial by

milk and tissue proteins
Inefficient killing of the bacteria and
intracellular survival of bacteria
Increased antimicrobial resistance
I ; The development of L-forms of
bacteria.

Dry cow therapy

j Dry cow therapy is the use of intra- i
! mammary antimicrobial therapy immedi-
j ately after the last milking of lactation and
j is an important component of an effective
j mastitis control program. 110 Intramammary
j infusions at drying off decrease the
| number of existing infections and pre-
! vent new infections during the early
i weeks of the dry period. Dry cow
! therapy should be routinely administered
and remains one of the cornerstones of
an effective mastitis control program.
Blanket dry cow therapy is treatment of
all four quarters at drying off, compared
to selective dry cow therapy based on
treatment of only those quarters that are
infected. When subclinical mastitis is very
low in some herds, selective dry cow
therapy can be considered, but nearly all
herds use blanket dry cow therapy. The
\ problem with selective dry cow therapy is
S the accuracy of available indirect tests
i to 'select' cows for treatment or non-
j treatment. Currently available indirect
tests are not sufficiently accurate (the
exception being quarter milk cultures) to
be used as a basis for selective dry cow
therapy.

Intramammary infusions approved for
dry cow therapy contain high levels of
antimicrobial agents in a slow-release
base that maintains therapeutic levels in
the dry udder for long periods of time.
Most dry cow therapy infusion products
are intended to eliminate existing infec-
tions due to S. aureus and S. agalactiae at
drying off and to prevent new infections
due to the same pathogens and environ-
mental streptococci in the early dry
period.

In herds with a high prevalence of con-
tagious mastitis, dry cow therapy has
been efficacious and economically ben-
eficial in reducing the prevalence of intra-
mammary infections. The consistent
application of effective mastitis control
procedures has reduced the prevalence of
contagious pathogens and the bulk tank
milk SCC (<300 000 cells/mL) and owners
of these herds questioned dry cow
therapy because of the economics and the
concerns of residues in the milk. Field
trials in herds with a low prevalence of
contagious mastitis indicate that dry cow
therapy at the end of lactation increased
17-week ■ milk production during the
subsequent lactation and was economically
beneficial compared to not treating
them. 111 However, in the subsequent
lactation, the incidence of clinical mastitis
was not reduced nor were the SCCs
significantly different from those of cows
not treated at the end of lactation.

The most effective time to treat sub-
clinical intramammary infections is at
drying off. Dry cow therapy has the
following advantages over lactation
therapy:

The cure rate is higher than that
achieved by treatment during
lactation

A much higher dose of antimicrobial
can be used safely

Retention time of the antimicrobial in
the udder is longer
j ° The incidence of new infections
during the dry period is reduced
Tissue damage by mastitis may be
regenerated before parturition
Clinical mastitis at calving may be
reduced

« The risk of contaminating milk with
antimicrobial residue is reduced.

Selection of a suitable dry period treat-
ment should take into account the fact
that Gram -negative infections are not
common at that time because of the high
concentration of lactoferrin in the dry
secretions. Accordingly attention should
be directed at the inclusion of a potent
antibiotic against Streptococcus spp., beta-
lactamase-producing S. aureus, and
A. pyogenes. Cloxacillin, nafcillin, and cepha-
losporins are popular for the purpose; for
example, a recommended treatment is
cephapirin or sodium cloxacillin in a
slow-release base with an expected cure
rate of 80% against streptococci and 60%
against S. aureus.

Most dry cow preparations maintain
an adequate minimum concentration in
the quarter for about 4 weeks, but some
persist for 6 weeks. There is little, if any,
value in treating cows again before the
due calving date. There is always a possi-
bility of introducing infection while

infusing an intramammary preparation \
and farmers are reluctant to break the teat j
canal seal, but it may be necessary to do ]
so if summer mastitis is prevalent in j
the area.

Prepartum antimicrobial therapy in
heifers

Intramammary infusion of a cephapirin dry
cow therapy preparation into pregnant
heifers 10-12 weeks prepartum eliminated
over 90% of the intramammary infection
due to S. aureus, Streptococcus spp.,
coagulase-negative staphylococci spp. and
coliforms. Tire SCCs of cured quarters were
comparable to uninfected control quarters
after parturition. 112 At parturition, 24% of
treated quarters were positive for the
antimicrobial; however, no quarters were
positive at 5 days postpartum.

Antimicrobial residues in milk and
withholding times

Label instructions must be followed to
insure that drug residues do not occur,
especially from cows with a shorter than
normal dry period. Antibiotic residue
testing of the milk of a recently calved
cow can be done if there is a suspicion of
residues, but this is a misuse of a test
designed for bulk tank milk testing and
therefore suffers from problems with
sensitivity and specificity.

Treatment and control of mastitis
accounts for the largest percentage of
antimicrobial use on dairy farms. Follow-
ing treatment by the intramammary or
parenteral route, the concentration of
antimicrobial agents in the milk declines
over time to levels that are considered
safe and tolerable for humans. The duration
of time for the concentrations to decline to
acceptable limits is known as the with-
holding time or the withdrawal period
during which the milk cannot be added to
the bulk tank supply but must be withheld
and discarded. The presence of residues in
milk is a major public health concern that
adversely affects the dairy industry, the
practicing veterinarian and the perception
the public has of the safety of milk for
human consumption. The public per-
ception of the safety of milk is crucial and
veterinarians have a responsibility to
respond to these concerns through public
education and quality control of milk
production.

Other serious consequences of anti-
microbial residues in milk are their effect
on the manufacture of dairy products and
the potential development of antimicrobial
sensitivity syndromes in humans. In most
countries the maximum intramammary
dose of antimicrobial agents is limited by
legislation and the presence of detectable
quantities of antimicrobial agents in milk
constitutes adulteration. Attention has
also been directed to the excretion of anti-

Bovine mastitis

microbial agents in milk from untreated
quarters, after treatment of infected
quarters and after their administration by
parenteral injection or by insertion into
the uterus. The degree to which this
excretion occurs varies widely between
animals and in the same animal at differ-
ent points in the lactation period, and
differs from one antibiotic to another.
Milk from cows subjected to dry period
treatment is usually required to be
withheld for 4 days after calving. The use
of any dry period treatments in lactating
cows causes prolonged retention of the
antimicrobial in milk and is a most serious
violation of the legislation.

Veterinarians have the responsibility to
warn farmers of the need to withhold
milk, and both should be aware of the
withholding times of each product, details
of which are usually required to be
included on its label. Marking the cow in
some way to remind the farmer, by appli-
cation of a leg band or placing dye on the
udder, is advisable.

Antimicrobial residue tests
Several cowside tests are available to
detect antimicrobial residues in the milk
of cows that have been treated for
mastitis. 113 The goal of cowside testing is
to assist in the production of high-quality,
antimicrobial-residue-free milk from
dairy herds. To be consistent with the
intent of a quality assurance program,
cowside testing would be used only on
cows recently treated with antimicrobial
agents and only after appropriate milk
withholding times had been followed.
The ideal test would have a high sensi-
tivity and high specificity.

Most of the cowside screening tests for
antimicrobial residues are imperfect
because of a high rate of false-positive
results when used on field samples. The
direct costs to producers can be high
because of the unnecessary disposal of
milk and imposition of fines and penalties.
False-positive results also cause the
unnecessary culling of some cows, and
concern about the interpretation of
positive assay results, the appropriateness
of withholding periods and the safety of
milk creates mistrust among consumers,
producers, veterinarians and regulatory
personnel. The specificity of four com-
mercially available tests ranged from
0.78-0. 95. 114 None of the test kits has
been validated to meet performance
standards for sensitivity and specificity.
This applies to individual cow samples,
bulk tank milk samples and tanker truck
samples.

The presence of naturally occurring
bactericidal products in the milk of cows
with acute and convalescent mastitis is
the most likely cause of the false-positive

results of the tests (such as Delvo-test®)
that are based on bacterial growth inhi-
bition of beta-lactam antimicrobial
agents. 113 Immunoglobulins, complement,
lysozyme, lactoferrin and phagocytic cells
are products of inflammation in the milk
of cows with mastitis that can inhibit
bacterial growth. The milk from cows with
experimental endotoxin-induced mastitis
is at increased risk for false-positive assay
results using commercial residue tests. 114
The incidence of false-positive results is
very low in milk from cows that have not
had a history of mastitis or antimicrobial
therapy. 115 Naturally occurring bactericidal
products in mastitic milk can be removed
by heating at 82°C for 5 minutes; this
temperature does not denature anti-
microbial agents present in milk. 116 Heat
treatment therefore appears to provide a
very practical way to reduce false-positive
results on milk from individual cows.

A sample of milk can be submitted for
antimicrobial residue testing up to three
times. First, a producer may test a sample
from a specific cow at the end of her with-
drawal period. Second, milk is sampled at
the tanker truck level. Third, should the
tanker truck sample have positive results,
bulk tank milk samples from each dairy
herd that contributed to that tanker truck
are tested.

There is a need for validation of the
diagnostic assays used to detect anti-
microbial residues in milk. 117 Acceptance
of assays for regulatory purposes must be
based on protocols that include field
estimates of assay performance before the
assays are used by the public. Three
strategies have been suggested to balance
public health concerns with economic
concerns of dairy producers caused by
false-positive results:

° Retest samples that yield positive
results with a confirmatory assay of
specificity close to 100%. Only those
samples that also yield positive results
on the second assay are considered to
be positive for violative residues
° Recalibrate the assay to increase
specificity. This will usually result in
loss of sensitivity

° Use an alternative assay of higher
specificity. 117

It is suggested that regulatory monitoring
of residues at a national level will be best
served by use of a combination of at least
two assays: initial screening with a highly
sensitive and inexpensive assay followed
by confirmation testing with an assay of
high specificity (> 99%) that can quantify
the concentration of the antimicrobial resi-
due. All tanker samples that yield positive
results with a screening assay should be
rechecked with a quantitative assay. If the
quantitative assay detects a concentration

696

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

greater than the safe level, safe concen-
tration or tolerance level, only then would
the milk be deemed to have violative
residue and fines and penalties be
imposed. 117 The complex dynamics of
current milk residue tests discourage
practitioners from recommending testing
procedures to dairy producers. 118

As an approximate guide, the rec-
ommended periods for which milk should
be withheld from sale after different
methods of antimicrobial administration
are (in times after last treatment):

0 Udder infusion in a lactating cow -
72 hours

° Parenteral injection, one only-
36 hours

° Parenteral injections, series of -
72 hours

° Antimicrobial agents parenterally in
long-acting bases - 10 days
o Intrauterine tablet - 72 hours
° Dry cow intramammary infusion - to
be administered at least 4 weeks
before calving and the milk withheld
for at least 96 hours afterwards.

Permanently drying off chronically
affected quarters

If a quarter does not respond to treatment
and is classified as incurable, the affected
animal should be isolated from the
milking herd or the affected quarter may
be permanently dried off by inducing
a chemical mastitis. Historically used
methods, arranged in decreasing order of
severity, are infusions of:

° 30-60 mL of 3% silver nitrate solution
0 20 mL of 5% copper sulfate solution
c 100-300 mL of 1:500, or 300-500 mL
of a 1:2000 acriflavine solution.

If a severe local reaction occurs, the quarter
should be milked out and stripped fre-
quently until the reaction subsides. If no
reaction occurs, the quarter is stripped out
10-14 days later. Two infusions of these
solutions may be necessary.

The best method for permanently
drying off a quarter is infusion of
120 mL of 5% povidone-iodine solution
(0.5% iodine) after complete milk-out
and administration of flunixin meglumine
(1 mg/kg BW, intravenously). This causes
permanent cessation of lactation in the
quarter but does not alter total milk pro-
duction by the cow. If the goal is chemical
sterilization, then three daily infusions of
60 mL of chlorhexidine suspension should
be administered after complete milk-out.
The majority of treated cows (5 17) returned
to milk production in the quarter in the
subsequent lactation. 119 The infusion of
60 mL of chlorhexidine, followed by milk-
ing out at the next subsequent milking
and repeat of the infusion 24 hours after
the initial treatment is also effective in

making infused quarters nonfunctional
within 14-63 days. 120 Histological evalu-
ation of the infused quarters revealed that
secretory tissues had involuted to a
nonsecretory state and appeared similar to
blind or nonfunctional quarters. However,
as noted above, milk production may return
in the gland in the subsequent lactation.

REVIEW LITERATURE

Burton JL, Erskine RJ. Immunity and mastitis: some
new ideas for an old disease. Vet Clin North Am
Food Anim Pract 2003; 19:1-46.

Constable PD, Morin DE. Treatment of clinical
mastitis: using antimicrobial susceptibility profiles
for treatment decisions. Vet Clin North Am Food
Anim Pract 2003; 19:139-156.

Erskine RJ, Wagner SA, DeGraves FJ. Mastitis therapy
and pharmacology. Vet Clin North Am Food Anim
Pract 2003; 19:109-138.

Pyorala S. Indicators of inflammation in the diagnosis
of mastitis. Vet Res 2003; 34:565-578.

Roberson JR. Establishing treatment protocols for
clinical mastitis. Vet Clin North Am Food Anim
Pract 2003; 19:223-234.

SchukkenYH et al. Monitoring udder health and milk
quality using somatic cell counts. Vet Res 2003;
34:579-596.

Sears PM, McCarthy KK. Diagnosis of mastitis for
therapy decisions. Vet Clin North Am Food Anim
Pract 2003; 19:93-108.

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Mastitis pathogens of cattle

In the sections which follow, the special
features of each mastitis associated with
one or a group of pathogens will be
described using the usual format of the
book. Mastitis in cattle is categorized as
being associated with contagious, teat
skin opportunistic or environmental patho-
gens, and as being common or less com-
mon . The features that are unique to the
diagnosis, treatment and control of each
mastitis pathogen will be outlined but
details applicable to all causes of mastitis
have been presented above.

Mastitis of cattle associated
with common contagious
pathogens

STAPHYLOCOCCUS AUREUS

Etiology Staphylococcus aureus is a
major pathogen of the mammary gland
and a common cause of contagious bovine
mastitis. 5. aureus also causes mastitis in
sheep and goats

Epidemiology Major cause of mastitis in
dairy herds without an effective mastitis
control program. Prevalence of infection
50-100%; prevalence of 1-10% in herds
with low bulk tank milk SCCs, 50% in
high-SCC herds, quarter infection rate
10-25% in high-SCC herds. Source of
infection is infected udder; infection
transmitted at milking. Chronic or
subclinical S. aureus mastitis is of major
economic importance
Clinical findings

• Chronic S. aureus mastitis is most
common and is characterized by high
SCC and gradual induration of udder,
drop in milk yield and atrophy with
occasional appearance of clots in milk
or wateriness

• Acute and peracute S. aureus mastitis
most common in early lactation. Acute
swelling of gland with fever; milk is
abnormal with thick clots and pus;
gangrene of gland and teat in peracute
form. Systemic reaction with anorexia,
toxemia, fever, ruminal stasis

Clinical pathology Culture individual
cow milk sample; indirect tests are high
SCC and California Mastitis Test results
Necropsy findings Peracute, acute, and
chronic (recurrent) clinical mastitis,
subclinical mastitis common
Diagnostic confirmation Culture milk
for pathogen

Differential diagnosis

• Peracute mastitis

• Peracute coliform mastitis

• Arcanobacterium (formerly Actinomyces
or Corynebacterium ) pyogenes mastitis

• Parturient paresis

• Acute and chronic mastitis. Not
clinically distinguishable from other
causes of mastitis. Must culture milk

Treatment

• Lactating cows - cure rates for
lactating cows with subacute
staphylococcal mastitis less than 50%.
Intramammary infusions daily for at
least 3 days, preferably 5-8 days

• Peracute mastitis - antimicrobial
agents parenterally and intramammary
that are beta-lactamase-resistant, fluid
and electrolyte therapy

• Dry cow therapy - chronic or
subclinical mastitis best treated at
drying off with long-acting
intramammary antimicrobial infusions
that are beta-lactamase-resistant

Control

• Prevent new infections by early
identification, culling infected cows and
good milking procedures, including
hygienic washing and drying of udders
and teats before milking and
postmilking germicidal teat dips.

Regular milking machine maintenance.
Consider segregation of infected cows

• Eliminate existing infections by dry cow
therapy

• Immunization with vaccines may be
possible in future

ETIOLOGY

Coagulase-positive S. aureus is a major
pathogen of the bovine mammary gland

and a common cause of contagious mastitis
in cattle. S. aureus also causes mastitis in
sheep and goats.

EPIDEMIOLOGY

Occurrence and prevalence of

infection

Coagulase-positive staphylococci
Historically, S. aureus was one of the most
common causes of bovine mastitis in
dairy cattle worldwide. In the last 25 years,
the prevalence of infection and the occur-
rence of clinical mastitis due to S. aureus
has decreased in herds using effective
mastitis control measures. However,
surveys indicate that 50-100% of herds
may be infected. In low-SCC herds, the
prevalence of infection in cows ranges
from 1-10%. In other herds, especially
those with high SCCs, up to 50% of cows
may be infected with S. aureus, with
quarter infection rates ranging from
10-25%. The prevalence of infection of
S. aureus in heifers at parturition can range
from 5-15%. The majority of intra-
mammary infections due to S. aureus
are subclinical. The incidence of clinical
mastitis due to S. aureus is dependent on
its prevalence of infection in the herd.
With an effective mastitis control program,
the most common causes of clinical mas-
titis are the environmental pathogens.
However, in some herds with a low rolling
SCC, incidence of clinical mastitis due
to S. aureus ranges from 190-240 cases/
100 cows/year, with about 47% of the clini-
cal cases being S. aureus .’

Source of infection and method of
transmission

S. aureus is ubiquitous in the environment
of dairy cattle. The infected mammary
gland of lactating cows is the major
reservoir and source of the organism. 2 The
prevalence of intramammaiy infection in
primiparous heifers at parturition ranges
from 2-50% and may represent an
important reservoir of infection in herds
with a low prevalence of infection. The
organism may be present on the skin of
the teats and external orifices of heifers,
bedding materials, feedstuffs, housing
materials, nonbovine animals on the
farm, and equipment. In herds with a
high prevalence of infection (> 10% of
cows), the organism was present in
bedding, the hands and noses of dairy
herd workers, insects and water supplies. 2
Transmission between cows occurs at the
time of milking by contaminated milkers'
hands and teat cup liners. Although
S. aureus can multiply on the surface of
the skin and provide a source of infection
for the udder, the teat skin lesions are
usually infected originally from the udder,

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

and teat skin is a minor source of
infection.

The hornfly (Hameotobia irritans ) is an
important vector for transmitting S. aureus
mastitis in heifers, particularly in herds
with scabs on the teat ends of heifers. 3,4
Prevention of high populations of flies in
heifers is therefore needed to decrease
new infections in this group.

Risk factors

Animal risk factors

Several animal risk factors influence the
prevalence of infection and the occur-
rence of clinical mastitis due to S. aureus.

Local defense mechanisms
Abrasions of the teat orifice epithelium
are an important risk factor for S. aureus
mastitis. 3 In experiments, teat canal infec-
tion or colonization may develop in 93%
of experimentally abraded teat canal
orifices compared to 53% in control
quarters. Chapping of the teats and thick-
ness of the teat barrel are correlated
and significantly influence recovery of
S. aureus from the skin. 6

Colonization with minor pathogens
The presence of minor pathogens such as
coagulase-negative staphylococci protects
against new intramammary infections
associated with the major pathogen
S. aureus. 7 This may be the result of an
elevated SCC or an antimicrobial-like
substance provided by the coagulase-
negative staphylococci that inhibits the
growth of S. aureus. Conversely, quarters
infected with coagulase-negative staphy-
lococci may be more susceptible to
new infections with S. agalactiae. Quarters
that are infected with C. bowl's are pro-
tected against S. aureus infection but not
protected against most streptococcal
species.

Parity of cow

The prevalence of intramammary infec-
tion and subclinical infection due to
S. aureus increases with parity of the cow.
This is probably due to the increased
opportunity of infection with time and
the prolonged duration of infection,
especially in a herd without a mastitis
control program.

Presence of other diseases
The presence of periparturient diseases
such as dystocia, parturient paresis,
retained placenta and ketosis has been
identified as a risk factor for mastitis.The
occurrence of sole ulcers in multiple digits
may be associated with S. aureus in the
first lactation. 8

Heredity

Experimentally, the presence of certain
bovine lymphocyte antigens increased
the susceptibility to S. aureus infection' 1
but heritability estimates of susceptibility

after experimental challenge were low
and unstable.

Immune system

The infection rate of S. aureus is dependent
on the ability of the immune system to
recognize and to eliminate the bacteria. 10
Staphylococcal antibodies are present in
the blood of infected cows but they
appear to afford little protection against
mastitis associated with S. aureus. This
may be due to the low titer of the anti-
bodies in the milk. Antibody titers in the
serum rise with age and after an attack of
mastitis.

The development or persistence of
S. aureus mastitis depends on the inter-
action between invading bacteria and the
host's defense system, principally the
somatic cells in an infected gland, which
are more than 95% polymorphonuclear
cells. The number of bacteria isolated
from milk samples of S. aureus -infected
mammary glands is characterized by a
cyclic increase and decrease concomitant
with an inverse cycling of the SCC. This
relationship between SCC and numbers
of bacteria indicates that the cells within
the mammary gland have a central role in
the pathogenesis of S. aureus infection. 11
There appear to be qualitative changes in
the ability of the animal's somatic cells to
phagocytose the bacteria. During the
period of high SCC, the cells are able to
kill bacteria 9000 times more efficiently
than during the low-SCC period. The
relative inability of the polymorphonuclear
cells to kill bacteria during the low-SCC
period may explain the source of
reinfection. Phagocytosis and killing of the
bacteria may also be inefficient because of
low concentrations of opsonins, a lack of
energy source, and the presence of casein
and fat globules in the milk. The function of
the intramammary polymorphonuclear cell
(somatic cells) may also be affected by
immunosuppression induced by cortisol
and dexamethasone in treated cows. 12

Environmental and management risk
factors

Several herd-level management risk
factors are important for the spread of
S. aureus. 13 Fbor teat and udder cleaning
can allow spread of the organism among
quarters of the same cow, and can allow
contamination of milking units, which are
commonly transferred among cows
without washing or rinsing. The use of
high-line parlors is a risk; this may be due
to the greater fluctuation in vacuum,
especially when units are removed, lead-
ing to a greater occurrence of teat end
impacts in which bacteria in the milking
unit may enter the teat canal to establish
a new udder infection.

Extensive surveys reveal that manage-
ment procedures that are most effective in

reducing infection rates and cell counts
associated with infections with S. aureus
are:

° Postmilking teat dipping
° Maintaining a good supply of dry
bedding for housed cows
° Thorough disinfection of the teat
orifice before infusing intramammary
preparations

° Milking clinical cases last.

Failure to use these management tech-
niques will increase the risk of intra-
mammary infection with S. aureus.

Pathogen risk factors
Virulence factors

S. aureus has several virulence factors that
account for its pathogenicity and per-
sistence in mammary tissue in spite of
adequate defense mechanisms and anti-
microbial therapy. Most isolates from
cattle appear to be host-adapted and
different from human S. aureus isolates.
S. aureus has the ability to colonize the
epithelium of the teat and the streak
canal, and can adhere and bind to
epithelial cells of the mammary gland.
The specific binding is to the extracellular
matrix proteins fibronectin and collagen,
which can induce the epithelial cell to
internalize the organism, protecting it
from both exogenous and endogenous
bactericidal factors. Some strains of
S. aureus are capable of invading bovine
mammary epithelial cells in culture,
and the invasion process requires eukaryotic
nucleic acid and protein synthesis as well
as bacterial synthesis. 14

Some strains of S. aureus produce
toxins, some of which may cause phago-
cytic dysfunction. The beta toxin, or a
combination of alpha toxins and beta
toxins, is produced by most pathogenic
strains isolated from cattle but its pathog-
enic significance is uncertain. The beta
toxin damages bovine mammary secretory
epithelial cells, increases the damaging
effects of alpha toxin, increases the
adherence of S. aureus to mammary
epithelial cells and increases the prolifer-
ation of the organism. 15 All strains produce
coagulase (hence the term coagulase
positive S. aureus), which converts
fibrinogen into fibrin; this appears to
assist the invasion of tissues. Leukocidin
produced by S. aureus may inactivate
neutrophils.

Many staphylococcal strains (coagulase-
negative and -positive) are able to produce
an extracellular exopolysaccharide layer
surrounding the cell wall. 16 This capsular
structure and its production of slime have
been associated with virulence against
host defense mechanisms.

A major pathogenic factor is the ability
of the organism to colonize and produce

Mastitis of cattle associated with common contagious pathogens

microabscesses in the mammary gland so
tli at it is protected from normal defense
mechanisms, including phagocytic activity
from neutrophils. The difficulty in removing
staphylococci from an infected quarter is
due largely to the bacteria's ability to
survive in intracellular sites. There is also an
ability to convert to a nonsusceptible
L-form when exposed to antimicrobial
agents, and to return to standard forms
when the antimicrobial is withdrawn.

Genotype of strains

Phage typing and ribotyping can be

used to classify strains from clinical and
subclinical S. aureus mastitis. 17

DNA fingerprinting techniques,
using polymerase chain reaction, are also
being used to differentiate various strains
of the organism. 18 A large number of
different types of S. aureus can be isolated
from cases of bovine mastitis but a few
types predominate within different
countries. 19 Surveys have found that only
a small number of genotypes cause most
cases of S. aureus mastitis, 18 which may be
useful information in determining the
dynamics of infection in a herd and how
infection spreads from cow to cow. Fine-
structure molecular epidemiological
analysis of S. aureus recovered from cows
in the USA and Ireland indicates that only
a few specialized clones of S. aureus are
responsible for the majority of cases of
bovine mastitis, and that these clones
have a broad geographical distribution. 2 *
A predominant strain is usually
responsible for most clinical and sub-
clinical S. aureus infections in a
herd , 21,22 and it is currently believed that
S. aureus is a clonal organism that spreads
from cow to cow. Moreover, most strains
isolated from milk are different from
strains isolated from the teat skin. In other
words, most S. aureus strains isolated from
mastitis demonstrate both host and site
specificity. 22 This has important impli-
cations in the control of mastitis associated
with S. aureus, as a rational and effective
strategy for control of intramammary
infections should be directed against clones
that commonly cause disease.

Economic importance

The overall prevalence of mastitis due
to S. aureus is much higher than for
S. agalactiae, and the need for culling
causes much greater economic con-
sequences. The risk of new infections is of
continuing concern. Response to treatment
is comparatively poor, and satisfactory
methods for the eradication of staphy-
lococcal mastitis from infected herds have
yet to be devised.

Zoonotic implications

The presence of S. aureus in market milk
may present a degree of risk to the

consumer because of the organism's j
capacity to produce enterotoxins and a I
toxic shock syndrome toxin, which cause i
serious food poisoning. Mastitic milk j
does not constitute any large risk for j
S. aureus enterotoxin food poisoning. 23 ■

PATHOGENESIS

The disease can be reproduced experi-
mentally by the injection of S. aureus
organisms into the udder of cattle and
sheep but there is considerable variation
in the type of mastitis produced. This does
not seem to be due to differences in
virulence of the strains used, although
strain variations do occur, but may be
related to the size of the inoculum used
or, more probably, to the lactational status
of the udder at the time of infection. It is
possible to induce S. aureus infection in
the bovine teat cistern; the teat tissues
are able to mount a marked local inflam-
matory response but in spite of large
numbers of neutrophils that invade the
teat, they are unable to control the infec-
tion, except when the numbers of bacteria
are low. 24

Infection during early lactation may
result in the peracute form of mastitis,
with gangrene of the udder. During the
later stages of lactation or during the dry
period new infections are not usually
accompanied by a systemic reaction but
result in the chronic or acute forms.
Chronic S. aureus mastitis in cows has
been converted to the peracute, gangrenous
form by the experimental production of
systemic neutropenia.

In the gangrenous form the death of
tissue is precipitated by thrombosis of
veins causing local edema and congestion
of the udder. S. aureus are the only bacteria
that commonly cause this reaction in the
udder of the cow, and the resulting
toxemia is due to bacterial toxins and
tissue destruction. Secondary invasion by
E. coli and Clostridium spp. contributes to
the severity of the lesion and production
of gas.

The pathogenesis of acute and chronic
S. aureus mastitis in the cow is the same,
the variation occurring only in degree of
involvement of mammary tissue. In both
forms each focus commences with an
acute stage characterized by proliferation
of the bacteria in the collecting ducts and,
to a lesser extent, in the alveoli. In acute
mastitis the small ducts are quickly
blocked by fibrin clots, leading to more
severe involvement of the obstructed
area.

In the chronic form there are fewer
foci of inflammation and the reaction is
milder; the inflammation is restricted to
the epithelium of the ducts. This subsides
within a few days and is replaced by
connective tissue proliferations around

the ducts, leading to their blockage and
atrophy of the drained area. The leukocyte
infiltration into the stroma, the epithelial
lining and the lumina indicate an obvious
deficiency of secretory and synthesizing
capacity due to limitation of the alveolar
lumina and the distension of the stroma
area.

A characteristic of chronic S. aureus
mastitis that is important in its diagnosis
is the cyclical shedding of the bacteria
from the affected quarter. Paralleling this
variation is a cyclical rise and fall in the
number of polymorphonuclear cells in
the milk, and their capacity to phago-
cytose bacteria. 11 In some cases abscesses
develop and botryomycosis of the udder,
in which granulomata develop containing
Gram-positive cocci in an amorphous
eosinophilic mass, is also seen.

CLINICAL FINDINGS

Chronic Staphylococcus aureus

mastitis

The most important losses are caused by
the chronic form or subclinical form of
mastitis. Although 50% of cattle in a herd
may be affected, only a few animals will
have abnormalities recognizable by the
milker. Many cases are characterized by a
slowly developing induration and atrophy
with the occasional appearance of clots in
the milk or wateriness of the first streams.
The SCC of the milk is increased, as well
as the CMT results of infected quarters,
but the disease may go unnoticed until
much of the functional capacity of the
gland is lost. The infection can persist and
the disease may progress slowly over a
period of many months.

Acute and peracute Staphylococcus
aureus mastitis

Acute and peracute staphylococcal mas-
titis are rare but do occur and can be fatal,
even if aggressively treated.

Acute S. aureus mastitis occurs most
commonly in early lactation. There is
severe swelling of the gland and the milk
is purulent or contains many thick clots.
Extensive fibrosis and severe loss of
function always result.

Peracute S. aureus mastitis occurs
usually in the first few days after calving
and is highly fatal. There is a severe
systemic reaction with elevation of the
temperature to 41-42°C (106-107°F),
rapid heart rate (100-120 beats/min),
complete anorexia, profound depression,
absence of ruminal movements and
muscular weakness, often to the point of
recumbency. The onset of the systemic
and local reactions is sudden. The cow
may be normal at one milking and
recumbent and comatose at the next. The
affected quarter is grossly swollen, hard
and sore to touch, and causes severe
lameness on the affected side.

700

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

Gangrene is a constant development
and may be evident very early. A bluish
discoloration develops that may eventually
spread to involve the floor of the udder
and the whole or part of the teat, or may
be restricted to patches on the sides and
floor of the udder. Within 24 hours the
gangrenous areas become black and ooze
serum and may be accompanied by sub-
cutaneous emphysema and the formation
of blisters. The secretion is reduced to a
small amount of bloodstained serous fluid
without odor, clots or flakes. Unaffected
quarters in the same cow are often
swollen, and there may be extensive
subcutaneous edema in front of the udder
caused by thrombosis of the mammary
veins. Toxemia is profound and death
usually occurs unless early, appropriate
treatment is provided. Even with early
treatment the quarter is invariably lost
and the gangrenous areas slough.
Separation begins after 6-7 days, but
without interference the gangrenous part
may remain attached for weeks. After
separation, pus drains from the site for
many more weeks before healing finally
occurs.

CLINICAL PATHOLOGY
Culture of individual cow milk

Bacteriological culture of milk is the best
method for identifying cows with
S. aureus intramammary infection. 23 A
problem in the laboratory identification of
S. aureus is that bacteria are shed
cyclically from infected quarters, so
that a series of samples are necessary
to increase overall test sensitivity. The
sensitivity of a single sample may be as
low as 75%. Factors that have the greatest
impact on the sensitivity of culture, in order
of importance, are:

0 The type of milk sample
0 The volume of milk cultured
° The time interval between repeated
milk sample collection strategies. 26

Quarter samples taken on day 1 and
repeated either on day 3 or 4, and
cultured separately using 0.1 mL of milk
for culture inoculum, were predicted to
have sensitivities of 90-95% and 94-99%,
respectively. 26 Repeated quarter samples
collected daily and cultured separately
gave a sensitivity of 97% and a specificity
from 97-100%. 2 ' Culturing of composite
milk samples instead of individual quarter
samples increases the number of false-
negative results in diagnosing S. aureus
mastitis, 28 but the sensitivity of composite
samples can be increased by using 0.05 mL
of milk for inoculation. Freezing of milk
samples before processing either does not
affect the bacterial count or enhances it by
about 200%; the latter response is attri-
buted to fracturing of cells containing

viable S. aureus bacteria. Bacterial counts
of more than 200 cfu/mL are commonly
used as a criterion for a positive diagnosis
of infection.

Culture of bulk tank milk

The culture of 0.3 mL of bulk tank milk
for S. aureus using special Baird-Parker
culture media is a practical method for
detecting the organism in bulk tank milk
and monitoring its spread in dairy
herds; 29 the sensitivity and specificity for
detection of the bacteria ranged from
90-100%.

Somatic cell counts and California
Mastitis Test

In an attempt to decrease the cost of
sampling all quarters for culture, an
alternative strategy is to use the SCC as a
screening test in order to identify which
cows to culture for S. aureus. For all intra-
mammary infections, the sensitivity and
specificity of SCC range from 15-40% and
92-99%, respectively. Composite milk
sample SCCs have a low sensitivity,
ranging from 31-54% for detecting cows
with S. aureus. 2 ' Individual quarter SCCs
have a higher sensitivity, ranging from
71-95% depending on the study and
cutpoint chosen, but quarter sampling is
impractical as SCC is usually performed
on a composite sample. 30 Both composite
and quarter milk SCC testing result in an
unacceptably high proportion of infected
cows being missed, 27-30 and are therefore
not currently recommended as a screen-
ing test if the goal is to identify all cows
with a S. aureus intramammary infection
in the herd.

The CMT has also been used as a
screening test to identify quarters or cows
to culture. Using a CMT trace, 1, 2, or 3 to
indicate the presence of an intra-
mammary infection produced a range of
sensitivities from 0.47-0.96 and specificities
of 0.41-0.80. 30

In summary, culture of quarter milk
samples (preferably) or a composite milk
sample is superior to a quarter SCC or
CMT for the diagnosis of S. aureus intra-
mammary infection. 30 Culture is strongly
preferred if it is important to identify all
positive cows in a herd because the sen-
sitivity of indirect tests (such as SCC,
CMT) is inadequate.

Enzyme-linked immunosorbent
assays for antibody in milk

ELISA tests for detecting S. aureus anti-
body in milk have been developed 25-31 but
are not widely used. Rapid laboratory tests
incorporating these ELISAs, including a
Staph-zym test, have demonstrated 84-90%
accuracy in identifying staphylococci. 32

Acriflavine disk assay

The acriflavine disk assay is a practical,
accurate method for differentiating

S. aureus isolates from non-S. aureus
staphylococci. 33

NECROPSY FINDINGS

In peracute staphylococcal mastitis, the
affected quarter is grossly swollen and
may contain bloodstained milk dorsally
but only serosanguineous fluid ventrally.
There is extreme vascular engorgement
and swelling, often progressing to moist
gangrene of the overlying skin. Bacteria
are not isolated from the bloodstream or
tissues other than the mammary tissue
and regional lymph nodes. H istologically
there is coagulation necrosis of glandular
tissue and thrombosis of veins.

In milder forms of staphylococcal mas-
titis the invading organisms often elicit a
granulomatous response. Microscopically,
such 'botryomycotic' cases are characterized
by granulomas with a central bacterial
colony and by progressive fibrosis of the
quarter.

Samples for confirmation of
diagnosis

° Bacteriology - chilled mammary
tissue, regional lymph node
° Histology - fixed mammary tissue.

DIFFERENTIAL DIAGNOSIS

Because of the occurrence of the peracute
form in the first few days after parturition,
the intense depression and inability to rise,
the dairy producer may conclude that the
cow has parturient paresis, which is
characterized by weakness, recumbency,
hypothermia, rumen stasis, dilated pupils,
tachycardia with weak heart sounds and a
rapid response to intravenous calcium
gluconate. The mammary gland is usually
normal in parturient paresis.

Peracute 5. aureus mastitis is
characterized by marked tachycardia, fever,
weakness and evidence of severe clinical
mastitis with swelling, heat, abnormal milk
with serum and blood, and sometimes gas
in the teat and often with gangrene of the
teat up to the base of the udder. Other
bacterial types of mastitis, particularly
E. coli and A. pyogenes, may cause severe
systemic reactions but gangrene of the
quarter is less common.

Peracute coliform mastitis is a much
more common cause of severe mastitis
than 5. aureus mastitis. The chronic and
acute forms of staphylococcal mastitis are
indistinguishable clinically from many other
bacterial types of mastitis and
bacteriological examination is necessary for
identification.

TREATMENT

The bacteriological cure rates for the
treatment of S. aureus mastitis with either
intramammary infusion or parenteral
antimicrobial administration are notoriously
less than satisfactory, particularly in the
lactating cow. Bacteriological cure rates
after antimicrobial treatment seldom

Mastitis of cattle associated with common contagious pathogens

701

exceed 50% and infections commonly
persist throughout the lifetime of the cow.
There are three likely reasons: inadequate
penetration of the antimicrobial agent to
the site of infection, formation of L-forms
of S. aureus, and beta-lactamase production.

Inadequate penetration of antimicrobial
agent

There is inadequate penetration of the
antimicrobial agent into the site of
intramammary infection in the lactating
cow and the organism survives in
phagocytes that are inaccessible. There
may also be inactivation of the anti-
microbial by milk and serum constituents,
and the formation of L-forms of the organ-
ism during treatment, varying between
0% and 80% of bacteria.

Antimicrobial resistance
Antimicrobial resistant strains of

S. aureus occur and are often beta-lactamase
producers, the enzyme conferring resist-
ance to beta-lactam antimicrobial agents
such as penicillin G, penethamate,
ampicillin and amoxicillin. Cloxacillin and
nafcillin are effective, but only against
Gram-positive bacteria; they are less
effective against nonlactamase staphy-
lococci. Clavulanic acid added to amoxi-
cillin overcomes this beta-lactamase
resistance. So does cloxacillin added to
ampicillin, and this is made use of in a
popular intramammary formulation. First -
and third-generation cephalosporins and
erythromycin are effective against beta-
lactamase-producing staphylococci, and
first- and third-generation cephalosporins
are also effective against Gram-negative
bacteria. A cephapirin dry cow product
administered to heifers with S. aureus
infections resulted in bacteriological cure
and left the quarters clear well into their first
lactation. 34 Intramammaiy cloxacillin and
ampicillin is generally considered to be the
preferred initial treatment for S. aureus
mastitis becausebeta-lactamase production
by S. aureus is sufficiently common.

Antimicrobial therapy for S. aureus
subclinical mastitis during the lactating
period is not economically attractive
because of low bacteriological cure rates,
discarding of milk during the withholding
period and the lack of an economically
beneficial increase in production follow-
ing treatment. Dry cow treatment at the
end of lactation is much more effective,
being successful in 40-70% of cases,
although treatment should be attempted
in heifers infected early in lactation. Cows
that are infected with S. aureus should be
appropriately identified, segregated if
possible and milked last or with separate
milking units. 35 Culling of infected cows
is also an option for consideration, but a
detailed economic analysis of this popular
recommendation is lacking.

Lactating cow therapy

The treatment of clinical cases of S. aureus
mastitis using intramammary anti-
microbial infusions is less than satis-
factory but is often done. However,
clinical recovery following therapy does
not necessarily eliminate the infection
and some of the published literature on
cure rates has not made the distinction
between clinical and bacteriological cure
rates. In general, the cure rate depends on
the duration of infection, the number of
quarters infected, whether the strain of
S. aureus is a beta-lactamase producer, the
immune status of the cow, the anti-
microbial agent administered and the
duration of treatment. Current recommen-
dations to ensure the best treatment success
rate are to combine intramammaiy and
parenteral antimicrobial treatment or use
extended intramammary treatment for
4-8 days. Penicillin G is regarded as the
antimicrobial agent of choice for S. aureus
strains that are penicillin-sensitive. 22

The following intramammary infu-
sions, given daily at 24-hour intervals for
three treatments (unless stated other-
wise) have been used for the treatment of
clinical cases of S. aureus mastitis, with
expected clinical cure rates of about
30-60% in lactating cows. Subclinical
cases are left until the cow is dried off:

° Sodium cloxacillin (200-600 mg for
three infusions)

° Tetracyclines (400 mg)

° Penicillin-streptomycin combination
(100 000 units - 250 mg)

° Penicillin-tylosin combination
(100 000 units - 240 mg)

° Novobiocin (250 mg per infusion for
three infusions)

° Cephalosporins - most strains of
S. aureus are sensitive to cephapirin 36
° Pirlimycin-extended therapy (two
50 mg doses, 24 hours apart, then
36-hour withhold, then cycle repeated
twice, equivalent to infusing at 0, 24,
60, 84, 120, and 144 hours).

In a study of 184 cases of subclinical
S. aureus mastitis in New York, com-
mercially available intramammaiy infusions
were not significantly more effective than
untreated controls (43% bacteriological
cure), with the following bacteriological
cure rates: erythromycin (65%), penicillin
(65%), cloxacillin (47%), amoxicillin
(43%), and cephapirin (43%). 37

A slightly more effective treatment for
subclinical S. aureus intramammaiy infec-
tion, with a cure rate of 50%, is simu-
ltaneous intramammary infusion of
amoxicillin (62.5 mg) and intramuscular
injection of procaine penicillin G (9 000 000
units). 38 This study was the first to demon-
strate that combined parenteral and intra-
mammary therapy was more effective

than intramammary infusion alone.
Because of the persistence of the infection
in each herd the final choice of the
antimicrobial to be used should be based
on a culture and susceptibility test; the
latter is to determine whether the pre-
dominant S. aureus strain in the herd is a
beta-lactamase producer; this is because
beta-lactamase-producing strains are
harder to cure and require a specific
antibiotic protocol . 22 The bacteriological
cure rate for penicillin-sensitive infections
treated with parenteral and intramammaiy
penicillin G was 76%, compared to beta-
lactamase-producing strains treated with
parenteral and intramammaiy amoxicillin-
clavulanic acid (29%). 22

The application of cytokines as an
adjunct to antimicrobial therapy may help
to increase the number of phagocytes in
the mammary gland and enhance cell
function. The experimental intra-
mammary infusion of recombinant inter-
leukin into infected or uninfected mammary
glands elicited an influx of polymorpho-
nuclear leukocytes exhibiting subsequent
enhanced activity and increased the cure
rate 20-30% in quarters infected with
S. aureus. 39

A novel method for decreasing the
transmission of S. aureus within a herd is
to selectively cease lactation in infected
quarters of lactating cattle. 40 The best
method for permanently drying off a
quarter is infusion of 120 mL of 5%
povidone-iodine solution (0.5% iodine)
after complete milk-out and adminis-
tration of flunixin meglumine (1 mg/kg
BW, intravenously). Therapeutic cessation
of milk production in one quarter does
not alter daily milk production but does
decrease individual cow SCC and its
contribution to the bulk tank milk SCC.
The final outcome of selectively drying off
infected quarters is a decrease in the rate
of new intramammaiy infections in the
herds and a lowering in the bulk tank
milk SCC.

Peracute mastitis

Early parenteral treatment of peracute
cases with adequate does of anti-
microbials such as trimethoprim-
sulfonamide or penicillin is deemed
necessary to improve the survival rate.
When penicillin is used the initial intra-
muscular injection should be supported
by an intravenous dose of crystalline
penicillin, with subsequent intramuscular
doses to maintain the highest possible
blood level of the antimicrobial over a
4-6-day period; tamethicillin or penthemate
hydriodide are preferred to achieve this.
Intramammary infusions are of little value
in such cases because of failure of the
drugs to diffuse into the gland. The intra-
venous administration of large quantities

i2

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

of electrolyte solutions is also rec-
ommended. Hypertonic saline, as rec-
ommended for peracute coliform mastitis,
has not yet been evaluated but may be
indicated. Frequent massage of the udder
with hot wet packs and milking out the
affected gland is recommended. Oxytocin
is used to promote milk-down but is
relatively ineffective in severely inflamed
glands. Surgical amputation of the teat
may be indicated to promote drainage of
the gland, but only in cows with necrotic
teats.

Dry cow therapy

It has become a common practice to leave
chronic S. aureus cases until they are dried
off before attempting to eliminate the
infection. The material is infused into
each gland after the last milking of the
lactation and left in situ. The major
benefits of dry cow therapy are the elimi-
nation of existing intramammary
infections and prevention of new intra-
mammary infections during the dry
period. In addition, milk is not discarded
and bacteriological cure rates are superior
to those obtained during lactation.

The factors associated with a bacterio-
logical cure after dry cow therapy of sub-
clinical S. aureus mastitis have been
examined. 41 The probability of cure of an
infected quarter decreased when:

0 SCC increased
« Age of cow increased
0 Another quarter was infected in the
same cow

° The infection was in a hind quarter
« The percentage of samples that were
positive for S. aureus was higher
before drying off.

Cows with more than one infected quarter
were 0.6 times less likely to be cured than
cows with one infected quarter. The cure
rate of quarters affected with S. aureus can
be predicted using a formula which
considers several cow factors and quarter
factors. 41 The prediction of the probability
of cure in an 8-year-old cow with three
quarters infected with the organism and a
SCC of 2300 000 is 36%. In a 3-year-old
cow with one quarter infected and a SCC
of 700 000, the probability of cure is 92%.
This information is often available at
drying off and can be used to select cows
that are unlikely to be cured to be
removed from the herd by designating
them as'do not breed' and culling when it
is economically opportune.

Most intramammary antimicrobial
infusions are satisfactory for dry cow
therapy provided they are combined with
slow-release bases. Bacteriological cure
rates vary between herds from 25-75%
and average about 50%. 42 The use of par-
enteral antimicrobials such as oxytetra-

cycline along with an intramammary
infusion of cephapirin did not improve
the cure rate for S. aureus. n

CONTROL

Because of the relatively poor results
obtained in the treatment of staphylococcal
mastitis, any attempt at control must
depend heavily on effective methods of
preventing the transmission of infection
from cow to cow S. aureus is a contagious
pathogen, the udder is the primary site of
infection, and hygiene in the milking
parlor is of major importance. To reduce
the source of the organism, a program of
early identification, culling, and segre-
gation is important to control S. aureus
mastitis in a dairy herd, although success-
ful implementation of all three aspects
is challenging. Satisfactory control of
S. aureus mastitis has historically been
difficult and unreliable; however, at the
present time the quarter infection rate
can be rapidly and profitably reduced
from the average level of 30% to 10%
or less.

The strategies and practices described
under the control of bovme mastitis later
in this chapter are highly successful for
the control of S. aureus mastitis when
applied and maintained rigorously. The
control program includes:

0 Hygienic washing and drying of
udders before milking
° Regular milking-machine
maintenance

° Teat dipping after milking. Teat
dipping in 1% iodine or 0.5%
chlorhexidine, either in 5-10%
glycerine, is completely effective
against S. aureus mastitis. 43 The
program helps to eliminate infected
quarters and reduces the new
infection rate by 50-65% compared to
controls. The disinfection of hands or
use of rubber gloves provides
additional advantages
° Dry cow treatment on all cows
° Culling cows with chronic mastitis
° Milking infected cows last (very
difficult to implement in free stall
housing or pasture feeding).

An alternative but radical control strategy
when all else has failed is to permanently
dry off the infected quarter using iodine
infusion.

Immunization against S. aureus mastitis
has been widely researched for 100 years.
Different vaccines based on cellular or
soluble antigens with and without adju-
vants have been given to dairy cows but
protection against infection and clinical
disease has been unsatisfactory when
used in the field. Currently available
vaccines are autogenous bacterins (made

to order using isolates from clinical cases
on the farm) or contain one or more
S. aureus strains that are believed to
provide good cross-protection. The goals
of such vaccines are to decrease the
severity of clinical signs and increase the
cure rate, particularly when administered
to heifers before they calve. Vaccination
has also been used simultaneously with
antimicrobial therapy during lactation or
at dry-off in an attempt to augment the
cows immune response, with mixed
success. 21 Development of an effective
S. aureus vaccine remains one of the most
important issues confronting control of
infectious diseases in cattle.

REVIEW LITERATURE

Sears PM. Management and treatment of staphy-
lococcal mastitis. Vet Clin North Am Food Anim
Pract 2003; 19:171-185.

REFERENCES

1. Torgerson PR et al.Vet Rec 1992; 130:54.

2. Roberson JR et al. J Dairy Sci 1994; 77:3354.

3. Gillespie BE et al. J Dairy Sci 1999; 82:1581.

4. Owens WE et al. Am J Vet Res 1998; 59:1122.

5. MyllysV et al. J Dairy Sci 1994; 77:446.

6. Fox LK, Cummings MS. J Dairy Res 1996; 63:369.

7. Nickerson SC, Boddie RL. J Dairy Sci 1994;
77:2526.

8. Enevoldsen C et al. J Dairy Res 1995; 62:69.

9. Schukken YH et al. J Dairy Sci 1994; 77:639.

10. Daley MJ, Hayes P. CornellVet 1992; 82:1.

11. Daley MJ et al. Am J Vet Res 1991; 52:474.

12. Burton JL, Kehill ME Jr. Am JVet Res 1995; 56:997.

13. Bartlett PC, Miller GY.PrevVetMed 1993; 17:33.

14. Almeida RA et al. JVet Med B 1997; 44:139.

15. Cifrian E et al.Vet Microbiol 1996; 48:187.

16. Baselga R et al.Vet Microbiol 1994; 39:195.

17. Aaerstrup FM et al. Can JVet Res 1995; 59:124.

18. LamTJGM et al. Am JVet Res 1996; 57:39.

19. Aaerstrup FM et al. Acta Vet Scand 1995; 38:243.

20. Fitzgerald JR et al. Epidemiol Infect 1997;
119:261.

21. Luby CD, Middleton JR. Vet Rec 2005; 157:89.

22. Smith EM et al. J Clin Microbiol 2005; 43:4737.

23. Aarestrup FM et al. Acta Vet Scand 1995;
36:273.

24. Persson K et al. JVet Med B 1995; 42:435.

25. Hicks CR et al. J AmVet Med Assoc 1994; 204:253.

26. Buelow KL et al. PrevVet Med 1996; 25:343.

27. Buelow KL et al. PrevVet Med 1996; 26:1.

28. Lam TJGM et al. J Am Vet Med Assoc 1996;
208:1705.

29. Ollis GW et al. Can Vet J 1995; 36:619.

30. Middleton JR et al. J AmVet Med Assoc 2004; 224:
419.

31. Matsushita T et al. J Vet Diagn Invest 1990; 2:163.

32. Watts JL, Washburn PJ. J Clin Microbiol 1991;
29:59.

33. Wallace RL et al. J Am Vet Med Assoc 1998;
213:394.

34. Owens WE et al. J Dairy Sci 1991; 74:3376.

35. Wilson DJ et al. J Dairy Sci 1995; 78:2083.

36. Lopes CAM, Moreno G. Res Vet Sci 1991; 51:339.

37. Wilson DJ et al. J Dairy Sci 1999; 82:1664.

38. Owens WE et al. J Dairy Sci 1988; 71:3143.

39. Sanchez MS et al. J Dairy Sci 1994; 77:1251.

40. Middleton JR, Fox LK. J Dairy Sci 2001; 84:1976.

41. Sol J et al. J Dairy Sci 1994; 77:75.

42. Erskine RJ et al. J Dairy Sci 1994; 77:3347.

43. Fox LK. J Dairy Sci 1992; 75:66.

Mastitis of cattle associated with common contagious pathogens

703

STREPTOCOCCUS AGALACTIAE

Etiology Streptococcus agalactiae is a
major pathogen of the mammary gland
and a common cause of contagious bovine
mastitis

Epidemiology Major cause of mastitis in
dairy herds without an effective mastitis
control program. Prevalence of infection
10-50% of cows and 25% of quarters. In
herds with effective control program
prevalence less than 10% of cows. Can be
eliminated from herd with treatment and
control. Highly contagious obligate
pathogen. Infection is transmitted at
milking

Clinical findings Individual repeated
episodes of subacute to acute mastitis are
most common. Gland is swollen, warm,
and milk is watery and contains clots.
Gradual induration of udder if not treated
Clinical pathology Culture of individual
cow milk samples or bulk tank milk
samples. Latex agglutination test
Necropsy findings Not important
Diagnostic confirmation Latex
agglutination test for specific identification
of organism

Differential diagnosis Cannot
differentiate clinically from other causes of
acute and chronic mastitis. Must culture
milk

Treatment Mastitis associated with
S. agalactiae in lactating cows is sensitive
to intramammary therapy with wide variety
of antimicrobial agents resulting in high
rate of clinical and bacteriological cures.
Blitz therapy (simultaneous treatment of all
positive cows in a herd) commonly used to
reduce prevalence of infection in herd
Control Eradication is possible. Identify
and treat infected quarters, cull incurable
cows. Premilking teat and udder sanitation,
postmilking teat dipping, and dry cow
therapy

ETIOLOGY

Streptococcus agalactiae. Infections with
environmental streptococci are described
in the next section.

EPIDEMIOLOGY

Occurrence and prevalence of

infection

S. agalactiae was the major cause of mas-
titis before the antimicrobial era and is
still a significant cause of chronic mastitis
where control procedures for contagious
mastitis are not used. 1 Herd prevalence
rates of infection range from 11-47%.
Typically, in a herd infected with the
pathogen, the prevalence of infection
could be as high as 50% of cows, but
more recent surveys indicate much lower
within -herd prevalences, ranging from
8-10%.’ Where good hygienic measures
and the efficient treatment of clinical
cases are in general use, the prevalence of
infection within a herd will be less than

10% of cows. Following the use of anti-
microbial agents, S. agalactiae was super-
seded by Staphylococcus aureus as the
major cause of bovine mastitis. In herds
with a high bulk tank milk SCC, the prob-
ability is high that S. agalactiae infection is
the most prevalent pathogen.

Source of infection

S. agalactiae is a highly contagious obligate
parasite of the bovine mammary gland.
The main source of infection is the udder
of infected cows although, when hygiene
is poor, contamination of the environment
may provide an additional source. The
teats and skin of cattle, milkers' hands,
floors, utensils and clothes are often
heavily contaminated. Sores on teats are
the commonest sites outside the udder
for persistence of the organism. The infec-
tion may persist for up to 3 weeks on hair
and skin and on manure and bricks. The
importance of environmental contami-
nation as a source of infection is given
due recognition in the general disinfection
technique of eradication.

Transmission of infection

Transmission from animal to animal
occurs most commonly by the medium of
milking machine liners, hands, udder
cloths and possibly bedding.

The streak canal is the portal of entry,
although there is doubt as to how
invasion into the teat canal and then
gland occurs. Suction into the teat during
milking or immediately afterwards does
occur, but growth of the bacteria into the
canal between milkings also appears to
be an important method of entry. It is
difficult to explain why heifers that have
never been milked may be found to
be infected with S. agalactiae, although
sucking between calves after ingestion of
infected milk or contact with infected
inanimate materials may be sources of
infection.

Risk factors

There is no particular breed susceptibility
but infection does become established
more readily in older cows and in the
early part of each lactation. Fbor hygiene,
incompetent milking personnel and
machinery that is faulty or maladjusted
are important risk factors. The most
important risk factors are the failure to
use postmilking teat dip and the selec-
tive or non-use of dry cow therapy The
use of a common wash rag or sponge is
also a risk factor. Inadequate treatment of
clinical cases of mastitis is also a frequent
risk factor in infected herds.

S. agalactiae has the ability to adhere to
the mammary gland tissue, and the specific
microenvironment of the udder is necess-
ary for growth of the organism. The
virulence of various strains of the organ

ism is related to differences in their ability
to adhere to the mammary epithelium.
Bacterial ribotyping has been used to
characterize strains of the organism to
determine their geographical distribution. 2
The physical characteristics of the teat
canal may influence the susceptibility to
streptococcal infection. 3 The mechanisms
used by S. agalactiae to penetrate the teat
canal are influenced more by the diameter
of the teat canal lumen, as reflected by the
peak flow rate, than by teat canal length.

Economic importance

The disease is of major economic import-
ance in milk production. In individual
cows, the loss of production associated
with S. agalactiae mastitis is about 25%
during the infected lactation, and in
affected herds the loss may be of the order
of 10-15% of the potential production.
Reduction of the productive life represents
an average loss of one lactation per cow in
an affected herd. Deaths due to S. agalactiae
infection rarely if ever occur and complete
loss of productivity of a quarter is un-
common, the losses being incurred in the
less dramatic but no less important fashion
of decreased production per cow.

PATHOGENESIS

When the primary barrier of the streak
canal is passed, if bacteria are not flushed
out by the physical act of milking they
proliferate and invasion of the udder
tissue follows. There is considerable vari-
ation between cows in the developments
that occur at each of the three stages of
invasion, infection and inflammation. The
reasons for this variation are not clear but
resistance appears to depend largely on
the integrity of the lining of the teat canal.
After the introduction of infection into
the teat, the invasion, if it occurs, takes
1-4 days and the appearance of inflam-
mation 3-5 days. Again there is much
variation between cows in the response to
tissue invasion, and a balance may be set
up between the virulence of the organism
and undefined defense mechanisms of
the host so that very little clinically
detectable inflammation may develop
despite the persistence of a permanent
bacterial flora.

The development of mastitis associ-
ated with S. agalactiae is essentially a pro-
cess of invasion and inflammation of
lobules of mammary tissue in a series of
crises, particularly during the first month
after infection, each crisis developing in
the same general pattern. Initially there is
a rapid multiplication of the organism in
the lactiferous ducts, followed by passage
of the bacteria through the duct walls into
lymphatic vessels and to the supra-
mammary lymph nodes, and an out-
pouring of neutrophils into the milk
ducts. At this stage of initial tissue invasion,

704

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

a shortlived systemic reaction occurs and
the milk yield falls sharply as a result of
inhibition and stasis of secretion caused
by damage to acinar and ductal epithelium.
Fibrosis of the interalveolar tissue and
involution of acini result even though the
tissue invasion is quickly cleared. Sub-
sequently, similar crises develop and more
lobules are affected in the same way, result-
ing in a stepwise loss of secretory function
with increasing fibrosis of the quarter and
eventual atrophy.

The clinicopathological findings

vary with the stage of development of the
disease. Bacterial counts in the milk are
high in the early stages but fall when the
SCC rises at the same time as swelling of
the quarter becomes apparent. In some
cases bacteria are not detectable culturally
at this acute stage. The SCC rises by
10-100 times normal during the first
2 days after infection and returns to
normal over the next 10 days. The febrile
reaction is often sufficiently mild and
shortlived to escape notice. When the
inflammatory changes in the epithelial
lining of the acini and ducts begin to
subside, the shedding of the lining results
in the clinical appearance of clots in the
milk. Thus the major damage has already
been done when clots are first observed.
At the stage of acute swelling, it is the
combination of inflamed interalveolar
tissue and retained secretion in distended
alveoli that causes the swelling. Removal
of the retained secretion at this stage may
considerably reduce the swelling and
permit better diffusion of drugs infused
into the quarter. Inflammatory reactions
also occur in the teat wall of affected
quarters.

The variations in resistance between
cows and the increased susceptibility with
advancing age are unexplained. Honnonal
changes and hypersensitivity of mam-
mary tissue to streptococcal protein have
both been advanced as possible causes of
the latter. Local immunity of mammary
tissue after an attack probably does not
occur but there is some evidence to
suggest that a low degree of general
immunity may develop. The rapid dis-
appearance of the infection in a small
proportion of cows in contrast to the
recurrent crises that are the normal
pattern of development suggests that
immunity does develop in some animals.
The antibodies are hyaluronidase inhi-
bitors and are markedly specific for
specific strains of the organism. A non-
specific rise in other antibodies may occur
simultaneously and this is thought to
account for the field observations that co-
incident streptococcal and staphylococcal
infections are unusual and that the
elimination of one infection may lead to
an increased incidence of the other.

CLINICAL FINDINGS

In the experimentally produced disease,
there is initially a sudden episode of acute
mastitis, accompanied by a transient
fever, followed at intervals by similar
attacks, which are usually less severe. In
natural cases fever, lasting for a day or
two, is occasionally observed with the
initial attack but the inflammation of the
gland persists and the subsequent crises
are usually of a relatively mild nature.
These degrees of severity may be
classified as abnormal cow when the
animal is febrile and off its feed, abnor-
mal gland when the inflammation of the
gland is severe but there is no marked
systemic reaction, and abnormal milk
when the gland is not greatly swollen,
pain and heat are absent and the pre-
sence of clots in watery foremilk may be
the only apparent abnonnality. Induration
is most readily palpable at the udder
cistern and in the lower part of the udder,
and varies in degree with the stage of
development of the disease.

The milk yield of affected glands is
markedly reduced during each crisis but,
with proper treatment administered early,
the yield may return to almost normal.
Even without treatment the appearance
of the milk soon becomes normal but the
yield is significantly reduced and sub-
sequent crises are likely to reduce it
further.

CLINICAL PATHOLOGY

The CAMP test, which has served as the
universally used means of identifying
S. agalactiae for many years, has been
displaced by a commercial latex aggluti-
nation test, which contains specific
reagents necessary for the identification
of S. agalactiae and is suitable for general
laboratory use. 1 When used on isolates of
samples from bulk tankmilk, the sensitivity
and specificity are 97.6% and 98.2%,
respectively. An ELISA test correlates well
with the bulk tank milk SCC and provides
a suitable alternative. 1

The critical judgment to be made is
deciding when the quarter infection rate
is so high that control or eradication
measures are necessary. A decision can be
made on the basis of the bulk tank milk
SCC as an indicator of the prevalence of
mastitis on a quarter basis, and on culture
of the bulk tank milk sample to indicate
that S. agalactiae is the important patho-
gen, but this approach is too inaccurate to
be recommended. There seems to be no
alternative to carrying out bacteriological
culture and determining SCC on milk
samples from individual cows or quarters.
Milk samples collected for bacteriological
examination for the presence of S. agalactiae
can be stored in the frozen state. The
number of samples that will be culturally

positive when the stored frozen samples
are thawed will either be unchanged or
enhanced up to 200%; the latter response
is attributing to fracturing of cellular
debris containing S. agalactiae.

Culture from bulk tank milk samples

The presence of the organism in bulk tank
milk is due to shedding of bacteria from
infected quarters, with cyclic shedding
being typical. The specificity of culture
from bulk tank milk is very high; the
sensitivity is much lower but can be
increased by using selective media.

Total bacterial count

The total bacterial count in bulk tank milk
can be markedly increased due to the
presence of S. agalactiae mastitis in the herd.
Samples of bulk tank milk from infected
herds commonly contain bacterial counts
in the range of 20 000-100 000 cfu/mL,
because a cow in the early stages of infec-
tion can shed up to 100 000 000 bacteria/mL.
The standard plate count can drop from
100 000 to 2000 cfu/mL after implemen-
tation of a modified blitz therapy and
control program to control S. agalactiae.

Culture from individual cow samples

Composite milk samples are satisfactory,
as the number of cows identified as posi-
tive does not increase by quarter sampling. 1
The sensitivity and specificity of a single
culture from individual cows ranges
between 95% and 100%. 1

Somatic cell count

S. agalactiae produces high SCC in indivi-
dual cows, which has a significant influence
on the bulk tank milk SCC.

NECROPSY FINDINGS

The gross and microscopic pathology of
mastitis associated with S. agalactiae are
not of importance in the diagnosis of the
disease.

TREATMENT

S. agalactiae is very sensitive to intra-
mammary therapy using a wide variety of
commercially available intramammary
infusion preparations. Systemic therapy
is also effective but offers no advantages
over the intramammary route. Clinical
cases should be treated whenever they
occur because of the need to prevent
transmission to uninfected quarters and
cows. Subclinical cases identified at any
stage of lactation should be treated

The clinical diagnosis of 5. agalactiae
mastitis depends entirely on the isolation
of 5. agalactiae from the milk.
Differentiation from other types of acute
and chronic mastitis is not possible
clinically.

Mastitis of cattle associated with common contagious pathogens

immediately because of the excellent
response to treatment. Treatment of
S. agalactiae mastitis with intramammary
infusions will result in a high percentage
of infections being eliminated economically
and with few residual concerns, provided
the milk withholding times are observed.

Infections at all stages of lactation have
90-100% cure rates with penicillin,
erythromycin, cloxacillin and cepha-
losporins. Gentamicin, neomycin, nitro-
furazone and polymyxin B have poor
activity. Procaine penicillin G is universally
used as a mammary infusion at a dose
rate of 100 000 units. Higher dose rates
have the disadvantage of increasing peni-
cillin residues in the milk. A moderate
increase in efficiency is obtained by using
procaine penicillin rather than the crystal-
line product, and by using 100 000 units of
penicillin in a long-acting base the cure
rate (96%) is significantly better than with
quick -acting preparations (83%).

To provide a broader spectrum of
antimicrobial efficiency penicillin is often
combined with other drugs that are more
effective against Gram-negative organisms.
A mixture of penicillin (100 000 units) and
novobiocin (150 mg) provides a cure rate
ranging from 89-98%. 4 It is necessary to
maintain adequate milk levels for 72 hours:
three infusions at intervals of 24 hours are
recommended, but dosing with two
infusions 72 hours apart, or one infusion
of 100 000 units, in a base containing
mineral oil and aluminum monostearate,
gives similar results. As a general rule
clinical cases should be treated with three
infusions, and subclinical cases, particularly
those detected by routine examination in
a control program, with one infusion.
Recovery, both clinically and bacterio-
logically, should be achieved in at least
90% of quarters if treatment has been
efficient. Intramuscular administration of
ceftiofur is not efficacious as a treatment
to eliminate the organism, compared to
intramammary infusion of penicillin
(100 000 units) and novobiocin (150 mg)
daily for two treatments. 4

Other antimicrobial agents used in the
treatment of S. agalactiae infections
include the tetracyclines and cephalothin,
which are as effective as penicillin and
have the added advantage of a wider anti-
bacterial spectrum, an obvious advantage
when the type of infection is unknown.
Neomycin is inferior to penicillin in the
treatment of S. agalactiae mastitis, while
tylosin and erythromycin appear to have
equal efficacy. A single treatment with
300 mg of erythromycin is recommended
as curing 100% of quarters infected with
S. agalactiae. Lincomycin (200 mg) com-
bined with neomycin (286 mg) and admin-
istered twice at 12-hour intervals also has
good efficacy. In a study of 1927 cases of

subclinical S. agalactiae mastitis in New
York, all commercially available intra-
mammary infusions were more effective
than untreated controls (27% bacteriological
cure), with the following bacteriological
cure rates: amoxicillin (86%), erythromycin
(81%), cloxacillin (77%), cephapiiin (66%),
penicillin (63%), hetacillin (62%), pirlimycin
(44%). 5

In dry cows, one infusion is sufficient,
milk levels of penicillin remaining high
for 72 hours. Cloxacillin eliminated the
organism from 98% and 100% of infected
cows in two different studies. 1

Blitz therapy

The prevalence of subclinical mastitis
due to S. agalactiae can be reduced more
rapidly by treatment of infected cows
during lactation than by dry cow therapy
and postmilking teat dipping. S. agalactiae
is one of the few pathogens causing sub-
clinical mastitis that can be treated econ-
omically during lactation, and can be
eliminated from herds with blitz anti-
microbial therapy followed by good
sanitation procedures. All cows are
sampled and those that are positive are
treated simultaneously with penicillin
and novobiocin. Cows not responsive to
the first treatment are identified and
retreated or culled. Failure to institute
sanitation procedures for the control of
the pathogen may result in subsequent
outbreaks of mastitis. 6

If blitz therapy of all infected cows is
not possible because of the short-term
effect of lost milk production on income,
a modified treatment protocol is rec-
ommended. The herd is divided into two
groups, based on a composite milk SCC
of 500 000. Those cows in the high category
are treated with 300 mg of erythromycin,
intramammarily. When lactating cow
numbers reach their lowest point, all
animals are treated with the same pro-
duct. At drying off, cows are treated with
500 mg cloxacillin and 250 mg ampicillin.

CONTROL

Eradication on a herd basis of mastitis
associated with S. agalactiae is an accepted
procedure and has been undertaken on
an area scale in some countries. The
control measures as outlined later in this
chapter are designed especially for this
disease and should be adopted in detail. If
suitable hygienic barriers against infec-
tion can be introduced and if the infection
can be eliminated from individual quarters
by treatment, the disease is eradicable fairly
simply and economically.

The control program consists of:

® Identifying infected quarters
o Treating infected quarters on two

occasions if necessary
= Culling incurable cows.

The control program is particularly appli-
cable in herds where an unacceptable
level of clinical cases is backed by a high
incidence of subclinical infections. Pre-
milking teat and udder sanitation,
postmilking teat dipping, and dry cow
therapy are vital aspects of the control
program.

Vaccination

Vaccination against S. agalactiae has been
attempted and elicits systemic hyper-
immunity but no apparent intramammary
resistance. Development of an effective
vaccine will be difficult because of the
multiplicity of strains involved and the
known variability between animals in
their reaction to intramammary infection.

Biosecurity

As with any eradication program a high
degree of vigilance is required to maintain
a 'clean' status. This is particularly so with
mastitis due to S. agalactiae. Breakdowns
are usually due to the introduction of
infected animals, even heifers that have
not yet calved, or the employment of
milkers who carry infection with them.
Most dairy farms in the USA are in an
ongoing process of herd expansion or
replacement acquisition by the addition
of purchased animals. Introduction of
contagious mastitis associated with
S. agalactiae, S. aureus and M. bovis is a
common result. It has been recommended
that herd additions should be screened
for these important pathogens;' however,
currently available screening tests do not
have perfect sensitivity.

REVIEW LITERATURE

Keefe GP. Streptococcus agalactiae mastitis: a review.
Can Vet J 1997; 38:429-437.

REFERENCES

1. Keefe GP. CanVet J 1997; 38:429.

2. Rivas AL et al. Am JVet Res 1997; 58:482.

3. Lacy-Hubert SJ, Hillerton JE. J Dairy Res 1995;
62:395.

4. Erskine RJ et al. J Am Vet Med Assoc 1996;
208:258.

5. Wilson DJ et al. J Dairy Sci 1999; 82:1664.

6. Boyer PJ. Vet Rec 1997; 141:55, 84, 108.

7. Wilson DJ, Gonzalez RN. In: Proceedings of 36th
Annual Meeting of National Mastitis Council,
1997:127.

MYCOPLASMA BOVIS AND
OTHER MYCOPLASMA SPECIES

ETIOLOGY

A number of species of Mycoplasma,
especially M. bovis and occasionally
Mycoplasma species group 7, 1 Mycoplasma
F-38, Mycoplasma arginini, Mycoplasma
bovirhinis, Mycoplasma canadensis, Myco-
plasma bovigenitalium, Mycoplasma
alkalescens, 2 Mycoplasma capricolium, 3
Mycoplasma califomicum 4,5 and Mycoplasma
dispar , 6 have been isolated from clinical
cases. Other mycoplasmas, not usually

i6

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

Etiology Mycoplasma bovis, other
Mycoplasma spp.

Epidemiology A highly contagious
mastitis causing outbreaks of clinical
mastitis. Most common in large herds with
recent introductions. Transmitted within
herds by bulk mastitis treatments and poor
milking hygiene. Cows of all ages and any
stage of lactation but those in early
lactation most severely affected
Clinical findings Sudden onset of
clinical mastitis in many cows, usually all
four quarters, marked drop in milk
production and may stop lactating,
swelling of the udder and gross
abnormality of the milk without obvious
signs of systemic illness, eventually udders
atrophy and do not return to production.
Can cause clinical, subclinical and chronic
intramammary infections. Calves suckling
milk from infected cows may develop otitis
media/interna

Clinical pathology Special culture and
staining of milk techniques
Necropsy findings Purulent interstitial
mastitis

Diagnostic confirmation Identification
of pathogen in milk

Differential diagnosis Epidemiology
and clinical findings are characteristic of
mycoplasma mastitis. May resemble other
causes of chronic mastitis unresponsive to
treatment

Treatment Not responsive to commonly
used mastitis treatments protocols. Identify
and cull affected cows for slaughter
Control Prevent entry of infected cows
into herd. Eradicate infection by culling
affected cows

associated with the development of
mastitis, also cause the disease when
injected into the udder. There is also
evidence of mastitis associated with
Ureaplasma spp. 7 A striking characteristic
of the mycoplasmas is that they seem to
be able to survive in the presence of
large numbers of leukocytes in the
milk. Antibodies to the bacteria have not
been detectable in sera or whey from
animals infected with some strains, but
complement-fixing antibodies are present
in the sera of animals recovered from
infection with other strains.

Acholeplasma laidlazuii is not a mastitis
pathogen, but it has been observed that a
high proportion of bulk tanks will give
positive cultural tests for it, especially
during wet, rainy weather. This increase is
accompanied by an increase of clinical
mycoplasmal mastitis due to pathogenic
mycoplasma. A. laidlawii is considered
to be a milk contaminant in these
circumstances.

The group of diseases, including mas-
titis, that are associated with Mycoplasma
spp. in sheep and goats are dealt with
separately.

EPIDEMIOLOGY

Occurrence and prevalence of

infection

The disease has been recorded since the
mid 1960s in the USA, Canada, UK, and
Israel and has been observed in Australia.
The quarter infection rate in infected
herds varies widely.

Source of infection

The epidemiology of the disease has been
incompletely characterized. 8 Mycoplasma
mastitis occurs most commonly in large
herds and in herds where milking hygiene
is poor and when cows are brought in
from other farms or from public saleyards.
Mycoplasma mastitis usually breaks out
subsequently after a delay of weeks or
even months. The delay in development
of an outbreak maybe related to the long-
term persistence of the organism (more
than 12 months) in some quarters, and
some cows become shedders of the
organism without ever exhibiting signs
of severe clinical mastitis. M. bovis was
isolated from milk samples of 5-12% of
cows during two lactations and two dry
periods. 9

M. bovis is capable of colonizing and
surviving in the upper respiratory tract
and the vagina, and extramammary
colonization explains many of its epi-
demiological paradoxes. An interesting
epidemiological observation is the detec-
tion of mycoplasmas and infectious
bovine rhinotracheitis virus in affected
udders at the same time. The virus could
be the much sought-after unknown factor
in the etiology of the disease. Outbreaks
of mastitis are recorded concurrently with
outbreaks of vaginitis and otitis media/
interna vestibulitis. 10

Transmission

Entry of the disease to a herd is usually by
the purchase of animals and their intro-
duction without quarantine. Transmission
within a herd is most commonly at
milking via machine milking or the hands
of milkers. Transmission can also be
through the use of bulk mastitis treat-
ments administered through a common
syringe and cannula. 11 Although the
disease occurs first in the inoculated
quarter there is usually rapid spread to all
other quarters.

Hematogenous spread of M. bovis has
been demonstrated. 1213 Colonization of
body sites other than the mammary gland
is common, and M. bovis isolates from the
respiratory and urogenital systems are
frequently the same M. bovis subtypes
that cause mastitis. 13

Mycoplasma spp. group 7 has also been
isolated from cases of pneumonia and
polyarthritis in calves fed milk from cows
with mycoplasmal mastitis.

Risk factors

Cows of all ages and at any stage of
lactation are affected, cows that have
recently calved showing the most severe
signs and dry cows the least. There are
several recorded outbreaks in dairy herds
in dry cows. 14 one of them immediately
after mammary infusions of dry period
treatment that affected all quarters of
all cows.

Experimental production of the disease 15
with M. bovis causes severe loss of milk
production, a positive CMT reaction and
clots in the milk. 16 Experimental infection
produces little tissue necrosis but Myco-
plasma are detectable in many tissues,
including blood, vagina, and fetus,
indicating that hematogenous spread has
occurred. It is also apparent that spread of
infection between quarters in one cow
can be hematogenous. There are no sig-
nificant pathological differences between
mastitis produced by M. bovigenitalium
and M. bovis ; however, M. bovis remains
the most common cause of mycoplasmal
mastitis in dairy cattle.

Economic importance

The disease is a disastrous one because of
the high incidence in affected herds and
the almost complete cessation of pro
duction for the lactation. Many cows
fail ever to return to milking; as many
as 75% of affected cows may have to be
culled.

PATHOGENESIS

This is a purulent interstitial mastitis.
Although infection probably occurs via
the streak canal, the rapid spread of the
disease to other quarters of the udder and
occasionally to joints suggests indicates
that hematogenous spread may occur.
The presence of the infection in heifers
milked for the first time also suggests that
systemic invasion may be followed by
localization in the udder.

CLINICAL FINDINGS

In lactating cows, there is a sudden onset
of swelling of the udder, a sharp drop in
milk production and grossly abnormal
secretion in one or more quarters. In most
cases all four quarters are affected and a
high -producing cow may fall in yield to
almost nil between one milking and the
next. Dry cows show little swelling of the
udder. Although there is no overt evidence
of systemic illness, and febrile reactions
are not observed in most field cases in
lactating cows, those that have recently
calved show most obvious swelling of the
udder and may be off their feed and have
a mild fever. However, cows infected
experimentally show fever up to 41°C
(105. 5°F) on the third or fourth day after
inoculation, at the same time as the udder
changes appear. The temperature returns

Mastitis of cattle associated with" common contagious pathogens

to normal in 24-96 hours. In some cases
the supramammary lymph nodes are
greatly enlarged. The classic clinical
presentation is severe clinical mastitis
in multiple quarters of multiple cows
with minimal systemic signs of disease.

A few cows, with or without mastitis,
develop arthritis in the knees and fetlocks.
The affected joints are swollen, with the
swelling extending up and down the leg.
Lameness may be so severe that the foot
is not put to the ground. Mycoplasma may
be present in the joint.

The secretion from affected quarters is
deceptive in the early stages in that it
appears fairly normal at collection; on
standing, however, a deposit, which may
be in the form of fine, sandy material,
flakes or floccules, settles out leaving
a turbid whey-like supernatant. Sub-
sequently the secretion becomes scanty
and resembles colostrum or soft cheese
curd in thin serum. The secretion may be
tinged pink with blood or show a gray or
brown discoloration. Within a few days
the secretion is frankly purulent or curdy
but there is an absence of large, firm clots.
This abnormal secretion persists for
weeks or even months.

Affected quarters are grossly swollen.
Response to treatment is very poor and
the swollen udders become grossly
atrophied. In infection with one strain of
the Mycoplasma, many cows do not sub-
sequently come back into production
although some may produce moderately
well at the next lactation. With other strains
there is clinical recovery in 1-4 weeks
without apparent residual damage to the
quarter.

Mycoplasmal mastitis due to
M. bovigenitalium may be very mild and
disappear from the herd spontaneously
and without causing loss of milk
production. 17

CLINICAL PATHOLOGY

The causative organism can be cultured
without great difficulty by a laboratory
skilled in working with Mycoplasma. \
Samples for culture should be freshly j
collected and transported at 4°C, and j
concurrent infection with other bacteria is
common. Diagnosis at the herd level can
be made by culturing bulk tank milk or
milk from cows with clinical mastitis or
increased SCC. However, the sensitivity
of bulk tank milk culturing is poor
(33-5 9%). 18-19 A marked leukopenia, with
counts as low as 1800-2500 cells/pL, is
present when clinical signs appear and
persists for up to 2 weeks. Somatic cell
counts in the milk are very high, usually
over 20 000 000 cells/mL. In the acute
stages the organisms may be able to be
visualized by the examination of a milk

film stained with Giemsa or Wright-
Leishman stain. Species identification of
Mycoplasma isolates is most commonly
done using immunofluorescence and
homologous fluorescein-conjugated anti-
body or an indirect immunoperoxidase
test (immunohistochemistry). Speciation
of the causative Mycoplasma species is
recommended.

NECROPSY FINDINGS

Grossly, diffuse fibrosis and granulomatous
lesions containing pus are present in the
mammary tissue. The lining of the milk
ducts and the teat sinus is thick and
roughened. On histological examination
the granulomatous nature of the lesions is
evident. Metastatic pulmonary lesions
have been found in a few long-standing
cases.

Samples for confirmation of
diagnosis

° Mycoplasmology - chilled mammary
tissue, regional lymph node (special
media)

° Histology - fixed mammary tissue.

DIFFERENTIAL DIAGNOSIS

A presumptive diagnosis can be made
based on the clinical findings, but
laboratory confirmation by culture of the
organism is desirable. The facts that the
organism does not grow on standard
media and that other pathogenic bacteria
are commonly present often lead to errors
in the laboratory diagnosis unless attention
is drawn to the characteristic field findings.

j TREATMENT

j The majority of M. bovis strains isolated
! from cattle are susceptible in vitro
! to fluoroquinolones, florfenicol and
| tiamulin. 20 ' 21 Approximately half of the
| isolates are susceptible to spectinomycin,
j tylosin and oxytetracycline, and very
| few isolates are susceptible in vitro to
gentamicin, tilmicosin, ceftiofur, ampicillin,
or erythromycin. 20,21 The clinical relevance
of these in vitro susceptibility data to
treating mycoplasmal mastitis remains
questionable.

Cows diagnosed with mycoplasmal
mastitis should be considered to be
infected for life. None of the commonly
used antimicrobial agents appear to be
effective and oil-water emulsions used
as intramammary infusions appear to
increase the severity of the disease.
Fhrenteral treatment with oxytetracycline
! (5 g intravenously, daily for 3 days) has
been shown to cause only temporary
improvement. A mixture of tylosin 500 mg j
and tetracycline 450 mg used as an j
infusion cured some quarters. 22 Unless
treatment is administered very early in

the course of the disease, the tissue damage
has already been done.

CONTROL

Prevention of introduction of the disease
into a herd appears to depend upon
avoidance of introductions, or isolating
introduced cows until they can be
checked for mastitis. A popular bio-
security recommendation is to culture the
milk of all replacement cows for M. bovis,
but the sensitivity and specificity of milk
culture in cows with subclinical infections
appears to be low. The disease spreads
rapidly in a herd and affected animals
should be culled immediately or placed in
strict isolation until sale. Eradication of
the disease can be achieved by culling
infected cows identified by culture of milk
and nasal swabs, especially at drying off
and calving. When eradication is com-
pleted the bulk tank milk SCC is the best
single monitoring device to guard against
reinfection. An alternative program
recommended for large herds is the
creation of an infected subherd that is
milked last. There appears to be merit in
the frequent culturing of bulk milk samples
as a surveillance strategy for problem herds
and areas. Frequent culturing overcomes
the poor sensitivity of bulk tank milk
culturing. Cows with infected quarters are
segregated into the subherd and cows
developing clinical illness or decreased
milk yield are culled. 23

Intramammary infusions must be
carried out with great attention to hygiene
and preferably with individual tubes
rather than multidose syringes. Most
commercial teat dips are effective in
control. Use of disposable latex gloves
with disinfection of the gloved hands
between cows may minimize transmission
at milking.

Vaccination is a possible development
but is unlikely to be a satisfactory control
measure because the observed resistance
of a quarter to infection after a natural
clinical episode is less than 1 year. A M. bovis
bacterin is commercially available in the
USA that contains multiple strains of
M. bovis. Autogenous bacterins have also
been made for specific herds; however, no
vaccine has proven efficacy for preventing,
decreasing the incidence of, or decreasing
the severity of clinical signs of mycoplasmal
bovine mastitis. 24

Mycoplasma are sensitive to drying and
osmotic changes, but more resistant
than bacteria to the effects of freezing or
thawing. Amputating the teats of affected
quarters may result in heavy contami-
nation of the environment and is not
recommended. Because M. bovis can cause
respiratory disease, otitis media/interna and
arthritis in calves, all colostrum and waste
j milk fed to calves should be pasteurized.

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

REVIEW LITERATURE

Gonzalez RN, Wilson DJ. Mycoplasmal mastitis in
dairy herds. Vet Clin North Am Large Anim Pract
2003; 19:199-221.

Fox LK, Kirk JH, Britten A. Mycoplasmal mastitis: a
review of transmission and control. J Vet Med B
2005; 52:153-160.

REFERENCES

1. Alexander PG et al. AustVet J 1985; 62:135.

2. Jackson G et al. Vet Rec 1981; 108:31.

3. Taoudi A, Kirchhoff H.Vet Rec 1986; 119:247.

4. Pfutzner H et al. Arch Exp Vet Med 1986;
40:56.

5. Mackie DP et al. Vet Rec 1982; 110:578.

6. Hodges RT et al. N Z Vet J 1983; 31:60.

7. Jurmanova K et al. Arch ExpVet Med 1986; 40:67.

8. Feenstra A et al. J Vet Med B 1991; 38:195.

9. Gonzalez RN, Sears PM. Proc Annu Conv Am
Assoc Bovine Pract 1994; 26:184.

10. Pfutzner H et al. MonatshVet Med 1986; 41:382.

11. Gonzalez RN et al. CornellVet 1992; 82:29.

12. Pfutzner H, Schimmel D. Zentralbl Vet Med A
1985; 32:265.

13. Biddle MK et al. J Am Vet Med Assoc 2005;
227:455.

14. Mackie DP et al. Vet Rec 1986; 119:350.

15. Ball HJ et al. IrVet J 1994; 47:45.

16. Boothby JT et al. Can J Vet Res 1986; 50:200.

17. Jackson G, Boughton E.Vet Rec 1991; 129:444.

18. Gonzalez RN et al. J Am Vet Med Assoc 1986;
189:442.

19. Gonzalez RN et al. J Am \fet Med Assoc 1988;
193:323.

20. Rosenbusch RF et al. J Vet Diagn Invest 2005;
17:436.

21. Thomas A et al. Vet Rec 2003; 153:428.

22. Ball HJ, Campbell AN. Vet Rec 1989; 125:377.

23. Brown MB et al. J Am Vet Med Assoc 1990;
196:1097.

24. Gonzalez RN, Wilson DJ.Vet Clin North Am Large
Anim Pract 2003; 19:199.

CORYNEBA CTERIUM BOVIS

ETIOLOGY

Corynebacterium bovis is a common and
very contagious pathogen that is most
commonly associated with subclinical
infection. However, C. bovis has been
cultured from dairy cattle with clinical
mastitis in 1.7% of cases 1 and, in a herd
that had controlled contagious mastitis
pathogens, C. bovis was the only patho-
gen isolated in 22% of clinical mastitis
episodes. 2 There is considerable debate
about the significance of C. bovis infec-
tions for mammary gland health and cow
productivity. For this reason, C. bovis is
classified as a minor pathogen.

EPIDEMIOLOGY

The main reservoir of infection appears to
be infected glands and teat ducts, and
C. bovis spreads rapidly from cow to cow
in the absence of adequate teat dipping.
C. bovis is extremely contagious and the
duration of intramammary infection is
long (many months). The prevalence of
C. bovis is typically low in herds using an

effective germicidal teat dip, good milking
hygiene and dry cow therapy.

In vivo and in vitro studies have
demonstrated that the bacteria has a
predilection for the streak canal, and this
predilection has been associated with a
requirement for lipids (possibly in the
keratin plug) for growth. 3 It is possible
that C. bovis infection in the streak canal
may compete with ascending bacterial
infections for nutrients and thereby
decrease the new intramammary infec-
tion rate. Alternatively, the mild increase
in SCC associated with C. bovis infection
might increase the ability of the quarter
to respond to a new intramammary
infection.

Intramammary infection with a minor
pathogen induces a higher than normal
SCC and thereby increases the resistance
of the colonized quarter to invasion by a
major pathogen. In particular, the lowest
rate of intramammary infection with
major pathogens is observed in quarters
infected with C. bovis , 4

CLINICAL FINDINGS

An intramammary infection with C. bovis
is infrequently associated with clinical
disease but usually causes a moderate
increase in the SCC and a small increase
in the CMT score. Milk production losses
are usually not detectable, and the mas-
titis is typically a thicker than normal milk
(abnormal milk); occasional cases also
have a large firm gland (abnormal gland). 2
There are clear herd to herd differences in
the apparent clinical pathogenicity of
C. bovis, suggesting that strains of differ-
ent virulence are present.

| TREATMENT

! C. bovis is very susceptible to penicillin,

! ampicillin, amoxicillin, cephapirin, and
| erythromycin, and most other com-
! mercially available intramammary infusions.

! There is no need for parenteral treatment,
i The duration of infection is prolonged
| (months) in animals not treated with
' antimicrobial agents.

[ CONTROL

j Long-term intensive programs of teat
j dipping and dry cow therapy will markedly
j reduce the prevalence of C. bovis. Because
\ of its status as a minor pathogen, specific
| control measures (such as vaccination)
i are not indicated.

i

| REFERENCES

| 1. Sargeant J et al. Can Vet J 1998; 39:33.

2. Morin DE, Constable PD. J Am Vet Med Assoc

1998; 213:855.

3. Black RT et al. J Dairy Sci 1972; 55:413.

4. Lam TJGM et al. Am JVet Res 1997; 58:17.

Mastitis of cattle associated
with teat skin opportunistic
pathogens

COAGULASE-NEGATIVE

STAPHYLOC OCCI

Because of the intense investigation
of coagulase positive staphylococcal mas-
titis (S. aureus), coagulase-negative staphy-
lococcal intramammary infections have
come under closer scrutiny and are now
among the most common bacteria found
in milk, especially in herds in which the
major pathogens have been adequately
controlled. There is considerable debate
about the significance of these pathogens
for the mammary gland and for cow
productivity. For this reason, these patho-
gens are classified as minor pathogens.

ETIOLOGY

Coagulase-negative staphylococci are
common but minor contagious pathogens
that include Staphylococcus epidermidis,
S. hyicus, S. chromogenes, S. simulans, and
Staphylococcus wameri that are normal
teat skin flora, and Staphylococcus xylosus
and Staphylococcus sciuri that come from
an uncertain site.

EPIDEMIOLOGY

Coagulase-negative staphylococci are teat
skin opportunistic pathogens and cause
mastitis by ascending infection via
the streak canal. Coagulase-negative
staphylococci appear to have a protective
effect against colonization of the teat duct
and teat skin by S. aureus and other major
pathogens, 1 with the exception of E. coli
and the environmental streptococci.

Studies in the US found that 20-70%
of heifer quarters are infected before
parturition with coagulase-negative
staphylococci, 2-3 but these infections are
usually eliminated spontaneously or with
antimicrobial therapy during early lactation.
A survey of the prevalence and duration
of intramammary infection in heifers in
Denmark in the peripartum period found
S. chromogenes in 15% of all quarters
before parturition, but this decreased to
1% of all quarters shortly after partur-
ition. 2 In Finland, coagulase-negative
staphylococci are the most commonly
isolated bacteria from milk samples of
heifers with mastitis. 4 Infections with
S. simulans and S. epidermidis occurred in
1-3% of quarters both before and after
parturition. 2 Infection with S. simulans
persisted in the same quarter for several
| weeks, but intramammary infections with
S. epidermidis were transient.

Coagulase-positive S. hyicus and
Staphylococcus intermedius have been
isolated from some dairy herds and can
cause chronic, low-grade intramammary

infection and be confused with S. aureus . 5
The prevalence of infection with S. hyicus
was 0.6% of all cows and 2% of heifers at
parturition; the prevalence of infection of
S. intermedius was less than 0.1% of cows.

CLINICAL FINDINGS

Coagulase-negative staphylococci are
usually associated with mild clinical
disease (abnormal secretion only, occasion-
ally abnormal gland) and are commonly
isolated from mild clinical cases of mas-
titis and subclinical infections. For example,
Staphylococcus spp. have been cultured
from dairy cattle with clinical mastitis in
29% of cases, 6 and subclinical infections
usually induce a moderate increase
in SCC.

CLINICAL PATHOLOGY

Intramammary infections by minor
pathogens such as coagulase-negative
staphylococci result in a higher than
normal SCC and thereby increase the
resistance of the colonized quarter to
invasion by a major pathogen. 7 Although
these bacteria are capable of causing
microscopic lesions, they are not nearly as
pathogenic as S. aureus , 8 and necropsy
reports are lacking.

TREATMENT

Spontaneous cure is common. Coagulase-
negative staphylococci, including
S. chromogenes, S. hyicus and others, are
very susceptible to penicillin, ampicillin,
amoxicillin, clavulanic acid, cephapirin,
erythromycin, gentamicin, potentiated
sulfonamides and tetracyclines. In a study
of 139 cases of subclinical coagulase-
negative staphylococcal mastitis in New
York, the bacteriological cure rates of
commercially available intramammary
infusions were similar to that of untreated
controls (72% bacteriological cure), with
the following bacteriological cure rates:
cephapirin (89%), amoxicillin (87%), j
cloxacillin (76%) and penicillin (68%). lJ j

The use of a combination of novo- j
biocin and penicillin, and cloxacillin as j
dry cow therapy for coagulase-negative j
staphylococci gave cure rates of over
90%. 10

CONTROL

Implementation of a mastitis control
program will be very effective in decreasing
intramammary infection due to coagulase-
negative staphylococci. Because of its
status as a minor pathogen, specific con-
trol measures (such as vaccination) are
not indicated.

REFERENCES

1. Matthews KR et al. J Dairy Sci 1991; 74:1855.

2. Aarestrup FM, Jensen NE. J Dairy Sci 1997;

80:307.

3. Erskine RJ et al. J Dairy Sci 1994; 77:3347.

4. MyllysV. J Dairy Res 1995; 62:51.

5. Roberson JR et al. Am J Vet Res 1996; 57:54.

Mastitis of cattle associated with common environmental pathogens

709

6. Sargeant J et al. Can Vet J 1998; 39:33.

7. Fox LK et al. J Am Vet Med Assocl996; 209:1143.

8. Jarp J.Vet Microbiol 1991; 27:151.

9. Wilson DJ et al. J Dairy Sci 1999; 82:1664.

10. Davidson TJ et al. Can Vet J 1994; 35:775.

Mastitis of cattle associated
with common
environmental pathogens

Environmental mastitis is associated
with bacteria that are transferred from the
environment to the cow rather than from
other infected quarters. E. coli, Klebsiella
spp. and environmental streptococci
are the major pathogens causing environ-
mental mastitis.

COLIFORM MASTITIS
ASSOCIATED WITH ESCHERICHIA
COLI, KLEBSIELLA SPECIES AND
E NTE ROBACTER A EROGENE S

ETIOLOGY

Many different serotypes of E. coli,
numerous capsular types of Klebsiella spp.

Etiology Many different serotypes of
Escherichia coli, numerous capsular types
of Klebsiella spp. and Enterobacter
aerogenes. These are commonly called
coliform bacteria; other Gram-negative
bacteria (such as Pseudomonas aeruginosa)
can cause environmental mastitis but are
not categorized as coliform bacteria.
Epidemiology Dairy cattle housed in
total confinement or drylot; uncommon in
pastured cattle. Most important mastitis
problem in well managed, low-SCC herds.
Quarter infection rate low at 2-4%.
Incidence highest in early lactation.

80-90% of coliform infections result in
clinical mastitis; 8-1 0% are peracute.
Causes clinical mastitis rather than
subclinical mastitis. Source of infection is
environment between milkings, during dry
period and prepartum in heifers. Isolates of
E. coli are opportunists. Sawdust and
shavings bedding contaminated with E. coli
and Klebsiella spp. (particularly
K. pneumoniae ) major source of bacteria;
much worse when wet (rainfall or high
humidity). Coliform intramammary
infection highest during 2 weeks following
drying off and in 2 weeks prior to calving.
Animal risk factors include:

• Low SCC

• Decrease of neutrophil function in
periparturient cow

• High susceptibility in early lactation

• Contamination of teat duct

• Selenium and vitamin E status.

Outbreaks of coliform mastitis do occur,
commonly associated with major change in
management of the environment
(introduction of sawdust for bedding may
result in outbreaks of Klebsiella mastitis).

Clinical findings Acute - swelling of
gland, watery milk with small flakes, mild
systemic response, recovery in few days.
Peracute - sudden onset of severe toxemia,
fever, tachycardia, impending shock; cow
may be recumbent. Quarter may or may
not be swollen and warm, secretions thin .
and serous and contain very small flakes.
May die in few days.

Clinical pathology Culture milk.
Somatic cell count. Marked leukopenia,
neutropenia and degenerative left shift.
Bacteremia may occur, particularly in
severely affected cattle.

Necropsy findings Edema, hyperemia,
hemorrhages and necrosis of mammary
tissue. Major changes in teat and
lactiferous sinuses and ducts; invasion of
organism into parenchyma not a feature of
E. coli.

Diagnostic confirmation. Culture of
organism from milk and high SCC.

Differential diagnosis

• Parturient hypocalcemia paresis

• Carbohydrate engorgement lactic
acidosis

Other causes of acute and severe mastitis
(must culture milk):

• Environmental streptococci

• S. aureus and S. agalactiae

Treatment Must consider status and
requirements for each case based on
severity. Use of antimicrobial agents is
indicated in moderately to severely affected
animals; efficacy uncertain in mild cases.
Some infections become persistent if
antibiotics are not administered. Severely
affected cattle also need supportive fluid
and electrolyte therapy (such as hypertonic
saline), and possibly NSAIDs for
endotoxemia.

Control Manage outbreaks by
examination of environment. Improve
sanitation and hygiene. Regular cleaning of
barns. Dry bedding. Avoid crowding. Keep
dry cows on pasture if possible. Replace
j sawdust and shavings with sand for
j bedding. Emphasize premilking hygiene,

i including premilking germicide teat dipping

| and keep cows standing for at least
j 30 minutes after milking. Core
! lipopolysaccharide antigen vaccine in dry
j period and early lactation to reduce
i incidence of clinical mastitis due to
I Gram-negative bacteria.

I (most commonly K. pneumoniae) and
| Enterobacter aerogenes are responsible for
\ coliform mastitis in cattle. E. coli isolated

I

j from the milk of cows with acute mastitis
i cannot be distinguished as a specific
; pathogenic group on the basis of bio-
: chemical and serological test reactions,
j The incidence of antimicrobial resistance
j is also low in these isolates because they
i are opportunists originating from the
| alimentary tract, from which antimicrobial
j resistant E. coli are rarely found in adults,
i Other Gram-negative bacteria which are

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

not categorized as coliforms but can cause
mastitis include Serratia, Pseudomonas,
and Proteus spp.

EPIDEMIOLOGY
Occurrence of clinical mastitis

The occurrence of coliform mastitis has
increased considerably in recent years
and is a cause for concern in the dairy
industry and amongst dairy practitioners.
Coliform mastitis occurs worldwide and is
most common in dairy cattle that are
housed in total confinement during the
winter or summer months. Where cows
are kept in total confinement in a drylot,
outbreaks of coliform mastitis may occur
during wet, heavy rainfall seasons. The
disease is uncommon in dairy cattle that
are continuously in pasture but it has
been reported in pastured dairy cattle in
New Zealand.

In contrast to contagious mastitis,
environmental mastitis associated with
coliform bacteria is primarily associated
with clinical mastitis rather than subclinical
mastitis. Clinical mastitis associated with
environmental pathogens (including the
environmental streptococci) is now the
most important mastitis problem in well
managed, low-SCC herds. In a survey of
the incidence of clinical mastitis and
distribution of pathogens in dairy herds in
the Netherlands, the average annual
incidence was 12.7 quarter cases per 100
cows per year. The most frequent isolates
from clinical cases were E. coli (16.9%), S.
aureus (14.4%), S. when's (11.9%) and S.
dysgalactiae (S.9%). 1

The incidence of clinical coliform mas-
titis is highest early in lactation and
decreases progressively as lactation
advances. 2 The rate of intramammary
infection is about four times greater
during the dry period than during
lactation. The rate of infection is also
higher during the first 2 weeks of the dry
period and during the 2 weeks before
calving. 80-90% of coliform infections
results in varying degrees of clinical
mastitis in the lactating cow; approxi-
mately 8-10% of coliform infections
result in peracute mastitis, usually within
a few days after calving. The disease also
occurs commonly in herds that concen-
trate calving over a short period of time.

Prevalence of infection

The prevalence of both intramammary
infection and the incidence of clinical
mastitis due to coliform bacteria has
increased, particularly in dairy herds with
a low prevalence of infection and inci-
dence of clinical mastitis due to
S. aureus and S. agalactiae as a result of an
effective mastitis control program. Com-
pared to other causes of mastitis, coliform
infections are relatively uncommon and,
in data based on herd surveys, the

percentage of quarters infected with these
pathogens is low. The percentage of
quarters infected at any one time is
generally low, at about 2-4%.

In the UK, about 0.2% of quarters of
cows may be infected at any one time. 3
Surveillance of a dairy herd in total
confinement in the USA indicated that
infection with coliform bacteria by either
day of lactation or day of the year never
exceeded 3.5% of quarters, and this
maximum was reached on the day of
calving. However, coliform infections may
cause 30-40% of clinical mastitis episodes.
In herds with a problem, up to 8% of cows
have been infected with coliform bacteria,
and 80% of the cases of clinical mastitis
may be due to coliform infections. 4

Duration of infection

Coliform intramammary infections are
usually of short duration. Over 50% last
less than 10 days; about 70% less than
30 days; and only 1.5% exceed 100 days in
duration.

Source of infection and mode of
transmission

The primary reservoir of coliform infec-
tion is the dairy cow's environment
(environmental pathogen); this is in con-
trast to the infected mammary gland,
which is the reservoir of major contagious
pathogens (S. aureus and S. agalactiae) and
the main reservoir of infection in cattle
with M. bovis. Exposure of uninfected
quarters to environmental pathogens can
occur at any time during the life of the
cow, including during milking, between
milkings, during the dry period and
before calving in heifers.

Morbidity and case fatality

In dairy herds with low bulk tank milk
SCCs the average herd incidence of clinical
| mastitis is 45-50 cases per 100 cows
annually, with coliforms isolated from
I 30-40% of the clinical cases. This is similar
to an average incidence of 15-20 cases of
colifonn mastitis per 100 cows in herds with
: low bulk tank milk SCCs. 5 Other obser-
. vations indicate that the number of clinical
cases of colifonn mastitis varies from 3 to
32 per 100 cows per year but the average
incidence in dairy herds can be as low as
6-8 per 100 cows per year.

Colifonn mastitis is one of the most
common causes of fatal mastitis in cattle.
The case fatality rate from peracute colifonn
mastitis is commonly high and may reach
• 80% in spite of intensive therapy. Outbreaks
: of the disease can occur with up to 25% of
recently calved cows affected within a few
| weeks of each other.

Risk factors

i Pathogen risk factors
: The isolates of E. coli from bovine mastitic
! milk are simply opportunist pathogens. 6

The isolates that cause coliform mastitis
possess lipopolysaccharides (endotoxin),
which form part of the outer layer of the
cell wall of all Gram-negative bacteria.
Coliform bacteria isolated from the milk
of cows or from their environment have
different degrees of susceptibility to the
bactericidal action of bovine sera, with
almost all the isolates that cause severe
mastitis being serum-resistant. 7 Serum-
sensitive organisms are unable to multiply
in normal glands because of the activity of
bactericidins reaching milk from the
blood. Of the strains of E. coli isolated
from cases of mastitis in cattle in England
and Wales, only those that were seaim-
resistant were re-isolated from expressed
milk following intramammary inoculation
of lactating cows. Other observations
indicate that serum -resistant coliforms
have no selected advantage over serum-
susceptible coliforms in naturally occur-
ring intramammary infections. There are
also somatic and capsular factors of
coliforms that affect resistance to bovine
bactericidal activity. Strains of Klebsiella
that cause mastitis are also resistant to
bovine serum. The fibronectin binding
property of E. coli from bovine mastitis
may be an important virulence factor that
allows the organism to adhere to the
ductular epithelium.

Environmental risk factors
All the environmental components that
come in contact with the udder of the cow
are considered potential sources of the
organisms. The coliform bacteria are
opportunists, and contamination of the
skin of the udder and teats occurs
primarily between milkings when the cow
is in contact with contaminated bedding
rather than at the time of milking. Feces,
which are a common source of E. coli, can
contaminate the perineum and the udder
directly or indirectly through bedding,
l calving stalls, drylot grounds, udder wash
water, udder wash sponges and cloth
rags, teat cups and milkers' hands. Cows
with chronic coliform mastitis also
provide an important source of bacteria,
and direct transmission probably occurs
through the milking machine. Inadequate
drying of the base of the udder and the
teats after washing them prior to milking
can lead to a drainage of coliform-
contaminated water down into the teat
cups and subsequent infection.

Bedding

Sawdust and shavings used as bedding
that are contaminated and harbor E. coli,
! and particularly K. pneumoniae, are major
: risk factors for coliform mastitis. Cows
; bedded on sawdust have the largest teat
i end population of total coliforms and
j klebsiellae; those bedded on shavings
! have an intermediate number and those

Mastitis of cattle associated with common environmental pathogens

on straw have the least. Experimentally,
the incubation of bedding samples at
30-44°C (86-lll°F) resulted in an
increase in the coliform count; at 22°C
(71°F) the count was maintained, and at
50°C (122°F) the bacteria were killed. Wet
bedding, particularly sawdust and
shavings, promotes the growth of
coliform bacteria, especially Klebsiella spp.

The relationship between the bedding
populations of Enterobacteriaceae was
studied over a 12-month period in a dairy
herd. The analyses revealed that rainfall
bedding populations of E. coli and coliform
mastitis incidence were statistically in-
dependent, while there was a strong
association between rainfall and
K. pneumoniae bedding populations and
the incidence of K. pneumoniae mastitis.
The lack of an association between
bedding population of E. coli and coliform
mastitis, along with the observation that
cows are most susceptible immediately
after parturition, suggest that the ability
of the bacteria to penetrate the streak
canal may be a factor of resistance in the
cow and not a characteristic of the
organism. Also, it appears that the cow in
early lactation is not as susceptible to
K. pneumoniae as to E. coli.

The ability of several different bedding
materials to support the growth of environ-
mental pathogens has been outlined under
controlled conditions. Bedding materials
vary in their ability to support growth of
different pathogens, and under barn
conditions it appears that high bacterial
counts are influenced by factors more
complex than type of bedding alone. Even
clean damp bedding may support
bacterial growth.

High populations of colifonn bacteria on
the teat end, unless accompanied by actual
chronic quarter infection, are probably
transitory and represent recent environ-
mental contamination that would usually
be eliminated by an effective sanitation
program at milking time. However, any teat
skin population, whether associated with
infection in another quarter, from contami-
nated teat cup liners or from other environ-
mental sources, must be considered as a
potential source of new infection.

Animal risk factors

Factors that influence the susceptibility of
cows to coliform mastitis include the SCC
of the milk, the stage of lactation and the
physiological characteristics and defense
mechanisms of the udder (particularly the
speed of neutrophil recruitment), teat
characteristics, and the ability of the cow
to counteract the effects of the endotoxins
elaborated by the organisms.

Somatic cell count

Experimentally, an SCC of 250 000 cells/mL
in the milk of a quarter may limit signifi-

cant growth of bacteria and development
of mastitis when small inocula of coliform
organisms are experimentally introduced
into the gland. 7 Somatic cell counts of
500 000 cells/mL provided complete
protection. 8 Thus cows in herds with a
low incidence of streptococcal and
staphylococcal mastitis have a low milk
SCC and are more susceptible to coliform
mastitis. Dairy herds with low herd bulk
tank milk SCCs may have a greater
incidence of severe toxic mastitis than
herds with higher counts. 8

Neutrophil recruitment and function
Increased susceptibility to coliform mas-
titis in the periparturient cow is primarily
due to impaired neutrophil recruitment
to the infected gland. 9 In fatal cases of
peracute mastitis in cows within 1 week
after parturition there may be large num-
bers of bacteria in mammary tissues and
an absence of neutrophilic infiltration.
Other observations indicate a high cor-
relation between poor preinfection chemo-
tactic activity of blood neutrophils and
susceptibility to intramammary E. coli
challenge exposure. 10 Experimentally, in
periparturient cows the inability to recruit
neutrophils rapidly into the mammary
gland following intramammary infection
is associated with an overwhelming
bacterial infection and peracute highly
fatal mastitis. 9 The periparturient cows are
unable to control bacterial growth during
the first few hours after bacterial inocu-
lation and consequently the bacterial load
is much higher when neutrophils finally
enter the milk. The lack of neutrophil
mobilization could be due to:

° Failure to recognize bacteria
° Lack of production of inflammatory
mediators

o A defect in the ability of the cells to
move into the milk compartment.

In ketonemic cows, experimental E. coli
mastitis is severe, regardless of pre-
infection chemotactic response. 11

High levels of cytokines are present in
the milk of cows that lack the ability to
recruit leukocytes, which is evidence that
the cells recognized the bacteria. 9 All of
this suggests that the critical defect is in
the neutrophils of the periparturient cow.
Certain cell-surface receptors on leuko-
cytes may be important defense mechan-
isms against E. coli polysaccharides. 12
Bovine mammary neutrophils possess
cell surface C14 and C18 and lectin-
carbohydrate interactions mediating non-
opsonic phagocytosis of E. coli, which
may be important in controlling these
infections.

Selenium and vitamin E status

The positive effects of supplemental

vitamin E and selenium on mammary

gland health are well established. An ade-
quate dietary level of selenium enhances
the resistance of the bovine mammary
gland to infectious agents. Experimentally
induced intramammary E. coli infections
are significantly more severe, and of
longer duration, in cows whose diets have
been deficient in selenium than in cows
whose diets were supplemented with
selenium. The enhanced resistance is
thought to be associated with a more
rapid diapedesis of neutrophils into the
gland of cows fed diets supplemented
with selenium, which limits the numbers
of bacteria in the gland during infection.

Vitamin E is especially important to
mammary gland health during the
peripartum period. Plasma concentrations
of alpha-tocopherol begin to decline at
7-10 days before parturition, reach nadir
at 3-5 days after calving and then start
increasing. 13 When plasma concentrations
are maintained during the peripartum
period by injections of alpha-tocopherol,
the killing ability of blood neutrophils is
improved. 14 The supplementation of the
diets of dry cows receiving 0.1 ppm of
selenium in their diets with vitamin E at
1000 IU/d reduced the incidence of
clinical mastitis by 30% compared to cows
receiving 100 IU/d. The reduction was
88% when cows were fed 4000 IU/d of
vitamin E during the last 14 days of the
dry period. 2

There are also marked effects of dietary
selenium on milk eicosanoid concen-
trations in response to an E. coli infection,
which may be associated with the altered
pathogenesis and outcome of mastitis in a
selenium-deficient state. 15

Stage of lactation and defense
mechanism

Coliform mastitis occurs almost entirely
in the lactating cow and rarely in the dry
cow. The disease can be produced experi-
mentally in lactating quarters much more
readily than in dry quarters.' The differ-
ence in the susceptibility may be due to
the much higher SCCs and lactoferrin con-
centrations in the secretion of dry quarters
than in the milk of lactating quarters. Cows
with known uninfected quarters at drying
off may develop peracute coliform mastitis
at calving, suggesting that infection
occurred during the dry period. New intra-
mammary infections can occur during the
nonlactating period, especially during the
last 30 days, remain latent until parturition
and cause peracute mastitis after parturition.

The rate of coliform intramammary
infection is highest during the 2 weeks
following drying off and in the 2 weeks
before calving. The fully involuted mam-
mary gland appears to be highly resistant
to experimental challenge by E. coli but it
becomes susceptible during the immediate

2

PART 1 GENERAL MEDICINE ■ Chapter 15: Diseases of the mammary gland

prepartum period. More than 93% of
E. coli intramammary infection associated
with the nonlactating period originated
during the second half of that period. 16

Several physiological factors may
influence the level of resistance of the
nonlactating gland to coliform infection.
The rate of new intramammary infection
is highest during transitions of the mam-
mary gland from lactation to involution
and during the period of colostrum
production to lactation. There can be a
sixfold increase in coliform infections
from late lactation to early involution but
50% of these new infections do not
persist into the next lactation. Also, the
rate of spontaneous elimination of minor
pathogens is high during the nonlactating
period. The difference in susceptibility or
resistance to new intramammary infec-
tion may be due, in part, to changes in
concentration of lactoferrin, IgG, bovine
serum albumin and citrate, which are
correlated with in vitro growth inhibition
of K. pneumoniae, E. coli, and S. uberis.

There is also a slower increase in
polymorphonuclear neutrophils in milk
after new intramammary infection in
early lactation than in mid and late
lactation. These conditions may explain
the occurrence of peracute coliform
mastitis in early lactation. This suggests
latent infection or, more likely, that
infection occurred at a critical time just a
few days before and after calving, when
the streak canal became patent and the
population of coliform bacteria on the
teat end was persistently high because
the cow was not being milked routinely
and thus would not be subjected to udder
washing and teat dipping. Coliform
bacteria can pass through the streak canal
unaided by machine milking - this may
be associated with the high incidence of
coliform mastitis in high-yielding older
cows, which may have increased patency
of the streak canal with age.

Newly calved cows can be classified as
moderate or severe responders to experi-
mentally induced coliform mastitis.
Following infection there is a diversity of
responses varying from very mild to very
acute inflammation of the gland and
evidence of systemic effects such as fever,
anorexia and discomfort. 17 Losses in milk
yield and compositional changes are most
pronounced in inflamed glands and, in
severe responders; milk yield and compo-
sition did not return to preinfection levels.
It is proposed that the severe and long-
lasting systemic disturbances in severe
responders can be attributed to absorp-
tion of endotoxin.

In summary, coliform mastitis is more
severe in periparturient cows because of
inability to slow bacterial growth early
after infection. This inability is associated

with low SCC before challenge and slow
recruitment of neutrophils. 9 There may
also be deficits in the ability of leukocytes
to kill bacterial pathogens.

Contamination of teat duct
The sporadic occurrence of the disease
may be associated with the use of
contaminated teat siphons and mastitis
tubes and infection following traumatic
injury to teats or following teat surgery.
Several teat factors are important in the
epidemiology of E. coli mastitis. It is
generally accepted that E. coli is common
in the environment of housed dairy cows
and that mastitis can be produced
experimentally by the introduction of as
few as 20 organisms into the teat cistern
via the teat duct. However, the processes
by which this occurs under natural
conditions are unknown. E. coli does not
colonize the healthy skin of the udder or
the teat duct.

The teat duct normally provides an
effective barrier to invasion of the mam-
mary gland by bacteria. As a result of
machine milking there is some relaxation
of the papillary duct, followed by gradual
reduction in the duct lumen diameter in
the 2 hours following milking. This period
of relaxation after milking may be a risk
factor predisposing to new intramammary
infection.

Experimental contamination of the
teat ends with a high concentration of
coliform bacteria by repeated wet contact,
however, does not necessarily result in an
increase in new intramammary infection.
The experimental application of high
levels of teat end contamination with
E. coli after milking repeatedly led to high
rates of intramammary infection, which
suggests that penetration of the teat duct
by E. coli occurs in the period between
contamination and milking. Milking
machines that produce cyclic and irregular
vacuum fluctuations during milking can
result in impacts of milk against the teat
ends, which may propel bacteria through
the streak canal and increase the rate of
new infections due to E. coli and out-
breaks of peracute coliform mastitis.

Downer cows

Cows affected with the downer cow
syndrome following parturient paresis, or
recently calved cows that are clinically
recumbent for any reason, are susceptible
to coliform mastitis because of the gross
contamination of the udder and teats
with feces and bedding.

Other defense factors

Lactoferrin and citrate

The failure of lactoferrin within mammary

secretions to prevent new infections and

mastitis near and after parturition may

be due to a decrease in lactoferrin before

parturition. Lactoferrin normally binds
the iron needed by iron-dependent
organisms; these multiply excessively i n
the absence of lactoferrin. Also, citrate
concentrations increase in mammary
secretions at parturition and may interfere
with iron-binding by lactoferrin.

Serum antibody to E. coli

The serum IgG t ELISA titers recognizing
core lipopolysaccharide antigens of E. coli
J5 in cattle are associated with a risk cf
clinical coliform mastitis. Titers less than
1:240 were associated with 5.3 times the
risk of clinical coliform mastitis. Older
cattle in the fourth or greater lactations
were also at greater risk, even though
titers increased with age. There is a titer-
independent age-related increase in
clinical coliform mastitis. Active immu-
nization of cattle with an Rc-mutant
E. coli Q5) vaccine resulted in a remark-
able decrease in the incidence of clinical
coliform mastitis. 18

PATHOGENESIS

After invasion and infection of the mam-
mary gland, E. coli proliferates in large
numbers and releases endotoxin on
bacterial death or during rapid growth
when excess bacterial cell wall is pro-
duced. Endotoxin causes a change in
vascular permeability, resulting in edema
and acute swelling of the gland and a
marked increase in the number of
neutrophils in the milk. 7 The neutrophil
concentrations may increase 40-250 times
and strongly inhibit the survival of E. colid
This marked diapedesis of neutrophils is
associated with the remarkable systemic
leukopenia and neutropenia that occurs
in peracute coliform mastitis. The severity
of the disease is influenced by:

• The degree of the pre-existing
neutrophils in the milk
0 The rate of invasion and total number
of neutrophils that invade the infected
gland

° The susceptibility of the bacteria to
serum bactericidins that are secreted
into the gland

° The amount of endotoxin produced. 19

Stage of lactation

The severity of disease is dependent on
the stage of lactation. Experimental infec-
tion of the mammary gland of recently
calved cows with E. coli produces a more
severe mastitis when compared with
animals in midlactation. This may be due
to a delay in diapedesis of neutrophils
into the mammary gland of recently
calved cows. Furthermore, because of this
delay there may be no visible changes in
the milk for up to 15 hours after infection,
but the systemic effects of the endotoxin
released by the bacteria are evident in the
cow (fever, tachycardia, anorexia, rumen

Mastitis of cattle associated with common environmental pathogens

hypomotility or atony, mild diarrhea). The
net result is endotoxemia, which persists
as long as bacteria are multiplying and
releasing endotoxin. This persistent
endotoxemia is probably a major cause
of failure to respond to therapy compared
to the transient endotoxemia in the
experimental inoculation of one dose of
endotoxin.

Neutrophil response

The final outcome is highly dependent on
the degree of neutrophil response. 20 If the
neutrophil response is delayed and
growth of the organisms is unrestricted,
the high levels of toxin produced could
cause severe destruction of udder tissue
and general toxemia. If the animal
responds quickly there is often little effect
on milk yield because the injury is
confined to the sinuses without involve-
ment of secretory tissues. 7 The ability of
the neutrophils to kill E. coli varies among
cows. Experimental infection of the mam-
mary gland of cows with E. coli results in
the stimulation of a long-lasting opsonic
activity for the phagocytosis and killing of
the homologous strain of the organism by
neutrophils. Thus it is not opsonic
deficiency that is the problem in early
lactation but rather a failure of rapid
migration of neutrophils into the gland
cistern.

The rapidity and efficiency of the
neutrophil response are major factors in
determining the outcome. 21 If the
neutrophil response is rapid, clinical
disease will be mild or go undetected,
self-cure will occur and the cow returns to
normal; the milk may be negative for the
bacteria. This may be one important cause
of an increase in the percentage of clinical
mastitis cases in which no pathogens can
be isolated from the milk. Failure of the
cow to mount a significant neutrophil
response results in the multiplication of
large numbers of bacteria, the elaboration
of large amounts of endotoxin and severe
highly fatal toxemia. In these cases,
bacteria are readily cultured from the
milk. In less serious and nonfatal cases,
the recruitment of neutrophils does not
fail but is delayed; this results in acute
clinical mastitis with progressive inflam-
mation and permanent loss of secretory
function. The bacteria are not always
readily eliminated from the infected gland
by the neutrophils. Coliform bacteria may
remain latent in neutrophils and, in
naturally occurring cases, it is not un-
common to be able to culture the organ-
ism from the mammary gland during and
after both parenteral and intramammary
antibacterial therapy.

Numbers of bacteria in milk

The numbers of bacteria in the milk also
influence the outcome. If bacterial num-

bers exceed 10 6 cfu/mL, the ability of the
neutrophil to phagocytose is impaired. If
the bacterial count is less than 10 3 cfu/mL
at 12 hours postinfection, the bacteria will
be rapidly eliminated and the prognosis
will be favorable. This response is seen as
a subacute form of the disease with
spontaneous self-cure. If the neutrophil
response is slow or delayed, the cow will
exhibit more severe signs of coliform
mastitis due to toxemia. This is most
common in recently calved cows and is
characterized clinically by a serous
secretion in the affected quarter that later
becomes watery, fever, depression,
ruminal hypomotility and mild diarrhea.
The prognosis in these cases is unfavor-
able. These more severe forms of coliform
mastitis usually occur after calving and in
the first 6 weeks of lactation. Cows with
coliform mastitis in mid to late lactation
generally generate a rapid neutrophil
response rate and their prognosis is likely
to be favorable.

Experimental endotoxin-induced
mastitis

In an attempt to further understand the
pathogenesis of coliform mastitis, the
effect of experimentally introducing E. coli
endotoxin into the mammary gland has
been examined. The intramammary infu-
sion of 1 mg E. coli endotoxin induces
acute mammary inflammation and tran-
sient, severe shock from which cows
recover within 48-72 hours. 22 Udder
edema is apparent within 2 hours but